Endocrine Disorders

Hypothyroidism

  • Causes (Primary): Chronic autoimmune thyroiditis (Hashimoto’s, most common), iatrogenic (thyroidectomy, radioiodine), iodine deficiency/excess, drug-induced (lithium, amiodarone, thionamides, interferon alfa, interleukin-2, tyrosine kinase inhibitors, checkpoint inhibitors), infiltrative disease (fibrous thyroiditis, hemochromatosis, sarcoidosis), transient forms (painless, subacute granulomatous, postpartum thyroiditis), congenital.
  • Causes (Central): TSH or TRH deficiency (pituitary/hypothalamic disorders).
  • Clinical Features:
    • Slowed metabolism: fatigue, weakness, cold intolerance, dyspnea, weight gain, cognitive dysfunction, constipation, growth failure, bradycardia, delayed tendon reflex relaxation.
    • Matrix accumulation: dry skin, hoarseness, edema, coarse skin, puffy facies, loss of outer eyebrows, enlarged tongue.
    • Other: decreased hearing, myalgia, depression, menorrhagia, diastolic hypertension, pleural/pericardial effusions, galactorrhea.
  • Diagnosis:
    • TSH first-line; confirm with FT4/FT3 if abnormal. TSH alone unreliable in suspected pituitary disease.
    • TPO antibodies: sensitive for autoimmune thyroiditis; useful in subclinical disease. Not needed routinely for overt hypothyroidism.
    • Thyroglobulin antibodies: support autoimmune diagnosis; relevant when monitoring thyroglobulin in thyroid cancer.
    • Ultrasound: for structural abnormality/nodules, not for uncomplicated hypothyroidism.
    • Radionuclide scan: not used for autoimmune hypothyroidism.
  • Subclinical Hypothyroidism:
    • Retest TSH in 1-3 months if abnormal.
    • TSH > 10 mIU/L: treat with levothyroxine.
    • TSH 4-10 mIU/L with positive TPO antibodies: consider treatment.
    • Symptomatic: trial of levothyroxine.
  • Levothyroxine Administration: Empty stomach, 30-60 minutes before breakfast, or at bedtime (2+ hours after last meal). Avoid concurrent bile acid resins, calcium carbonate, ferrous sulfate, PPIs.
  • Starting Dose: Partial replacement (25-50 mcg daily) for mild elevation, subclinical disease, cardiovascular disease, or older patients. Full replacement for overt hypothyroidism.
  • Dose Adjustment: Every 4-8 weeks, guided by age-specific TSH targets:
    • Age < 60: TSH 0.5-2.5 mIU/L
    • Age ≥ 60: TSH 1-5 mIU/L
    • Age > 80: TSH 4-6 mIU/L
  • Overtreatment Risk: Atrial fibrillation, accelerated bone loss.
  • Perioperative: Safe to withhold up to 7 days if euthyroid; treat hypothyroidism before elective surgery.
Specialist Referral Red Flags:
  • Age ≤ 18 years
  • Unresponsive to therapy
  • Pregnant
  • Cardiac disease
  • Structural thyroid changes
  • Other coexisting endocrine disease

