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// ==============================
// DOCUMENT CONTENT
// ==============================

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  blankLine(),
  new Paragraph({
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    spacing: { before: 400, after: 80 },
    children: [
      new TextRun({ text: "HYPOTHYROIDISM", bold: true, size: 52, color: BLUE_DARK, font: "Calibri" })
    ]
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// ---- SECTION 1: Overview ----
const section1 = [
  sectionHeading("1. Overview and Definition"),
  bodyText("Hypothyroidism is a hypometabolic state resulting from levels of circulating thyroid hormone insufficient to meet body requirements. It is one of the most common endocrine disorders, affecting up to 20% of women over age 50."),
  blankLine(),
  subHeading("Classification"),
  makeTable(
    ["Type", "TSH", "Free T4", "Notes"],
    [
      ["Subclinical (Grade 1-2)", "4-10 mIU/L", "Normal", "Mild elevation; treat if symptomatic or TSH >10"],
      ["Subclinical (Grade 3)", ">10 mIU/L", "Normal", "Treatment recommended by all major guidelines"],
      ["Overt / Clinical", "Elevated (often >10)", "Low", "Classic symptomatic hypothyroidism"],
      ["Central (Secondary)", "Low or normal", "Low", "Pituitary / hypothalamic failure; rare"],
      ["Myxedema Coma", "Very high", "Very low", "Life-threatening emergency; ICU admission"]
    ]
  ),
  blankLine(),
];

// ---- SECTION 2: Etiology ----
const section2 = [
  sectionHeading("2. Etiology"),
  subHeading("Primary Hypothyroidism (Most Common)"),
  bulletText("Hashimoto's (Chronic Autoimmune) Thyroiditis - most common cause in developed countries; female:male ratio 10-14:1, typically diagnosed in 5th decade", null),
  bulletText("Iodine deficiency - most common cause worldwide; rare in developed countries due to iodized salt"),
  bulletText("Post-thyroidectomy (surgical)"),
  bulletText("Post-radioiodine (131I) therapy"),
  bulletText("External beam radiation to head/neck"),
  bulletText("Medications: amiodarone, lithium, interferon-alpha, tyrosine kinase inhibitors, immune checkpoint inhibitors"),
  bulletText("Postpartum thyroiditis (usually transient, 3-6 months)"),
  blankLine(),
  subHeading("Secondary / Central Hypothyroidism"),
  bulletText("Pituitary adenoma, Sheehan's syndrome, traumatic brain injury, infiltrative disease"),
  bulletText("Key: TSH is low or inappropriately normal despite low free T4"),
  bulletText("Always assess for other pituitary hormone deficiencies (especially ACTH - replace cortisol before starting T4)"),
  blankLine(),
];

// ---- SECTION 3: Clinical Features ----
const section3 = [
  sectionHeading("3. Clinical Features"),
  bodyText("Symptoms are proportional to severity and duration of hypothyroidism. Mild or subclinical disease may be asymptomatic."),
  blankLine(),
  makeTable(
    ["System", "Symptoms", "Signs"],
    [
      ["General", "Fatigue, weight gain, cold intolerance, decreased appetite", "Hypothermia, periorbital/facial puffiness (myxedema)"],
      ["Cardiovascular", "Exertional dyspnea", "Bradycardia, diastolic hypertension, pericardial effusion"],
      ["Neurological", "Poor concentration, depression, memory impairment", "Delayed relaxation of deep tendon reflexes (hallmark)"],
      ["Musculoskeletal", "Proximal muscle weakness, myalgia, arthralgia", "Goiter (in Hashimoto's), carpal tunnel syndrome"],
      ["Dermatological", "Dry skin, hair loss/thinning, brittle nails", "Coarse dry skin, non-pitting edema, macroglossia"],
      ["Reproductive", "Menorrhagia, infertility, anovulation", "Galactorrhea (elevated prolactin)"],
      ["GI", "Constipation", "Ascites (severe cases)"],
      ["Metabolic", "None specific", "Hypercholesterolemia, hyponatremia, elevated CK, anemia"]
    ]
  ),
  blankLine(),
  alertBox("MYXEDEMA COMA RED FLAGS: Altered consciousness + hypothermia + bradycardia + hypoventilation. Mortality up to 30-60%. Admit to ICU immediately.", ORANGE),
  blankLine(),
];

