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pres.title = "Biochemical Basis of Diagnosis & Disorders of Pituitary, Adrenal & Thyroid";

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// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 1 – TITLE
// ════════════════════════════════════════════════════════════════════════════
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  s.addText("Cushing's · DI · SIADH · Phaeochromocytoma · Addison's · Conn's · CAH\nHyperthyroidism · Hypothyroidism · Ca Thyroid · Goitre", {
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  });
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 2 – SEMINAR OUTLINE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Seminar Outline");
  twoCol(s,
    [
      { text: "PITUITARY DISORDERS", bold: true, color: GOLD },
      "Cushing's Disease (Pituitary Cushing's)",
      "Diabetes Insipidus (DI)",
      "SIADH",
      { text: "ADRENAL MEDULLA", bold: true, color: GOLD },
      "Phaeochromocytoma"
    ],
    [
      { text: "ADRENAL CORTEX", bold: true, color: GOLD },
      "Cushing's Syndrome (Adrenal)",
      "Addison's Disease",
      "Conn's Syndrome (Primary Aldosteronism)",
      "Congenital Adrenal Hyperplasia (CAH)",
      { text: "THYROID", bold: true, color: GOLD },
      "Hyper- & Hypothyroidism",
      "Carcinoma Thyroid & Goitre"
    ]
  );
  ref(s, "Tietz Textbook of Laboratory Medicine, 7th Ed. Chapters 55–57 (Endocrine Disorders)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 3 – HPA AXIS OVERVIEW
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "The Hypothalamic-Pituitary-Adrenal (HPA) Axis – Biochemistry");
  bullets(s, [
    { text: "Hypothalamus → CRH (Corticotropin-Releasing Hormone)", bold: true },
    { text: "↓ Portal blood → Anterior Pituitary Corticotrophs", level: 1 },
    { text: "Anterior Pituitary → ACTH (pro-opiomelanocortin cleavage product)", bold: true },
    { text: "↓ Bloodstream → Adrenal Cortex Zona Fasciculata", level: 1 },
    { text: "Adrenal Cortex → Cortisol (glucocorticoid)", bold: true },
    { text: "Negative feedback: Cortisol suppresses both CRH and ACTH secretion", level: 1 },
    { text: "Diurnal rhythm: Peak cortisol ~2 h before awakening; nadir shortly after sleep onset", bold: false },
    { text: "Reference range (morning): 5–23 µg/dL (138–635 nmol/L)", level: 1, color: GOLD },
    { text: "Cosyntropin (synthetic ACTH) stimulation: Cortisol should rise >18 µg/dL at 30–60 min", level: 1, color: GOLD }
  ]);
  ref(s, "Tietz 7th Ed., p.2242 – Hypothalamic-Pituitary-Adrenal Axis, Chapter 55");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 4 – PITUITARY CUSHING'S (CUSHING'S DISEASE)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Pituitary Cushing's Disease – Biochemical Basis & Diagnosis");
  bullets(s, [
    { text: "Definition: ACTH-secreting pituitary microadenoma → hypercortisolism (ACTH-dependent)", bold: true },
    { text: "Most common cause of endogenous Cushing's syndrome (~80% of ACTH-dependent cases)", level: 1 },
    { text: "Biochemical Features:", bold: true },
    { text: "Elevated UFC (24-h Urine Free Cortisol) — best screening test", level: 1 },
    { text: "Elevated late-night salivary cortisol (loss of diurnal rhythm)", level: 1 },
    { text: "Failure to suppress on overnight 1 mg DST (cortisol >1.8 µg/dL = positive)", level: 1 },
    { text: "Elevated plasma ACTH (not suppressed; distinguishes from adrenal Cushing's)", level: 1 },
    { text: "Diagnostic Algorithm (Tietz):", bold: true, color: GOLD },
    { text: "Step 1: Screening — UFC / evening salivary cortisol / overnight DST", level: 1 },
    { text: "Step 2: Low-dose DST (2 mg/day × 2 days) confirmation", level: 1 },
    { text: "Step 3: High-dose DST — UFC suppresses >50% = Cushing's Disease", level: 1 },
    { text: "Step 4: ACTH >50 pg/mL after high-dose DST + MRI pituitary / BIPSS", level: 1 }
  ]);
  ref(s, "Tietz 7th Ed., pp.2283–2287 – Cushing Syndrome; Dexamethasone Suppression Test");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 5 – DST & CRH TESTS
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Dynamic Tests for Cushing's Disease");
  table(s,
    [
      [
        { text: "Test", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Protocol", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Interpretation", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Overnight DST (1 mg)", "1 mg dexamethasone at 23:00; serum cortisol at 08:00", "Cortisol >1.8 µg/dL = abnormal (screening)"],
      ["Low-Dose DST (LDDST)", "0.5 mg q6h × 2 days; UFC measured", "UFC not suppressed = Cushing's confirmed"],
      ["High-Dose DST (HDDST)", "2 mg q6h × 2 days or 8 mg overnight", "UFC suppresses >50% = Cushing's Disease (pituitary)"],
      ["CRH Stimulation Test", "1 µg/kg ovine CRH IV; ACTH + cortisol at 0,5,15,30,60 min", "Pituitary: ↑ACTH peak ≥35%; Ectopic: no rise; Adrenal: no rise"],
      ["BIPSS (CRH-stimulated)", "Bilateral inferior petrosal sinus sampling after CRH", "IPS:peripheral ACTH ratio >3 confirms pituitary adenoma"]
    ],
