Acromegaly
Chronic excess of growth hormone (GH) in adults, almost always caused by a GH-secreting pituitary adenoma. Characterised by acral enlargement (hands, feet, jaw), coarsened facial features, and multi-organ complications. Diagnosed by failure to suppress GH on OGTT. Treated with transsphenoidal surgery, somatostatin analogues, or pegvisomant.
Key Facts
Cause: GH-secreting pituitary adenoma (>95%) (usually macroadenoma); very rarely ectopic GHRH (carcinoid, pancreatic tumour) Clinical features: acral enlargement (hands — ring size increase; feet — shoe size increase), coarsened facial features (prognathism, frontal bossing, macroglossia), sweating, headache, bitemporal hemianopia Complications: cardiomyopathy/heart failure, hypertension, diabetes mellitus (~25%), obstructive sleep apnoea (~50%), colonic polyps (increased CRC risk), carpal tunnel syndrome, arthropathy Diagnosis: raised IGF-1 (screening); OGTT with GH measurement (diagnostic — GH fails to suppress below 1 μg/L after 75g glucose); pituitary MRI Treatment: transsphenoidal surgery (first-line — cure rate ~60-80% for microadenoma, ~40-60% for macroadenoma); somatostatin analogues (octreotide LAR 20-30mg monthly, lanreotide 60-120mg monthly); pegvisomant (GH receptor antagonist); radiotherapy Mortality: 2-3× increased if GH/IGF-1 not normalised; cardiovascular disease is the leading cause of death
Overview
Key Facts
Acromegaly is insidious — average delay from symptom onset to diagnosis is ~7-10 years. Early diagnosis and normalisation of GH/IGF-1 are essential to prevent irreversible complications. Comparing old photographs is a useful diagnostic clue.
Epidemiology
Prevalence ~60-70 per million. Incidence ~3-4 per million/year. Mean age at diagnosis ~40-50 years. Equal sex distribution.
Aetiology
GH-secreting pituitary adenoma (>95%): sporadic mostly; ~5% familial (MEN1, familial isolated pituitary adenoma — AIP mutations, Carney complex). Ectopic GHRH (<5%): bronchial/pancreatic carcinoid.
Pathophysiology
Excess GH → hepatic IGF-1 production → tissue growth (soft tissue, cartilage, bone) and metabolic effects (insulin resistance, lipolysis). GH itself: diabetogenic, sodium retaining, directly promotes cardiac hypertrophy. Tumour mass effects: headache, bitemporal hemianopia (optic chiasm compression), hypopituitarism.
Clinical Presentation
Slow-Onset Features (Compare Old Photos)
- Hands: spade-like, increased ring/glove size, doughy palms
- Feet: increased shoe size
- Face: prognathism (jaw protrusion), frontal bossing, increased interdental spacing, macroglossia, coarsened features, thickened skin
- Sweating (excess), oily skin
- Headache
- Deepened voice (vocal cord thickening)
- Arthralgia (large joint osteoarthropathy)
Complications
- Cardiovascular: LVH, cardiomyopathy, hypertension (~40%), heart failure
- Metabolic: diabetes mellitus (~25%), impaired glucose tolerance (~40%)
- Respiratory: obstructive sleep apnoea (~50%)
- Colonic: polyps → increased colorectal cancer risk (colonoscopy at diagnosis, then 3-5 yearly)
- Musculoskeletal: arthropathy, carpal tunnel syndrome, spinal stenosis
- Visual: bitemporal hemianopia (macroadenoma)
- Hypopituitarism: from tumour compression
Red Flags
- Visual field defect → urgent pituitary MRI
- Heart failure in young patient → consider acromegaly
- Pituitary apoplexy: sudden headache, visual loss, meningism
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Familial tall stature | Constitutional, no acral changes | Normal IGF-1/GH |
| Hypothyroidism | Coarsened features, but no acral enlargement | TFTs |
| Paget disease | Skull enlargement, bone pain, raised ALP | ALP, X-ray |
| Pachydermoperiostosis | Skin thickening, digital clubbing, periostitis | Clinical, X-ray |
Diagnosis / Investigation
Screening
- Serum IGF-1: elevated (age and sex-adjusted); correlates with GH secretion; single best screening test
Confirmatory
- Oral glucose tolerance test (OGTT) with GH: 75g glucose load; GH measured at 0, 30, 60, 90, 120 minutes; GH fails to suppress below 1 μg/L (or <0.4 μg/L with newer assays) = diagnostic
Imaging
- Pituitary MRI (gadolinium-enhanced): localise/size adenoma; assess chiasmal compression
Complications Assessment
- Visual fields: formal perimetry
- Echocardiogram: LVH, cardiomyopathy
- Sleep study: OSA
- Colonoscopy: polyps/CRC screening
- HbA1c, OGTT: diabetes
- Pituitary function tests: full anterior pituitary hormones (LH/FSH, testosterone/oestradiol, TSH/T4, cortisol, prolactin)
- Calcium/PTH: if MEN1 suspected
Management
First-Line: Transsphenoidal Surgery
- Transsphenoidal pituitary adenomectomy: cure rate ~60-80% (microadenoma), ~40-60% (macroadenoma)
- Post-operative: check GH/IGF-1 at 6-12 weeks; OGTT for biochemical remission
Medical Therapy
Somatostatin analogues (first-line medical):
- Octreotide LAR 20-30mg IM monthly; lanreotide 60-120mg SC monthly
- Normalise IGF-1 in ~50-60%; reduce tumour size in ~30-50%
- Side effects: GI (diarrhoea, steatorrhoea), gallstones (~20%), glucose intolerance
GH receptor antagonist:
- Pegvisomant 10-30mg SC daily: normalises IGF-1 in ~90%; does not reduce tumour size; monitor LFTs
Dopamine agonist:
- Cabergoline 0.5-3mg/week: effective in ~10-20% (mainly if co-secretion of prolactin)
Radiotherapy
- Stereotactic radiosurgery or fractionated RT: for residual/recurrent disease after surgery
- Slow onset of effect (years); risk of hypopituitarism (~50% at 10 years)
Monitoring
- GH and IGF-1: 3-6 monthly until stable, then annually
- Pituitary MRI: annually until stable
- Complication screening: ongoing
Referral Criteria
- Endocrinology: all suspected/confirmed acromegaly
- Neurosurgery: transsphenoidal surgery
- Ophthalmology: visual field assessment
Prognosis
Untreated: 2-3× increased mortality (cardiovascular disease is leading cause). If GH and IGF-1 normalised: mortality approaches normal population. Biochemical remission with surgery: ~60-80% microadenoma, ~40-60% macroadenoma. Many complications are reversible with treatment (soft tissue changes, diabetes, OSA, cardiac function). Skeletal changes and arthropathy are often irreversible. Average 7-10 year diagnostic delay.
Other Relevant Information
Acromegaly Complications Screening
| Complication | Investigation | Frequency |
|---|---|---|
| Cardiovascular | Echo, ECG, BP | At diagnosis, then as indicated |
| Diabetes | HbA1c, OGTT | At diagnosis, annually |
| OSA | Sleep study | At diagnosis |
| Colonic polyps | Colonoscopy | At diagnosis, 3-5 yearly |
| Visual fields | Perimetry | At diagnosis, pre/post surgery |
Treatment Algorithm
| Step | Treatment | Notes |
|---|---|---|
| 1 | Transsphenoidal surgery | First-line |
| 2 | Somatostatin analogue | If surgery fails/incomplete |
| 3 | Pegvisomant | If SSA fails to normalise IGF-1 |
| 4 | Radiotherapy | Adjunctive for resistant disease |