23rd May 2025

Acromegaly

Acromegaly is an insidious chronic and progressive disorder caused by the overproduction of GH and characterised by features of gigantism. It is usually caused by a somatotroph adenoma in the adenohypophysis. The incidence of acromegaly is between 40-130 cases per million adults. An excess of GH leads to increased secretion of insulin-like-growth factor-1 (IGF-1) leading to multi-systemic symptoms. 

Clinical effects 

• Facial: Frontal bossing, macroglossia, prognathism, large nose
• Skin: Hyperhidrosis, increased skin thickness 
• Respiratory: Sleep apnoea
• Joint: Osteoarthritis, arthropathy, bone enlargement 
• Cardiovascular: Hypertension, arrhythmias, valvular heart disease, congestive cardiac failure, ischaemic heart disease
• Metabolic and electrolyte: diabetes mellitus, impaired glucose tolerance, hypercalciuria 
• Organomegaly 
• Increased height

Image Source: Wikimedia Commons (2008). Acromegaly facial Features, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?curid=15072125 (Accessed 13 May 2025).

Investigations

Biochemical

• Excluded in most cases of normal IGF-1 levels
• Random GH >1 microgram/L or >2.5 micrograms/L 
• Glucose tolerance test with 75g oral glucose and measuring plasma glucose and GH every 30 mins for 2 hrs. Lack of GH suppression <1 microgram/L (<1 nanogram/mL) suggestive of acromegaly 
• Other pituitary hormone plasma levels: cortisol, prolactin, thyroid-stimulating hormone and free thyroxine, follicle-stimulating hormone, luteinising hormone, oestradiol, or testosterone
• Consider genetic testing for AIP

Imaging 

• MRI with contrast of pituitary gland 
• In <1% of the cases, the above is negative. In this case a CT Thorax, Abdo, Pelvis will likely be needed to locate ectopic hormones producing GH/GHRH

Management

• Transsphenoidal surgery is first-line for enclosed somatotroph microadenomas (< 10mm diameter) and macroadenomas (>10mm diameter)
• If surgery fails, or the tumour is unresectable, somatostatin analogues (SSAs) are used e.g., octreotide with an initial dose of 20mg every month
• If there is mixed GH/PRL release, or IGF-1 levels are <1.5 the upper limit of normal a dopamine agonist, e.g., cabergoline, can be used as an additional treatment
• Pegvisomant, a growth hormone receptor antagonist, is considered in patients who are unsuitable or who have not responded to the above
• If medical and surgical treatments fail, radiotherapy can be attempted 

Monitoring

Lifelong monitoring of GH and IGF-1 will be required

Complications

• Cardiovascular (including HTN) (30-40%) 
• Sleep apnoea (60-80%)
• Joint (70%)
• Endocrine (50%)
• Pre-cancerous polyps 
• Carpal tunnel (64%)
• Hypopituitarism

Prognosis

Surgery is effective in 70-90% of microadenomas and 30-60% of macroadenomas. SSAs control disease in 30-40% of cases.