    { y: 0.82, colW: [2.2, 3.8, 3.4], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., pp.2285–2287 – DST; CRH Stimulation; BIPSS (Box 56.3, 56.4)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 6 – DIABETES INSIPIDUS (DI)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Diabetes Insipidus (DI) – Biochemical Basis & Classification");
  twoCol(s,
    [
      { text: "Pathophysiology", bold: true, color: GOLD },
      "Deficiency or resistance to ADH (Arginine Vasopressin, AVP) → inability to concentrate urine",
      { text: "Central DI (Neurogenic)", bold: true },
      { text: "Hypothalamic/posterior pituitary failure → ↓ADH production", level: 1 },
      { text: "Causes: trauma, surgery, tumors, autoimmune, idiopathic", level: 1 },
      { text: "Nephrogenic DI", bold: true },
      { text: "Renal collecting duct resistance to ADH; V2-receptor or AQP2 mutations", level: 1 }
    ],
    [
      { text: "Biochemical Findings", bold: true, color: GOLD },
      "Polyuria: Urine output >3 L/day",
      "Urine osmolality <300 mOsm/kg (hypotonic)",
      "Plasma osmolality >295 mOsm/kg (hypernatraemia risk)",
      { text: "Water Deprivation Test:", bold: true, color: ACCENT },
      { text: "Urine osmolality fails to rise >800 mOsm/kg → DI confirmed", level: 1 },
      { text: "Central DI: Urine concentrates after dDAVP (>50% rise)", level: 1 },
      { text: "Nephrogenic DI: No response to dDAVP", level: 1 },
      { text: "Plasma ADH (AVP) measurement: Low in central, High in nephrogenic", level: 1, color: GOLD }
    ]
  );
  ref(s, "Tietz 7th Ed., Chapter 55 (Pituitary); also Chapter 25 (Water Homeostasis) – AVP physiology");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 7 – SIADH
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "SIADH – Syndrome of Inappropriate ADH Secretion");
  twoCol(s,
    [
      { text: "Definition & Mechanism", bold: true, color: GOLD },
      "Excessive ADH activity → excessive free water reabsorption → dilutional hyponatraemia",
      "Euvolemic state despite hyponatraemia (no oedema, no hypovolaemia)",
      { text: "Causes", bold: true, color: ACCENT },
      { text: "CNS: meningitis, trauma, SAH, stroke", level: 1 },
      { text: "Pulmonary: TB, pneumonia, SCLC (ectopic ADH)", level: 1 },
      { text: "Drugs: carbamazepine, SSRIs, cyclophosphamide, chlorpropamide", level: 1 },
      { text: "Hypothyroidism, Addison's disease (secondary SIADH)", level: 1 }
    ],
    [
      { text: "Diagnostic Criteria (Schwartz-Bartter)", bold: true, color: GOLD },
      "Plasma osmolality <280 mOsm/kg",
      "Serum Na⁺ <135 mmol/L",
      "Urine osmolality >100 mOsm/kg (inappropriately concentrated)",
      "Urine Na⁺ >20 mmol/L (renal salt wasting)",
      "Euvolaemia (normal skin turgor, no oedema)",
      "Absence of adrenal/thyroid insufficiency, diuretics, renal failure",
      { text: "Management guide: serum Na⁺ correction ≤8–10 mmol/L per 24 h (risk of ODS)", level: 1, color: GOLD }
    ]
  );
  ref(s, "Tietz 7th Ed., Chapter 35 (Water, Electrolytes); also Chapter 55 – posterior pituitary, AVP disorders");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 8 – ADRENAL CORTEX ANATOMY & STEROIDOGENESIS
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Adrenal Cortex – Anatomy, Zones & Steroidogenesis");
  bullets(s, [
    { text: "Three functional zones (outside→in):", bold: true },
    { text: "Zona Glomerulosa → Mineralocorticoids (Aldosterone) — regulated by Ang II and K⁺", level: 1 },
    { text: "Zona Fasciculata → Glucocorticoids (Cortisol) — regulated by ACTH", level: 1 },
    { text: "Zona Reticularis → Androgens (DHEA, DHEAS, Androstenedione) — regulated by ACTH", level: 1 },
    { text: "Steroidogenesis Pathway (key enzymes):", bold: true, color: GOLD },
    { text: "Cholesterol → Pregnenolone (CYP11A1 / StAR rate-limiting)", level: 1 },
    { text: "Pregnenolone → Progesterone → 17-OHP (CYP17A1)", level: 1 },
    { text: "17-OHP → 11-Deoxycortisol (21-Hydroxylase CYP21A2)", level: 1, color: ACCENT2 },
    { text: "11-Deoxycortisol → Cortisol (11β-Hydroxylase CYP11B1)", level: 1, color: ACCENT2 },
    { text: "Progesterone → 11-DOC → Aldosterone (CYP21A2 → CYP11B2)", level: 1 },
    { text: "CYP21A2 & CYP11B1 deficiencies → CAH (see Slide 14)", level: 1, color: GOLD }
  ]);
  ref(s, "Tietz 7th Ed., p.2267–2275 – Adrenal Steroid Biochemistry & Biosynthesis (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 9 – CUSHING'S SYNDROME (ADRENAL CAUSES)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Cushing's Syndrome – Classification & Adrenal Causes");
  table(s,
    [
      [
        { text: "Type", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "ACTH Level", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Cause / Key Feature", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Cushing's Disease (pituitary)", "↑ (not suppressed by HDDST)", "ACTH-secreting pituitary adenoma (80% of ACTH-dependent)"],
      ["Ectopic ACTH", "↑↑↑ (>300 pg/mL)", "SCLC, carcinoid, pancreatic tumour"],
      ["Adrenal Adenoma", "↓ Suppressed", "Autonomous cortisol; ACTH <10 pg/mL on HDDST"],
      ["Adrenal Carcinoma", "↓ Suppressed", "Large mass; excess androgens; poor prognosis"],
      ["Iatrogenic (exogenous)", "↓↓ Suppressed", "Therapeutic corticosteroid use — rule out first"],
