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Key Clinical Updates in Acromegaly & Gigantism

Pasireotide is a long-acting somatostatin analog that can be effective at suppressing growth hormone secretion in patients resistant to octreotide LAR and lanreotide; however, hyperglycemia is common and distribution is restricted in the United States.

ESSENTIALS OF DIAGNOSIS

  • Pituitary neuroendocrine tumor.

  • Gigantism before closure of epiphyses.

  • Acromegaly: excessive growth of hands, feet, jaw, internal organs.

  • Amenorrhea, hypertension, headaches, visual field loss, weakness.

  • Soft, doughy, sweaty handshake.

  • Elevated serum IGF-1.

  • Serum GH not suppressed following oral glucose.

GENERAL CONSIDERATIONS

GH exerts much of its growth-promoting effects by stimulating the release of IGF-1 from the liver and other tissues.

Acromegaly is nearly always caused by a pituitary adenoma. Most are macroadenomas (over 1 cm). These tumors may be locally invasive, particularly into the cavernous sinus. Less than 1% are malignant. Acromegaly is usually sporadic but may rarely be familial, with less than 3% being due to multiple endocrine neoplasia (MEN) types 1 or 4. Acromegaly may also be seen rarely in McCune-Albright syndrome and Carney complex. Patients with Carney complex develop spotty cutaneous pigmentation; peripheral nerve schwanommas; myxomas of the skin, heart, and breast; and testicular, adrenal, and GH-secreting pituitary tumors (mnemonic SPM TAG). Carney complex is inherited as an autosomal dominant trait and most patients harbor a germline mutation in the PRKAR1A gene. Acromegaly is very occasionally caused by ectopic secretion of GHRH or GH secreted by a lymphoma, hypothalamic tumor, bronchial carcinoid, or pancreatic tumor.

CLINICAL FINDINGS

A. Symptoms and Signs

Excessive GH causes tall stature and gigantism if it occurs in youth, before closure of epiphyses. Afterward, acromegaly develops. The term “acromegaly,” meaning extremity enlargement, seriously understates the manifestations. The hands enlarge and a doughy, moist handshake is characteristic (eFigure 26–1). The fingers widen, causing patients to enlarge their rings. Carpal tunnel syndrome is common. The feet also grow, particularly in shoe width. Facial features coarsen since the bones and sinuses of the skull enlarge; hat size increases. The mandible becomes more prominent, causing prognathism and malocclusion. Tooth spacing widens (eFigure 26–2). Older photographs of the patient can be a useful comparison.

eFigure 26–1.

Markedly increased soft tissue bulk and blunt fingers in a middle-aged man with acromegaly. (Reproduced, with permission, from Greenspan FS, Strewler GJ [editors]. Basic & Clinical Endocrinology, 5th ed. Copyright © 1997 by The McGraw-Hill Companies, Inc.)

eFigure 26–2.

Serial photographs of an acromegalic patient at the ages indicated. Note the gradual increase in size of the nose, lips, and skin folds. (Reproduced, with permission, from Reichlin SR. Acromegaly. Med Grand Rounds. 1982;1:9.)

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