@precisa-saude/fhir 0.37.0 → 0.37.1

package/dist/chunk-H64L6SOV.cjs.map

@@ -1 +0,0 @@
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* Biomarker Reference Ranges\n *\n * Single source of truth for biomarker reference ranges used by both\n * web app (for display) and API (for fallback when LLM doesn't extract ranges).\n *\n * Data sources (priority order):\n * 1. Brazilian Government - SBPC/ML (Sociedade Brasileira de Patologia Clínica) guidelines\n * 2. International Standards - WHO, clinical laboratory guidelines\n * 3. Specific Labs - Fleury, Weinmann, Quest, LabCorp (when above unavailable)\n */\n\nimport { getCanonicalUnit as getCanonicalUnitForCode } from './units';\n\n// =============================================================================\n// TYPES\n// =============================================================================\n\n/**\n * Sex-specific key for reference ranges\n */\nexport type SexKey = 'M' | 'F' | 'all';\n\n/**\n * Pré-condição de jejum para a faixa de referência.\n *\n * - `strict`: coleta exige jejum mínimo (ex.: glicemia de jejum, insulina).\n * - `preferred`: jejum recomendado, mas faixa aplicável em não-jejum\n *   (ex.: perfil lipídico pós-SBC 2017, com corte de triglicérides distinto).\n * - `not-required`: valor independe do estado prandial (ex.: HbA1c, TSH).\n */\nexport type FastingRequirement = 'strict' | 'preferred' | 'not-required';\n\n/**\n * Que tipo de afirmação a faixa faz. As três respondem perguntas diferentes, e\n * uma banda de \"faixa normal\" que as misture diz coisas diferentes conforme o\n * marcador.\n *\n * - `reference-interval`: o intervalo de referência do ensaio, tirado de uma\n *   população de referência saudável (percentis centrais, ou o percentil 99\n *   no caso das troponinas). Estar fora dele é estar fora do esperado para\n *   quem não tem a doença.\n * - `decision-threshold`: limiar de decisão de diretriz ou de estudo de risco\n *   (meta de LDL, corte de pré-diabetes, estágio de DRC). Diz o que fazer, e\n *   não como o valor se distribui em gente saudável.\n * - `population`: como o valor se distribui numa população, sem filtrar por\n *   saúde (NHANES, coortes de base populacional). Descreve, não julga.\n *\n * Em FHIR, o primeiro vira `normal` e o segundo `recommended` no\n * `referenceRange.type`; o terceiro não tem código próprio no\n * `referencerange-meaning`. Ver `referenceRangeMeaning`.\n */\nexport type RangeKind = 'reference-interval' | 'decision-threshold' | 'population';\n\n/**\n * Se um limite da faixa é corte clínico ou está ali para o desenho.\n *\n * `display` é o limite que existe para a faixa ter dois lados no gauge ou na\n * banda, e que não deve virar flag: o teto de 100 mg/dL do HDL, o piso 2 da\n * HbA1c. Ausente quer dizer `clinical`, que é o caso comum e o comportamento\n * de sempre da comparação crua.\n */\nexport type BoundKind = 'clinical' | 'display';\n\n/**\n * Reference range configuration for a biomarker\n */\nexport interface BiomarkerReferenceRange {\n  /**\n   * Pré-condição de jejum para a interpretação da faixa. Opcional;\n   * consumidores devem aplicar sinalização adequada quando `strict`.\n   */\n  fastingRequired?: FastingRequirement;\n  /**\n   * Tipo da faixa. Propagado do `BiomarkerRangeDefinition` (ou da variante que\n   * casou) no momento da consulta, como o `source`.\n   */\n  kind?: RangeKind;\n  max?: number;\n  /** Ver `BoundKind`. Ausente vale `clinical`. */\n  maxKind?: BoundKind;\n  min?: number;\n  /** Ver `BoundKind`. Ausente vale `clinical`. */\n  minKind?: BoundKind;\n  optimalMax?: number;\n  optimalMin?: number;\n  /**\n   * Chave de fonte bibliográfica (ex.: `'sbc-lipids-2025'`). Propagada\n   * do `BiomarkerRangeDefinition` no momento da consulta; ausente em\n   * faixas declaradas diretamente sem uma definição completa.\n   */\n  source?: string;\n  unit: string;\n  warningMax?: number;\n  /**\n   * Análogo de `warningMax` para marcadores `higher-better`. Define o limite\n   * inferior da zona de atenção (âmbar): valores entre `warningMin` e `min`\n   * são âmbar e abaixo de `warningMin` são vermelhos. (`warningMax` cobre o\n   * caso `lower-better`, com a zona âmbar acima de `max`.)\n   */\n  warningMin?: number;\n}\n\n/**\n * Trimestre gestacional. Usado em variantes e no contexto de consulta\n * para matching de faixas específicas da gestação.\n */\nexport type PregnancyTrimester = 1 | 2 | 3;\n\n/**\n * A variant of a reference range that applies to a specific sex, age group,\n * and/or pregnancy state.\n *\n * Ordem de avaliação: variantes são processadas na ordem em que aparecem.\n * Para que usuárias gestantes recebam a variante gestacional correta,\n * essas variantes devem ser listadas **antes** das variantes por idade/sexo.\n */\nexport interface RangeVariant {\n  ageMax?: number;\n  ageMin?: number;\n  /**\n   * Tipo da faixa desta variante, quando ela vem de outra fonte que a da\n   * definição. Ausente herda o `kind` da definição.\n   */\n  kind?: RangeKind;\n  pregnancyTrimester?: PregnancyTrimester;\n  /**\n   * Quando `true`, a variante só se aplica a contextos de gestação.\n   * Se `pregnancyTrimester` estiver definido, o trimestre deve coincidir.\n   */\n  pregnant?: boolean;\n  range: BiomarkerReferenceRange;\n  sex: SexKey;\n}\n\n/**\n * Extended biomarker range definition with sex/age-specific variants\n */\n/**\n * Direction indicates whether exceeding the reference range on one side is benign.\n * - 'range': both above-max and below-min are abnormal (default)\n * - 'higher-better': above-max is normal (e.g., BMC, HDL)\n * - 'lower-better': below-min is normal (e.g., LDL, CRP)\n */\nexport type RangeDirection = 'range' | 'higher-better' | 'lower-better';\n\nexport interface BiomarkerRangeDefinition {\n  default: BiomarkerReferenceRange;\n  /**\n   * Para que lado o marcador melhora. Serve à cor e ao gauge.\n   *\n   * Não decide flag: se um limite é corte clínico é o `minKind`/`maxKind` da\n   * faixa que diz, e quem compara valor com faixa usa `flagAgainstCatalogRange`.\n   * Até a 0.33 o `direction` fazia os dois trabalhos, e eles se separam na\n   * composição corporal: o `BodyFatPct` é `lower-better` e o piso dele é\n   * clínico.\n   */\n  direction?: RangeDirection;\n  /**\n   * Tipo da faixa. Opcional no tipo para não quebrar quem monta definições\n   * próprias; todo o catálogo declara, e um teste garante.\n   */\n  kind?: RangeKind;\n  /**\n   * O código LOINC para o qual a faixa vale, quando ela depende do ensaio ou\n   * da convenção de medida: o D-dímero em FEU, a troponina de um ensaio\n   * específico, a Lp(a) molar. Um teste exige que seja o mesmo código do\n   * biomarcador em `biomarkers.ts`.\n   *\n   * Só nessas faixas, e não em todas: a maioria das fontes (Tietz, a PNS) não\n   * é de um código ou ensaio, e declarar ali só copiaria o código do catálogo\n   * sem conferir nada. Foi esse descasamento, entre o código DDU e a faixa FEU\n   * do D-dímero, que nenhum teste de eixo pegou.\n   */\n  loinc?: string;\n  /**\n   * Chave de fonte bibliográfica, opcionalmente com localizador.\n   *\n   * Formato: `'chave'` ou `'chave:localizador'`\n   *\n   * Exemplos:\n   * - `'sbc-lipids-2017'` — fonte sem localização específica\n   * - `'sbc-lipids-2017:p15'` — página 15\n   * - `'sbpc-ml-2021:t4.1'` — tabela 4.1\n   *\n   * As chaves devem corresponder a entradas em `SOURCE_REGISTRY` (sources.ts).\n   * Consulte `docs/fontes-referencia.md` para a bibliografia completa em formato ABNT.\n   */\n  source?: string;\n  variants?: RangeVariant[];\n}\n\n/**\n * User context for personalized reference range lookup.\n *\n * Para gestação, defina `pregnant: true` e, quando disponível,\n * `pregnancyTrimester` para obter a variante trimestre-específica.\n */\nexport interface ReferenceRangeContext {\n  age?: number;\n  biologicalSex?: 'M' | 'F';\n  pregnancyTrimester?: PregnancyTrimester;\n  pregnant?: boolean;\n}\n\n// =============================================================================\n// BIOMARKER RANGE DEFINITIONS\n// =============================================================================\n\n/**\n * Comprehensive biomarker reference range definitions with sex/age-specific variants\n *\n * Each marker has a default range (used as fallback) and optional variants\n * for sex/age-specific ranges.\n */\nexport const biomarkerRangeDefinitions: Record<string, BiomarkerRangeDefinition> = {\n  Albumin_Creatinine_Ratio: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/g' },\n    kind: 'decision-threshold',\n    source: 'tietz-7ed-2015',\n  },\n\n  Adiponectin: {\n    default: { max: 26, min: 4, optimalMax: 20, optimalMin: 8, unit: 'mcg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  ADMA: {\n    default: { max: 0.7, min: 0.3, optimalMax: 0.55, optimalMin: 0.3, unit: 'umol/L' },\n    kind: 'reference-interval',\n    source: 'nemeth-adma-2017',\n  },\n\n  AFP: {\n    default: { max: 10, min: 0, optimalMax: 8, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  Albumin_Globulin_Ratio: {\n    default: { max: 2.5, min: 1.0, optimalMax: 2.2, optimalMin: 1.2, unit: '' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Albumin: {\n    default: { max: 5.0, min: 3.5, optimalMax: 4.8, optimalMin: 4.0, unit: 'g/dL' },\n    kind: 'reference-interval',\n    source: 'pns-bioquimica-2019',\n  },\n\n  AlkalinePhosphatase: {\n    default: { max: 147, min: 44, optimalMax: 120, optimalMin: 50, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 147, min: 44, optimalMax: 120, optimalMin: 50, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 104, min: 35, optimalMax: 90, optimalMin: 40, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  ALT: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 56, min: 7, optimalMax: 35, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 45, min: 7, optimalMax: 30, optimalMin: 10, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // AMH — fortemente dependente de idade e sexo. As variantes femininas por\n  // faixa etária são a referência clínica; o `default` foi ajustado para\n  // refletir uma faixa adulta conservadora (~18-40 anos, mulheres em idade\n  // reprodutiva geral). optimalMax anterior (6.9 ng/mL) sobrepunha-se a\n  // valores sugestivos de SOP ou risco de OHSS; clinicamente, valores acima\n  // de ~4 ng/mL já merecem investigação.\n  AMH: {\n    default: { max: 6.0, min: 1.0, optimalMax: 4.0, optimalMin: 1.5, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 24,\n        ageMin: 18,\n        range: { max: 13.0, min: 1.5, optimalMax: 10.0, optimalMin: 3.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 30,\n        ageMin: 25,\n        range: { max: 10.0, min: 1.5, optimalMax: 8.0, optimalMin: 2.5, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 35,\n        ageMin: 31,\n        range: { max: 8.0, min: 1.0, optimalMax: 6.0, optimalMin: 2.