Hyperthyroidism

  • Aetiologies: Graves’ disease (TSH receptor antibodies), toxic adenoma, toxic multinodular goitre, factitious ingestion, drug-induced (amiodarone), postpartum thyroiditis, painful subacute thyroiditis.
  • Diagnosis:
    • Low TSH, elevated FT4/FT3.
    • TRAb/TSI confirms Graves’ disease.
    • Radionuclide scan if aetiology unclear:
      • Diffuse uptake: Graves’ disease
      • Focal uptake with suppression: toxic adenoma
      • Multifocal uptake with suppression: toxic multinodular goitre
      • Near-absent uptake: thyroiditis or exogenous hormone intake
  • Antithyroid Drugs (Thionamides):
    • First-line: Carbimazole. Both inhibit thyroid peroxidase.
    • PTU used if carbimazole not tolerated, pre-conception/1st trimester, or thyroid storm (also blocks peripheral T4→T3 conversion).
    • Initial dosing based on severity: Carbimazole 10-45 mg/day; PTU 100-450 mg/day.
    • Titrate every 4-6 weeks using FT3/FT4 (TSH may remain suppressed). Halve dose if hormone levels halve.
    • Continue 12-18 months for Graves’ disease to improve remission; do not stop abruptly.
  • Beta-blockers: Propranolol/atenolol for rapid symptom control (palpitations, tremor, sweating); do not alter metabolic state. Diltiazem if beta-blockers contraindicated.
  • Radioiodine: Severe/recurrent Graves’, severe hyperthyroidism in older patients, toxic adenoma/multinodular goitre, young patients with persistent high TRAb.
  • Thyroidectomy: Severe/recurrent Graves’, toxic adenoma/multinodular goitre, thyroid cancer.
Thionamide Safety Red Flags:
  • Agranulocytosis: rare, life-threatening, usually early in therapy — stop drug immediately if fever/infection.
  • Severe liver injury with PTU; PTU contraindicated in children.
  • Vasculitis (ANCA-positive) associated with PTU.

Thyroid Nodules

  • Initial Evaluation: Check TSH.
    • TSH normal/high → thyroid ultrasound.
    • TSH low → thyroid scintigraphy.
  • ACR TI-RADS Risk Stratification:
    • TR1 (Benign): ~0% malignancy risk, no biopsy, no follow-up.
    • TR3 (Mildly suspicious): ~5% malignancy risk, biopsy if ≥ 2.5 cm, follow-up USS at 1, 3, 5 years.
    • TR5 (Highly suspicious): >20% malignancy risk, biopsy if ≥ 1 cm, yearly USS for 5 years.

Thyroid Disease & Pregnancy

  • TSH Target Ranges:
    • 1st trimester: 0.1-2.5 mIU/L
    • 2nd trimester: 0.2-3.0 mIU/L
    • 3rd trimester: 0.3-3.0 mIU/L
  • Hypothyroidism Risks: Premature birth, low birth weight, miscarriage, impaired fetal neurocognitive development.
  • Hyperthyroidism: Low TSH in 1st trimester often due to elevated hCG (gestational, self-limiting, usually no treatment needed). Differentiate from Graves’ disease via positive TRAb. Radionuclide scans contraindicated in pregnancy.
  • Pre-existing Hypothyroidism: Optimize levothyroxine to preconception TSH < 2.5 mIU/L. Increase dose 25-30% at 4-6 weeks gestation. Monitor TSH every 4-6 weeks in 1st trimester, then at 30 weeks if stable.
  • Postpartum: Reduce thyroxine to pre-pregnancy dose; recheck TSH at ~6 weeks postpartum.
  • Postpartum Thyroid Dysfunction: Affects 1 in 20 women; autoimmune follicle destruction.
    • Hyperthyroid phase (3-6 months postpartum): self-limiting, manage with beta-blockers; thionamides not indicated.
    • Hypothyroid phase (6-12 months postpartum): treat with thyroxine if symptomatic or planning conception.
    • 20-40% risk of permanent hypothyroidism within 10 years.
  • Iodine Supplementation: 150 µg daily for pregnant, planning, or breastfeeding women.
Pregnancy Prescribing Red Flag: Avoid combination T4/T3 therapy in pregnancy.

Thyroiditis

  • Subacute (de Quervain) Thyroiditis: Possibly viral. Pain radiating to ears/jaw, fever, malaise. Transient thyrotoxicosis → hypothyroidism → euthyroidism.
  • Diagnosis: Markedly elevated ESR, near-absent uptake on nuclear scan.
  • Treatment: Aspirin, ibuprofen, or indometacin for pain. Prednisolone (40 mg daily, tapering over 2-4 weeks) for severe/persistent cases. Antithyroid drugs ineffective. Thyroxine if hypothyroid phase persists/symptomatic.
  • Painless Postpartum Thyroiditis: Managed as per postpartum thyroid dysfunction above.