      ["Pseudo-Cushing", "Normal", "Alcoholism, depression; CRH test: normal response"]
    ],
    { y: 0.82, colW: [3.0, 2.4, 4.0], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., p.2283 – Classification of Disorders Producing Glucocorticoid Excess (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 10 – CLINICAL FEATURES OF CUSHING'S SYNDROME
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Cushing's Syndrome – Clinical & Biochemical Features");
  twoCol(s,
    [
      { text: "Clinical Features", bold: true, color: GOLD },
      "Central obesity, moon face, buffalo hump",
      "Hypertension, diabetes mellitus",
      "Purple striae, easy bruising, thin skin",
      "Proximal myopathy, osteoporosis",
      "Hirsutism, menstrual irregularities",
      "Psychiatric disturbances, cognitive impairment",
      "Immunosuppression, increased infection risk"
    ],
    [
      { text: "Biochemical Abnormalities", bold: true, color: GOLD },
      "↑ UFC (24-h urine free cortisol)",
      "↑ Late-night salivary cortisol",
      "Failure to suppress on DST",
      "Hyperglycaemia / IGT",
      "Hypokalaemia (mineralocorticoid spillover)",
      "↑ Serum cortisol (loss of diurnal rhythm)",
      "ACTH level guides source (see table)",
      { text: "In adrenal Cushing's: suppressed ACTH <10 pg/mL", level: 1, color: ACCENT2 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2283–2286 – Cushing Syndrome clinical/biochemical features (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 11 – ADRENAL MEDULLA – PHAEOCHROMOCYTOMA
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Adrenal Medulla & Phaeochromocytoma – Biochemical Basis");
  bullets(s, [
    { text: "Adrenal Medulla: Chromaffin Cells", bold: true },
    { text: "Produce: Epinephrine (91% of circulating Epi), Norepinephrine, Dopamine", level: 1 },
    { text: "Epinephrine: metabolic hormone (lipolysis, glycogenolysis, gluconeogenesis, ketogenesis)", level: 1 },
    { text: "PNMT enzyme: NE → Epi (only in adrenal medulla, expression requires cortisol)", level: 1 },
    { text: "Phaeochromocytoma – 'Rule of 10's'", bold: true, color: GOLD },
    { text: "10% malignant, 10% bilateral, 10% extra-adrenal (paraganglioma), 10% familial", level: 1 },
    { text: "Biochemical Diagnosis — Preferred Tests:", bold: true, color: ACCENT },
    { text: "Plasma FREE Metanephrines (sensitivity ~99%): Metanephrine + Normetanephrine", level: 1 },
    { text: "24-h Urine Fractionated Metanephrines + Catecholamines (specificity ~98%)", level: 1 },
    { text: "Adrenal venous drainage: Metanephrine 91% adrenal-derived; Normetanephrine 23% adrenal", level: 1 },
    { text: "Clonidine Suppression Test: In true PHEO, plasma catecholamines NOT suppressed by clonidine", level: 1, color: GOLD }
  ]);
  ref(s, "Tietz 7th Ed., p.2082–2085 – The Adrenal Medulla (Chapter 53); Table 53.3 catecholamine contributions");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 12 – PHAEOCHROMOCYTOMA DIAGNOSTIC MARKERS
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Phaeochromocytoma – Laboratory Workup & Interpretation");
  table(s,
    [
      [
        { text: "Analyte", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Specimen", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Threshold / Comment", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Plasma Metanephrine", "EDTA plasma (supine 30 min)", ">0.5 nmol/L — high sensitivity; preferred 1st-line"],
      ["Plasma Normetanephrine", "EDTA plasma", ">0.9 nmol/L — essential for extra-adrenal tumours"],
      ["24-h Urine Metanephrines", "Acidified 24-h urine", "Most specific; less affected by sympathetic surges"],
      ["24-h Urine Catecholamines", "Acidified 24-h urine", "Epi, NE, Dopamine; less sensitive than metanephrines"],
      ["Chromogranin A (CgA)", "Serum", "Raised in PHEO and paraganglioma; also neuroendocrine tumours"],
      ["Clonidine Suppression Test", "Plasma NE 3 h post 0.3 mg clonidine", "NE fails to suppress to <500 pg/mL = PHEO likely"]
    ],
    { y: 0.82, colW: [2.8, 2.4, 4.2], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., Chapter 53 (Catecholamines & Phaeochromocytoma); Adrenal Contribution Table 53.3");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 13 – ADDISON'S DISEASE (PRIMARY ADRENOCORTICAL INSUFFICIENCY)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Addison's Disease – Primary Adrenocortical Insufficiency");
  twoCol(s,
    [
      { text: "Definition & Aetiology", bold: true, color: GOLD },
      "Non-functioning adrenal cortex → glucocorticoid + mineralocorticoid deficiency",
      "Prevalence ~1/10,000; >90% of adrenal tissue lost before symptoms",
      { text: "Causes:", bold: true },
      { text: "Autoimmune adrenalitis (most common in developed world)", level: 1 },
      { text: "Tuberculosis (most common worldwide)", level: 1 },
      { text: "Metastatic carcinoma, haemorrhage (Waterhouse-Friderichsen)", level: 1 },
      { text: "Genetic (>80% of childhood AD)", level: 1 },
      { text: "Secondary AI: pituitary ACTH deficiency; Tertiary: CRH deficiency", level: 1 }
    ],
    [
      { text: "Clinical & Biochemical Features", bold: true, color: GOLD },