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 40,\n        ageMin: 36,\n        range: { max: 6.0, min: 0.5, optimalMax: 4.0, optimalMin: 1.0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 41,\n        range: { max: 3.0, min: 0.1, optimalMax: 2.0, optimalMin: 0.5, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Ammonia: {\n    default: { max: 45, min: 15, optimalMax: 40, optimalMin: 20, unit: 'umol/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  AntiThyroglobulin: {\n    default: { max: 115, min: 0, optimalMax: 40, optimalMin: 0, unit: 'IU/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  AntiTPO: {\n    default: { max: 34, min: 0, optimalMax: 9, optimalMin: 0, unit: 'IU/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Aortic valve calcium — no standardized clinical threshold; use mild cutoff\n  // Cálcio de válvula aórtica — usa mesma classificação Agatston\n  AorticValveCalcium: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  ApoA1: {\n    default: { max: 200, min: 100, optimalMax: 180, optimalMin: 120, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'contois-apoa1-1996',\n  },\n\n  ApoB: {\n    default: { max: 90, min: 0, optimalMax: 70, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  ApoCIII: {\n    default: { max: 10, min: 0, optimalMax: 7, optimalMin: 0, unit: 'mg/dL' },\n    kind: 'decision-threshold',\n    source: 'khetarpal-apociii-2016',\n  },\n\n  Omega6_AA: {\n    default: { max: 15.0, min: 5.0, optimalMax: 12.0, optimalMin: 7.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  // Razão Ácido Araquidônico/EPA (sangue total) — `lower-better`: razão menor =\n  // menos eicosanoides pró-inflamatórios. NÃO há intervalo de referência\n  // validado em periódico para esta razão; o intervalo 3,7–40,7 é o de\n  // referência laboratorial do ensaio Quest/Cleveland HeartLab OmegaCheck®\n  // (população interna do laboratório, sem fonte primária publicada). É\n  // corroborado por Torrissen 2025 (>500 mil amostras de sangue total): a\n  // mediana brasileira (≈18,8) e as ocidentais (EUA ≈22,3; Europa ≈14,2) caem\n  // dentro do intervalo. Sem `optimal*`: não há corte ótimo de AA/EPA com fonte.\n  // Em telas de relatório único, prefira o intervalo impresso pelo laboratório.\n  AA_EPA_Ratio: {\n    default: { max: 40.7, min: 3.7, minKind: 'display', unit: '' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'torrissen-omega3-dbs-2025',\n  },\n\n  Arsenic: {\n    default: { max: 35, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mcg/L' },\n    kind: 'decision-threshold',\n    source: 'nr7-pcmso-2020',\n  },\n\n  AST: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 40, min: 10, optimalMax: 30, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 32, min: 9, optimalMax: 25, optimalMin: 10, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // `Basophils` (%) fica sem faixa de propósito e `Basophils_Abs` usa os limites da\n  // Tabela 2 da PNS 2019. Ver o comentário em `Neutrophils_Abs`.\n  Basophils_Abs: {\n    default: { max: 0.072, min: 0, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      { ageMin: 18, range: { max: 0.062, min: 0, unit: 'K/uL' }, sex: 'M' },\n      { ageMin: 18, range: { max: 0.072, min: 0, unit: 'K/uL' }, sex: 'F' },\n    ],\n  },\n\n  Bicarbonate: {\n    default: { max: 29, min: 23, optimalMax: 28, optimalMin: 24, unit: 'mEq/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // β-Hidroxibutirato (BHB) sérico — corpos cetônicos. Faixa derivada de\n  // amostra populacional não-jejum (German National Cohort, n=304, 20–69 a)\n  // como percentis 2,5–97,5: 0,02–0,28 mmol/L. Em jejum prolongado ou\n  // cetose nutricional, valores acima de 0,5 mmol/L são esperados; o limite\n  // superior aqui reflete estado pós-prandial habitual, não jejum.\n  BetaHydroxybutyrate: {\n    default: { max: 0.28, min: 0.02, optimalMax: 0.28, optimalMin: 0.02, unit: 'mmol/L' },\n    kind: 'reference-interval',\n    source: 'klee-bhb-2020',\n  },\n\n  BilirubinDirect: {\n    default: { max: 0.3, min: 0, optimalMax: 0.2, optimalMin: 0, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  BilirubinIndirect: {\n    default: { max: 0.8, min: 0, optimalMax: 0.6, optimalMin: 0, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  BilirubinTotal: {\n    default: { max: 1.2, min: 0.1, optimalMax: 0.9, optimalMin: 0.2, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // BNP: 35 pg/mL = corte não-agudo para triagem de IC (SBC IC 2018)\n  BNP: {\n    default: { max: 35, min: 0, optimalMax: 20, optimalMin: 0, unit: 'pg/mL' },\n    kind: 'decision-threshold',\n    source: 'sbc-ic-2018',\n  },\n\n  // Razão BUN/Creatinina — faixa 10-20 aplica-se ao Nitrogênio Ureico (BUN).\n  // Laboratórios brasileiros que reportam Ureia (e não BUN) usam razão\n  // Ureia/Creatinina, cuja faixa normal é aproximadamente 21-43\n  // (Ureia ≈ BUN × 2,14). O biomarcador atualmente assume a convenção BUN;\n  // consumidores que dosem Ureia devem converter ou reportar como razão\n  // distinta. Ver issue #41 para alinhamento de nomenclatura/LOINC.\n  BUN_Creatinine_Ratio: {\n    default: { max: 20, min: 10, optimalMax: 18, optimalMin: 12, unit: '' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  CA125: {\n    default: { max: 35, min: 0, optimalMax: 25, optimalMin: 0, unit: 'U/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  CA199: {\n    default: { max: 37, min: 0, optimalMax: 30, optimalMin: 0, unit: 'U/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // CAC: Agatston classification — 0=none, 1-99=mild, 100-399=moderate, 400+=severe\n  // max=99 so only moderate+ scores (≥100) flag as ANORMAL; optimalMax=0 (zero is ideal)\n  CAC: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  // Per-vessel scores — same Agatston classification applied per vessel\n  CAC_LAD: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_LCX: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_LMA: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_Percentile: {\n    default: { max: 50, min: 0, optimalMax: 25, optimalMin: 0, unit: '%', warningMax: 75 },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  CAC_RCA: {\n    default: { max: 99, min: 0, optimalMax: 0, optimalMin: 0, unit: 'AU' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'rumberger-cac-1999',\n  },\n\n  Cadmium: {\n    default: { max: 1.2, min: 0, optimalMax: 0.5, optimalMin: 0, unit: 'mcg/L' },\n    kind: 'decision-threshold',\n    source: 'nr7-pcmso-2020',\n  },\n\n  Calcium: {\n    default: { max: 10.5, min: 8.5, optimalMax: 10.0, optimalMin: 9.0, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  CEA: {\n    default: { max: 3.0, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // CK: valores conservadores baseados em faixas laboratoriais típicas\n  // CK — o teto masculino era 190 U/L, bem abaixo de qualquer limite superior\n  // derivado de população: 314 no Kalaria 2026 (homens brancos) e 382 no McLeod\n  // 2016 (NHANES, brancos, p97.5). Sinalizava como alterado um monte de gente\n  // com músculo, exercício recente ou simplesmente CK alto normal.\n  //\n  // Passa a 314, que é o mais baixo entre os limites populacionais disponíveis\n  // — a escolha que menos deixa passar elevação real. O `optimalMax` fica em\n  // 170, então a faixa 170–314 lê como \"acima do ótimo, dentro da referência\",\n  // e não como alteração.\n  //\n  // O teto feminino de 170 já coincide com o limite de mulheres brancas do\n  // mesmo estudo, e fica como está.\n  //\n  // Estratificação por ancestralidade NÃO foi adotada, apesar de o estudo\n  // mostrar limites bem maiores em pessoas negras (389 ♀ / 757 ♂). As\n  // categorias do estudo são britânicas e não mapeiam na população brasileira:\n  // SUAREZ-KURTZ et al. (Front Pharmacol, 2012, PMID 23133420) mostram que a\n  // variação relevante é contínua entre brasileiros e \"não é capturada pela\n  // autodeclaração de raça/Cor\". Ver a issue #3 para a decisão registrada.\n  CK: {\n    default: { max: 314, min: 30, optimalMax: 170, optimalMin: 40, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'kalaria-ck-ri-2026',\n    variants: [\n      { sex: 'F', range: { max: 170, min: 30, optimalMax: 150, optimalMin: 40, unit: 'U/L' } },\n    ],\n  },\n\n  Chloride: {\n    default: { max: 106, min: 98, optimalMax: 105, optimalMin: 100, unit: 'mEq/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Colesterol total — SBC 2017/2025: valor desejável < 190 mg/dL para adultos,\n  // com ou sem jejum. Limite anterior (200 mg/dL) refletia a diretriz ATP III\n  // (NCEP, 2002), superada pelas atualizações brasileiras.\n  Cholesterol: {\n    default: { max: 190, min: 0, optimalMax: 170, optimalMin: 0, unit: 'mg/dL' },\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  // Índice de Castelli I (CT/HDL-c)\n  Cholesterol_HDL_Ratio: {\n    // Índice de Castelli I — SBC 2017: M <4.9, F <4.3\n    default: { max: 4.9, min: 0, optimalMax: 3.5, optimalMin: 0, unit: '' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'castelli-ratio-1992',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 4.9, min: 0, optimalMax: 4.0, optimalMin: 0, unit: '' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 4.3, min: 0, optimalMax: 3.5, optimalMin: 0, unit: '' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  CO2: {\n    default: { max: 29, min: 23, optimalMax: 28, optimalMin: 24, unit: 'mEq/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Copper: {\n    default: { max: 175, min: 70, optimalMax: 150, optimalMin: 85, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  CoQ10: {\n    default: { max: 1.5, min: 0.5, optimalMax: 1.3, optimalMin: 0.7, unit: 'mg/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Cortisol: {\n    default: { max: 25, min: 5, optimalMax: 20, optimalMin: 10, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  CortisolFree: {\n    default: { max: 2.5, min: 0.5, optimalMax: 2.0, optimalMin: 0.8, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  CPeptide: {\n    default: {\n      fastingRequired: 'strict',\n      max: 3.9,\n      min: 0.8,\n      optimalMax: 3.0,\n      optimalMin: 1.0,\n      unit: 'ng/mL',\n    },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Creatinine: {\n    default: { max: 1.2, min: 0.6, optimalMax: 1.0, optimalMin: 0.7, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'pns-bioquimica-2019',\n    variants: [\n      // Gestação: hiperfiltração glomerular (↑ 40–50% GFR) reduz a creatinina\n      // sérica. Valores \"normais\" de não-gestante podem sinalizar disfunção\n      // renal em gestante. Limites tipicamente citados: 0.4–0.8 mg/dL.