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Acromegaly: Causes, Symptoms, Complications, and Treatment

Acromegaly is a rare disorder (prevalence ~60/million) caused by chronic GH excess, almost always from a pituitary somatotroph adenoma. Onset is insidious—average diagnosis delay 5–10 years.

Etiology

  • Pituitary adenoma (95%): Benign monoclonal somatotroph tumor; sporadic (mostly), rarely familial (MEN1, Carney complex, McCune-Albright, FIPA)
  • Ectopic GHRH secretion (<1%): Pancreatic NET, bronchial carcinoid, SCLC → pituitary hyperplasia
  • Ectopic GH secretion (extremely rare): Same tumors producing GH directly

Clinical Features (Slow, Progressive)

  • Acral enlargement: Hands/feet (ring/shoe size increase)
  • Facial changes: Prognathism, macroglossia, thick lips, frontal bossing
  • Soft tissue: Hyperhidrosis, oily skin, skin tags, deepened voice
  • Musculoskeletal: Arthralgia, carpal tunnel, kyphosis, vertebral fractures
  • Visceral: Cardiomegaly, hypertension, sleep apnea, goiter, colon polyps
  • Metabolic: Insulin resistance → DM (25–50%), dyslipidemia
  • Reproductive: Hypogonadism, infertility, galactorrhea (if prolactin co-secretion)
  • Neurological: Headaches, visual field defects (bitemporal hemianopsia)

Diagnosis

  1. Screening: IGF-1 (age/sex-matched) – elevated = high sensitivity
  2. Confirmatory: Oral glucose tolerance test (OGTT) – GH fails to suppress <1 µg/L (or <0.4 µg/L modern assays)
  3. Imaging: Pituitary MRI (dedicated protocol) – localize adenoma
  4. Assessment: Visual fields, echocardiogram, colonoscopy, sleep study, glucose tolerance

Treatment Algorithm

  1. Transsphenoidal surgery: First-line for macroadenomas; remission ~80% micro, 40–50% macro (expert surgeon)
  2. Medical therapy (if surgery fails/contraindicated):
    • Somatostatin analogs (octreotide LAR, lanreotide, pasireotide) – ↓ GH/IGF-1, tumor shrinkage
    • GH receptor antagonist (pegvisomant) – blocks GH action; normalizes IGF-1 in 90%
    • Dopamine agonists (cabergoline) – modest effect; adjunct
  3. Radiation: Stereotactic (Gamma Knife) or fractionated – for residual/recurrent; delayed effect (years)

Long-Term Outcomes

  • Biochemical control → normal mortality
  • Uncontrolled → 2–3× mortality (cardiovascular, respiratory, cancer)
  • Multidisciplinary follow-up lifelong

Early diagnosis changes the trajectory. Screen for IGF-1 in patients with suggestive features.

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