      "Fatigue, weakness, weight loss, hyperpigmentation",
      "Hypotension, postural dizziness",
      "Nausea, vomiting, diarrhoea",
      { text: "Lab Findings:", bold: true, color: ACCENT },
      { text: "Hyponatraemia, Hyperkalaemia, Hypoglycaemia, Hypercalcaemia", level: 1 },
      { text: "↓ Morning cortisol (<3 µg/dL = diagnostic; 3–15 = equivocal)", level: 1, color: GOLD },
      { text: "↑ Plasma ACTH (primary AD)", level: 1 },
      { text: "Cosyntropin stimulation: Cortisol fails to rise >18 µg/dL", level: 1, color: GOLD },
      { text: "Anti-21-hydroxylase antibodies: positive in autoimmune AD", level: 1 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2274–2280 – Addison Disease; ADRENOcortical insufficiency (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 14 – CONN'S SYNDROME (PRIMARY ALDOSTERONISM)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Conn's Syndrome – Primary Aldosteronism");
  twoCol(s,
    [
      { text: "Pathophysiology", bold: true, color: GOLD },
      "Autonomous aldosterone secretion from adrenal (adenoma 60% or bilateral hyperplasia 40%)",
      "Most common cause of secondary hypertension (~10% of hypertensives)",
      { text: "Mechanism:", bold: true },
      { text: "↑ Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ excretion → HTN + hypokalaemia", level: 1 },
      { text: "Suppressed PRA (Plasma Renin Activity)", level: 1 },
      { text: "Clinical: Hypertension (often resistant), hypokalaemia, metabolic alkalosis", level: 1 }
    ],
    [
      { text: "Biochemical Diagnosis", bold: true, color: GOLD },
      "Step 1 — Screening: Aldosterone-to-Renin Ratio (ARR)",
      { text: "ARR >30 ng/dL per ng/mL/h (or >750 pmol/L per mU/L) = positive", level: 1, color: GOLD },
      "Step 2 — Confirmatory tests:",
      { text: "Captopril Challenge Test: ARR >200 ng/dL per ng/mL/h at 90 min; Sens 70–90%", level: 1 },
      { text: "Fludrocortisone Suppression / IV saline loading: Aldosterone fails to suppress", level: 1 },
      { text: "Furosemide Stimulation: Low renin response in primary aldosteronism", level: 1 },
      "Step 3 — Subtype: Adrenal Vein Sampling (AVS)",
      { text: "Lateralisation ratio >4 = unilateral adenoma (surgery); bilateral = medical Rx", level: 1 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2592–2634 – Primary Aldosteronism, ARR, Captopril/Furosemide tests (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 15 – CONGENITAL ADRENAL HYPERPLASIA (CAH)
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Congenital Adrenal Hyperplasia (CAH) – Enzyme Deficiencies");
  table(s,
    [
      [
        { text: "Enzyme Defect", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Frequency", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Biochemical Hallmarks & Clinical", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["21-Hydroxylase (CYP21A2)", "~95% of CAH", "↑ 17-OHP (>1000 ng/dL), ↑ Androstenedione (5–10× normal); Salt-wasting (↓ aldosterone, ↓ cortisol) or Simple-virilising; Ambiguous genitalia in females; Addisonian crisis in neonates"],
      ["11β-Hydroxylase (CYP11B1)", "~5% of CAH", "↑ 11-Deoxycortisol, ↑ 11-DOC (→ HTN + hypokalaemia); ↑ androgens → virilisation; Distinguishable: 11-DOC elevated (vs. low in 21-OH deficiency)"],
      ["3β-HSD Deficiency", "Rare", "Impaired conversion of Δ5→Δ4 steroids; ↓ all active steroids; Ambiguous genitalia in both sexes"],
      ["17α-Hydroxylase (CYP17A1)", "Rare", "↑ DOC, Corticosterone; ↓ sex steroids → female phenotype in XY; HTN + hypokalaemia; ↓ Cortisol, ↓ Androgens"],
      ["Neonatal Screening", "Universal", "17-OHP on dried blood spot (heel-prick); confirmatory liquid chromatography-MS/MS"]
    ],
    { y: 0.82, colW: [2.5, 1.4, 5.5], fontSize: 10 }
  );
  ref(s, "Tietz 7th Ed., p.2105–2130 – Congenital Adrenal Hyperplasia (Chapter 56, also Chapter 14)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 16 – THYROID HORMONE BIOCHEMISTRY
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Thyroid Hormones – Synthesis, Structure & Regulation");
  bullets(s, [
    { text: "Thyroid Hormones: T4 (Thyroxine, 3,5,3',5'-tetraiodothyronine) & T3 (3,5,3'-triiodothyronine)", bold: true },
    { text: "T4: primarily secreted by thyroid; T3: mainly via peripheral deiodination of T4 (deiodinase D1/D2)", level: 1 },
    { text: "T3 is the biologically active form (binds thyroid hormone receptors with 10× greater affinity)", level: 1 },
    { text: "rT3 (reverse T3): inactive; produced in illness / fasting (Non-Thyroidal Illness Syndrome)", level: 1 },
    { text: "HPT Axis Regulation:", bold: true, color: GOLD },
    { text: "Hypothalamus: TRH → Anterior Pituitary: TSH → Thyroid: T3/T4 production", level: 1 },
    { text: "Negative feedback: T3/T4 suppress both TRH and TSH secretion", level: 1 },
    { text: "Functions of Thyroid Hormones:", bold: true },
    { text: "↑ BMR, calorigenesis, mitochondrial oxidation", level: 1 },
    { text: "Stimulate neural development and growth; promote sexual maturation", level: 1 },
    { text: "↑ Cardiac rate & contractility (↑ adrenergic sensitivity)", level: 1 },
    { text: "Regulate cholesterol metabolism, protein synthesis, carbohydrate metabolism", level: 1 }
