4.3 Thyroid, Adrenal, Pituitary, & Electrolyte Disturbances

4.3 Thyroid, Adrenal, Pituitary, & Electrolyte Disturbances

Thyroid Disorders & Emergency Management

Diagnostic Interpretation Matrix

Thyroid Storm (Thyrotoxic Crisis)

A life-threatening hypermetabolic state triggered by infection, surgery, trauma, or iodine load in uncontrolled hyperthyroidism. Diagnosed using the Burch-Wartofsky Point Scale (Score > 45).

• Clinical Features: High fever (>40°C), severe tachycardia / atrial fibrillation, agitation, delirium, jaundice, high-output heart failure.
• Mandatory Treatment Sequence:
  1. Beta-Blockers: Propranolol 60–80 mg PO q4h or IV (controls adrenergic hyperactivation and blocks peripheral T4-to-T3 conversion).
  2. Thionamides: Propylthiouracil (PTU) 500–1000 mg loading dose then 250 mg PO q4h (blocks synthesis and peripheral conversion) OR Methimazole 20 mg PO q4h.
  3. Iodine Solution: Lugol's solution 5 drops PO q8h or SSKI administered AT LEAST 1 HOUR AFTER thionamide administration (prevents organification of iodine into new hormone substrate - Jod-Basedow effect).
  4. Corticosteroids: Hydrocortisone 100 mg IV q8h (inhibits peripheral T4-to-T3 conversion and treats relative adrenal exhaustion).

Myxedema Coma

Severe hypothyroid emergency presenting with the triad of hypothermia (<35°C), hyponatremia, and altered mental status (lethargy/coma), plus hypoventilation and bradycardia.

• Treatment: Administer IV Levothyroxine (300–500 µg IV loading dose) combined with IV Hydrocortisone 100 mg q8h (hydrocortisone must be administered concurrently or prior to levothyroxine to prevent precipitating acute adrenal crisis).

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Adrenal Axis Disorders & Adrenal Crisis

Primary vs Secondary Adrenal Insufficiency

• Primary Adrenal Insufficiency (Addison's Disease): Autoimmune destruction of adrenal cortex involving all three zones. Loss of BOTH cortisol and aldosterone. Features: Hyperpigmentation (high ACTH stimulates melanocytes), hyponatremia, hyperkalemia, non-anion gap metabolic acidosis, and postural hypotension. Diagnostics: Morning 8 AM cortisol (<80 nmol/L diagnostic; >500 nmol/L rules out) and Cosyntropin (ACTH) Stimulation Test (failure of cortisol to rise >500 nmol/L 30–60 min post 250 µg synthetic ACTH).
• Secondary Adrenal Insufficiency: ACTH deficiency (e.g., abrupt withdrawal of chronic exogenous steroids). Aldosterone production via RAAS remains INTACT. Features: No hyperpigmentation, normal serum potassium, normal aldosterone.

Acute Adrenal Crisis

Emergency characterized by refractory hypovolemic shock, severe abdominal pain, high fever, hypoglycemia, hyponatremia, and hyperkalemia.

• Emergency Management: Do NOT delay treatment for diagnostic testing! Administer immediate bolus of Hydrocortisone 100 mg IV, followed by 50–100 mg IV q6h, alongside rapid infusion of 0.9% Normal Saline with 5% Dextrose.

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Pituitary Pathology & Cushing's Syndrome Workup

Pituitary Adenomas

• Prolactinoma: Most common functional pituitary tumor. Microadenoma (<10 mm) vs Macroadenoma (≥10 mm causing bitemporal hemianopsia via optic chiasm compression). Symptoms: Galactorrhea, amenorrhea, hypogonadism, erectile dysfunction. Serum prolactin > 200 µg/L diagnostic. First-line therapy: Dopamine agonists (Cabergoline or Bromocriptine).

