{
  "engine": {
    "id": "cpe-001",
    "code": "CPE-001",
    "name": "Thyroid Function Pattern Engine",
    "version": "1.1.0",
    "url": "https://biod.ai/tools/thyroid",
    "status": "Specification v1.1.0. Reviewed by Dr. Vinicius Amaral, D.O. Not for clinical production use."
  },
  "notice": "Clinical decision support for licensed clinicians. Synthetic-data demonstration. Not FDA cleared. Physician adjudication required.",
  "rules": [
    {
      "id": "PR-HT-01",
      "name": "Overt Primary Hypothyroidism Biochemical Pattern",
      "group": "Functional-state patterns",
      "status": "active",
      "classification": "definite biochemical pattern",
      "summary": "Overt Primary Hypothyroidism Biochemical Pattern. Definite biochemical pattern. Requires TSH above laboratory upper reference limit.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "TSH > laboratory upper reference limit",
            "FT4 < laboratory lower reference limit"
          ]
        },
        {
          "heading": "Supportive, not required",
          "items": [
            "Compatible symptoms",
            "Anti TPO positive",
            "Dyslipidemia",
            "CK elevation"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Functional state: overt primary hypothyroidism pattern"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Confirm clinical context, etiology modifiers and medication/exposure history.",
            "Assess Anti_TPO if autoimmune etiology is clinically relevant and not previously known.",
            "Consider lipid panel, CBC and CK if clinically indicated.",
            "Physician to determine levothyroxine initiation and dose using age and cardiovascular context."
          ]
        }
      ],
      "evidence": [
        "EV-ATA-HYPO-2014",
        "EV-AACE-ATA-2012"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-01"
    },
    {
      "id": "PR-HT-02",
      "name": "Possible Subclinical Hypothyroidism Pattern",
      "group": "Functional-state patterns",
      "status": "active",
      "classification": "biochemical pattern requiring context",
      "summary": "Possible Subclinical Hypothyroidism Pattern. Biochemical pattern requiring context. Requires TSH above laboratory upper reference limit.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "TSH > laboratory upper reference limit",
            "FT4 within laboratory reference range"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Functional state: possible subclinical hypothyroidism pattern"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Confirm persistence with repeat TSH and FT4 when clinically appropriate before long-term therapy decisions.",
            "Review symptoms, age, TSH magnitude/persistence, Anti_TPO status, cardiovascular context, goiter and special-population routing.",
            "If pregnant or attempting conception/fertility treatment, apply dedicated context module."
          ]
        },
        {
          "heading": "Never outputs",
          "items": [
            "Automatic treatment",
            "Overt hypothyroidism"
          ]
        }
      ],
      "evidence": [
        "EV-AACE-ATA-2012",
        "EV-ATA-PREG",
        "EV-ASRM-2024"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-02"
    },
    {
      "id": "PR-HT-03",
      "name": "Possible Central Hypothyroidism Pattern",
      "group": "Safety patterns",
      "status": "active",
      "classification": "safety critical pattern",
      "summary": "Possible Central Hypothyroidism Pattern. Safety critical pattern. Requires FT4 below laboratory lower reference limit.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "FT4 < laboratory lower reference limit",
            "TSH low or normal or mildly elevated inappropriately for low FT4"
          ]
        },
        {
          "heading": "Supportive, not required",
          "items": [
            "Pituitary or hypothalamic disease",
            "TBI",
            "Pituitary surgery or radiation",
            "Headache or visual symptoms",
            "Other pituitary hormone deficits"
          ]
        },
        {
          "heading": "Exclusions the engine asks you to review",
          "items": [
            "Acute severe systemic illness",
            "Drug effect",
            "Analytical interference"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Functional state: possible central hypothyroidism pattern",
            "Etiology: pituitary or hypothalamic cause possible",
            "Safety alert: adrenal insufficiency must be assessed before levothyroxine"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Assess morning cortisol/ACTH and adrenal safety before thyroid hormone replacement in suspected central disease.",
            "Evaluate additional pituitary axes as clinically appropriate.",
            "Consider pituitary MRI when pituitary disease is suspected or supported by the clinical context."