  ]);
  ref(s, "Tietz 7th Ed., p.2304–2307 – Thyroid Hormones: Structure, Biological Function, Physiology (Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 17 – HYPOTHYROIDISM
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Hypothyroidism – Classification, Biochemistry & Diagnosis");
  twoCol(s,
    [
      { text: "Classification", bold: true, color: GOLD },
      "Primary (thyroid failure): Hashimoto's, post-radioiodine, iodine deficiency, post-thyroidectomy, drugs (amiodarone, lithium)",
      "Secondary (pituitary): ↓ TSH",
      "Tertiary (hypothalamic): ↓ TRH → ↓ TSH → ↓ T4",
      "Congenital (neonatal screening essential)",
      { text: "Severe form: Myxoedema (glycosaminoglycan skin infiltration)", level: 1, color: ACCENT2 },
      { text: "Clinical: fatigue, cold intolerance, weight gain, constipation, bradycardia, dry skin, hair loss", level: 1 }
    ],
    [
      { text: "Biochemical Diagnosis", bold: true, color: GOLD },
      "Primary Hypothyroidism:",
      { text: "↑ TSH (most sensitive marker; detects subclinical disease)", level: 1, color: GOLD },
      { text: "↓ Free T4 (overt hypothyroidism)", level: 1 },
      { text: "Anti-TPO antibodies (+) in Hashimoto's (90% sensitivity)", level: 1 },
      { text: "Anti-Tg antibodies (+) in 20–50% of Hashimoto's", level: 1 },
      "Secondary Hypothyroidism:",
      { text: "↓ TSH + ↓ Free T4 (low/low pattern)", level: 1 },
      "Overt vs Subclinical:",
      { text: "Subclinical: ↑ TSH, normal FT4 — treat if TSH >10 or symptoms", level: 1, color: ACCENT2 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2315–2323 – Hypothyroidism; Hashimoto Thyroiditis; Anti-TPO antibodies (Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 18 – HYPERTHYROIDISM
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Hyperthyroidism & Thyrotoxicosis – Causes & Biochemical Diagnosis");
  twoCol(s,
    [
      { text: "Causes (Endogenous)", bold: true, color: GOLD },
      "Graves' Disease (most common) — TSH-receptor stimulating antibodies (TRAb/TSI)",
      "Toxic Multinodular Goitre",
      "Toxic Adenoma",
      "Subacute (De Quervain's) Thyroiditis — transient",
      "Postpartum Thyroiditis",
      "hCG-induced (gestational), TSH-secreting pituitary adenoma",
      { text: "Exogenous: Iodine excess (Jod-Basedow), amiodarone, thyrotoxicosis factitia", level: 1 }
    ],
    [
      { text: "Biochemical Diagnosis", bold: true, color: GOLD },
      "↓ TSH (<0.01 mIU/L in overt; <0.1 in subclinical)",
      "↑ Free T4 and/or ↑ Free T3",
      "Subclinical: ↓ TSH + normal FT4/FT3",
      { text: "Graves' specific markers:", bold: true, color: ACCENT },
      { text: "TRAb (TSH receptor antibodies): (+) in 97% of Graves'", level: 1 },
      { text: "Anti-TPO, Anti-Tg: less specific but often elevated", level: 1 },
      "Cardiovascular biochemistry:",
      { text: "↑ Renin & aldosterone; ↑ cardiac enzymes in severe thyrotoxicosis", level: 1, color: ACCENT2 },
      { text: "Radioiodine uptake scan: ↑↑ diffuse (Graves') vs. focal (toxic adenoma)", level: 1 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2316–2320 (Graves Disease); p.2325 (Endogenous/Exogenous Causes – Box 57.6, Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 19 – TSH ASSAY & THYROID FUNCTION TEST INTERPRETATION
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Thyroid Function Tests – Interpretation Framework");
  table(s,
    [
      [
        { text: "TSH", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Free T4", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Diagnosis", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Additional Tests", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["↑↑", "↓", "Primary Hypothyroidism (overt)", "Anti-TPO, Anti-Tg"],
      ["↑", "Normal", "Subclinical Hypothyroidism", "Anti-TPO; monitor or treat if TSH >10"],
      ["↓↓", "↑", "Primary Hyperthyroidism (overt)", "TRAb/TSI, RAIU, FT3"],
      ["↓", "Normal", "Subclinical Hyperthyroidism", "FT3, RAIU; repeat in 3–6 months"],
      ["↓↓", "↓", "Secondary/Tertiary Hypothyroidism", "Pituitary MRI, TRH test"],
      ["↑", "↑", "TSH-secreting pituitary adenoma", "MRI pituitary; alpha-subunit"],
      ["Normal", "↓", "Non-Thyroidal Illness (NTI)", "rT3 ↑; TBG, clinical context"]
    ],
    { y: 0.82, colW: [1.3, 1.3, 3.4, 3.4], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., p.2304–2330 – TFT interpretation, TSH assay (ultrasensitive), Chapter 57");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 20 – AUTOIMMUNE THYROID DISEASE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Autoimmune Thyroid Disease – Hashimoto's & Graves'");
  twoCol(s,
    [
      { text: "Hashimoto Thyroiditis", bold: true, color: GOLD },
      "Most common thyroid disorder; leading cause of hypothyroidism in iodine-sufficient regions",
      "T-cell-mediated autoimmune destruction of follicular cells",
      "Histology: lymphocyte + plasma cell infiltrate; secondary follicles; Hürthle cells",
      { text: "Antibodies: Anti-TPO (90%), Anti-Tg (20–50%)", level: 1, color: GOLD },
      "Initial goitre → eventual atrophy",
      "↑ Risk of primary B-cell lymphoma and papillary carcinoma"
    ],
    [
