Acromegaly: A High-Yield USMLE Review
Acromegaly results from excess growth hormone (GH) secretion in an adult, most often from a GH-secreting pituitary adenoma. Because it develops after epiphyseal growth plates have closed, it causes bone and soft-tissue thickening rather than increased height. It is a high-yield endocrine topic on the USMLE, testing the classic clinical features, the IGF-1/OGTT diagnostic sequence, and the mass-effect consequences of a pituitary tumor.
Pathophysiology
A GH-secreting pituitary adenoma autonomously produces excess growth hormone. GH drives hepatic production of IGF-1, which mediates growth of bone and soft tissue. When this excess occurs after epiphyseal closure in adults, the result is thickening of bone and soft tissue (acromegaly) rather than increased height (gigantism, which occurs when GH excess precedes epiphyseal closure). As the adenoma enlarges into a macroadenoma with suprasellar extension, it compresses adjacent structures — producing headaches and, when it abuts the optic chiasm, visual field defects.
Presentation
- Enlarged hands and feet — patients notice increasing ring and shoe size
- Coarse facial features with a prominent brow and enlarged jaw
- Headaches from mass effect on the sella and dura
- Peripheral vision problems (bitemporal visual field loss) from optic chiasm compression by a macroadenoma
Diagnosis
- IGF-1 is the single best screening test — it is produced by the liver in response to GH and remains stable throughout the day, unlike random GH which is unreliable because GH is secreted in pulses
- Oral glucose tolerance test with GH measurement is confirmatory when IGF-1 is elevated: normally glucose suppresses GH to <1 ng/mL, but in acromegaly GH fails to suppress because secretion is autonomous
- MRI of the pituitary with gadolinium contrast to localize the tumor, distinguish microadenoma (<10 mm) from macroadenoma (≥10 mm), and evaluate for invasion of surrounding structures
Management
- Surgical resection of the GH-secreting pituitary adenoma to remove the source of hormone excess and relieve mass effect
- Medical therapy directed at lowering GH/IGF-1 as an adjunct or when surgery is not curative
High-yield
- IGF-1 is the screening test of choice; random GH is unreliable because it is secreted in pulses
- Failure of GH to suppress after an oral glucose load confirms the diagnosis
- GH excess before epiphyseal closure → gigantism; after closure → acromegaly
- Enlarged hands/feet, coarse facial features, prominent brow, and enlarged jaw are the classic exam findings
- A macroadenoma (≥10 mm) with suprasellar extension can compress the optic chiasm, causing bitemporal visual field loss
Pitfalls
- Do not rely on a random GH level to make the diagnosis — GH is pulsatile, so a normal random value does not exclude acromegaly; screen with IGF-1 instead
- Do not confuse acromegaly with gigantism — the distinction hinges on whether GH excess occurs after or before epiphyseal closure
- Overlooking headaches or visual field changes misses the mass effect of a macroadenoma abutting the optic chiasm
Don't just memorize Acromegaly — practice reasoning through it on branching cases where your decisions shape the patient.