\n      {\n        pregnant: true,\n        range: { max: 0.8, min: 0.4, optimalMax: 0.7, optimalMin: 0.5, unit: 'mg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.3, min: 0.7, optimalMax: 1.1, optimalMin: 0.8, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.1, min: 0.5, optimalMax: 0.9, optimalMin: 0.6, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  CRP: {\n    default: { max: 3.0, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'mg/L' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'tietz-7ed-2015',\n  },\n\n  CystatinC: {\n    default: { max: 1.0, min: 0.5, optimalMax: 0.9, optimalMin: 0.6, unit: 'mg/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // D-Dímero — exame de exclusão de TEV (tromboembolismo venoso) com\n  // ponto de corte único, não uma faixa graduada. Valores < 500 ng/mL\n  // têm alto valor preditivo negativo; acima disso a investigação\n  // clínica decide. Removidos `optimalMin/optimalMax` porque a\n  // dicotomia clínica (positivo/negativo para exclusão) não é melhor\n  // representada por zonas verde/amarela. Em pacientes > 50 anos,\n  // diretrizes (ESC 2019, ACEP) recomendam corte ajustado pela idade:\n  // idade × 10 ng/mL (até 750 ng/mL aos 75+).\n  //\n  // Todos os valores são em FEU (unidades equivalentes de fibrinogênio), e o\n  // código do catálogo é o do FEU (48065-7). Em DDU os cortes caem pela\n  // metade; não existe faixa DDU aqui.\n  DDimer: {\n    default: { max: 500, min: 0, unit: 'ng/mL' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    loinc: '48065-7',\n    source: 'wells-ddimer-2003',\n    variants: [\n      // Corte ajustado por idade — ESC 2019 (Konstantinides et al.) e\n      // ACEP recomendam em pacientes não gestantes ≥ 50 anos com\n      // probabilidade clínica baixa/intermediária de TEV. Fórmula:\n      // idade × 10 ng/mL. Aproximação por faixas etárias.\n      { ageMax: 59, ageMin: 50, range: { max: 590, min: 0, unit: 'ng/mL' }, sex: 'all' },\n      { ageMax: 69, ageMin: 60, range: { max: 690, min: 0, unit: 'ng/mL' }, sex: 'all' },\n      { ageMin: 70, range: { max: 750, min: 0, unit: 'ng/mL' }, sex: 'all' },\n    ],\n  },\n\n  Omega3_DHA: {\n    default: { max: 8.0, min: 2.0, optimalMax: 6.5, optimalMin: 3.5, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  DHEAS: {\n    default: { max: 500, min: 100, optimalMax: 400, optimalMin: 150, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 39,\n        ageMin: 18,\n        range: { max: 640, min: 280, optimalMax: 500, optimalMin: 300, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 59,\n        ageMin: 40,\n        range: { max: 520, min: 120, optimalMax: 400, optimalMin: 150, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 60,\n        range: { max: 290, min: 42, optimalMax: 220, optimalMin: 80, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 39,\n        ageMin: 18,\n        range: { max: 380, min: 65, optimalMax: 300, optimalMin: 100, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMax: 59,\n        ageMin: 40,\n        range: { max: 240, min: 32, optimalMax: 180, optimalMin: 60, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 60,\n        range: { max: 140, min: 18, optimalMax: 100, optimalMin: 30, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Omega3_DPA: {\n    default: { max: 2.0, min: 0.3, optimalMax: 1.5, optimalMin: 0.5, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  eGFR: {\n    default: {\n      max: 120,\n      maxKind: 'display',\n      min: 60,\n      optimalMax: 120,\n      optimalMin: 90,\n      unit: 'mL/min/1.73m²',\n    },\n    // KDIGO 2024: TFG 60-89 (G2) sem marcador de lesão renal não é DRC, em\n    // nenhuma faixa etária. A variante por idade que existia aqui rebaixava o\n    // piso só para 60+ e ainda limitava o teto a 90, o que sinalizava como\n    // alterado qualquer idoso com função preservada.\n    kind: 'decision-threshold',\n    source: 'kdigo-ckd-2024',\n  },\n\n  // `Eosinophils` (%) fica sem faixa de propósito e `Eosinophils_Abs` usa os limites da\n  // Tabela 2 da PNS 2019. Ver o comentário em `Neutrophils_Abs`.\n  Eosinophils_Abs: {\n    default: { max: 0.66, min: 0, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      { ageMin: 18, range: { max: 0.66, min: 0, unit: 'K/uL' }, sex: 'M' },\n      { ageMin: 18, range: { max: 0.55, min: 0, unit: 'K/uL' }, sex: 'F' },\n    ],\n  },\n\n  Omega3_EPA: {\n    default: { max: 3.5, min: 0.5, optimalMax: 2.5, optimalMin: 1.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  EPADPADHA: {\n    default: { max: 10.0, min: 3.0, optimalMax: 9.0, optimalMin: 5.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  ESR: {\n    default: { max: 20, min: 0, optimalMax: 10, optimalMin: 0, unit: 'mm/hr' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Estradiol: {\n    default: { max: 40, min: 10, optimalMax: 35, optimalMin: 15, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 40, min: 10, optimalMax: 30, optimalMin: 15, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 400, min: 30, optimalMax: 300, optimalMin: 50, unit: 'pg/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'pg/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  F2Isoprostanes: {\n    default: { max: 86, min: 0, optimalMax: 60, optimalMin: 0, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Ferritina — WHO 2020 é o documento de referência específico para avaliação\n  // do status de ferro via ferritina. Importante: inflamação aguda eleva\n  // ferritina (proteína de fase aguda); WHO 2020 recomenda dosagem concomitante\n  // de PCR para interpretação em contexto inflamatório (fora do escopo deste\n  // tipo de faixa, mas documentado aqui para consumidores).\n  Ferritin: {\n    default: { max: 150, min: 12, optimalMax: 120, optimalMin: 30, unit: 'ng/mL' },\n    kind: 'decision-threshold',\n    source: 'who-iron-2020',\n    variants: [\n      // Gestação: ferritina cai fisiologicamente no 2º/3º trimestre pela expansão\n      // do volume plasmático e maior demanda fetal. WHO 2020: <15 ng/mL sugere\n      // depleção; muitas diretrizes nacionais usam <30 como gatilho mais sensível\n      // na gestação dada a alta prevalência de deficiência subclínica.\n      {\n        pregnant: true,\n        range: { max: 120, min: 15, optimalMax: 80, optimalMin: 30, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 250, min: 20, optimalMax: 200, optimalMin: 40, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 120, min: 10, optimalMax: 80, optimalMin: 20, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 200, min: 20, optimalMax: 150, optimalMin: 30, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Fibrinogênio: 200-400 mg/dL — faixa de referência padrão (método de Clauss)\n  Fibrinogen: {\n    default: { max: 400, min: 200, optimalMax: 350, optimalMin: 250, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  FolicAcid: {\n    default: { max: 20, min: 3, optimalMax: 15, optimalMin: 5, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  FSH: {\n    default: { max: 12.4, min: 1.5, optimalMax: 10.0, optimalMin: 3.0, unit: 'mIU/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 12.4, min: 1.5, optimalMax: 8.0, optimalMin: 1.5, unit: 'mIU/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 12.5, min: 3.5, optimalMax: 10.0, optimalMin: 3.5, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 134.8, min: 25.8, optimalMax: 80.0, optimalMin: 25.8, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GGT: {\n    default: { max: 55, min: 0, optimalMax: 30, optimalMin: 0, unit: 'U/L' },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 61, min: 8, minKind: 'display', optimalMax: 40, optimalMin: 10, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 36, min: 5, minKind: 'display', optimalMax: 25, optimalMin: 8, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Ghrelin: {\n    default: { max: 1000, min: 300, optimalMax: 800, optimalMin: 400, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Globulin: {\n    default: { max: 3.5, min: 2.0, optimalMax: 3.2, optimalMin: 2.3, unit: 'g/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // A faixa é de jejum, então mora na definição que afirma jejum. Glicose\n  // genérica (`Glucose`, `2345-7`) ficou sem faixa de propósito: a SBD 2024\n  // publica o intervalo de jejum, não o de coleta casual, e inventar um\n  // intervalo sem fonte é pior do que não ter. Na prática o laudo costuma\n  // imprimir a própria faixa, e é ela que o consumidor usa.\n  //\n  // Glicemia de jejum — 70–99 mg/dL é a faixa de normalidade (SBD 2024, ADA);\n  // hipoglicemia clinicamente acionável em não-diabético é <54 mg/dL (Level 2\n  // ADA/SBD), não 70. O corte 70 era Level 1 (alerta em diabético em tratamento)\n  // e gerava falsos \"abaixo do normal\" em indivíduos saudáveis cuja glicemia\n  // em jejum está fisiologicamente entre 54–70. optimalMin preserva o alvo.\n  Glucose_Fasting: {\n    default: {\n      fastingRequired: 'strict',\n      max: 100,\n      min: 54,\n      optimalMax: 90,\n      optimalMin: 70,\n      unit: 'mg/dL',\n    },\n    kind: 'decision-threshold',\n    source: 'sbd-diabetes-2024',\n    variants: [\n      // Gestação: DMG (IADPSG/SBD 2024) usa cortes mais restritivos na glicemia\n      // de jejum — ≥92 mg/dL já indica diabetes mellitus gestacional. Portanto\n      // a faixa \"normal\" em gestante vai até 91 mg/dL no jejum.\n      {\n        pregnant: true,\n        range: {\n          fastingRequired: 'strict',\n          max: 91,\n          min: 54,\n          optimalMax: 85,\n          optimalMin: 70,\n          unit: 'mg/dL',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GlycoMark: {\n    default: { max: 40, min: 10, optimalMax: 35, optimalMin: 15, unit: 'mcg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  GrowthHormone: {\n    default: { max: 5, min: 0, optimalMax: 3, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // HbA1c — SBD 2024 não estabelece piso de referência clinicamente acionável.\n  // Valores <4.0% podem refletir anemia hemolítica, perda sanguínea recente ou\n  // hemoglobinopatia, não patologia do metabolismo glicêmico. Usamos min=2 como\n  // piso de sanidade (HbA1c <2% é quase sempre erro instrumental/entrada) sem\n  // criar flag clínico em valores fisiologicamente baixos. optimalMin preserva\n  // o alvo fisiológico da fração glicada.\n  HbA1c: {\n    default: { max: 5.7, min: 2, minKind: 'display', optimalMax: 5.3, optimalMin: 4.5, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'sbd-diabetes-2024',\n  },\n\n  Hct: {\n    default: { max: 50, min: 36, optimalMax: 48, optimalMin: 40, unit: '%' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 54, min: 40, optimalMax: 50, optimalMin: 42, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 48, min: 36, optimalMax: 45, optimalMin: 38, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // HDL — SBC 2017/2025: desejável > 40 mg/dL (♂) e > 50 mg/dL (♀).\n  // A diretriz NÃO define teto de normalidade — HDL alto é cardioprotetor.\n  // Limites superiores anteriormente fixados em 60 mg/dL geravam falsos\n  // alertas. Mantém-se `max` apenas como limite técnico do gauge (100 mg/dL),\n  // não como ponto de corte clínico; consumidores devem tratar `direction:\n  // higher-better` como sinal autoritativo.