      { text: "Graves' Disease", bold: true, color: GOLD },
      "Autoantibody (TRAb/TSI) stimulates TSH receptor → hyperthyroidism",
      "Diffuse goitre + pretibial myxoedema + exophthalmos (triad)",
      { text: "TRAb (TSH receptor Ab): 97% sensitivity for Graves' — test of choice", level: 1, color: GOLD },
      "Anti-TPO elevated in majority",
      { text: "Prevalence of AITD: ~5% population; antibodies in 10–20%", level: 1, color: ACCENT2 },
      "T-cell mediated with genetic susceptibility (HLA-DR3, CTLA-4 polymorphisms)",
      "Associated with T1DM, RA, SLE (autoimmune polyglandular syndrome)"
    ]
  );
  ref(s, "Tietz 7th Ed., p.2315–2320 – Autoimmune Thyroid Disease, Hashimoto & Graves' (Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 21 – GOITRE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Goitre – Types, Biochemistry & Evaluation");
  twoCol(s,
    [
      { text: "Classification", bold: true, color: GOLD },
      "Simple (diffuse) goitre: Iodine deficiency — most common worldwide cause",
      "Multinodular Goitre (MNG): Multiple nodules; may be toxic (↓ TSH) or non-toxic",
      "Toxic Adenoma: Single autonomous nodule; ↓ TSH, ↑ T3/T4",
      "Hashimoto's goitre: Initial enlargement before atrophy",
      "Graves' goitre: Diffuse hyperplastic; ↑ vascularity on Doppler",
      "Riedel thyroiditis: Fibrotic; rare; IgG4-related",
    ],
    [
      { text: "Biochemical Evaluation of Goitre", bold: true, color: GOLD },
      "1st step: TSH (ultrasensitive assay, detect to ≤0.01 mIU/L)",
      { text: "↓ TSH → autonomous tissue; ↑ TSH → Hashimoto's / iodine deficiency", level: 1 },
      "If TSH low: FT4 + FT3; RAIU scan",
      "Iodine status: Urinary iodine excretion (population screening)",
      "Thyroid antibodies: Anti-TPO, TRAb (for autoimmune aetiology)",
      "Thyroglobulin (Tg): Elevated in simple goitre; not specific for malignancy",
      { text: "FNA cytology for nodules with suspicious USS features", level: 1, color: GOLD }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2313 – Goitre, Thyroid nodules; Thyroid-stimulating Hormone (Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 22 – THYROID CARCINOMA
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Thyroid Carcinoma – Types, Markers & Biochemical Monitoring");
  table(s,
    [
      [
        { text: "Type (% of Ca)", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Cell Origin", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Tumour Markers & Notes", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Papillary (75–80%)", "Follicular cell", "Tg (post-thyroidectomy monitoring); BRAF V600E mutation; best prognosis"],
      ["Follicular (10–15%)", "Follicular cell", "Tg marker; RAS/PAX8-PPARγ; vascular/capsular invasion on histology"],
      ["Medullary (MTC) (~5%)", "C-cells (parafollicular)", "Calcitonin (diagnostic + follow-up); CEA; RET proto-oncogene mutation; CgA elevated"],
      ["Anaplastic (~2%)", "Follicular cell (de-differentiated)", "No specific tumour marker; TSH undetectable; worst prognosis; rapidly fatal"],
      ["Biochemical Role of Lab:", "", "TSH suppression (target <0.1 after thyroidectomy + RAI for DTC); Tg ± anti-Tg-Ab every 6–12 months; Stimulated Tg after rhTSH (>2 ng/mL = recurrence)"]
    ],
    { y: 0.82, colW: [2.4, 2.0, 5.0], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., p.2328–2340 – Thyroid Neoplasia, Differentiated Thyroid Cancer, Medullary Ca, Anaplastic Ca (Chapter 57)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 23 – MEDULLARY THYROID CARCINOMA – CALCITONIN
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Medullary Thyroid Carcinoma (MTC) – Calcitonin & RET Gene");
  bullets(s, [
    { text: "MTC arises from calcitonin-producing C-cells (parafollicular cells)", bold: true },
    { text: "80% sporadic; 20% hereditary (MEN2A, MEN2B, Familial MTC) — all via RET proto-oncogene mutations", level: 1 },
    { text: "Calcitonin as Tumour Marker:", bold: true, color: GOLD },
    { text: "Serum calcitonin: Highly sensitive and specific for MTC (>10 pg/mL suspicious)", level: 1 },
    { text: "Pentagastrin / calcium stimulation test: Stimulated calcitonin >100 pg/mL = MTC", level: 1 },
    { text: "Post-thyroidectomy: Calcitonin should be undetectable; rising = recurrence", level: 1 },
    { text: "CEA (Carcinoembryonic Antigen): Secondary marker; ↑ correlates with tumour burden and dedifferentiation", level: 1 },
    { text: "Chromogranin A (CgA): General neuroendocrine tumour marker; elevated in MTC", level: 1 },
    { text: "Genetic testing:", bold: true, color: ACCENT },
    { text: "All MTC patients: RET germline mutation testing (codons 609,611,618,620,634 in exons 10–11 for MEN2A)", level: 1 },
    { text: "Positive → prophylactic thyroidectomy in carriers; screen for PHEO + Hyperparathyroidism (MEN2A)", level: 1 }
  ]);
  ref(s, "Tietz 7th Ed., p.2333–2340 – Medullary Thyroid Cancer; Calcitonin; RET mutation (Chapter 57, p.2335)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 24 – SUMMARY: PITUITARY DISORDERS AT A GLANCE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Summary Table – Pituitary Disorders");
  table(s,
    [
      [
