Acromegaly: Symptoms, Causes & Treatment

Acromegaly is a rare chronic endocrine disorder resulting from sustained hypersecretion of growth hormone (GH), almost always from a pituitary adenoma (benign tumor of the pituitary gland) — responsible for >95% of cases. Excess GH stimulates hepatic production of insulin-like growth factor 1 (IGF-1), which drives progressive hypertrophy of bone, soft tissue, and visceral organs. When GH hypersecretion occurs before epiphyseal closure (in children/adolescents), the result is gigantism rather than acromegaly.

Acromegaly is rare, affecting approximately 60 per million population, with an annual incidence of 3–4 per million. The insidious, slowly progressive nature of physical changes leads to an average diagnostic delay of 4–10 years from symptom onset — patients often notice old photos looking different rather than perceiving day-to-day change. The characteristic physical changes (prognathism, frontal bossing, broad nose, increased hat/ring/shoe size) result from periosteal new bone formation and soft tissue hypertrophy.

The most clinically significant consequences are systemic comorbidities: type 2 diabetes (30%), hypertension (35%), obstructive sleep apnea (60–80%), cardiovascular disease (the major cause of excess mortality), colonic polyps/colon cancer, carpal tunnel syndrome, and arthropathy. Untreated acromegaly reduces life expectancy by approximately 10 years, primarily from cardiovascular disease. With successful biochemical control (GH normalization and IGF-1 normalization), mortality returns to near-normal.

• Facial coarsening: frontal bossing, prognathism (prominent jaw), broad nasal bridge, enlarged lips and tongue
• Enlargement of hands and feet: increased ring, glove, and shoe size; spade-like hands
• Interdental spacing and malocclusion
• Hyperhidrosis (excessive sweating) with oily skin and body odor
• Arthralgias and myalgias from cartilage and soft tissue hypertrophy
• Carpal tunnel syndrome — bilateral median nerve compression from soft tissue swelling
• Obstructive sleep apnea (OSA) in 60–80% from macroglossia and pharyngeal soft tissue hypertrophy
• Headache from pituitary tumor mass effect; visual field defects (bitemporal hemianopia) from optic chiasm compression by macroadenoma
• Hyperprolactinemia symptoms (co-secretion) in 40%: galactorrhea, amenorrhea, erectile dysfunction

• Pituitary somatotroph adenoma (GH-secreting): >95% of cases — microadenoma (<10 mm) in 30%, macroadenoma (≥10 mm) in 70%
• Ectopic GHRH secretion: carcinoid tumors of the lung or gut, pancreatic islet cell tumors — <1% of cases; GHRH stimulates pituitary GH excess
• McCune-Albright syndrome (somatic GNAS mutation causing constitutive Gs-α activation in pituitary somatotrophs)
• Multiple endocrine neoplasia type 1 (MEN1): pituitary + parathyroid + pancreatic tumors
• Primary pituitary carcinoma: extremely rare

Biochemical diagnosis: IGF-1 (age- and sex-adjusted): elevated IGF-1 is the best screening test; correlates with integrated GH secretion. Oral glucose tolerance test (OGTT): administer 75 g glucose — in acromegaly, GH fails to suppress to <0.4 ng/mL (updated ultrasensitive assay cutoffs); GH nadir <0.4 µg/L confirms normal. Random GH is unreliable due to pulsatile secretion. Pituitary MRI with gadolinium: identifies tumor size, location, and optic chiasm proximity. Visual field testing: Humphrey perimetry for chiasmal compression assessment. Cardiac echo: assess cardiomyopathy, LVH, valvular disease. Colonoscopy: increased colon polyp/cancer risk. Glucose tolerance testing for diabetes screening.

Transsphenoidal surgery (TSS): first-line treatment — pituitary microsurgery or endoscopic TSS; remission rates 70–90% for microadenomas, 40–50% for macroadenomas. Medical therapy for unresected or recurrent disease: somatostatin receptor ligands (SRL) — octreotide LAR or lanreotide — reduce GH/IGF-1 by 50–70% and normalize IGF-1 in 25–45%; pegvisomant (GH receptor antagonist) — normalizes IGF-1 in >90% but does not shrink tumor; cabergoline (dopamine agonist) — effective in 30–40% with co-secreting tumors. Radiotherapy (stereotactic radiosurgery such as Gamma Knife): third-line when surgery and medical therapy fail; takes 5–10 years for full effect. Pasireotide (second-generation SRL): superior biochemical control but higher hyperglycemia rates.

• Type 2 diabetes mellitus and insulin resistance (30%)
• Hypertension (35%) and cardiomyopathy — acromegalic cardiomyopathy; major cause of excess mortality
• Obstructive sleep apnea (60–80%)
• Colonic adenomatous polyps and colorectal cancer (higher risk — regular colonoscopy essential)
• Visual field loss from optic chiasm compression
• Debilitating arthropathy from cartilage overgrowth
• Hypopituitarism from tumor compression of normal pituitary tissue

• No known primary prevention for sporadic pituitary adenoma formation
• Genetic testing for MEN1 syndrome in patients with family history of pituitary/parathyroid/pancreatic tumors
• Post-treatment surveillance: IGF-1 and GH every 6 months; MRI every 1–2 years; colonoscopy at diagnosis and every 3–5 years; cardiac assessment