\n  HDL: {\n    default: {\n      max: 100,\n      maxKind: 'display',\n      min: 40,\n      optimalMax: 100,\n      optimalMin: 50,\n      unit: 'mg/dL',\n    },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n    variants: [\n      {\n        ageMin: 18,\n        range: {\n          max: 100,\n          maxKind: 'display',\n          min: 40,\n          optimalMax: 100,\n          optimalMin: 45,\n          unit: 'mg/dL',\n        },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: {\n          max: 100,\n          maxKind: 'display',\n          min: 50,\n          optimalMax: 100,\n          optimalMin: 55,\n          unit: 'mg/dL',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  HDL_Large: {\n    // HDL Large: higher is better\n    // Quest Ion Mobility reference: Male 4334-10815, Female 5038-17886 nmol/L, optimal >6729\n    default: {\n      max: 17886,\n      maxKind: 'display',\n      min: 4334,\n      optimalMax: 17886,\n      optimalMin: 6729,\n      unit: 'nmol/L',\n    },\n    direction: 'higher-better',\n    kind: 'reference-interval',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  Hgb: {\n    default: { max: 17.5, min: 12.0, optimalMax: 16.0, optimalMin: 13.5, unit: 'g/dL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      // Gestação: hemodiluição fisiológica reduz o piso aceitável.\n      // OMS e CDC: anemia gestacional quando Hgb <11 g/dL (1º e 3º tri) ou\n      // <10.5 g/dL (2º tri, dilucional mais acentuada). Catch-all adota a\n      // faixa mais conservadora (2º tri) quando trimestre é desconhecido.\n      {\n        pregnant: true,\n        pregnancyTrimester: 1,\n        range: { max: 14.0, min: 11.0, optimalMax: 13.0, optimalMin: 11.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 2,\n        range: { max: 14.0, min: 10.5, optimalMax: 13.0, optimalMin: 11.0, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 3,\n        range: { max: 14.0, min: 11.0, optimalMax: 13.0, optimalMin: 11.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        range: { max: 14.0, min: 10.5, optimalMax: 13.0, optimalMin: 11.0, unit: 'g/dL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 18,\n        range: { max: 17.5, min: 13.5, optimalMax: 16.5, optimalMin: 14.0, unit: 'g/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 15.5, min: 12.0, optimalMax: 14.5, optimalMin: 12.5, unit: 'g/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // HOMA-IR — três faixas do estudo BRAMS (Geloneze et al., 2009) validado em\n  // população urbana brasileira: ótimo até 1.5; sensibilidade reduzida (zona de\n  // atenção) entre 1.5 e 2.71; resistência à insulina acima de 2.71. Tietz 7ª\n  // ed. não publica corte próprio de HOMA-IR. `max` (1.5) delimita o verde,\n  // `warningMax` (2.71) o âmbar e acima disso o vermelho.\n  HOMA_IR: {\n    default: {\n      fastingRequired: 'strict',\n      max: 1.5,\n      min: 0,\n      unit: '',\n      warningMax: 2.71,\n    },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'geloneze-brams-2009',\n  },\n\n  Homocysteine: {\n    default: { max: 15, min: 4, minKind: 'display', optimalMax: 10, optimalMin: 5, unit: 'umol/L' },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'selhub-homocysteine-1999',\n  },\n\n  IGF1: {\n    default: { max: 350, min: 100, optimalMax: 300, optimalMin: 150, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  ImmatureGranulocytes: {\n    default: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Insulin: {\n    default: {\n      fastingRequired: 'strict',\n      max: 25,\n      min: 2,\n      optimalMax: 8,\n      optimalMin: 3,\n      unit: 'uIU/mL',\n    },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Iron: {\n    default: { max: 170, min: 60, optimalMax: 140, optimalMin: 80, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'sbpc-ml-2021',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 175, min: 65, optimalMax: 150, optimalMin: 80, unit: 'mcg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 170, min: 50, optimalMax: 130, optimalMin: 60, unit: 'mcg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Lactate: {\n    default: { max: 2.2, min: 0.5, optimalMax: 1.8, optimalMin: 0.7, unit: 'mmol/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // DHL/LDH — método IFCC a 37 °C (padrão atual na maioria dos laboratórios\n  // brasileiros). Limites superiores de referência (97,5° percentil) obtidos\n  // por Schumann & Klauke (2002) em indivíduos ≥17 anos: 247 U/L (mulheres)\n  // e 248 U/L (homens). O IFCC publica apenas o limite superior; o limite\n  // inferior é fixado em 0 pois DHL baixa não tem significado clínico.\n  // Não comparar com método Wróblewski-LaDue (faixas mais antigas, ~240–480).\n  LDH: {\n    default: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: 'U/L' },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'schumann-ifcc-ldh-2002',\n    variants: [\n      {\n        ageMin: 17,\n        range: { max: 248, min: 0, optimalMax: 248, optimalMin: 0, unit: 'U/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 17,\n        range: { max: 247, min: 0, optimalMax: 247, optimalMin: 0, unit: 'U/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LDL: {\n    default: { max: 100, min: 0, optimalMax: 70, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  LDL_Medium: {\n    // LDL Medium (LDL Média): lower is better\n    // Quest Ion Mobility reference: Male 167-485, Female 121-397 nmol/L, optimal <215\n    default: {\n      max: 485,\n      min: 121,\n      minKind: 'display',\n      optimalMax: 215,\n      optimalMin: 121,\n      unit: 'nmol/L',\n    },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_ParticleNumber: {\n    // LDL Particle Number: lower is better\n    // Quest Ion Mobility reference: 1016-2185 nmol/L, optimal <1138\n    default: {\n      max: 2185,\n      min: 1016,\n      minKind: 'display',\n      optimalMax: 1138,\n      optimalMin: 1016,\n      unit: 'nmol/L',\n    },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_Peak_Size: {\n    // LDL Peak Size: higher is better (larger particles less atherogenic)\n    // Quest Ion Mobility reference: optimal >222.9 Å (22.29 nm)\n    default: {\n      max: 250.0,\n      maxKind: 'display',\n      min: 217.4,\n      optimalMax: 250.0,\n      optimalMin: 222.9,\n      unit: 'Angstrom',\n    },\n    direction: 'higher-better',\n    kind: 'reference-interval',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  LDL_Small: {\n    // LDL Small (LDL Pequena): lower is better (small dense LDL is most atherogenic)\n    // Quest Ion Mobility reference: Male 123-441, Female 126-382 nmol/L, optimal <142\n    default: {\n      max: 441,\n      min: 123,\n      minKind: 'display',\n      optimalMax: 142,\n      optimalMin: 123,\n      unit: 'nmol/L',\n    },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'caulfield-ionmobility-2008',\n  },\n\n  Lead: {\n    default: { max: 5, min: 0, optimalMax: 2, optimalMin: 0, unit: 'mcg/dL' },\n    kind: 'decision-threshold',\n    source: 'nr7-pcmso-2020',\n  },\n\n  Leptin: {\n    default: { max: 15, min: 2, minKind: 'clinical', optimalMax: 12, optimalMin: 3, unit: 'ng/mL' },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: {\n          max: 10,\n          min: 1,\n          minKind: 'clinical',\n          optimalMax: 8,\n          optimalMin: 2,\n          unit: 'ng/mL',\n        },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: {\n          max: 25,\n          min: 4,\n          minKind: 'clinical',\n          optimalMax: 18,\n          optimalMin: 5,\n          unit: 'ng/mL',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LH: {\n    default: { max: 8.6, min: 1.7, optimalMax: 8.0, optimalMin: 2.0, unit: 'mIU/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 8.6, min: 1.7, optimalMax: 6.0, optimalMin: 1.7, unit: 'mIU/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 12.6, min: 2.4, optimalMax: 10.0, optimalMin: 2.4, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 51,\n        range: { max: 58.5, min: 7.7, optimalMax: 40.0, optimalMin: 10.0, unit: 'mIU/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Omega6_LA: {\n    default: { max: 35.0, min: 15.0, optimalMax: 28.0, optimalMin: 18.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  // Lp(a) — SBC 2025 (seção 3.1.1.2.7): níveis ≥ 50 mg/dL ou ≥ 125 nmol/L são\n  // considerados aumentados, com indicação de rastreamento em cascata familiar.\n  // A diretriz recomenda ensaio independente de isoforma medido em nmol/L; a\n  // unidade nmol/L é mantida aqui por refletir o padrão laboratorial atual.\n  // Limites anteriores (max=75) refletiam pontos de corte expressos em mg/dL,\n  // gerando incompatibilidade com a unidade nmol/L declarada.\n  Lipoprotein_a: {\n    default: { max: 125, min: 0, optimalMax: 75, optimalMin: 0, unit: 'nmol/L' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    loinc: '43583-4',\n    source: 'sbc-lipids-2025',\n  },\n\n  // `Lymphocytes` (%) fica sem faixa de propósito e `Lymphocytes_Abs` usa os limites da\n  // Tabela 2 da PNS 2019. Ver o comentário em `Neutrophils_Abs`.\n  Lymphocytes_Abs: {\n    default: { max: 3.414, min: 0.72, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      { ageMin: 18, range: { max: 3.37, min: 0.72, unit: 'K/uL' }, sex: 'M' },\n      { ageMin: 18, range: { max: 3.414, min: 0.796, unit: 'K/uL' }, sex: 'F' },\n    ],\n  },\n\n  Magnesium: {\n    default: { max: 2.2, min: 1.7, optimalMax: 2.1, optimalMin: 1.9, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Magnesium_RBC: {\n    default: { max: 6.8, min: 4.0, optimalMax: 6.0, optimalMin: 4.5, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  MCH: {\n    default: { max: 33, min: 27, optimalMax: 32, optimalMin: 28, unit: 'pg' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  MCHC: {\n    default: { max: 36, min: 32, optimalMax: 35, optimalMin: 33, unit: 'g/dL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  MCV: {\n    default: { max: 100, min: 80, optimalMax: 98, optimalMin: 82, unit: 'fL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  Mercury: {\n    default: { max: 10, min: 0, optimalMax: 5, optimalMin: 0, unit: 'mcg/L' },\n    kind: 'decision-threshold',\n    source: 'nr7-pcmso-2020',\n  },\n\n  Microalbumin: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/L' },\n    kind: 'decision-threshold',\n    source: 'kdigo-ckd-2024',\n  },\n\n  MMA: {\n    default: { max: 378, min: 0, optimalMax: 270, optimalMin: 0, unit: 'nmol/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // `Monocytes` (%) fica sem faixa de propósito e `Monocytes_Abs` usa os limites da\n  // Tabela 2 da PNS 2019. Ver o comentário em `Neutrophils_Abs`.\n  Monocytes_Abs: {\n    default: { max: 0.812, min: 0.011, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      { ageMin: 18, range: { max: 0.812, min: 0.011, unit: 'K/uL' }, sex: 'M' },\n      { ageMin: 18, range: { max: 0.692, min: 0.022, unit: 'K/uL' }, sex: 'F' },\n    ],\n  },\n\n  MPV: {\n    default: { max: 11.5, min: 7.5, optimalMax: 10.5, optimalMin: 8.0, unit: 'fL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  // MPO: Meuwese 2007 (EPIC-Norfolk) — risco CV elevado >322 pmol/L\n  Myeloperoxidase: {\n    default: { max: 470, min: 0, optimalMax: 322, optimalMin: 0, unit: 'pmol/L' },\n    kind: 'decision-threshold',\n    source: 'meuwese-mpo-2007',\n  },\n\n  // Leucograma diferencial em percentual (`Neutrophils`, `Lymphocytes`,\n  // `Monocytes`, `Eosinophils`, `Basophils`) fica sem faixa de propósito.