        { text: "Disorder", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Key Biochemistry", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Diagnostic Test(s)", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Cushing's Disease (pituitary ACTH)", "↑UFC, ↑ACTH, ↑Cortisol (no diurnal rhythm)", "HDDST suppression; CRH test; BIPSS ratio >3"],
      ["Diabetes Insipidus (Central)", "↑Plasma Osm, ↓Urine Osm, ↓AVP", "Water deprivation + dDAVP response (>50% rise urine Osm)"],
      ["Diabetes Insipidus (Nephrogenic)", "↑Plasma Osm, ↓Urine Osm, ↑AVP", "No response to dDAVP; V2R or AQP2 mutation testing"],
      ["SIADH", "↓Plasma Osm, ↓Na⁺, Inappropriately ↑Urine Osm, ↑Urine Na⁺", "Schwartz-Bartter criteria; rule out adrenal/thyroid insufficiency"],
      ["Pituitary Insufficiency (Pan-hypopituitarism)", "↓Multiple hormones; ↓cortisol, ↓T4, ↓LH/FSH", "Insulin Tolerance Test (ITT); morning cortisol <5 µg/dL + cosyntropin stimulation"]
    ],
    { y: 0.82, colW: [3.0, 3.2, 3.2], fontSize: 10 }
  );
  ref(s, "Tietz 7th Ed., Chapters 55–56 – Pituitary & HPA Axis Testing; Box 55.5, Box 56.1");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 25 – SUMMARY: ADRENAL DISORDERS AT A GLANCE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Summary Table – Adrenal Disorders");
  table(s,
    [
      [
        { text: "Disorder", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Key Biochemistry", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Primary Diagnostic Test", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Cushing's Syndrome (Adrenal)", "↑UFC, ↑Cortisol, ↓ACTH (<10 pg/mL)", "High-dose DST (no suppression); CT/MRI adrenal"],
      ["Addison's Disease", "↓Cortisol, ↑ACTH, ↓Na⁺, ↑K⁺, Hypoglycaemia", "Cosyntropin stimulation (cortisol <18 µg/dL); anti-21-OH Ab"],
      ["Conn's Syndrome (Primary Aldosteronism)", "↑Aldosterone, ↓Renin, ↑ARR, Hypokalaemia, HTN", "ARR >30; Captopril challenge; Adrenal Vein Sampling"],
      ["Phaeochromocytoma", "↑Plasma metanephrines (Met + NMet), ↑Urine catecholamines", "Plasma free metanephrines; 24-h urine metanephrines; CgA"],
      ["CAH – 21-OH Deficiency", "↑17-OHP (>1000 ng/dL), ↑Androstenedione, ↓Cortisol, ±↓Aldosterone", "Serum 17-OHP; neonatal heel-prick; ACTH stimulation"],
      ["CAH – 11β-OH Deficiency", "↑11-Deoxycortisol, ↑11-DOC, ↑Androgens; HTN", "Serum 11-Deoxycortisol and 11-DOC; steroid panel by LC-MS/MS"]
    ],
    { y: 0.82, colW: [2.8, 3.4, 3.2], fontSize: 10 }
  );
  ref(s, "Tietz 7th Ed., Chapter 56 – Adrenal Cortex; Chapter 53 – Phaeochromocytoma");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 26 – SUMMARY: THYROID DISORDERS AT A GLANCE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Summary Table – Thyroid Disorders");
  table(s,
    [
      [
        { text: "Disorder", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Key Biochemistry", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Primary Diagnostic Test", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Primary Hypothyroidism", "↑TSH, ↓FT4, ↓FT3", "TSH (most sensitive); Anti-TPO for aetiology"],
      ["Hashimoto's Thyroiditis", "↑TSH, ↓FT4, Anti-TPO (+) 90%, Anti-Tg (+) 20–50%", "Anti-TPO (titre correlates with severity)"],
      ["Graves' Hyperthyroidism", "↓TSH, ↑FT4, ↑FT3; TRAb/TSI (+) 97%", "TRAb; RAIU (diffusely ↑); Anti-TPO"],
      ["Toxic MNG / Toxic Adenoma", "↓TSH, ↑FT3/FT4; TRAb (–)", "RAIU scan + USS for focal nodule"],
      ["Medullary Ca Thyroid", "Normal TFTs; ↑Calcitonin, ↑CEA, ↑CgA", "Stimulated Calcitonin; RET mutation testing"],
      ["Differentiated Ca Thyroid", "Post-thyroidectomy: ↑Tg = recurrence", "Stimulated Tg (rhTSH); Tg every 6–12 months"],
      ["Non-Thyroidal Illness (NTI)", "↓FT3, ↑rT3, Normal/↓TSH", "Clinical context; rT3; resolve underlying illness"]
    ],
    { y: 0.82, colW: [2.8, 3.2, 3.4], fontSize: 10 }
  );
  ref(s, "Tietz 7th Ed., Chapter 57 – Thyroid Disorders; Chapters 26, 57 (Thyroid Autoantibodies, Tg monitoring)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 27 – LABORATORY METHODS FOR ENDOCRINE TESTING
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Analytical Methods in Endocrine Biochemistry");
  twoCol(s,
    [
      { text: "Immunoassay Platforms", bold: true, color: GOLD },
      "ECLIA, CLIA, RIA — Used for TSH, FT4, FT3, cortisol, aldosterone, ACTH, calcitonin",
      "TSH: 3rd-generation assays detect to ≤0.01 mIU/L (key for subclinical thyroid disease)",
      "Limitations: Biotin interference, heterophilic antibodies, cortisol metabolite cross-reactivity",
      { text: "Plasma metanephrines: Preferably by LC-MS/MS for highest specificity", level: 1 },
      { text: "Cortisol: EDTA interference reported; saliva matrix less affected", level: 1 }
    ],
    [
      { text: "Mass Spectrometry (LC-MS/MS)", bold: true, color: GOLD },
      "Gold standard for steroid hormones (cortisol, aldosterone, 17-OHP, androgens)",
      "Steroid hormone panel: Simultaneous quantification of multiple steroids",
      "CAH diagnosis and monitoring: 17-OHP, 11-deoxycortisol, androstenedione by LC-MS/MS",
      "Advantages: No antibody cross-reactivity; precise measurement of low concentrations",