          ]
        }
      ],
      "evidence": [
        "EV-ENDO-HYPOPIT-2016"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-03"
    },
    {
      "id": "PR-HT-04",
      "name": "Secondary-Cause Screening Trigger from Metabolic or Muscular Findings",
      "group": "Screening triggers",
      "status": "active",
      "classification": "screening trigger not diagnosis",
      "summary": "Secondary-Cause Screening Trigger from Metabolic or Muscular Findings. Screening trigger not diagnosis. Triggered by unexpected or worsening LDL elevation with compatible context.",
      "sections": [
        {
          "heading": "Fires on any of",
          "items": [
            "Unexpected or worsening LDL elevation with compatible context",
            "CK elevation with myopathy or statins and no explanation",
            "Hyperprolactinemia without thyroid function assessment",
            "Compatible multisystem symptom pattern without recent TSH"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Consider ordering TSH and FT4; evaluate Anti_TPO only after biochemical/context review when etiology matters."
          ]
        },
        {
          "heading": "Never outputs",
          "items": [
            "Hypothyroidism diagnosis",
            "Numeric probability",
            "Statin resistance due to hypothyroidism"
          ]
        }
      ],
      "evidence": [],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-04"
    },
    {
      "id": "PR-HT-05",
      "name": "Thyrotoxicosis with Autoimmune Marker - Etiology Not Yet Classified",
      "group": "Functional-state patterns",
      "status": "active",
      "classification": "differential required",
      "summary": "Thyrotoxicosis with Autoimmune Marker - Etiology Not Yet Classified. Differential required. Requires TSH below laboratory lower reference limit or suppressed.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "TSH below laboratory lower reference limit or suppressed",
            "FT4 above laboratory upper reference limit or T3 elevated"
          ]
        },
        {
          "heading": "Supportive, not required",
          "items": [
            "Anti TPO positive",
            "Anti TG positive"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Functional state: thyrotoxicosis pattern",
            "Safety alert: thyrotoxicosis requires etiologic differentiation"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Evaluate Graves disease versus destructive thyroiditis using clinical context and TRAb/TSI when appropriate.",
            "Consider imaging or uptake assessment only when clinically appropriate and not contraindicated by pregnancy or lactation."
          ]
        },
        {
          "heading": "Never outputs",
          "items": [
            "Hashitoxicosis confirmed from Anti TPO alone",
            "Automatic antithyroid therapy recommendation"
          ]
        }
      ],
      "evidence": [
        "EV-ATA-THYROIDITIS"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-05"
    },
    {
      "id": "PR-HT-06",
      "name": "Autoimmune Thyroiditis with Euthyroid Function",
      "group": "Etiology patterns",
      "status": "active",
      "classification": "etiology without functional failure",
      "summary": "Autoimmune Thyroiditis with Euthyroid Function. Etiology without functional failure. Requires Anti TPO above assay reference limit or documented autoimmune thyroiditis.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "Anti TPO above assay reference limit or documented autoimmune thyroiditis",
            "TSH within laboratory reference range",
            "FT4 within laboratory reference range"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Functional state: no biochemical evidence of thyroid dysfunction",
            "Etiology: autoimmune thyroiditis supported"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Monitor thyroid function over time based on clinical context; do not recommend thyroid hormone solely from antibody positivity."