// ---- SECTION 4: Diagnosis ----
const section4 = [
  sectionHeading("4. Diagnosis"),
  subHeading("Initial Workup"),
  bulletText("Serum TSH - single best screening test; normal range 0.4-4.0 mIU/L"),
  bulletText("Free T4 (FT4) - order if TSH is abnormal to classify severity"),
  bulletText("Anti-TPO antibodies - confirms Hashimoto's autoimmune etiology; predicts progression to overt hypothyroidism"),
  bulletText("Free T3 - not routinely needed for initial diagnosis"),
  blankLine(),
  subHeading("Interpretation Algorithm"),
  makeTable(
    ["TSH", "Free T4", "Diagnosis", "Action"],
    [
      ["0.4-4.0", "Normal", "Euthyroid", "No treatment; reassess if symptomatic"],
      ["4-10", "Normal", "Subclinical Hypothyroid", "Treat if symptomatic, or TSH trending up, or TPO+"],
      [">10", "Normal", "Subclinical Hypothyroid Grade 3", "Treat - levothyroxine indicated"],
      [">10 (or high)", "Low", "Overt Hypothyroidism", "Treat - levothyroxine, full replacement"],
      ["Low/normal", "Low", "Central Hypothyroidism", "Evaluate pituitary; rule out cortisol deficiency first"],
      ["Suppressed", "High", "Hyperthyroidism", "Separate workup required"]
    ]
  ),
  blankLine(),
  subHeading("Additional Investigations (when indicated)"),
  bulletText("Lipid panel - dyslipidemia is common; often improves with treatment"),
  bulletText("CBC - normocytic anemia common"),
  bulletText("Serum electrolytes - hyponatremia in severe cases"),
  bulletText("CK - elevated in hypothyroid myopathy"),
  bulletText("Thyroid ultrasound - if goiter, nodule, or suspicion of structural disease"),
  bulletText("ECG - bradycardia, low-voltage complexes, non-specific ST-T changes"),
  blankLine(),
];

// ---- SECTION 5: Treatment ----
const section5 = [
  sectionHeading("5. Treatment"),
  subHeading("Drug of Choice: Levothyroxine (L-T4)"),
  bodyText("Synthetic levothyroxine is the standard of care. It is a levo isomer of endogenous thyroxine with identical hormonal activity. Approximately 70-80% is absorbed in the small intestine; peak serum T4 levels occur ~4 hours post-ingestion. T3 rises more slowly as T4 is peripherally deiodinated."),
  blankLine(),
  subHeading("Dosing by Patient Population"),
  makeTable(
    ["Patient Type", "Starting Dose", "Target TSH", "Notes"],
    [
      ["Young, healthy adult (overt hypothyroid)", "1.6 mcg/kg/day (full replacement)", "0.5-2.5 mIU/L", "Can start at full dose"],
      ["TSH ~100 + normal T3/T4 (subclinical Grade 3)", "1.6 mcg/kg/day OR 50-75 mcg/day", "0.5-2.5 mIU/L", "Treat promptly; high TSH warrants full dosing"],
      ["Age >50-60, no cardiac disease", "50 mcg/day; increase by 25 mcg q1-2wks", "0.5-4.5 mIU/L", "Slower titration to avoid cardiac stress"],
      ["Elderly / known coronary artery disease", "12.5-25 mcg/day; increase very slowly", "1.0-4.0 mIU/L", "Risk of precipitating angina/arrhythmia"],
      ["Pregnant (known hypothyroid)", "Increase dose by 25-30% immediately", "First tri: 0.1-2.5 | Second: 0.2-3.0 | Third: 0.3-3.0 mIU/L", "Take 4h apart from prenatal vitamins/calcium"],
      ["Subclinical (TSH 5-10, symptomatic)", "50 mcg/day", "0.5-4.5 mIU/L", "Consider especially if TPO-Ab positive"],
      ["Central (secondary) hypothyroidism", "1.6 mcg/kg/day; titrate to FT4 (not TSH)", "FT4 in upper-normal range", "TSH unreliable; replace cortisol first if needed"]
    ]
  ),
  blankLine(),
  subHeading("Administration Instructions"),
  bulletText("Take on an EMPTY STOMACH - either 60 minutes before breakfast OR at bedtime (improved absorption shown at bedtime)"),
  bulletText("Separate from calcium supplements, iron, antacids, sucralfate, PPIs, cholestyramine - by at least 4 hours (these reduce T4 absorption)"),
  bulletText("Consistent timing daily is important for stable levels"),
  blankLine(),
  subHeading("Combination T4+T3 Therapy (Liothyronine)"),
  bodyText("NOT routinely recommended. Studies comparing levothyroxine monotherapy vs. T4+T3 combination have not demonstrated significant benefit for the majority of patients. The American Thyroid Association endorses levothyroxine monotherapy as standard of care."),
  bulletText("Consider only in: persistent hypothyroid symptoms despite TSH in target range AND after ruling out other causes"),
  bulletText("If trialled: maintain TSH above 1.0 mIU/L to avoid iatrogenic hyperthyroidism"),
  blankLine(),
  subHeading("Drug-Induced Hypothyroidism"),
  bulletText("Amiodarone: levothyroxine may be needed even after stopping amiodarone (very long half-life)"),
  bulletText("Lithium, interferon-alpha, tyrosine kinase inhibitors: manage with levothyroxine if unable to stop offending agent"),
  blankLine(),
];