\n  // As faixas em % que existiam aqui citavam `pns-hemograma-2019`, mas o\n  // artigo (ROSENFELD et al., Rev. Bras. Epidemiol., v. 22, supl. 2, 2019,\n  // DOI 10.1590/1980-549720190003.supl.2) publica o diferencial só em\n  // contagem absoluta por mm³, separado por sexo (Tabela 2: basófilos 0–62\n  // em homens e 0–72 em mulheres, eosinófilos 0–660 e 0–550, e assim por\n  // diante). Não há intervalo percentual em nenhuma tabela. Sem fonte, a\n  // lacuna é melhor que um intervalo inventado: o consumidor usa a faixa\n  // impressa no laudo, como já acontece com `Glucose`.\n  //\n  // Diferencial absoluto (`*_Abs`): limites inferior e superior da Tabela 2\n  // do mesmo artigo, por sexo, exatamente como publicados. São limites da\n  // distribuição amostral de adultos (18 anos ou mais), não cortes clínicos.\n  // O artigo informa células/mm³ (= células/µL); aqui a unidade é K/uL, então\n  // cada limite foi dividido por 1.000 sem arredondar (62/mm³ = 0,062 K/uL).\n  // O artigo não publica faixa ótima, por isso não há optimalMin/optimalMax.\n  // Quando o sexo não é informado, o default é a união das duas faixas\n  // (menor mínimo e maior máximo entre homens e mulheres).\n  Neutrophils_Abs: {\n    default: { max: 6.474, min: 0.576, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      { ageMin: 18, range: { max: 5.971, min: 0.576, unit: 'K/uL' }, sex: 'M' },\n      { ageMin: 18, range: { max: 6.474, min: 0.612, unit: 'K/uL' }, sex: 'F' },\n    ],\n  },\n\n  NonHDL_Cholesterol: {\n    default: { max: 130, min: 0, optimalMax: 100, optimalMin: 0, unit: 'mg/dL' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  NRBC: {\n    default: { max: 0, min: 0, optimalMax: 0, optimalMin: 0, unit: '/100WBC' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  NTproBNP: {\n    default: { max: 125, min: 0, optimalMax: 75, optimalMin: 0, unit: 'pg/mL' },\n    kind: 'decision-threshold',\n    source: 'sbc-ic-2018',\n  },\n\n  Oleic_Acid: {\n    default: { max: 25.0, min: 15.0, optimalMax: 22.0, optimalMin: 18.0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Omega3_Index: {\n    default: { max: 8.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.5, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  // Ômega-3 Total (% de ácidos graxos eritrocitários) — Harris & von Schacky\n  // (2004) propõem ≥ 8% como zona ótima de proteção cardiovascular; valores\n  // entre 4% e 8% representam risco intermediário, < 4% risco alto.\n  // optimalMin anterior (5.5%) ficava em zona intermediária, contradizendo\n  // a literatura e o próprio texto educacional do `platform`.\n  Omega3_Total: {\n    default: { max: 12.0, min: 3.0, optimalMax: 10.0, optimalMin: 8.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  Omega6_Total: {\n    default: { max: 40.0, min: 20.0, optimalMax: 35.0, optimalMin: 25.0, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  Omega6_Omega3_Ratio: {\n    default: {\n      max: 10.0,\n      min: 1.0,\n      minKind: 'display',\n      optimalMax: 4.0,\n      optimalMin: 1.0,\n      unit: '',\n    },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'simopoulos-omega-ratio-2002',\n  },\n\n  OmegaCheck: {\n    default: { max: 8.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.5, unit: '%' },\n    kind: 'decision-threshold',\n    source: 'harris-omega3-2004',\n  },\n\n  Palmitic_Acid: {\n    default: { max: 30.0, min: 20.0, optimalMax: 27.0, optimalMin: 22.0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Phosphorus: {\n    default: { max: 4.5, min: 2.5, optimalMax: 4.0, optimalMin: 3.0, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Platelets: {\n    default: { max: 400, min: 150, optimalMax: 350, optimalMin: 180, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  Potassium: {\n    default: { max: 5.0, min: 3.5, optimalMax: 4.6, optimalMin: 3.8, unit: 'mEq/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Prealbumin: {\n    default: { max: 38, min: 18, optimalMax: 35, optimalMin: 20, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Progesterona — varia drasticamente com a fase do ciclo menstrual.\n  // O schema atual não modela fase do ciclo, então adotamos faixas amplas\n  // por sexo: o `default` cobre homens/fase folicular/pós-menopausa; a\n  // variante feminina expande até a faixa esperada de fase lútea\n  // (~3-20 ng/mL). Interpretação correta exige correlação com a fase do\n  // ciclo, indisponível neste contexto.\n  Progesterone: {\n    default: { max: 0.9, min: 0.1, optimalMax: 0.7, optimalMin: 0.2, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 0.9, min: 0.1, optimalMax: 0.6, optimalMin: 0.2, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      // Mulheres em idade reprodutiva: faixa que abarca fases folicular\n      // (0.1-0.9 ng/mL) e lútea (3-20 ng/mL). Sem contexto de fase do ciclo,\n      // valores intermediários (1-3 ng/mL) ficam em zona ambígua.\n      {\n        ageMax: 50,\n        ageMin: 18,\n        range: { max: 20.0, min: 0.1, optimalMax: 15.0, optimalMin: 0.2, unit: 'ng/mL' },\n        sex: 'F',\n      },\n      // Pós-menopausa: valores tipicamente < 0.5 ng/mL (sem ovulação).\n      {\n        ageMin: 51,\n        range: { max: 0.5, min: 0, optimalMax: 0.3, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Prolactin: {\n    default: { max: 18, min: 2, optimalMax: 15, optimalMin: 4, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 18, min: 2, optimalMax: 15, optimalMin: 4, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 29, min: 2, optimalMax: 23, optimalMin: 4, unit: 'ng/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  PSA: {\n    default: { max: 4.0, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 2.5, min: 0, optimalMax: 1.5, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 59,\n        ageMin: 50,\n        range: { max: 3.5, min: 0, optimalMax: 2.5, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMax: 69,\n        ageMin: 60,\n        range: { max: 4.5, min: 0, optimalMax: 3.0, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 70,\n        range: { max: 6.5, min: 0, optimalMax: 4.0, optimalMin: 0, unit: 'ng/mL' },\n        sex: 'M',\n      },\n    ],\n  },\n\n  RBC: {\n    default: { max: 5.5, min: 4.0, optimalMax: 5.2, optimalMin: 4.3, unit: 'M/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 5.9, min: 4.5, optimalMax: 5.5, optimalMin: 4.7, unit: 'M/uL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 5.2, min: 4.0, optimalMax: 5.0, optimalMin: 4.2, unit: 'M/uL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  RDW: {\n    default: { max: 14.5, min: 11.5, optimalMax: 14.0, optimalMin: 12.0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  Reticulocytes: {\n    default: { max: 2.5, min: 0.5, optimalMax: 2.0, optimalMin: 0.8, unit: '%' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  SDMA: {\n    default: { max: 0.6, min: 0.3, optimalMax: 0.5, optimalMin: 0.3, unit: 'umol/L' },\n    kind: 'reference-interval',\n    source: 'schwedhelm-sdma-2011',\n  },\n\n  Selenium: {\n    default: { max: 150, min: 70, optimalMax: 125, optimalMin: 85, unit: 'µg/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  SHBG: {\n    default: { max: 54, min: 18, optimalMax: 50, optimalMin: 20, unit: 'nmol/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 54, min: 18, optimalMax: 45, optimalMin: 20, unit: 'nmol/L' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 122, min: 24, optimalMax: 90, optimalMin: 30, unit: 'nmol/L' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Sodium: {\n    default: { max: 145, min: 136, optimalMax: 143, optimalMin: 138, unit: 'mEq/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  SpecificGravity_Urine: {\n    default: { max: 1.03, min: 1.005, optimalMax: 1.025, optimalMin: 1.01, unit: 'SG' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Stearic_Acid: {\n    default: { max: 14.0, min: 8.0, optimalMax: 12.0, optimalMin: 10.0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  T3Free: {\n    default: { max: 4.2, min: 2.3, optimalMax: 3.8, optimalMin: 2.8, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  T3Reverse: {\n    default: { max: 24, min: 10, optimalMax: 20, optimalMin: 12, unit: 'ng/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  T4Free: {\n    default: { max: 1.8, min: 0.8, optimalMax: 1.5, optimalMin: 1.0, unit: 'ng/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  T4Total: {\n    default: { max: 12.0, min: 4.5, optimalMax: 10.0, optimalMin: 6.0, unit: 'ug/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Testosterone: {\n    default: { max: 1000, min: 300, optimalMax: 800, optimalMin: 500, unit: 'ng/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 1000, min: 300, optimalMax: 800, optimalMin: 500, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 50,\n        range: { max: 800, min: 200, optimalMax: 650, optimalMin: 400, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 70, min: 15, optimalMax: 50, optimalMin: 20, unit: 'ng/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TestosteroneBioavailable: {\n    default: { max: 200, min: 50, optimalMax: 150, optimalMin: 80, unit: 'ng/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // TestosteroneFree - using direct immunoassay ranges (Quest/LabCorp standard)\n  // Previous values (9.3-26.5 pg/mL) were based on equilibrium dialysis method\n  TestosteroneFree: {\n    default: { max: 155, min: 35, optimalMax: 120, optimalMin: 50, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMax: 49,\n        ageMin: 18,\n        range: { max: 155, min: 35, optimalMax: 120, optimalMin: 50, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 50,\n        range: { max: 130, min: 30, optimalMax: 100, optimalMin: 40, unit: 'pg/mL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 5.0, min: 0.2, optimalMax: 3.0, optimalMin: 0.5, unit: 'pg/mL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TIBC: {\n    default: { max: 370, min: 250, optimalMax: 350, optimalMin: 280, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  TotalProtein: {\n    default: { max: 8.3, min: 6.0, optimalMax: 7.8, optimalMin: 6.5, unit: 'g/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Trans_Fat_Index: {\n    default: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Transferrin: {\n    default: { max: 360, min: 200, optimalMax: 340, optimalMin: 220, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  TransferrinSaturation: {\n    default: { max: 50, min: 20, optimalMax: 45, optimalMin: 25, unit: '%' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 55, min: 20, optimalMax: 45, optimalMin: 25, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 50, min: 15, optimalMax: 40, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Triglicérides — SBC 2017/2025 permite dosagem não-jejum com corte distinto\n  // (<175 mg/dL pós-prandial). Marcamos `preferred` para indicar que a faixa\n  // padrão é de jejum, mas não bloqueamos interpretação em não-jejum.