          ]
        }
      ],
      "evidence": [
        "EV-ATA-HASHIMOTO"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-06"
    },
    {
      "id": "PR-HT-07",
      "name": "Severe Decompensated Hypothyroidism / Myxedema Coma Risk Alert",
      "group": "Safety patterns",
      "status": "active",
      "classification": "urgent safety alert",
      "summary": "Severe Decompensated Hypothyroidism / Myxedema Coma Risk Alert. Urgent safety alert. Requires overt primary hypothyroidism pattern or known severe hypothyroidism.",
      "sections": [
        {
          "heading": "Required to fire",
          "items": [
            "Overt primary hypothyroidism pattern or known severe hypothyroidism"
          ]
        },
        {
          "heading": "Red flags (any)",
          "items": [
            "Altered mental status",
            "Hypothermia",
            "Hypoventilation",
            "Hemodynamic instability",
            "Marked bradycardia",
            "Severe hyponatremia",
            "Hypoglycemia",
            "Precipitating infection or sedative exposure"
          ]
        },
        {
          "heading": "What it reports",
          "items": [
            "Safety alert: possible severe decompensated hypothyroidism needs urgent clinical assessment"
          ]
        },
        {
          "heading": "Recommended next steps (for physician review)",
          "items": [
            "Urgent physician assessment or emergency escalation based on clinical severity; do not manage through routine outpatient rule pathway."
          ]
        }
      ],
      "evidence": [],
      "url": "https://biod.ai/tools/thyroid/rules/pr-ht-07"
    },
    {
      "id": "CTX-HT-PREG",
      "name": "Pregnancy Thyroid Context",
      "group": "Context modules",
      "status": "module",
      "classification": "Context module",
      "summary": "Pregnancy Thyroid Context. Routed when pregnant.",
      "sections": [
        {
          "heading": "Routing trigger",
          "items": [
            "Pregnant"
          ]
        },
        {
          "heading": "Behavior",
          "items": [
            "Use trimester- and assay-specific reference intervals where available.",
            "Do not apply a universal automatic treatment rule at TSH > 2.5.",
            "For TPO-positive pregnancy, treatment is recommended when TSH is above 4.0 and may be considered when TSH is between 2.5 and 4.0 under ATA guidance.",
            "Require physician-managed obstetric/endocrine pathway."
          ]
        }
      ],
      "evidence": [
        "EV-ATA-PREG"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/ctx-ht-preg"
    },
    {
      "id": "CTX-HT-FERTILITY",
      "name": "Preconception / Infertility Thyroid Context",
      "group": "Context modules",
      "status": "module",
      "classification": "Context module",
      "summary": "Preconception / Infertility Thyroid Context. Routed when trying to conceive or fertility treatment == true.",
      "sections": [
        {
          "heading": "Routing trigger",
          "items": [
            "Trying to conceive or fertility treatment == true"
          ]
        },
        {
          "heading": "Behavior",
          "items": [
            "Flag guideline sensitivity and do not make automatic treatment claims from TSH 2.5-4.0 or antibody positivity alone.",
            "Surface ATA pregnancy-related context and ASRM 2024 fertility guideline for physician interpretation."
          ]
        }
      ],
      "evidence": [
        "EV-ATA-PREG",
        "EV-ASRM-2024"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/ctx-ht-fertility"
    },
    {
      "id": "CTX-HT-POSTPARTUM",
      "name": "Postpartum Thyroiditis Context",
      "group": "Context modules",
      "status": "module",
      "classification": "Context module",
      "summary": "Postpartum Thyroiditis Context. Routed when postpartum within 12 months == true.",
      "sections": [
        {
          "heading": "Routing trigger",
          "items": [
            "Postpartum within 12 months == true"
          ]
        },
        {
          "heading": "Behavior",
          "items": [
            "Consider postpartum thyroiditis when thyrotoxicosis or hypothyroidism occurs within one year postpartum.",
            "Differentiate thyroid symptoms from overlapping postpartum mood, fatigue, anemia and lactation-related contexts.",
            "Do not apply radioactive iodine uptake recommendations without considering lactation status."