Primary Adrenal Insufficiency (Addison’s Disease)

  • Causes: Most commonly autoimmune adrenal cortex atrophy; also infection, metastatic cancer, drugs.
  • Clinical Features: Fatigue, anorexia, weight loss, postural hypotension, hyperpigmentation, dizziness/syncope, decreased axillary/pubic hair (females), vitiligo (10-20% of autoimmune cases).
  • Electrolytes: Hyponatraemia and hyperkalaemia common.
  • Diagnosis:
    • 8 AM serum cortisol (low), plasma ACTH (elevated).
    • Definitive: short Synacthen stimulation test.
    • Supportive: elevated plasma renin, electrolyte abnormalities.
    • Adrenal autoantibodies (not initial). CT reserved for anatomy after biochemical confirmation.
  • Corticosteroid Replacement: Hydrocortisone (glucocorticoid) and fludrocortisone acetate (mineralocorticoid).
  • Non-pharmacological: Increased dietary salt, education on early crisis signs, sick day/stress dose adjustment, medical alert bracelet, osteoporosis prevention (baseline DEXA, weight-bearing exercise).
  • Monitoring: Annual review of well-being and glucocorticoid excess/deficiency signs; serum sodium, potassium, plasma renin (upper-normal indicates optimal mineralocorticoid dose); BMD every 2 years. ACTH not useful for dose titration.
Adrenal Crisis — Medical Emergency:
  • Precipitants: acute illness, surgery, trauma, abrupt glucocorticoid cessation.
  • Features: nausea, vomiting, abdominal pain, severe hypotension/shock, drowsiness, confusion; can mimic sepsis.
  • Labs: hypoglycaemia, hyponatraemia, hyperkalaemia, hypercalcaemia, raised urea/creatinine.
  • Do not delay treatment for lab results.
  • Immediate IV isotonic saline (e.g. 1L 0.9% NaCl over 1 hour).
  • Urgent IV hydrocortisone: 100 mg bolus, then 50 mg IV every 6 hours.
  • Vasopressor (norepinephrine) if hypotension persists after fluids/steroids.
  • Arrange urgent hospital admission.

Cushing’s Syndrome

  • Clinical Features:
    • Appearance: facial plethora, buffalo hump, central obesity with thin limbs (“lemon with matchsticks”).
    • Skin: purple striae >1 cm, thin skin, easy bruising.
    • Musculoskeletal: proximal muscle weakness.
    • Females: hirsutism, acne, amenorrhea/oligomenorrhoea.
    • Associated: hypertension (often resistant), early-onset osteoporosis, diabetes, decreased libido, depression, insomnia.
  • When to Test: Unusual findings for age, multiple progressive features, unexplained severe features, adrenal incidentaloma.
  • Diagnostic Tests:
    • Low suspicion: one of late-night salivary cortisol (x2), 24-hour urinary free cortisol (x2), overnight 1 mg dexamethasone suppression test.
    • High suspicion: two of the above.

Phaeochromocytoma

  • Clinical Features: Classic triad — paroxysmal hypertension with throbbing headache, palpitations, sweating. Also anxiety, pallor, rising chest/throat tightness, angina.
  • Investigations:
    • Plasma free metanephrines/normetanephrines (recommended screening).
    • Urine total metanephrines (alternative).
    • Series of three 24-hour urine free catecholamines (elevated VMA).
    • Abdominal CT/MRI for localization after biochemical confirmation.