// ---- SECTION 6: Monitoring ----
const section6 = [
  sectionHeading("6. Monitoring and Dose Adjustment"),
  makeTable(
    ["Phase", "What to Monitor", "Frequency", "Action"],
    [
      ["Initiation", "Serum TSH (+ FT4 if central)", "6-8 weeks after starting", "Adjust dose if TSH out of target range"],
      ["Titration phase", "Serum TSH; symptoms", "Every 6-8 weeks after each dose change", "Increase by 12.5-25 mcg if TSH still high"],
      ["Stable maintenance", "Serum TSH", "Annually", "Re-check if symptoms recur or new medications added"],
      ["Pregnancy", "TSH (and FT4)", "Every 4 weeks in 1st trimester; q4-6wks thereafter", "Immediately increase dose ~25-30% upon confirmed pregnancy"]
    ]
  ),
  blankLine(),
  alertBox("OVERDOSE WARNING: TSH <0.1 mIU/L = iatrogenic hyperthyroidism. Risks: atrial fibrillation, osteoporosis, cardiac arrhythmias. Reduce dose immediately.", ORANGE),
  blankLine(),
  subHeading("TSH Target Summary"),
  makeTable(
    ["Population", "Target TSH (mIU/L)"],
    [
      ["General adult", "0.5-2.5 (mean 2.0)"],
      ["Elderly (>65)", "1.0-4.0 (slightly higher acceptable)"],
      ["Pregnancy - 1st trimester", "0.1-2.5"],
      ["Pregnancy - 2nd trimester", "0.2-3.0"],
      ["Pregnancy - 3rd trimester", "0.3-3.0"],
      ["Post-thyroid cancer (high risk)", "0.1-0.5 (suppressed)"],
      ["Central hypothyroidism", "Use FT4 (upper normal); TSH unreliable"]
    ]
  ),
  blankLine(),
];

// ---- SECTION 7: Special Populations ----
const section7 = [
  sectionHeading("7. Special Populations"),
  subHeading("Pregnancy"),
  bulletText("Hypothyroid women have anovulatory cycles and relative infertility; restoration of euthyroid state improves fertility"),
  bulletText("Early fetal brain development depends on maternal T4 - adequate dosing is critical in first trimester"),
  bulletText("Dose increase of 25-30% typically needed during pregnancy; counsel women to take 1 extra tablet twice weekly when pregnancy confirmed"),
  bulletText("Separate levothyroxine from prenatal vitamins and calcium by at least 4 hours"),
  bulletText("Postpartum: monitor TSH - dose may need reduction back to pre-pregnancy levels"),
  blankLine(),
  subHeading("Elderly Patients"),
  bulletText("Start with very low doses (12.5-25 mcg) and titrate slowly over weeks to months"),
  bulletText("Risk of unmasking coronary artery disease or precipitating arrhythmia if started too aggressively"),
  bulletText("Higher TSH targets (1.0-4.0) are acceptable in older adults"),
  blankLine(),
  subHeading("Cardiac Disease"),
  bulletText("T4 increases cardiac contractility and heart rate - start very cautiously"),
  bulletText("If angina worsens during initiation, slow titration or address cardiac disease first"),
  blankLine(),
  subHeading("Secondary (Central) Hypothyroidism"),
  bulletText("Always assess ACTH axis first - thyroid replacement increases cortisol clearance and can precipitate adrenal crisis"),
  bulletText("Start glucocorticoid replacement BEFORE levothyroxine if adrenal insufficiency is present or suspected"),
  bulletText("Monitor FT4 levels (not TSH) to guide dosing"),
  blankLine(),
  subHeading("Congenital Hypothyroidism"),
  bulletText("Neonatal screening (TSH on heel prick) is standard in most countries"),
  bulletText("If untreated: intellectual impairment (cretinism) and growth retardation"),
  bulletText("Treatment: levothyroxine, with dose adjusted as child grows"),
  blankLine(),
];

