Thyroid emergencies and adrenal disease

Thyroid Storm (Accelerated Thyrotoxicosis)

• Precipitants: Infection, surgery, trauma, radioiodine therapy, myocardial infarction, or abrupt cessation of antithyroid medications in a patient with uncontrolled thyrotoxicosis.

• Clinical Presentation: Extreme hyperpyrexia ($> 40^\circ\text{C}$), profuse diaphoresis, severe sinus tachycardia or atrial fibrillation, high-output congestive heart failure, agitation, delirium, psychosis, nausea, vomiting, diarrhoea, and jaundice. Scored using the Burch-Wartofsky Point Scale (score $\ge 45$ highly suggestive).

• Multimodal Emergency Pharmacotherapy:

• Thyroid storm rate control: Beta-blockade needs haemodynamic assessment. Severe low-output heart failure can collapse after long-acting or large-dose blockade; use expert-guided titration, often a short-acting agent in monitored care. Give thionamide before iodine and treat the precipitant.

• 2: Drug & Dose: Propylthiouracil (PTU) ($200\text{ mg}$ orally/NG every 4h) or Carbimazole ($20-30\text{ mg}$ every 6h); Mechanism of Action & Critical Clinical Rule: Thionamide; immediately blocks de novo thyroid hormone synthesis. PTU also inhibits peripheral T4 to T3 conversion

• 3: Drug & Dose: Inorganic Iodine (Lugol's solution) ($4-8$ drops orally every 6-8h) or Potassium Iodide; Mechanism of Action & Critical Clinical Rule: Induces the Wolff-Chaikoff effect, rapidly blocking thyroid hormone release from the gland. MANDATORY RULE: Administer strictly $\ge 1\text{ hour}$ AFTER thionamides to prevent the iodine from serving as substrate for new hormone synthesis

• Adrenal crisis: Give hydrocortisone 100 mg IV/IM immediately, followed by 200 mg over 24 hours or 50 mg every six hours, with isotonic fluid and correction of hypoglycaemia. Obtain cortisol/ACTH before treatment if feasible, but never delay rescue treatment for tests.

• 5: Drug & Dose: Supportive Care; Mechanism of Action & Critical Clinical Rule: Active surface cooling, paracetamol. Avoid aspirin/salicylates (they displace thyroid hormones from thyroid-binding globulin [TBG], worsening free hormone levels)

Myxoedema Coma

• Extreme decompensation of severe, long-standing hypothyroidism triggered by hypothermia, sepsis, myocardial infarction, or central nervous system depressants.
• Hallmarks: Hypothermia (core temp $< 35^\circ\text{C}$), severe bradycardia, hypoventilation/hypercapnia, delayed 'hung-up' deep tendon reflexes, periorbital and non-pitting puffiness, and hyponatraemia.
• Management: Intensive care admission, mechanical ventilation, passive warming (avoid active external warming which induces peripheral vasodilation and shock), intravenous hydrocortisone $100\text{ mg}$ stat (prior to thyroid hormone), followed by loading doses of intravenous levothyroxine ($200-400\ \mu\text{g}$) and liothyronine (T3).

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Adrenal Insufficiency

Adrenal insufficiency results from failure of the adrenal cortex (primary) or deficiency of pituitary ACTH secretion (secondary).

Primary vs Secondary Adrenal Insufficiency

• Aetiology: Primary Adrenal Insufficiency (Addison's Disease): Autoimmune adrenalitis ($> 80\%$ in Australia); tuberculosis; bilateral adrenal haemorrhage (antiphospholipid syndrome, meningococcal sepsis); Secondary / Tertiary Adrenal Insufficiency: Abrupt withdrawal of chronic high-dose corticosteroid therapy; pituitary macroadenoma; hypophysectomy; lymphocytic hypophysitis
• Hormones Deficient: Primary Adrenal Insufficiency (Addison's Disease): Both Cortisol and Aldosterone (entire cortex destroyed); Secondary / Tertiary Adrenal Insufficiency: Cortisol Only (Aldosterone preserved via the RAAS)
• Skin Pigmentation: Primary Adrenal Insufficiency (Addison's Disease): Hyperpigmentation (palmar creases, buccal mucosa, vermilion border, friction sites, scars) due to elevated POMC cleavage into ACTH and $\alpha$-MSH; Secondary / Tertiary Adrenal Insufficiency: Pale / Normal skin (low or undetectable ACTH)
• Electrolyte Derangements: Primary Adrenal Insufficiency (Addison's Disease): Hyponatraemia and Hyperkalaemia with mild metabolic acidosis (aldosterone deficiency $\to$ renal sodium wasting and potassium retention); Secondary / Tertiary Adrenal Insufficiency: Hyponatraemia only (dilutional due to unsuppressed ADH); potassium is normal
• Plasma ACTH: Primary Adrenal Insufficiency (Addison's Disease): Markedly elevated ($> 100\text{ pg/mL}$); Secondary / Tertiary Adrenal Insufficiency: Inappropriately low or normal