Primary Aldosteronism (Conn’s Syndrome)

  • Causes: Aldosterone-producing adenomas, bilateral adrenal hyperplasia.
  • Clinical Features: Hypertension, often with hypokalemia (normokalemia also common). Hypokalemia symptoms: weakness, cramps, paraesthesia, polyuria, polydipsia.
  • Screening Indications: Hypertension with hypokalemia; severe (>150/100) or resistant hypertension; hypertension with adrenal incidentaloma, sleep apnea, or early-onset family history (<40 yrs); first-degree relatives of diagnosed patients; hypertension with atrial fibrillation.
  • Case-Detection Testing: Morning seated sample; plasma aldosterone concentration (PAC) and plasma renin activity (PRA)/concentration (PRC). Suggestive: PAC ≥ 10 ng/dL AND PRA < 1.0 ng/mL/hour.
  • Interfering Drugs: ACE inhibitors, ARBs, direct renin inhibitors affect PRA/PRC. Mineralocorticoid receptor antagonists usually discontinued 4-6 weeks before retesting.
  • Confirmation Testing: 24-hour urine aldosterone/sodium/creatinine on high-sodium diet, OR fludrocortisone suppression test, OR saline suppression test.

Hypomagnesaemia

  • Normal Range: 0.8-1.0 mmol/L. Depletion < 0.8; severe < 0.4 mmol/L.
  • Causes: Malnutrition, GI losses (NG suction, diarrhoea, malabsorption, fistulae), kidney losses, drugs (diuretics, alcohol, aminoglycosides, cisplatin, amphotericin B, cyclosporin, PPIs), phosphate depletion, hungry bone syndrome, Gitelman syndrome.
  • Clinical Features: Mild — asymptomatic. Moderate-severe — tetany, muscle weakness, arrhythmias (prolonged QT), neuropsychiatric changes, convulsions. Often coexists with hypocalcaemia, hypokalaemia.
  • Treatment: Correct underlying cause.
    • Mild: oral magnesium aspartate 1000-3000 mg daily in divided doses.
    • Moderate-severe: IV magnesium chloride/sulfate 25-50 mmol in 500-1000 mL 0.9% NaCl over 12-24 hours. Goal serum magnesium > 0.4 mmol/L.

Hypermagnesaemia

  • Normal Range: 0.8-1.0 mmol/L; hypermagnesaemia > 1.0 mmol/L.
  • Causes: Excessive intake (antacids, enemas, IV infusion) usually with kidney impairment; decreased excretion (kidney failure, volume depletion); rhabdomyolysis; lithium.
  • Clinical Features: Loss of deep tendon reflexes, muscle paralysis, impaired consciousness, respiratory depression, anorexia, nausea, flushing, hypotension, bradycardia/heart block, cardiac arrest. Often induces hypocalcaemia.
  • Management: Stop magnesium therapy.
    • Severe intoxication: IV calcium infusion (transient antagonism).
    • Promote excretion with IV 0.9% NaCl (target urine output ≥ 60 mL/hr); add IV frusemide if needed.
    • Dialysis if kidney impairment present.

Hypercalcaemia

  • Normal Range: Total calcium 2.10-2.60 mmol/L.
  • Symptoms (Bones, moans, stones, abdominal groans):
    • Bones: bone pain, osteopenia/osteoporosis, muscle weakness.
    • Moans: decreased concentration, lethargy, depression, confusion.
    • Stones: nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, renal insufficiency.
    • Abdominal groans: anorexia, nausea, vomiting, constipation, pancreatitis, peptic ulcer disease.
  • Causes: Most common — primary hyperparathyroidism, hypercalcaemia of malignancy. Less common — thiazides, vitamin D toxicity, sarcoidosis/granulomatous disease, severe hyperthyroidism, milk-alkali syndrome, renal osteodystrophy with tertiary hyperparathyroidism, adrenal insufficiency, familial hypocalciuric hypercalcaemia, prolonged immobilisation, and several rare paediatric/genetic causes.
  • Diagnosis: Total calcium corrected for albumin; measure ionised calcium if albumin abnormal.
  • Investigations: ESR, serum PTH, serum ACE (for sarcoidosis), alkaline phosphatase, chest X-ray, sestamibi scan, bone scan. Requires specialist referral.

