Acromegaly

Pathophysiology

• Pituitary adenoma secretes excess GH

• Leads to increased hepatic IGF-1 production

• Causes overgrowth of bone, cartilage, soft tissue, and organs

• Impairs glucose tolerance and can precipitate diabetes mellitus

Clinical Presentation

Bones and Cartilage

• Enlarged facial bones (prognathism, coarse facial features)

• Increased hand/foot size, requiring larger rings or shoe size

• Jaw protrusion leading to malocclusion

• Joint pain, early degenerative arthritis

Soft Tissue

• Oily skin, hyperhidrosis (excessive sweating)

• Carpal tunnel syndrome, paraesthesia

• Deepened voice from laryngeal thickening

Systemic Features

• Hypertension, cardiomegaly, heart failure (acral cardiomyopathy)

• Sleep apnoea (obstructive or mixed)

• Insulin resistance or overt T2DM

• Colonic polyps with increased neoplasia risk

Diagnosis

Biochemical Tests

• Elevated serum IGF-1 (age-adjusted reference range)

• Oral glucose tolerance test (75 g glucose) with GH measurement

  • Lack of GH suppression (GH >1 µg/L) confirms acromegaly

  • Normal physiology: GH should suppress to <1 µg/L

Pituitary Imaging

• MRI of the pituitary gland to locate and characterise adenoma

• Consider macroadenoma compressing other pituitary tissue (possible hypopituitarism)

Baseline Investigations

• Echocardiography to assess for cardiomyopathy

• Sleep study (polysomnography) to evaluate for sleep apnoea

• Colonoscopy to screen for colonic polyps, especially in older patients or those with long-standing disease

• Evaluate other pituitary hormones (LH, FSH, TSH, ACTH) to detect co-secretion or hypopituitarism

Management

Surgery (First-Line)

• Transsphenoidal resection of pituitary adenoma

• Can achieve rapid reduction in GH levels and tumour bulk

• Aim is biochemical remission (GH <1 µg/L on OGTT and normal IGF-1)

Medical Therapy

• Somatostatin Analogues (reduce GH secretion)

  • Octreotide LAR 10–30 mg IM every 4 weeks or Lanreotide (60–120 mg deep SC every 4–8 weeks)

  • Pasireotide for resistant cases

  • Monitor IGF-1 and GH levels, dose adjustments based on response

• Dopamine Agonists (Cabergoline, Bromocriptine)

  • Effective in ~50% of patients, usually mild disease or co-secreting prolactin

  • Cabergoline 0.5 mg twice weekly up to 2 mg twice weekly

• GH Receptor Antagonist (Pegvisomant)

  • Blocks peripheral GH action, lowers IGF-1

  • Start with loading dose 80 mg SC, then 10 mg SC daily (up to 30 mg daily)

  • Monitor IGF-1 but not GH (GH remains elevated)

Radiotherapy

• Consider if surgery is incomplete or tumours recur and medical therapy is insufficient

• Long latency to see full effect, risk of hypopituitarism post-radiation

Follow-Up and Monitoring

Biochemical Targets

• GH <1 µg/L after OGTT or random GH <2.5 µg/L

• Age-normalised IGF-1 within reference range

Comorbidity Screening

• Annual cardiovascular assessment (ECG, echocardiogram if needed), as cardiomyopathy is a major mortality factor

• Diabetes or glucose intolerance monitoring (HbA1c or fasting glucose)

• Repeat colonoscopy if polyps found or based on guidelines (some patients require 3-5 yearly scopes)

• Periodic pituitary MRI if residual tumour or rising IGF-1

Specific Management Points

• Address sleep apnoea, including CPAP if severe

• Monitor blood pressure and treat hypertension aggressively

• Evaluate for hypopituitarism (e.g. secondary adrenal insufficiency, hypothyroidism)

• Educate on signs of tumour recurrence (headache, visual changes)

Notes

• Suspect acromegaly in patients with slowly evolving facial feature changes, enlarged hands/feet, or jaw malocclusion

• Elevated IGF-1 is the best initial screening test

• Confirm diagnosis with lack of GH suppression on OGTT

• Early transsphenoidal surgery can be curative, but medical therapy often needed if not fully resected

• Comorbidities (hypertension, DM, sleep apnoea, arthropathy) significantly impact quality of life and mortality risk

• Long-term follow-up ensures control of GH/IGF-1, detection of tumour recurrence, and management of complications