6.2 Thyroid & Calcium Disorders
Key Takeaways
- In thyroid storm (Burch-Wartofsky score > 45), propylthiouracil (PTU) must be administered at least 1 hour before potassium iodide (Lugol's solution) to prevent iodine substrate organification into new thyroid hormones.
- Acute severe hypercalcemia (> 3.5 mmol/L) requires aggressive volume expansion with 3–6 L of 0.9% NaCl over 24 hours prior to or alongside IV zoledronic acid (4 mg over 15 mins).
- Familial Hypocalciuric Hypercalcemia (FHH) is differentiated from primary hyperparathyroidism by a urine calcium-to-creatinine clearance ratio (UCCCR) < 0.01 (< 1%), preventing unnecessary surgery.
- Levothyroxine replacement is indicated in subclinical hypothyroidism when serum TSH is ≥ 10 mU/L, during pregnancy, or when TSH is 5–10 mU/L with positive anti-TPO antibodies or symptoms.
6.2 Thyroid & Calcium Disorders
Diagnostic Interpretation of Thyroid Function Tests
Evaluating serum thyroid-stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) requires systematic evaluation of hypothalamic-pituitary-thyroid axis negative feedback loops. Standard reference ranges typically define normal TSH as 0.4–4.5 mU/L, free T4 as 10–22 pmol/L, and free T3 as 3.5–6.5 pmol/L.
Biochemical Diagnostic Matrix
| Clinical Condition | TSH | Free T4 | Free T3 | Key Diagnostic / Management Features |
|---|---|---|---|---|
| Primary Hypothyroidism | High | Low | Low/Normal | Anti-TPO antibodies positive in > 90% (Hashimoto's) |
| Primary Hyperthyroidism | Low (< 0.05) | High | High | TSH-receptor antibodies (TRAb) confirm Graves' disease |
| Subclinical Hypothyroidism | High (5–10) | Normal | Normal | Treat if TSH ≥ 10 mU/L, pregnant, or anti-TPO positive |
| Subclinical Hyperthyroidism | Low (< 0.1) | Normal | Normal | Associated with atrial fibrillation and osteoporosis |
| Sick Euthyroid Syndrome | Low/Normal | Low/Normal | Low | Non-thyroidal illness in acute ICU illness; recheck post-recovery |
| Central Hypothyroidism | Low/Normal | Low | Low | Pituitary failure; evaluate full anterior pituitary panel |
| TSH-Secreting Adenoma | High/Normal | High | High | Pituitary MRI; elevated serum alpha-subunit |
Thyrotoxicosis & Thyroid Storm
Etiologies of Thyrotoxicosis
- Graves' Disease: Autoimmune hyperthyroidism driven by TSH-receptor stimulating antibodies (TRAb). Features include a diffuse smooth goitre with vascular bruit, exophthalmos, pretibial myxedema, and thyroid acropachy. Radionuclide technetium-99m scan shows diffuse, homogenous high uptake. Treatment: Carbimazole (or Propylthiouracil in 1st trimester pregnancy due to carbimazole aplasia cutis risk). Severe active Graves' orbitopathy is treated with pulse intravenous Methylprednisolone (500 mg weekly for 6 weeks, then 250 mg weekly for 6 weeks).
- Subacute (De Quervain's) Thyroiditis: Post-viral granulomatous thyroiditis. Presents with a painful, exquisitely tender goitre, fever, elevated ESR (> 50 mm/hr), and low radionuclide uptake (< 1%). Follows a triphasic course (thyrotoxic -> hypothyroid -> recovery). Treated with high-dose NSAIDs or Prednisolone (20–40 mg daily).
- Toxic Multinodular Goitre (TMNG) & Toxic Adenoma: Hyperfunctioning autonomous nodules in older adults. Radionuclide scan shows patchy or focal high uptake with background suppression.
- Amiodarone-Induced Thyrotoxicosis (AIT): Type 1 (hyper-vascular, underlying Graves/nodules; treat with thionamides) vs. Type 2 (destructive inflammatory thyroiditis; treat with oral prednisolone).
Emergency Management of Thyroid Storm
Thyroid storm is a hypermetabolic emergency quantified by a Burch-Wartofsky Point Scale > 45. Features include hyperpyrexia (> 38.5°C), severe tachycardia/atrial fibrillation, delirium/psychosis, and jaundice.
Sequential Pharmacological Protocol:
- Propylthiouracil (PTU): 400–600 mg loading dose orally/via NG tube, then 200 mg every 4 hours. Blocks new thyroid hormone synthesis and peripheral T4-to-T3 conversion.
- Lugol's Iodine or Potassium Iodide: Administered at least 1 hour AFTER PTU. Inhibits pre-formed thyroid hormone release (Wolff-Chaikoff effect). Crucial Exam Pearl: Giving iodine prior to PTU provides substrate for further hormone synthesis (Jod-Basedow effect), worsening crisis.
- Propranolol: 60–80 mg orally every 4 hours (or 1–2 mg IV) to control sympathetic hyperactivity and block peripheral T4-to-T3 conversion.