// ---- SECTION 8: Myxedema Coma ----
const section8 = [
  sectionHeading("8. Myxedema Coma (Emergency Management)"),
  alertBox("EMERGENCY: High mortality (30-60%). Admit to ICU. Do NOT delay treatment pending lab confirmation.", ORANGE),
  blankLine(),
  subHeading("Precipitating Factors"),
  bulletText("Cold exposure, infection/sepsis, medications (sedatives, opioids, anesthetics), trauma, stroke, GI bleed"),
  blankLine(),
  subHeading("Clinical Features"),
  bulletText("Altered consciousness / coma"),
  bulletText("Hypothermia"),
  bulletText("Bradycardia, hypotension, hypoventilation"),
  bulletText("Hyponatremia, hypoglycemia"),
  bulletText("Respiratory failure (CO2 retention)"),
  blankLine(),
  subHeading("Management Protocol"),
  makeTable(
    ["Priority", "Intervention", "Details"],
    [
      ["1. Airway", "Ventilatory support", "Protect airway; monitor for alkalosis during correction"],
      ["2. Thyroid hormone", "IV Levothyroxine loading", "T4: 200-400 mcg IV loading dose (lower end for elderly / cardiac disease)"],
      ["3. Thyroid hormone", "Maintenance", "1.6 mcg/kg/day PO; give 75% of dose IV if IV route used"],
      ["4. Steroids", "Hydrocortisone", "100 mg IV q8h (rule out concurrent adrenal insufficiency)"],
      ["5. Fluids", "0.9% Normal Saline", "For hypotension and hyponatremia; avoid hypotonic fluids"],
      ["6. Hyponatremia", "Fluid restriction +/- 3% saline", "If Na <120 mEq/L: 3% saline in 50-100 mL boluses; monitor closely"],
      ["7. Rewarming", "Passive rewarming", "Use regular blankets only; heating blankets risk vasodilation and hypotension"],
      ["8. Monitoring", "Continuous cardiac monitoring", "Bradycardia, arrhythmias, hypoventilation"]
    ]
  ),
  blankLine(),
];

// ---- SECTION 9: Causes of Treatment Failure ----
const section9 = [
  sectionHeading("9. Causes of Persistent Elevated TSH on Treatment"),
  bulletText("Non-adherence - most common cause"),
  bulletText("Malabsorption - celiac disease, inflammatory bowel disease, bariatric surgery"),
  bulletText("Drug interactions - calcium, iron, antacids, cholestyramine, PPIs taken too close to levothyroxine"),
  bulletText("Inadequate dose - underdosing relative to weight; dose not increased during pregnancy"),
  bulletText("Worsening of underlying disease (progressive Hashimoto's)"),
  bulletText("Interference from high biotin supplementation (falsely suppressed TSH on immunoassays)"),
  bulletText("Medication changes - amiodarone, rifampicin, phenytoin affecting T4 metabolism"),
  blankLine(),
];

// ---- SECTION 10: Quick Reference ----
const section10 = [
  sectionHeading("10. Quick Reference Summary"),
  makeTable(
    ["Parameter", "Value / Action"],
    [
      ["Drug of choice", "Levothyroxine (L-T4) - monotherapy"],
      ["Standard replacement dose", "1.6 mcg/kg/day"],
      ["Elderly starting dose", "12.5-25 mcg/day; titrate slowly"],
      ["TSH >10 with normal T4", "TREAT - start levothyroxine"],
      ["TSH 4-10 with normal T4", "Consider treatment if symptomatic or TPO-Ab positive"],
      ["Normal TSH range", "0.4-4.0 mIU/L"],
      ["Treatment target TSH (general)", "0.5-2.5 mIU/L"],
      ["TSH monitoring after dose change", "6-8 weeks"],
      ["Stable patient monitoring", "Annually"],
      ["Take levothyroxine", "60 min before breakfast OR at bedtime on empty stomach"],
      ["Separate from calcium/iron/antacids", "At least 4 hours"],
      ["Pregnancy dose increase", "25-30% increase upon confirmed pregnancy"],
      ["T4 + T3 combination", "NOT routinely recommended (ATA guideline)"],
      ["TSH <0.1 mIU/L on treatment", "Over-replacement - reduce dose"]
    ]
  ),
  blankLine(),
  subHeading("Key References"),
  bulletText("Katzung's Basic and Clinical Pharmacology, 16th Ed. - Chapter 38"),
  bulletText("Rosen's Emergency Medicine, 9th Ed. - Chapter 117"),
  bulletText("Textbook of Family Medicine, 9th Ed. - Chapter 35"),
  bulletText("Frameworks for Internal Medicine - Thyroid Section"),
  bulletText("Lippincott Illustrated Reviews: Pharmacology"),
  bulletText("Creasy & Resnik's Maternal-Fetal Medicine - Thyroid Disease in Pregnancy"),
  bulletText("Goldman-Cecil Medicine, International Edition"),
  bulletText("Harrison's Principles of Internal Medicine, 22nd Ed. (2025)"),
  blankLine(),
];

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