          ]
        }
      ],
      "evidence": [
        "EV-ATA-THYROIDITIS"
      ],
      "url": "https://biod.ai/tools/thyroid/rules/ctx-ht-postpartum"
    },
    {
      "id": "CTX-HT-DRUG",
      "name": "Medication / Exposure Modifier",
      "group": "Context modules",
      "status": "module",
      "classification": "Context module",
      "summary": "Medication / Exposure Modifier. Routed when relevant medication or exposure present.",
      "sections": [
        {
          "heading": "Routing trigger",
          "items": [
            "Relevant medication or exposure present"
          ]
        },
        {
          "heading": "Behavior",
          "items": [
            "Flag possible drug- or exposure-associated thyroid dysfunction.",
            "Do not automatically assign autoimmune etiology.",
            "Recommend specialist review for complex medication-related patterns."
          ]
        }
      ],
      "evidence": [],
      "url": "https://biod.ai/tools/thyroid/rules/ctx-ht-drug"
    },
    {
      "id": "CTX-HT-ASSAY",
      "name": "Analytical Interference and Discordant Results",
      "group": "Context modules",
      "status": "module",
      "classification": "Context module",
      "summary": "Analytical Interference and Discordant Results. Routed when discordant results or biotin or assay interference suspected.",
      "sections": [
        {
          "heading": "Routing trigger",
          "items": [
            "Discordant results or biotin or assay interference suspected"
          ]
        },
        {
          "heading": "Behavior",
          "items": [
            "Review supplements, biotin exposure and assay/platform issues.",
            "Repeat or confirm testing before classifying atypical patterns when clinically safe."
          ]
        }
      ],
      "evidence": [],
      "url": "https://biod.ai/tools/thyroid/rules/ctx-ht-assay"
    }
  ],
  "evidence": [
    {
      "id": "EV-AACE-ATA-2012",
      "citation": "Garber JR et al. Clinical Practice Guidelines for Hypothyroidism in Adults. Endocr Pract. 2012;18(6):988-1028.",
      "supports": [
        "Subclinical hypothyroidism below TSH 10 requires individualized treatment decision."
      ]
    },
    {
      "id": "EV-ATA-HYPO-2014",
      "citation": "Jonklaas J et al. Guidelines for the Treatment of Hypothyroidism. Thyroid. 2014;24(12):1670-1751.",
      "supports": [
        "Levothyroxine management framework for hypothyroidism."
      ]
    },
    {
      "id": "EV-ENDO-HYPOPIT-2016",
      "citation": "Fleseriu M et al. Hormonal Replacement in Hypopituitarism in Adults. J Clin Endocrinol Metab. 2016;101(11):3888-3921.",
      "supports": [
        "FT4 low with low, normal or mildly elevated TSH in pituitary disease supports central hypothyroidism; adrenal safety review."
      ]
    },
    {
      "id": "EV-ATA-PREG",
      "citation": "American Thyroid Association. Hypothyroidism in Pregnancy; based on ATA pregnancy guidance.",
      "supports": [
        "TPO-positive pregnancy: treat when TSH above 4.0; consider treatment at 2.5-4.0; special-population routing."
      ]
    },
    {
      "id": "EV-ASRM-2024",
      "citation": "ASRM Practice Committee. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril. 2024;121:765-782.",
      "supports": [
        "Fertility-specific uncertainty and avoidance of blanket treatment logic."
      ]
    },
    {
      "id": "EV-ATA-HASHIMOTO",
      "citation": "American Thyroid Association. Hashimoto's Thyroiditis.",
      "supports": [
        "Positive antibodies with normal TSH and FT4 do not alone require thyroid hormone treatment."
      ]
    },
    {
      "id": "EV-ATA-THYROIDITIS",
      "citation": "American Thyroid Association. Thyroiditis.",
      "supports": [
        "Destructive/postpartum thyroiditis can have thyrotoxic then hypothyroid phases; etiologic differentiation needed."
      ]
    },
    {
      "id": "EV-ATA-TFT",
      "citation": "American Thyroid Association. Thyroid Function Tests.",
      "supports": [
        "Reverse T3 is not clinically useful for determining hypothyroidism in healthy nonhospitalized adults."
      ]
    }
  ]
}