Diagnostic Evaluation

1. Morning Serum Cortisol (8:00 - 9:00 AM): Physiological peak of diurnal cortisol. Cortisol $< 100\text{ nmol/L}$ strongly suggests adrenal insufficiency; cortisol $> 450-500\text{ nmol/L}$ makes the diagnosis highly improbable.

• ACTH stimulation: Interpret cortisol against the assay-specific threshold. A recent central adrenal deficiency can have a misleadingly normal response before adrenal atrophy. A single cut-off cannot replace the clinical context.

1. Maintenance Therapy: Oral hydrocortisone ($15 - 25\text{ mg}$ daily in divided doses, e.g. 10 mg on waking, 5 mg at midday, 2.5 mg late afternoon to mimic diurnal rhythm) combined with mineralocorticoid replacement (fludrocortisone $50 - 200\ \mu\text{g}$ daily) in Addison's disease.
2. Sick-Day Rules: Patients must carry a medical alert bracelet. During intercurrent febrile illness, double the daily oral hydrocortisone dose. If persistent vomiting or diarrhoea occurs, administer intramuscular or subcutaneous hydrocortisone ($100\text{ mg}$) and seek emergency hospital care.

Acute Adrenal Crisis

• A life-threatening medical emergency presenting with refractory circulatory shock, severe abdominal pain simulating an acute abdomen, intractable vomiting, fever, hypoglycaemia, hyponatraemia, and hyperkalaemia.
• Emergency Protocol:
  • Administer intravenous hydrocortisone 100 mg stat bolus immediately.
  • Rapid fluid resuscitation with intravenous 0.9% sodium chloride ($1 - 2\text{ litres}$ in the first 2 hours) to correct severe intravascular hypovolaemia.
  • Clinical Rule: Never delay hydrocortisone administration to perform a Synacthen test in a patient suspected of acute adrenal crisis. Hydrocortisone cross-reacts with cortisol immunoassays and must not hold up resuscitation.

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Cushing Syndrome (Hypercortisolism)

Cushing syndrome reflects sustained, pathological tissue exposure to excess glucocorticoids.

Clinical Manifestations

• Central adiposity with moon facies, dorsocervical fat pad ('buffalo hump'), and supraclavicular fullness.
• Cutaneous: Wide ($> 1\text{ cm}$), violaceous, purple abdominal striae; easy bruising (ecchymoses) after minimal trauma; thin, fragile skin.
• Musculoskeletal: Proximal muscle wasting and weakness (difficulty climbing stairs or rising from a chair without hand support); severe osteopenia/osteoporosis.
• Neuropsychiatric: Insomnia, emotional lability, depression, cognitive impairment, or overt steroid psychosis.
• Metabolic: Systemic hypertension, secondary diabetes mellitus / impaired glucose tolerance, hypokalaemic metabolic alkalosis (in severe ectopic ACTH excess).

Screening and Diagnostic Workup

1. Screening (First-Line Tests): Must perform at least two separate first-line tests:

• Cushing assessment: Check exogenous steroid exposure and conditions causing false-positive tests. An abnormal screening test needs endocrine evaluation and confirmation using another validated method. High-dose dexamethasone alone does not reliably distinguish a pituitary from ectopic source.
  • 24-Hour Urinary Free Cortisol (UFC): Elevated $> 3\times$ upper reference limit.
  • Late-Night Salivary Cortisol: Assesses loss of the normal circadian cortisol nadir at midnight.

1. Plasma ACTH Measurement: Differentiates adrenal ACTH-independent causes from pituitary/ectopic ACTH-dependent causes.
2. Inferior Petrosal Sinus Sampling (IPSS): Catheterisation of both petrosal sinuses with simultaneous peripheral blood sampling before and after CRH administration; definitive gold standard when pituitary MRI is equivocal ($< 6\text{ mm}$ adenoma).

Primary references (checked 7 October 2026): Endocrine Society adrenal guidance.