\n  Triglycerides: {\n    default: {\n      fastingRequired: 'preferred',\n      max: 150,\n      min: 0,\n      optimalMax: 100,\n      optimalMin: 0,\n      unit: 'mg/dL',\n    },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  // TroponinI: 0.04 ng/mL = percentil 99 (ensaio Siemens TnI-Ultra)\n  TroponinI: {\n    default: { max: 0.04, min: 0, optimalMax: 0.02, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    loinc: '49563-0',\n    source: 'keller-tni-2013',\n  },\n\n  // TroponinT: 14 ng/L = percentil 99 hs-cTnT (ensaio Roche Elecsys 5ª geração)\n  TroponinT: {\n    default: { max: 14, min: 0, optimalMax: 10, optimalMin: 0, unit: 'ng/L' },\n    kind: 'reference-interval',\n    source: 'giannitsis-hstnt-2010',\n  },\n\n  // TSH — 0.4–4.0 é a faixa de referência adulta geral. O alvo 2.5 µIU/mL é\n  // específico do 1º trimestre gestacional (ATA 2017) e não se aplica a\n  // não-gestantes; optimalMax=3.0 reflete o limite superior do tercil \"ótimo\"\n  // sem invadir a faixa subclínica. Variante ageMin=65 mantém limite superior\n  // expandido (tolerância fisiológica do eixo em idosos, SBEM 2013).\n  TSH: {\n    default: { max: 4.0, min: 0.4, optimalMax: 3.0, optimalMin: 1.0, unit: 'uIU/mL' },\n    kind: 'reference-interval',\n    source: 'sbem-thyroid-2013',\n    variants: [\n      // Variantes gestacionais (ATA 2017 / SBEM): supressão fisiológica por hCG\n      // no 1º trimestre, recuperação progressiva no 2º/3º. Trimestre-específicas\n      // precedem a catch-all; catch-all cobre contexto gestante sem trimestre\n      // conhecido.\n      // optimalMin/optimalMax definem subfaixa \"alvo\" mais estreita que o\n      // intervalo de referência — ex.: 1º tri aceita 0.1–2.5, mas o alvo\n      // terapêutico é 0.5–2.5.\n      {\n        pregnant: true,\n        pregnancyTrimester: 1,\n        range: { max: 2.5, min: 0.1, optimalMax: 2.0, optimalMin: 0.5, unit: 'uIU/mL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 2,\n        range: { max: 3.0, min: 0.2, optimalMax: 2.5, optimalMin: 0.5, unit: 'uIU/mL' },\n        sex: 'F',\n      },\n      {\n        pregnant: true,\n        pregnancyTrimester: 3,\n        range: { max: 3.0, min: 0.3, optimalMax: 2.5, optimalMin: 0.5, unit: 'uIU/mL' },\n        sex: 'F',\n      },\n      // Catch-all gestacional — usada quando o trimestre não é informado.\n      // Adota a faixa mais conservadora (2º/3º trimestre: 0.2–3.0).\n      {\n        pregnant: true,\n        range: { max: 3.0, min: 0.2, optimalMax: 2.5, optimalMin: 0.5, unit: 'uIU/mL' },\n        sex: 'F',\n      },\n      {\n        ageMin: 65,\n        range: { max: 6.0, min: 0.4, optimalMax: 4.0, optimalMin: 1.0, unit: 'uIU/mL' },\n        sex: 'all',\n      },\n    ],\n  },\n\n  // Ureia — convenção brasileira (laboratórios reportam Ureia, não BUN).\n  // Faixa adulta de 15-50 mg/dL (Ureia ≈ BUN × 2,14). Limites anteriores\n  // (7-20 mg/dL) refletiam BUN/Nitrogênio Ureico, gerando falsos diagnósticos\n  // de azotemia em pacientes com Ureia normal. LOINC 3094-0 (BUN) também\n  // deve ser revisto em biomarkers.ts — ver issue #41.\n  Urea: {\n    default: { max: 50, min: 15, optimalMax: 40, optimalMin: 20, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  UricAcid: {\n    default: { max: 7.0, min: 2.5, optimalMax: 5.5, optimalMin: 3.0, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 7.0, min: 3.4, optimalMax: 6.0, optimalMin: 4.0, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 6.0, min: 2.4, optimalMax: 5.0, optimalMin: 3.0, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  Urobilinogen_Urine: {\n    default: { max: 1.0, min: 0.1, optimalMax: 1.0, optimalMin: 0.1, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  pH_Urine: {\n    default: { max: 8.0, min: 4.5, optimalMax: 7.0, optimalMin: 5.5, unit: 'pH' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  HyalineCasts_Urine: {\n    default: { max: 2, min: 0, optimalMax: 1, optimalMin: 0, unit: '/LPF' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  RBC_Urine: {\n    default: { max: 3, min: 0, optimalMax: 1, optimalMin: 0, unit: '/HPF' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  SquamousEpithelial_Urine: {\n    default: { max: 15, min: 0, optimalMax: 5, optimalMin: 0, unit: '/HPF' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Leukocytes_Urine: {\n    default: { max: 5, min: 0, optimalMax: 2, optimalMin: 0, unit: '/HPF' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Folate: {\n    default: { max: 20, min: 3.9, optimalMax: 17, optimalMin: 5, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminA: {\n    default: { max: 100, min: 20, optimalMax: 80, optimalMin: 30, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB1: {\n    default: { max: 180, min: 70, optimalMax: 150, optimalMin: 80, unit: 'nmol/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB12: {\n    default: { max: 900, min: 200, optimalMax: 800, optimalMin: 400, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminB6: {\n    default: { max: 50, min: 5, optimalMax: 40, optimalMin: 10, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminC: {\n    default: { max: 2.0, min: 0.4, optimalMax: 1.5, optimalMin: 0.6, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Vitamina D — posicionamento conjunto SBEM/SBPC-ML 2017:\n  // ≥20 ng/mL é desejável para população saudável <60 anos\n  // ≥30 ng/mL é recomendado para grupos de risco (idosos, gestantes, DRC,\n  // osteoporose, hiperparatireoidismo secundário).\n  // A variante ageMin=60 cobre idosos. Gestação, doença renal crônica,\n  // osteoporose e hiperparatireoidismo secundário também exigem min=30;\n  // o tipo `BiomarkerReferenceRange` atual não expressa esses contextos\n  // clínicos além de gestação e idade, portanto consumidores devem aplicar\n  // o limiar ≥30 nessas populações quando souberem a comorbidade. Gestação\n  // será modelada quando `pregnant: true` — aceita-se TODO até lá.\n  // TODO(PR-vitd-pregnancy): adicionar variante `pregnant: true` com min=30\n  // quando a modelagem de comorbidades chegar ao schema.\n  VitaminD: {\n    default: { max: 100, min: 20, optimalMax: 70, optimalMin: 40, unit: 'ng/mL' },\n    kind: 'decision-threshold',\n    source: 'ferreira-vitd-2017',\n    variants: [\n      {\n        ageMin: 60,\n        range: { max: 100, min: 30, optimalMax: 70, optimalMin: 40, unit: 'ng/mL' },\n        sex: 'all',\n      },\n    ],\n  },\n\n  VitaminD_1_25: {\n    default: { max: 72, min: 18, optimalMax: 60, optimalMin: 25, unit: 'pg/mL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  VitaminE: {\n    default: { max: 17, min: 5.5, optimalMax: 14, optimalMin: 7, unit: 'mg/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // VLDL — estimado clinicamente via TG/5 (método Friedewald). O corte de\n  // referência deriva de triglicérides <150 mg/dL (SBC 2025, dislipidemias),\n  // portanto VLDL <30. Friedewald-1972 permanece registrada como fonte do\n  // método de cálculo, mas a faixa de referência tem respaldo na diretriz\n  // SBC 2025.\n  VLDL: {\n    default: { max: 30, min: 2, minKind: 'display', optimalMax: 20, optimalMin: 5, unit: 'mg/dL' },\n    kind: 'decision-threshold',\n    source: 'sbc-lipids-2025',\n  },\n\n  WBC: {\n    default: { max: 11.0, min: 4.0, optimalMax: 8.0, optimalMin: 5.0, unit: 'K/uL' },\n    kind: 'reference-interval',\n    source: 'pns-hemograma-2019',\n  },\n\n  Zinc: {\n    default: { max: 120, min: 60, optimalMax: 100, optimalMin: 70, unit: 'mcg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  AndroidFatPct: {\n    default: { max: 35, min: 10, minKind: 'display', optimalMax: 25, optimalMin: 15, unit: '%' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 30, min: 10, minKind: 'display', optimalMax: 22, optimalMin: 12, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 42, min: 15, minKind: 'display', optimalMax: 32, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Revisão sistemática de 78 estudos, catorze países, incluindo população\n  // centro-americana: o limite médio ficou em 0,50 para homens e para\n  // mulheres, e é o mesmo para os dois sexos, daí não haver variantes.\n  //\n  // Só `max`. O limite inferior não entra porque a revisão não estabelece\n  // piso, e inventar um transformaria em alteração um valor que a fonte não\n  // classifica.\n  // O EWGSOP2 traz um único corte, <31 cm, e o enuncia restrito: \"Calf\n  // circumference has been shown to predict performance and survival in\n  // older people (cut-off point <31 cm)\". Por isso entra como variante por\n  // idade, e não como padrão para todo adulto — estender o número para\n  // gente de 30 anos seria ir além do que a fonte diz.\n  //\n  // O padrão fica sem `min` de propósito: não há corte publicado para\n  // adulto jovem, e o consumidor lê a medida sem zona em vez de ler uma\n  // zona inventada.\n  //\n  // Como interpretar, por faixa etária:\n  //\n  //   60+   a medida tem corte e classifica: abaixo de 31 cm é sinal de\n  //         alerta para perda de massa muscular.\n  //   <60   a medida é válida e comparável com ela mesma ao longo do tempo,\n  //         mas não classifica. Uma queda consistente entre exames importa\n  //         mais do que o valor absoluto num único dia, e é assim que o\n  //         conteúdo do marcador orienta o usuário.\n  //\n  // A ausência de zona abaixo dos 60 não é lacuna a preencher com o número\n  // dos idosos: massa muscular tem trajetória própria por idade, e o\n  // consenso deriva o corte justamente na faixa em que a perda vira\n  // desfecho.\n  //\n  // Recência conferida em 28/08/2026. Existe consenso mais novo, o GLIS\n  // 2024 (Age and Ageing, DOI 10.1093/ageing/afae052), primeiro global\n  // sobre sarcopenia, com Cruz-Jentoft e Chen entre os autores — ou seja,\n  // os líderes do EWGSOP2 e do AWGS. Ele **não** substitui este corte: é\n  // conceitual, e o próprio texto diz que servirá \"to develop an\n  // operational definition for clinical and research settings\". Enquanto a\n  // definição operacional não sai, o EWGSOP2 segue sendo a referência de\n  // ponto de corte.\n  //\n  // Nota: o consenso asiático (AWGS 2019) usa 34 cm para homens e 33 para\n  // mulheres, em outra população e como triagem, não como corte de massa.\n  // Os números não são intercambiáveis.\n  CalfCircumference: {\n    default: { unit: 'cm' },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'ewgsop2-2019',\n    // O corte não é específico por sexo na fonte; as duas variantes existem\n    // porque `RangeVariant` exige o campo, e carregam o mesmo número.