Laboratory Diagnosis of Endocrine Diseases

Intro to Endocrine Testing - Hormonal Hullabaloo

• Assays: RIA, ELISA, Chemiluminescence (CLIA).
• Specimens: Critical timing (circadian/pulsatile rhythms), stability, specific anticoagulants (e.g., EDTA for PTH).
• Pre-analytical factors: Stress, posture (e.g., renin), medications can alter hormone levels.
• Secretion patterns: Pulsatile (e.g., LH, GH), Circadian (e.g., cortisol, ACTH), Feedback loops (mostly negative).
• Testing types:
  • Static: Basal hormone levels (e.g., TSH, HbA1c).
  • Dynamic: Stimulation (e.g., ACTH for adrenal reserve) or Suppression (e.g., Dexamethasone for Cushing's).

⭐ Hook effect in immunoassays: Very high antigen levels (e.g., prolactin in prolactinoma) can cause falsely low readings. Overcome by sample dilution.

Hypothalamic-Pituitary Tests - Master Gland Metrics

• Growth Hormone (GH):
  • Screen: IGF-1 (more stable).
  • Acromegaly/Gigantism: Oral Glucose Tolerance Test (OGTT) - GH fails to suppress <1 ng/mL.
  • Deficiency: Insulin Tolerance Test (ITT) is gold standard; GH stimulation tests (e.g., Arginine, Clonidine).
• Prolactin (PRL):
  • Basal PRL: >200 ng/mL highly suggestive of prolactinoma.
  • Dynamic tests (e.g., TRH stimulation) less common; screen for macroprolactin if indicated.
• ACTH (Cushing's Syndrome Workup):
  • Basal: Morning ACTH & Cortisol.
  • Low-Dose Dexamethasone Suppression Test (LDDST - 1mg overnight): Failure to suppress cortisol suggests Cushing's Syndrome.
  • High-Dose Dexamethasone Suppression Test (HDDST - 8mg overnight): Cortisol suppression → Cushing's Disease (pituitary); No suppression → Ectopic ACTH / Adrenal tumor.
  • CRH Stimulation Test: Exaggerated ACTH/cortisol response in Cushing's Disease.
• TSH: Assessed with free T4 (FT4) & T3 as part of thyroid function tests.
• ADH (Vasopressin) - Diabetes Insipidus (DI):
  • Water Deprivation Test: Differentiates Central DI (Urine Osm ↑ >50% post-DDAVP) from Nephrogenic DI (minimal/no Urine Osm ↑ post-DDAVP).

⭐ Paradoxical GH rise with TRH or GnRH stimulation occurs in approximately 50% of patients with acromegaly.

Thyroid & Parathyroid Tests - Neck Check Diagnostics

• Thyroid Function Tests (TFTs):
  • TSH: 0.4-4.0 mIU/L. Best initial. ↑Primary Hypo, ↓Primary Hyper.
  • fT4: 0.8-1.8 ng/dL; fT3: 2.3-4.2 pg/mL (more potent).
  • Antibodies: TPOAb/TgAb (Hashimoto’s), TRAb (Graves’).
  • Subclinical Hypo: ↑TSH, Normal fT4. Subclinical Hyper: ↓TSH, Normal fT4/fT3.
  • Non-Thyroidal Illness (NTI): ↓T3, ↓/Normal T4, Normal/↓ TSH.
• Parathyroid Tests:
  • PTH, Serum Ca (Total: 8.5-10.5 mg/dL; Ionized: 4.65-5.25 mg/dL), Phosphate (2.5-4.5 mg/dL), Vit D (25-OH, 1,25-(OH)2).
  • Corrected Ca: $Ca_{corr} (mg/dL) = Ca_{total} (mg/dL) + 0.8 \times (4.0 - Albumin [g/dL])$.
  • Primary Hyperparathyroidism: ↑PTH, ↑Ca, ↓PO4.
  • Hypoparathyroidism: ↓PTH, ↓Ca, ↑PO4.

⭐ TSH is the single most sensitive test for primary thyroid dysfunction.

Adrenal & Pancreatic Tests - Stress & Sugar Sleuthing

• Adrenal Tests:
  • Cortisol: Serum, 24hr urine free cortisol (UFC), late-night salivary.
  • ACTH: Basal, stimulated.
  • Dexamethasone Suppression Test (DST):
    • Low Dose (LDDST): 1mg overnight; failure to suppress cortisol → Cushing's syndrome.
    • High Dose (HDDST): 8mg; differentiates pituitary vs. ectopic ACTH.
  • CRH Stimulation: Differentiates Cushing's disease from ectopic ACTH.
  • Aldosterone & Renin: For hyperaldosteronism (ARR).
  • Metanephrines (plasma/urine), VMA (urine): For pheochromocytoma.
  • 📌 Mnemonic (Adrenal Cortex): GFR - Salt (Glomerulosa-Aldosterone), Sugar (Fasciculata-Cortisol), Sex (Reticularis-Androgens).
• Pancreatic Endocrine Tests:
  • Glucose: Fasting (FPG), Post-prandial (PPG), Random.
    • Diabetes: FPG ≥ 126 mg/dL; PPG (OGTT) ≥ 200 mg/dL.
  • HbA1c: Glycated hemoglobin.
    • Diabetes: ≥ 6.5%.
  • Oral Glucose Tolerance Test (OGTT): 75g glucose load.
  • Insulin, C-peptide: Assess insulin secretion/resistance.

⭐ HbA1c reflects glycemic control over the preceding 2-3 months.

High‑Yield Points - ⚡ Biggest Takeaways

• Basal hormone levels screen; dynamic tests (stimulation/suppression) confirm dysfunction (e.g., Cushing's, Addison's).
• Immunoassays (ELISA, RIA) are pivotal for quantifying most hormone concentrations.
• Urinary Free Cortisol (UFC) and metanephrines/VMA are crucial for Cushing's syndrome and pheochromocytoma.
• Autoantibodies (anti-TPO, anti-TSHR, anti-GAD) diagnose autoimmune thyroiditis and Type 1 DM.
• HbA1c reflects long-term glycemic control (2-3 months) in diabetes.
• FNAC is the primary diagnostic tool for thyroid nodules.