Acromegaly

Acromegaly is an insidious condition with a typical delay in diagnosis of 7-10 years. It results from a GH-secreting pituitary adenoma (usually a macroadenoma >10mm). If GH excess occurs before the fusion of the epiphyses in childhood, it results in 'Gigantism'. In adults, it leads to the characteristic acral overgrowth and multi-organ morbidity. Growth hormone stimulates the liver to produce Insulin-like Growth Factor 1 (IGF-1), which mediates most of the growth-promoting effects. Chronic GH excess is associated with significant complications, including Type 2 Diabetes (as GH antagonises insulin), hypertension, obstructive sleep apnoea, and an increased risk of colorectal cancer. Mortality is increased, primarily due to cardiovascular disease (cardiomyopathy). Management is multidisciplinary, with trans-sphenoidal surgery being the first-line treatment. Medical therapy (Somatostatin analogues) and radiotherapy are reserved for adjuvant treatment or when surgery is contraindicated.

Growth Hormone is secreted by the somatotroph cells of the anterior pituitary under the stimulation of GHRH and inhibition by Somatostatin. GH secretion is pulsatile, peaking during sleep. Primary action is the hepatic production of IGF-1. Growth hormone itself has direct metabolic effects, including lipolysis and inhibition of glucose uptake (diabetogenic). The excess IGF-1 causes hypertrophy of dermal and subcutaneous tissue (skin thickening, sweating) and periosteal bone growth (prognathism, hand widening). It also causes organomegaly (heart, liver, spleen). Pathologically, most acromegaly cases are due to a benign monoclonal expansion of pituitary cells.

Physical appearance: Enlargement of hands and feet (increased glove/shoe size), coarse facial features, frontal bossing, large fleshy nose, macroglossia (large tongue), and prognathism (protruding jaw) with widely spaced teeth (diastema). Symptoms: Excessive sweating (hyperhidrosis), oily skin (seborrhoea), carpal tunnel syndrome (soft tissue compression), sleep apnoea, and arthralgia. Local tumour effects: Headache and bitemporal hemianopia. Systemic: Hypertension and signs of heart failure (cardiomyopathy). Metabolic: Impaired glucose tolerance or T2DM in up to 50% of patients.

Screening: Serum IGF-1 (elevated for age/sex). Confirmatory: Oral Glucose Tolerance Test (OGTT) – 75g of glucose is given; GH should normally suppress to <1 mcg/L. In acromegaly, GH fails to suppress or may even rise. Localisation: MRI Brain/Pituitary (the most sensitive imaging). Others: Visual field assessment (Perimetry); Screening for complications (ECG/ECHO for cardiomyopathy, Glucose monitoring, Colonoscopy from age 40).

1. Surgical: Trans-sphenoidal resection of the pituitary adenoma. This is the first-line treatment and can be curative. 2. Medical: Used if surgery is unsuccessful, inappropriate, or as bridge to surgery/radiotherapy. Options: Somatostatin analogues (e.g., Octreotide, Lanreotide) which inhibit GH release; Dopamine agonists (e.g., Cabergoline) for smaller tumours; GH-receptor antagonists (Pegvisomant). 3. Radiotherapy: Used for residual tumour or when surgery/medical therapy fails. Success takes years and carries a high risk of hypopituitarism.