\n    variants: [\n      { ageMin: 60, range: { min: 31, unit: 'cm' }, sex: 'F' },\n      { ageMin: 60, range: { min: 31, unit: 'cm' }, sex: 'M' },\n    ],\n  },\n\n  WaistToHeightRatio: {\n    default: { max: 0.5, unit: '' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'browning-ashwell-2010',\n  },\n\n  AndroidGynoidRatio: {\n    default: { max: 1.2, min: 0.5, minKind: 'display', optimalMax: 1.0, optimalMin: 0.6, unit: '' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: {\n          max: 1.2,\n          min: 0.6,\n          minKind: 'display',\n          optimalMax: 1.0,\n          optimalMin: 0.7,\n          unit: '',\n        },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: {\n          max: 1.0,\n          min: 0.4,\n          minKind: 'display',\n          optimalMax: 0.8,\n          optimalMin: 0.5,\n          unit: '',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  BMC: {\n    default: {\n      max: 3.5,\n      maxKind: 'display',\n      min: 2.0,\n      optimalMax: 3.2,\n      optimalMin: 2.3,\n      unit: 'kg',\n    },\n    direction: 'higher-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: {\n          max: 4.0,\n          maxKind: 'display',\n          min: 2.5,\n          optimalMax: 3.5,\n          optimalMin: 2.8,\n          unit: 'kg',\n        },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: {\n          max: 3.0,\n          maxKind: 'display',\n          min: 1.8,\n          optimalMax: 2.7,\n          optimalMin: 2.0,\n          unit: 'kg',\n        },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // BodyFatPct — Age-bracketed ranges from Gallagher et al. Am J Clin Nutr 2000;72:694-701\n  // (PMID: 10966886) and ACSM Guidelines for Exercise Testing, 11th Ed (2021)\n  BodyFatPct: {\n    default: { max: 30, min: 10, minKind: 'clinical', optimalMax: 25, optimalMin: 15, unit: '%' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'gallagher-bodyfat-2000',\n    variants: [\n      // Men — age brackets\n      {\n        ageMax: 25,\n        ageMin: 18,\n        range: { max: 25, min: 5, minKind: 'clinical', optimalMax: 20, optimalMin: 10, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 35,\n        ageMin: 26,\n        range: { max: 26, min: 5, minKind: 'clinical', optimalMax: 21, optimalMin: 11, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 45,\n        ageMin: 36,\n        range: { max: 27, min: 5, minKind: 'clinical', optimalMax: 22, optimalMin: 12, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMax: 55,\n        ageMin: 46,\n        range: { max: 28, min: 5, minKind: 'clinical', optimalMax: 23, optimalMin: 13, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 56,\n        range: { max: 29, min: 5, minKind: 'clinical', optimalMax: 24, optimalMin: 14, unit: '%' },\n        sex: 'M',\n      },\n      // Women — age brackets\n      {\n        ageMax: 25,\n        ageMin: 18,\n        range: { max: 32, min: 13, minKind: 'clinical', optimalMax: 28, optimalMin: 18, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 35,\n        ageMin: 26,\n        range: { max: 33, min: 13, minKind: 'clinical', optimalMax: 29, optimalMin: 18, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 45,\n        ageMin: 36,\n        range: { max: 34, min: 13, minKind: 'clinical', optimalMax: 30, optimalMin: 19, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMax: 55,\n        ageMin: 46,\n        range: { max: 35, min: 13, minKind: 'clinical', optimalMax: 31, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n      {\n        ageMin: 56,\n        range: { max: 36, min: 13, minKind: 'clinical', optimalMax: 32, optimalMin: 20, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  FatFreeMass: {\n    default: { max: 80, maxKind: 'display', min: 40, optimalMax: 70, optimalMin: 45, unit: 'kg' },\n    direction: 'higher-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 90, maxKind: 'display', min: 50, optimalMax: 80, optimalMin: 55, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 60, maxKind: 'display', min: 35, optimalMax: 52, optimalMin: 38, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  FatMass: {\n    default: { max: 30, min: 5, minKind: 'clinical', optimalMax: 20, optimalMin: 8, unit: 'kg' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 25, min: 5, minKind: 'clinical', optimalMax: 18, optimalMin: 7, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 30, min: 8, minKind: 'clinical', optimalMax: 22, optimalMin: 10, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  GynoidFatPct: {\n    default: { max: 45, min: 15, minKind: 'display', optimalMax: 35, optimalMin: 20, unit: '%' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 35, min: 12, minKind: 'display', optimalMax: 28, optimalMin: 15, unit: '%' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 50, min: 20, minKind: 'display', optimalMax: 40, optimalMin: 25, unit: '%' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  LeanMass: {\n    default: { max: 75, maxKind: 'display', min: 35, optimalMax: 65, optimalMin: 40, unit: 'kg' },\n    direction: 'higher-better',\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 85, maxKind: 'display', min: 45, optimalMax: 75, optimalMin: 50, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 55, maxKind: 'display', min: 30, optimalMax: 48, optimalMin: 35, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  TotalMass: {\n    default: { max: 100, min: 50, optimalMax: 85, optimalMin: 55, unit: 'kg' },\n    kind: 'population',\n    source: 'kelly-dxa-2009',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 100, min: 55, optimalMax: 90, optimalMin: 60, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 85, min: 45, optimalMax: 75, optimalMin: 50, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  VATMass: {\n    default: { max: 1.5, min: 0, optimalMax: 0.8, optimalMin: 0, unit: 'kg' },\n    direction: 'lower-better',\n    kind: 'population',\n    source: 'ofenheimer-vat-2020',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 1.5, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'kg' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 1.0, min: 0, optimalMax: 0.5, optimalMin: 0, unit: 'kg' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  VATVolume: {\n    default: {\n      max: 852,\n      min: 0,\n      optimalMax: 600,\n      optimalMin: 0,\n      unit: 'cm³',\n      warningMax: 1837,\n    },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'ge-corescan',\n  },\n\n  BMD_Total: {\n    default: {\n      max: 1.4,\n      maxKind: 'display',\n      min: 0.9,\n      optimalMax: 1.3,\n      optimalMin: 1.0,\n      unit: 'g/cm²',\n    },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'who-osteoporosis-1994',\n  },\n\n  TScore_Total: {\n    default: {\n      max: 4.0,\n      maxKind: 'display',\n      min: -1.0,\n      optimalMax: 2.0,\n      optimalMin: -0.5,\n      unit: '',\n    },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'who-osteoporosis-1994',\n  },\n\n  ZScore_Total: {\n    default: {\n      max: 2.0,\n      maxKind: 'display',\n      min: -2.0,\n      optimalMax: 1.0,\n      optimalMin: -1.0,\n      unit: '',\n    },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'who-osteoporosis-1994',\n  },\n\n  Amylase: {\n    default: { max: 100, min: 28, optimalMax: 90, optimalMin: 35, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Creatinine_Urine: {\n    default: { max: 300, min: 20, optimalMax: 250, optimalMin: 40, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 300, min: 40, optimalMax: 260, optimalMin: 60, unit: 'mg/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 220, min: 20, optimalMax: 180, optimalMin: 40, unit: 'mg/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  IgA: {\n    default: { max: 400, min: 70, optimalMax: 350, optimalMin: 100, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Lipase: {\n    default: { max: 60, min: 0, optimalMax: 50, optimalMin: 10, unit: 'U/L' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  Microalbumin_Urine: {\n    default: { max: 30, min: 0, optimalMax: 20, optimalMin: 0, unit: 'mg/L' },\n    kind: 'decision-threshold',\n    source: 'kdigo-ckd-2024',\n  },\n\n  PSA_Free: {\n    default: { max: 1.5, min: 0, optimalMax: 1.0, optimalMin: 0, unit: 'ng/mL' },\n    kind: 'reference-interval',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // Relação PSA livre/total — `higher-better`: razão maior = menor risco de\n  // câncer de próstata, logo não há limite superior \"ruim\" (acima do normal é\n  // verde). Faixas alinhadas à tabela clínica: ≥25% baixo risco (verde),\n  // 10–25% atenção — intermediário/moderado (âmbar), <10% alto risco >50%\n  // (vermelho). Limites: `min` (25) é o piso do verde e `warningMin` (10) o\n  // piso do âmbar — o vermelho é estritamente abaixo de 10% (< 10%); 10%\n  // pertence ao âmbar, conforme a faixa \"10–15% moderado\" da tabela.\n  PSA_FreeRatio: {\n    default: {\n      max: 100,\n      maxKind: 'display',\n      min: 25,\n      optimalMax: 100,\n      optimalMin: 30,\n      unit: '%',\n      warningMin: 10,\n    },\n    direction: 'higher-better',\n    kind: 'decision-threshold',\n    source: 'sturgeon-nacb-2008',\n  },\n\n  // BMI - WHO classification: 18.5–24.9 normal, 25–29.9 overweight, ≥30 obese\n  BMI: {\n    default: { max: 30, min: 18.5, optimalMax: 24.9, optimalMin: 18.5, unit: 'kg/m2' },\n    kind: 'decision-threshold',\n    source: 'who-obesity-2000',\n  },\n\n  // eAG — Estimated Average Glucose, derivada da HbA1c pela fórmula ADAG:\n  // eAG (mg/dL) = 28,7 × HbA1c(%) − 46,7 (NATHAN, D. M. et al. Translating the\n  // A1C assay into estimated average glucose values. Diabetes Care, v. 31, n. 8,\n  // p. 1473-1478, 2008. DOI: 10.2337/dc08-0545).\n  //\n  // As faixas espelham os cortes diagnósticos de HbA1c da SBD (ver entrada\n  // `HbA1c`) convertidos por essa fórmula, mantendo a eAG coerente com o\n  // marcador de origem:\n  //   optimalMax 105  ← HbA1c 5,3 % (teto do controle ótimo)\n  //   max        117  ← HbA1c 5,7 % (teto do não diabético → início do pré-diabetes)\n  //   warningMax 137  ← HbA1c 6,4 % (teto do pré-diabetes → acima disso, diabetes)\n  //   optimalMin  82  ← HbA1c 4,5 % (piso do alvo fisiológico da entrada HbA1c)\n  //   min         11  ← HbA1c 2,0 % (mesmo piso de sanidade da entrada HbA1c)\n  //\n  // O piso era 70 nos dois campos, e não vinha desta conversão: 70 é o limite\n  // inferior clássico da glicemia **de jejum**, transplantado para uma média\n  // estimada de ~3 meses. Pela fórmula, 70 equivale a HbA1c 4,07 % — ou seja,\n  // marcava como alterado exatamente quem a entrada `HbA1c` documenta que não\n  // deve ser sinalizado, já que HbA1c baixa reflete hemólise, perda sanguínea\n  // ou hemoglobinopatia, e não doença do metabolismo glicêmico. Espelhar o piso\n  // do HbA1c mantém as duas entradas coerentes, que é o que o comentário sempre\n  // afirmou fazer.\n  //\n  // Substitui a faixa anterior (optimalMax 126 = corte de glicemia de jejum;\n  // max 154 = meta terapêutica do diabético, HbA1c 7 %), que classificava como\n  // \"Normal\" valores já pré-diabéticos e diabéticos.