Acromegaly

Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1), which is produced in the liver and many other tissues. IGF-1 is the main mediator of the actions of growth hormone.

• Acromegaly is caused by excessive secretion of growth hormone from
• Pituitary macroadenoma
• Pituitary microadenoma
• Growth Hormone-Releasing Hormone (GHRH) from
• Hypothalamic tumours
• Non-endocrine tumours
• Lung
• Pancreas
• Thyroid (medullary)
• Carcinoid

Acromegaly causes an overgrowth of all organ systems, bones, joints, and soft tissues

Incidence

• 3-4 per million subjects per year
• 40-45 age range

Presentation

• Local effects of the tumour
• Headaches
• Bitemporal hemianopia
• Hypopituitarism
• Excess GH
• ENLARGEMENT - Gradual change of appearance due to the effects on cartilage and soft tissues: enlargement of hands and feet (increase in ring and shoe size), frontal bossing, thickening of the nose, enlarged tongue (macroglossia), growth of the jaw (prognathism), and coarsening of facial features
• OBSTRUCTIVE SLEEP APNOEA - Macroglossia may cause obstructive sleep apnoea
• EXCESSIVE SWEATING/HIRSUITISM - Excessive sweating and oily skin, with development of skin tags. Women may have slight hirsuitism
• OSTEOARTHRITIS - Articular overgrowth of synovial tissue and arthropathy leading to arthritis (widespread osteoarthritis of the weight-bearing joints), back pain and kyphosis
• VISCERAL HYPERTROPHY - Heart, liver, thyroid (with multinodular goitre), prostate and kidneys
• NERVE COMPRESSION SYMPTOMS - Carpal tunnel syndrome
• CARDIAC FEATURES - Hypertension, left ventricular hypertrophy, cardiomyopathy and arrhythmias
• Hyperprolactinaemia
• Amenorrhoea
• Galactorrhoea

Complications

• Ischaemic heart disease, cardiac failure and cerebrovascular disease
• Diabetes
• Acromegalic arthropathy, affecting both appendicular and axial skeleton
• Obstructive sleep apnoea
• Increased incidence of colonic polyps and adenocarcinoma of the colon
• Hypopituitarism after surgery
• Hyperprolactinaemia - mass effect causing deficiencies in glucocorticoids
• Gestational diabetes and gravid hypertension in pregnant women

Investigations

• Visual field defects
• Blood glucose, serum phosphate, urinary calcium and serum triglycerides may be raised
• Assessment of growth hormone
• Random growth hormone
• Glucose tolerance test (glucose normally inhibits GH)
• IGF-1
• IGF binding-protein 3
• GHRH concentration
• Assessment of other pituitary hormones
• MRI for pituitary
• CT for distant tumours secreting GH
• OctreoScan(R) (somatostatin) to aid localisation of the tumour
• Cardiac assessment: Electrocardiogram and echocardiogram
• Screen for colorectal cancer

Differentials

• Pseudo-acromegaly
• Insulin resistance
• Minoxidil treatment

Management

• Manage symptoms
• Manage cause
• Trans-sphenoidal first line
• Drug treatment
• Somatostatin analogues (Octreotide and Lanreotide)
• Dopamine agonists (Cabergoline and Bromocriptine)
• Pegvisomant (Genetically modified analogue of GH)
• Radiotherapy for residual disease

Prognosis

• High GH = 2-3 times more mortality
• Microadenoma > Macroadenoma
• Remission rates 80% for microadenoma and 50% for macroadenoma
• Hypertension, cardiovascular disease, diabetes and long duration of symptoms are also poor prognostic factors