Acromegaly
Overview
Acromegaly - chronic GH excess after epiphyseal fusion, most commonly from a GH-secreting pituitary macroadenoma. Diagnosis is typically delayed 4-5 years; onset is insidious.
Presentation
•Key clue - rings, gloves, and shoes no longer fit; old photographs invaluable for comparison
•Acral enlargement - large, doughy ('spade-like') hands and feet
•Coarse facial features - frontal bossing, enlarged nose and lips, prominent supraorbital ridge
•Prognathism - lower jaw protrusion, interdental separation, malocclusion
•Macroglossia - tongue enlargement; contributes to obstructive sleep apnoea and deeper voice
•Hyperhidrosis - excessive sweating (~65%) and oily skin
•Carpal tunnel syndrome - 20-40%; IGF-1-driven soft tissue swelling compresses median nerve
•Arthralgia/arthropathy - synovial overgrowth, cartilage hypertrophy; osteoarthritis in ~25%
•Hypertension - ~35-40%; major cardiovascular risk factor
•Diabetes mellitus - polyuria/polydipsia due to GH-induced insulin resistance
•Goitre - diffuse or multinodular; IGF-1-driven visceromegaly
•Skin tags - axilla/neck; associated with colonic polyps
•Acanthosis nigricans - skin folds due to insulin resistance
•Headache (~55%) and bitemporal hemianopia - tumour mass compressing optic chiasm
•Hypopituitarism - compression of surrounding pituitary tissue (FSH, LH, TSH, ACTH deficiency)
•Galactorrhoea / menstrual irregularity / erectile dysfunction - ~30% of adenomas co-secrete prolactin
Investigations
•First-line screening: IGF-1 - elevated; reflects integrated 24-hour GH; normal IGF-1 makes acromegaly very unlikely
•Gold standard confirmation: oral glucose tolerance test (OGTT) with serial GH - GH normally suppresses to <0.4 micrograms/L; in acromegaly, GH fails to suppress (or paradoxically rises)
•MRI pituitary with gadolinium - identify and characterise adenoma (size, invasion, proximity to optic chiasm); most are macroadenomas at diagnosis
•Full anterior pituitary hormone profile - detect prolactin co-secretion and hypopituitarism
•Formal visual fields (Humphrey perimetry) - if adenoma is near optic chiasm
•HbA1c and fasting glucose - screen for T2DM
•Echocardiogram - cardiomyopathy, LV hypertrophy, valvular disease
•Colonoscopy - elevated colorectal polyp and cancer risk at diagnosis
•Sleep study (polysomnography) - if obstructive sleep apnoea suspected
•CT chest/abdomen/pelvis - if ectopic GHRH/GH source suspected (no adenoma on MRI)
Management
•Goals: normalise GH and IGF-1, reduce tumour bulk, relieve mass effects, prevent complications
•First-line (curative): transsphenoidal surgery (hypophysectomy) - treatment of choice for most pituitary adenomas
•Medical therapy (adjunct or if surgery not possible):
•Octreotide / lanreotide (somatostatin analogues) - first-line medical option; suppress GH secretion
•Pegvisomant - GH receptor antagonist; used when somatostatin analogues insufficient
•Cabergoline - dopamine agonist; useful if prolactin co-secretion
•Radiotherapy - stereotactic or conventional; used for residual/recurrent disease not amenable to further surgery
Pathophysiology (brief)
•>95% due to benign GH-secreting pituitary adenoma → autonomous GH → elevated IGF-1 → soft tissue, cartilage, and bone hypertrophy
•GH also causes insulin resistance, gluconeogenesis, and lipolysis - explaining metabolic complications
•Rare causes: ectopic GHRH (carcinoid, pancreatic islet cell, small cell lung cancer); genetic - AIP mutation (younger patients, larger tumours), MEN1, McCune-Albright
Follow-up and remission criteria
•Biochemical remission: normalised IGF-1 for age/sex AND GH suppression to <1 microgram/L on OGTT
•Serial IGF-1 every 6-12 months; MRI pituitary at defined post-operative intervals
•Ongoing echocardiogram, colonoscopy, anterior pituitary profile, visual fields, HbA1c, and BP monitoring