      { text: "Catecholamines/metanephrines: HPLC-ECD or LC-MS/MS (preferred)", level: 1, color: ACCENT2 },
      { text: "Dried blood spot 17-OHP: Immunoassay screen; confirmation by LC-MS/MS", level: 1 }
    ]
  );
  ref(s, "Tietz 7th Ed., p.2288–2292 – Adrenal Steroids; Renin; Mass Spectrometry methods (Chapter 56)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 28 – CLINICAL INTEGRATION: APPROACH TO HYPERTENSION WITH ENDOCRINE CAUSE
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Clinical Integration: Endocrine Hypertension – Differential Diagnosis");
  table(s,
    [
      [
        { text: "Condition", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Hormone Profile", options: { bold: true, color: GOLD, fill: DIVIDER } },
        { text: "Clinical Clues", options: { bold: true, color: GOLD, fill: DIVIDER } }
      ],
      ["Conn's Syndrome (PA)", "↑Aldosterone, ↓Renin, ↑ARR, ↓K⁺", "Resistant HTN; spontaneous hypokalaemia; metabolic alkalosis"],
      ["Phaeochromocytoma", "↑Plasma metanephrines, ↑urine catecholamines", "Paroxysmal HTN, headache, sweating, palpitations; 'Rule of 10'"],
      ["Cushing's Syndrome", "↑UFC, ↑Cortisol, ± ↑ACTH", "Centripetal obesity; striae; proximal myopathy; diabetes"],
      ["CAH (11β-OH deficiency)", "↑11-DOC, ↑Androgens; ↓K⁺", "Young patient + virilisation; absent with 21-OH deficiency"],
      ["Hypothyroidism", "↑TSH, ↓FT4", "Diastolic HTN; bradycardia; weight gain; dyslipidaemia"],
      ["Acromegaly (GH excess)", "↑IGF-1, ↑GH (non-suppressible on OGTT)", "Coarse features; diabetes; carpal tunnel; sleep apnoea"]
    ],
    { y: 0.82, colW: [2.5, 3.2, 3.7], fontSize: 10.5 }
  );
  ref(s, "Tietz 7th Ed., Chapters 53, 56, 57 – Endocrine hypertension differential; PA, PHEO, Cushing's, CAH, Thyroid");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 29 – SPECIMEN COLLECTION & PRE-ANALYTICAL CONSIDERATIONS
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "Pre-Analytical Considerations for Endocrine Tests");
  bullets(s, [
    { text: "Cortisol / ACTH:", bold: true },
    { text: "Cortisol: Morning fasting sample preferred; ACTH in EDTA on ice → separate immediately (labile peptide)", level: 1 },
    { text: "Cosyntropin test: Baseline + 30 + 60 min after 250 µg IM/IV; ensure no exogenous steroids", level: 1 },
    { text: "Plasma Metanephrines (Phaeochromocytoma):", bold: true },
    { text: "Patient supine for ≥30 min before venepuncture; avoid caffeine, tricyclics, levodopa, sympathomimetics", level: 1 },
    { text: "Avoid sampling during hypertensive crisis (false positives); preferably fasting", level: 1 },
    { text: "Aldosterone / Renin (ARR):", bold: true },
    { text: "Ideally collected after 2-week washout of ACEi, ARBs, β-blockers, spironolactone", level: 1 },
    { text: "Upright posture for ≥2 h; sodium-replete diet (aldosterone is posture and salt-sensitive)", level: 1 },
    { text: "Thyroid Function Tests:", bold: true },
    { text: "TSH: No specific timing; levothyroxine taken after sample (false ↑ if taken before)", level: 1 },
    { text: "Biotin supplementation: Causes falsely ↓ TSH and falsely ↑/↓ FT4 — stop 48–72 h before testing", level: 1, color: GOLD },
    { text: "Thyroglobulin (Tg): Must check anti-Tg antibodies simultaneously (false low Tg if anti-Tg (+))", level: 1 }
  ]);
  ref(s, "Tietz 7th Ed., Chapter 56 (pre-analytical for steroids, renin); Chapter 57 (TFTs, Tg anti-Tg interference)");
}

// ════════════════════════════════════════════════════════════════════════════
//  SLIDE 30 – REFERENCES & CONCLUSION
// ════════════════════════════════════════════════════════════════════════════
{
  const s = addSlide();
  heading(s, "References & Key Learning Points");
  twoCol(s,
    [
      { text: "Primary Reference", bold: true, color: GOLD },
      "Tietz Textbook of Laboratory Medicine, 7th Edition (2023)",
      { text: "Ch. 53: Catecholamines & Phaeochromocytoma (p.2082–2085)", level: 1 },
      { text: "Ch. 55: Pituitary Disorders — HPA axis, DI, SIADH (p.2240–2245)", level: 1 },
      { text: "Ch. 56: Adrenal Cortex — Steroidogenesis, Cushing's, Addison's, Conn's, CAH (p.2267–2295)", level: 1 },
      { text: "Ch. 57: Thyroid — Hormone biochemistry, Hypo/Hyperthyroidism, Ca Thyroid, Goitre (p.2304–2340)", level: 1 },
      { text: "Ch. 26: Thyroid Autoantibodies (p.179–200)", level: 1 }
    ],
    [
      { text: "Key Take-Home Messages", bold: true, color: GOLD },
      "TSH is the single most sensitive test for thyroid dysfunction",
      "Plasma free metanephrines: preferred 1st-line for phaeochromocytoma",
      "ARR is the best screening test for primary aldosteronism",
      "17-OHP is the hallmark of 21-hydroxylase deficiency (commonest CAH)",
      "ACTH level differentiates ACTH-dependent vs. ACTH-independent hypercortisolism",
      "High-dose DST: pituitary Cushing's suppresses; ectopic/adrenal does not",
      "Calcitonin + RET mutation = cornerstone of MTC workup",
      { text: "LC-MS/MS is replacing immunoassay for steroid hormone measurement in endocrine biochemistry", level: 1, color: ACCENT2 }
    ]
  );
  ref(s, "Tietz Textbook of Laboratory Medicine, 7th Ed. (Rifai et al., 2023) — Elsevier");
}

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