\n  eAG: {\n    default: {\n      max: 117,\n      min: 11,\n      minKind: 'display',\n      optimalMax: 105,\n      optimalMin: 82,\n      unit: 'mg/dL',\n      warningMax: 137,\n    },\n    kind: 'decision-threshold',\n    source: 'sbd-diabetes-2024',\n  },\n\n  // INR - International Normalized Ratio (non-anticoagulated patients)\n  INR: {\n    default: { max: 1.2, min: 0.8, optimalMax: 1.1, optimalMin: 0.9, unit: 'ratio' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // Prothrombin Time\n  ProthrombinTime: {\n    default: { max: 13.5, min: 11, optimalMax: 13, optimalMin: 11, unit: 'seconds' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // DHT - Dihydrotestosterone (adult male reference; female values are much lower)\n  DHT: {\n    default: { max: 85, min: 30, optimalMax: 85, optimalMin: 30, unit: 'ng/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n    variants: [\n      {\n        ageMin: 18,\n        range: { max: 85, min: 30, optimalMax: 85, optimalMin: 30, unit: 'ng/dL' },\n        sex: 'M',\n      },\n      {\n        ageMin: 18,\n        range: { max: 22, min: 4, optimalMax: 22, optimalMin: 4, unit: 'ng/dL' },\n        sex: 'F',\n      },\n    ],\n  },\n\n  // Total IgE - higher values suggest atopy/allergic sensitization\n  IgE_Total: {\n    default: { max: 100, min: 0, optimalMax: 100, optimalMin: 0, unit: 'IU/mL' },\n    direction: 'lower-better',\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgG - Immunoglobulin G\n  IgG: {\n    default: { max: 1600, min: 700, optimalMax: 1600, optimalMin: 700, unit: 'mg/dL' },\n    kind: 'reference-interval',\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgE E1 Cat Dander - Class 0 (≤0.35 kU/L) = negative\n  IgE_E1_CatDander: {\n    default: { max: 0.35, min: 0, optimalMax: 0.35, optimalMin: 0, unit: 'kU/L' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'tietz-7ed-2015',\n  },\n\n  // IgE GX1 Grasses - Class 0 (≤0.35 kU/L) = negative\n  IgE_GX1_Grasses: {\n    default: { max: 0.35, min: 0, optimalMax: 0.35, optimalMin: 0, unit: 'kU/L' },\n    direction: 'lower-better',\n    kind: 'decision-threshold',\n    source: 'tietz-7ed-2015',\n  },\n};\n\n// =============================================================================\n// HELPER FUNCTIONS\n// =============================================================================\n\n/**\n * Legacy flat reference ranges for backward compatibility\n * This is derived from biomarkerRangeDefinitions defaults\n */\nexport const defaultReferenceRanges: Record<string, BiomarkerReferenceRange> = Object.fromEntries(\n  Object.entries(biomarkerRangeDefinitions).map(([code, def]) => [\n    code,\n    {\n      ...def.default,\n      ...(def.kind && { kind: def.kind }),\n      ...(def.source && { source: def.source }),\n    },\n  ]),\n);\n\n/**\n * Get the reference range for a biomarker code, optionally personalized for user context\n * @param testCode - The biomarker code (e.g., \"HDL\", \"Testosterone\")\n * @param context - Optional user context for personalized ranges\n * @returns Reference range or undefined if not found\n */\nexport function getReferenceRange(\n  testCode: string,\n  context?: ReferenceRangeContext,\n): BiomarkerReferenceRange | undefined {\n  const definition = biomarkerRangeDefinitions[testCode];\n  if (!definition) return undefined;\n\n  const withSource = (\n    range: BiomarkerReferenceRange,\n    kind: RangeKind | undefined = definition.kind,\n  ): BiomarkerReferenceRange => ({\n    ...range,\n    ...(kind && { kind }),\n    ...(definition.source && { source: definition.source }),\n  });\n\n  // If no context or no variants, return default\n  if (!context || !definition.variants || definition.variants.length === 0) {\n    return withSource(definition.default);\n  }\n\n  const { age, biologicalSex, pregnancyTrimester, pregnant } = context;\n\n  // Detect whether the biomarker has pregnancy-specific variants at all.\n  // Se o biomarcador não modela gestação, uma usuária gestante deve continuar\n  // recebendo a variante por sexo/idade (mais informativa que o default). Apenas\n  // quando existe ao menos uma variante gestacional é que bloqueamos as variantes\n  // não-gestacionais para contextos gestantes — evitando mistura de faixas.\n  //\n  // Precedência quando pregnant=true: variantes gestacionais têm precedência\n  // absoluta sobre variantes etárias. Uma gestante de 65+ anos consultando\n  // TSH recebe a faixa gestacional, não a variante ageMin=65. Isto é\n  // intencional — em gestação, o eixo HPG domina sobre o envelhecimento\n  // fisiológico. Casos raros de gestação pós-menopausa (FIV) seguem essa\n  // regra; o consumidor que precise distinguir deve aplicar lógica de\n  // contexto adicional.\n  //\n  // Tratamento de `pregnant: undefined` vs `false`: ambos são tratados como\n  // \"não-gestante\" (fallback seguro). O consumidor deve setar pregnant: true\n  // explicitamente para ativar variantes gestacionais; contexto sem a flag\n  // recebe a faixa padrão da população geral.\n  const hasPregnancyVariant = definition.variants.some((v) => v.pregnant === true);\n\n  // Find matching variant (first match wins — more specific variants must be\n  // listed first). Ordem obrigatória quando há variantes gestacionais:\n  //   1. variantes trimestre-específicas (pregnant=true + pregnancyTrimester=N)\n  //   2. catch-all gestacional (pregnant=true, sem trimester)\n  //   3. variantes por sexo/idade não-gestacionais\n  // Reordenar quebraria o matching; a verificação `variant.pregnancyTrimester\n  // !== pregnancyTrimester` depende da catch-all vir por último.\n  for (const variant of definition.variants) {\n    if (variant.pregnant === true) {\n      if (!pregnant) continue;\n      // Variante com trimestre específico só casa quando o contexto também\n      // especifica o mesmo trimestre. Variantes gestacionais sem trimestre\n      // (catch-all) casam com qualquer contexto gestante, servindo de fallback.\n      if (\n        variant.pregnancyTrimester !== undefined &&\n        variant.pregnancyTrimester !== pregnancyTrimester\n      ) {\n        continue;\n      }\n    } else if (pregnant && hasPregnancyVariant) {\n      // Só pulamos variantes não-gestacionais se o biomarcador tem variantes\n      // gestacionais; caso contrário, a variante por sexo/idade é aplicável.\n      continue;\n    }\n\n    // Check sex match ('all' matches everyone)\n    if (variant.sex !== 'all' && variant.sex !== biologicalSex) {\n      continue;\n    }\n\n    // Check age range\n    if (variant.ageMin !== undefined && (age === undefined || age < variant.ageMin)) {\n      continue;\n    }\n    if (variant.ageMax !== undefined && (age === undefined || age > variant.ageMax)) {\n      continue;\n    }\n\n    return withSource(variant.range, variant.kind ?? definition.kind);\n  }\n\n  // No matching variant found - return default\n  return withSource(definition.default);\n}\n\n/**\n * Get the range direction for a biomarker code.\n * Returns 'range' (default) if not specified.\n */\nexport function getRangeDirection(testCode: string): RangeDirection {\n  return biomarkerRangeDefinitions[testCode]?.direction ?? 'range';\n}\n\n/**\n * A flag de um valor contra a faixa do catálogo, só pelos limites clínicos.\n *\n * Compara contra a faixa que o `getReferenceRange` devolve para o contexto, e\n * ignora o limite marcado como `display`. Não olha o `direction`: o HDL de 105\n * sai sem flag porque o teto de 100 é `display`, e o `BodyFatPct` de 8% sai\n * `L` porque o piso é clínico, embora o marcador seja `lower-better`.\n *\n * **Só serve para a faixa do catálogo.** Faixa que o laboratório imprimiu é\n * afirmação dele sobre aquela amostra, e a comparação contra ela é crua.\n *\n * Devolve `''` quando o código não tem faixa ou o valor está dentro dela.\n */\nexport function flagAgainstCatalogRange(\n  testCode: string,\n  value: number,\n  context?: ReferenceRangeContext,\n): 'H' | 'L' | '' {\n  const range = getReferenceRange(testCode, context);\n  if (!range) return '';\n  if (range.max !== undefined && range.maxKind !== 'display' && value > range.max) return 'H';\n  if (range.min !== undefined && range.minKind !== 'display' && value < range.min) return 'L';\n  return '';\n}\n\n/**\n * O `referenceRange.type` do FHIR para um tipo de faixa.\n *\n * `population` não tem código no `referencerange-meaning`, e a função devolve\n * `undefined` em vez de escolher um parecido.\n */\nexport function referenceRangeMeaning(\n  kind: RangeKind,\n): { code: 'normal' | 'recommended'; display: string; system: string } | undefined {\n  const system = 'http://terminology.hl7.org/CodeSystem/referencerange-meaning';\n  if (kind === 'reference-interval') return { code: 'normal', display: 'Normal Range', system };\n  if (kind === 'decision-threshold') {\n    return { code: 'recommended', display: 'Recommended Range', system };\n  }\n  return undefined;\n}\n\n/**\n * Get fallback reference range for a biomarker code (default only, no personalization)\n * Used by API when LLM doesn't extract reference values\n * @param biomarkerCode - The biomarker code\n * @returns Reference range with min/max/unit or undefined\n */\nexport function getFallbackReferenceRange(\n  biomarkerCode: string,\n): { min: number; max: number; unit: string } | undefined {\n  const definition = biomarkerRangeDefinitions[biomarkerCode];\n  if (!definition || definition.default.min === undefined || definition.default.max === undefined) {\n    return undefined;\n  }\n  return {\n    max: definition.default.max,\n    min: definition.default.min,\n    unit: definition.default.unit,\n  };\n}\n\n/**\n * Apply fallback reference ranges to biomarkers that are missing them\n * @param biomarkers - Array of parsed biomarkers\n * @returns Count of biomarkers that received fallback references\n */\nexport function applyFallbackReferenceRanges<\n  T extends {\n    code: string;\n    referenceMin?: number | null;\n    referenceMax?: number | null;\n    unit?: string;\n  },\n>(biomarkers: T[]): number {\n  let fallbackCount = 0;\n\n  for (const biomarker of biomarkers) {\n    // Skip if already has reference values\n    if (biomarker.referenceMin != null && biomarker.referenceMax != null) {\n      continue;\n    }\n\n    const fallback = getFallbackReferenceRange(biomarker.code);\n    if (fallback) {\n      // Only apply if units are compatible or biomarker has no unit\n      const canonicalUnit = getCanonicalUnitForCode(biomarker.code);\n      const unitsMatch =\n        !biomarker.unit ||\n        biomarker.unit.toLowerCase() === fallback.unit.toLowerCase() ||\n        (canonicalUnit && biomarker.unit.toLowerCase() === canonicalUnit.toLowerCase()) ||\n        // Handle common unit variations\n        (biomarker.unit === '%' && fallback.unit === '%');\n\n      if (unitsMatch) {\n        if (biomarker.referenceMin == null) {\n          biomarker.referenceMin = fallback.min;\n        }\n        if (biomarker.referenceMax == null) {\n          biomarker.referenceMax = fallback.max;\n        }\n        fallbackCount++;\n      }\n    }\n  }\n\n  return fallbackCount;\n}\n"]}