Cushing's Syndrome Diagnostic Algorithmic Pathway

1. Step 1: Confirm Hypercortisolism (Requires 2 positive screening tests):
   • 1 mg Overnight Dexamethasone Suppression Test (8 AM serum cortisol > 50 nmol/L is abnormal).
   • 24-Hour Urinary Free Cortisol (> 3x ULN).
   • Late-Night Salivary Cortisol.
2. Step 2: Measure Plasma ACTH:
   • Low ACTH (< 2.0 pmol/L): ACTH-Independent Cushing's (Adrenal adenoma/carcinoma, exogenous steroids). Perform Abdominal CT/MRI.
   • High ACTH (> 4.0 pmol/L): ACTH-Dependent Cushing's. Proceed to High-Dose (8 mg) Dexamethasone Suppression Test or Pituitary MRI:
     • Cortisol Suppression > 50%: Cushing's Disease (Pituitary ACTH-secreting adenoma).
     • No Cortisol Suppression: Ectopic ACTH Secretion (Small cell lung carcinoma).

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Algorithmic Evaluation of Hyponatremia

Step 1: Measured Serum Osmolality
 ├── > 295 mOsm/kg  ──> Hypertonic Hyponatremia (Hyperglycemia, Mannitol)
 ├── 275-295 mOsm/kg ──> Isotonic / Pseudohyponatremia (Hypertriglyceridemia, Paraproteinemia)
 └── < 275 mOsm/kg  ──> True Hypotonic Hyponatremia (Proceed to Step 2)

Step 2: Urine Osmolality (UOsm)
 ├── < 100 mOsm/kg  ──> Primary Polydipsia, Beer Potomania, Low-Solute Intake
 └── > 100 mOsm/kg  ──> Impaired Renal Water Excretion (Proceed to Step 3)

Step 3: Clinical Volume Status & Urine Sodium (UNa)
 ├── Hypovolemic
 │    ├── UNa < 20 mmol/L ──> Extra-renal loss (Vomiting, Diarrhea, Dehydration)
 │    └── UNa > 20 mmol/L ──> Renal loss (Diuretics, Mineralocorticoid deficiency)
 ├── Euvolemic (UNa > 30 mmol/L)
 │    └── SIADH, Hypothyroidism, Adrenal Insufficiency
 └── Hypervolemic
      ├── UNa < 20 mmol/L ──> Heart Failure, Cirrhosis, Nephrotic Syndrome
      └── UNa > 20 mmol/L ──> Acute or Chronic Renal Failure

SIADH Diagnostic Criteria

Hypotonic euvolemic hyponatremia, UOsm > 100 mOsm/kg, UNa > 30 mmol/L, with normal thyroid, adrenal, and renal function. Etiologies: Small cell lung cancer, CNS disorders, SSRIs, Carbamazepine. Treatment: Fluid restriction (800–1000 mL/day), oral salt tablets, loop diuretics.

Correction Speed Limits & Osmotic Demyelination Syndrome (ODS)

• Safety Limit: In chronic hyponatremia (>48h), serum sodium must be corrected by NO MORE THAN 8–10 mmol/L in 24 hours (and <18 mmol/L in 48 hours).
• ODS Risk: Overly rapid correction causes brain demyelination, presenting days later with dysarthria, dysphagia, quadriparesis, and locked-in syndrome.
• Severe Symptomatic Hyponatremia (Seizures/Coma): Administer 3% Hypertonic Saline 150 mL IV bolus over 20 minutes, repeated up to two times until symptoms resolve or serum Na increases by 4–6 mmol/L.

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Hyperkalemia & Calcium Emergencies

Hyperkalemia Emergency Protocol (Serum K+ > 5.0 mmol/L)

• ECG Sequence: Peaked T waves → PR prolongation → QRS widening → Sine wave pattern → V-Fib / Asystole.
• Treatment Steps:
  1. Membrane Stabilization: Calcium Gluconate 10% 10 mL IV over 2–5 min. Membrane protection acts within 1–3 minutes. Does NOT lower serum potassium!
  2. Intracellular Shift: Regular Insulin 10 units IV + D50W 50 mL IV; Salbutamol 10–20 mg nebulized; Sodium Bicarbonate 50 mmol IV (if metabolic acidosis).
  3. Potassium Elimination: Furosemide IV; Sodium Zirconium Cyclosilicate (SZC) PO; Emergency Hemodialysis.

[!IMPORTANT] MCCQE1 Exam Trap: Iodine Timing in Thyroid Storm In Thyroid Storm, NEVER administer Iodine (Lugol's solution or SSKI) before starting Thionamides (PTU or Methimazole)! Giving iodine first provides substrate for thyroid peroxidase and accelerates thyroid hormone synthesis. Always wait AT LEAST 1 hour after thionamide administration before giving iodine.