- IV Hydrocortisone: 100 mg IV 6-hourly to prevent relative adrenal exhaustion and reduce peripheral T4-to-T3 conversion.
Hypothyroidism & Myxedema Coma
- Replacement Therapy: Levothyroxine (T4) starting dose ~1.6 mcg/kg/day in young adults. In elderly patients or those with ischemic heart disease, start at 25–50 mcg/day to avoid precipitating angina. Monitor TSH at 6–8 weeks (target TSH 0.4–2.5 mU/L).
- Myxedema Coma: Severe hypothyroidism presenting with hypothermia, hyponatremia, hypercapnia, and altered mental state. Management requires IV Levothyroxine (200–400 mcg loading) PLUS IV Hydrocortisone (100 mg stat) to prevent precipitating adrenal crisis in unrecognized concomitant hypopituitarism.
Disorders of Calcium & Parathyroid Homeostasis
Corrected Calcium Calculation
Total serum calcium must be corrected for serum albumin concentration:
Corrected Ca²⁺ (mmol/L) = Measured Ca²⁺ + 0.02 × (40 - Serum Albumin [g/L])
Hypercalcemia Differential Diagnosis Matrix
| Feature | Primary Hyperparathyroidism (PHPT) | Malignancy (PTHrP Secretion) | Familial Hypocalciuric Hypercalcemia (FHH) |
|---|---|---|---|
| Corrected Calcium | Mildly/Moderately Elevated | Severely Elevated (> 3.5 mmol/L) | Mildly Elevated |
| Intact PTH | High or Inappropriately Normal | Suppressed (< 1.0 pmol/L) | High or Inappropriately Normal |
| Serum Phosphate | Low (< 0.8 mmol/L) | Variable | Normal/Low |
| Urine Ca:Cr Clearance Ratio | > 0.02 (> 2%) | High | < 0.01 (< 1%) |
| Management | Parathyroidectomy | IV 0.9% NaCl + Zoledronic Acid | Reassurance (Surgery Contraindicated) |
Emergency Management of Acute Severe Hypercalcemia (> 3.5 mmol/L)
- Isotonic Saline Hydration: Infuse 3–6 Liters of 0.9% NaCl over 24 hours to restore volume status and promote renal calcium clearance.
- Intravenous Bisphosphonates: Administer Zoledronic Acid 4 mg IV over 15 minutes (or Pamidronate 60–90 mg). Full hypocalcemic onset requires 48–72 hours.
- Calcitonin: 4–8 IU/kg SC/IM 12-hourly provides rapid calcium lowering within 2–4 hours (used as a bridge while awaiting bisphosphonate effect); limited by tachyphylaxis after 48 hours.
Hypocalcemia & Hypoparathyroidism
- Etiologies: Surgical damage during thyroidectomy/parathyroidectomy (most common), autoimmune destruction, or magnesium depletion (hypomagnesemia inhibits PTH release and induces end-organ resistance).
- Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy): End-organ PTH resistance due to GNAS gene mutations. Clinical signs include short stature, round facies, and short 4th/5th metacarpals. Biochemical panel demonstrates hypocalcemia, hyperphosphatemia, and elevated PTH.
- Emergency Management of Acute Hypocalcemia: Symptomatic patients present with carpopedal spasm (Trousseau's sign), neuromuscular irritability (Chvostek's sign), or prolonged QTc interval. Administer 10 mL of 10% Calcium Gluconate IV over 10 minutes, followed by continuous IV infusion if required.
A 32-year-old woman with known Graves' disease presents to the emergency department with fever (39.2°C), marked agitation, profuse sweating, and rapid atrial fibrillation with a ventricular response of 160 bpm. Her Burch-Wartofsky point score is calculated as 55, confirming thyroid storm. The medical team plans to initiate propylthiouracil (PTU), Lugol's iodine, propranolol, and hydrocortisone. What is the crucial sequencing requirement regarding iodine administration in this setting?
A 48-year-old asymptomatic man is found to have a total serum calcium of 2.78 mmol/L (normal range 2.15–2.55 mmol/L) on routine biochemical screening. Repeat testing confirms corrected calcium 2.76 mmol/L, serum phosphate 0.75 mmol/L (normal 0.8–1.4 mmol/L), intact PTH 6.8 pmol/L (normal 1.6–6.9 pmol/L), and normal renal function. A 24-hour urinary calcium-to-creatinine clearance ratio (UCCCR) is calculated as 0.006 (0.6%). What is the most likely diagnosis?
A 36-year-old woman presents with a 2-week history of severe anterior neck pain radiating to her ears, associated with fever, malaise, and palpitations. On examination, her thyroid gland is diffusely enlarged and exquisitely tender to palpation. Serum TSH is < 0.01 mU/L, free T4 is elevated at 34 pmol/L, and ESR is 88 mm/hr. A technetium-99m thyroid uptake scan demonstrates a radionuclide uptake of < 0.5%. What is the management of choice?