Syndrome of Inappropriate ADH (SIADH)

  • Causes: Cancers (small cell lung, lymphoma, kidney, pancreas), pulmonary disorders, intracranial lesions, drugs (carbamazepine, many antipsychotics).
  • Diagnosis (Triad): Hyponatraemia, hypoosmolality, urine osmolality > 100 mosmol/kg.
  • Management: Treat underlying disease (e.g. adrenal insufficiency, hypothyroidism, infection). Fluid restriction (< 800 mL/day) is the mainstay.

Male Androgen Deficiency

  • Classification:
    • Hypergonadotrophic (primary): testicular disorders — low testosterone, high LH/FSH. Causes: Klinefelter syndrome, cryptorchidism, orchidectomy, orchitis, cytotoxic/radiation damage, testicular torsion/trauma.
    • Hypogonadotrophic (central): hypothalamic/pituitary disorders — low testosterone, low/normal LH/FSH. Causes: hyperprolactinaemia, pituitary tumours/surgery/radiotherapy, hemochromatosis, hypophysitis, idiopathic hypogonadotrophic hypogonadism (including Kallmann syndrome).
  • Clinical Features: Most indicative — reduced libido, decreased spontaneous erections, hot flushes, reduced facial hair, gynaecomastia, loss of axillary/pubic hair, small testes (< 5 mL), low bone mass. Less specific — low energy/mood, disturbed sleep, reduced muscle bulk, increased BMI, mild anaemia. Normal adult testes: 15-25 mL.
  • Diagnosis Criteria: Symptoms/signs + unequivocally low fasting early-morning testosterone (repeat on different day, 8-10 AM) + confirmed HPT axis dysfunction. Avoid testing during acute illness. Functionally low testosterone (obesity, diabetes, depression, opioid/glucocorticoid use) — treat underlying condition, testosterone therapy not recommended.
  • Testosterone Replacement Therapy Goals: Relieve symptoms/signs of confirmed deficiency; not for isolated low libido/erectile dysfunction.
  • Formulations:
    • Transdermal: creams/gels/patches applied to trunk/proximal limbs each morning.
    • Injectable: testosterone enantate/esters 250 mg IM every 2-3 weeks; testosterone undecanoate (Reandron) 1000 mg IM after 6 weeks, then every 10-14 weeks.
    • Oral: rarely used, less effective.
  • Monitoring: Symptom review at 3 months then annually; serum testosterone at 3-6 months; BMD at 12+ months. FBE at baseline, 3 months, then annually (polycythaemia risk, especially short-acting injectables). Assess baseline prostate/cardiovascular risk; discuss PSA screening limitations.
  • Common Adverse Effects: Acne, modest weight gain, reduced spermatogenesis, increased truncal hair, temporal hair loss, gynaecomastia — generally reversible on cessation.
TRT Contraindications:
  • Current prostate or breast cancer
  • Desire for fertility (suppresses spermatogenesis)
  • Elite athletes (prohibited substance)
  • Specialist assessment required if history of curative treatment for prostate/breast cancer

Carcinoid Syndrome

  • Clinical Features: Classic triad — skin flushing (especially face), diarrhoea with abdominal cramps, valvular heart disease (especially right heart). Also wheezing, telangiectasia, hypotension, cyanosis, pellagra.
  • Common Tumour Sites: Appendix/ileum, stomach, bronchi.
  • Diagnosis: 24-hour urinary 5-HIAA (end product of serotonin metabolism) is the most useful initial test.
  • Putative Mediators:
    • Flushing: kinins, histamine, kallikreins.
    • Diarrhoea/cramping: serotonin.
    • Valvular lesions: serotonin.

Presentations

Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood
Shelf Wood