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ESSENTIALS OF DIAGNOSIS

ESSENTIALS OF DIAGNOSIS

  • Pituitary neuroendocrine tumor with over secretion of GH.

  • Gigantism: begins before puberty before closure of epiphyses.

  • Acromegaly: occurs after puberty with 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 a rare condition, with a yearly incidence of about 10 cases per million. It is nearly always caused by a pituitary adenoma. About 70% are macroadenomas (1 cm or larger) when diagnosed. 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 rarely caused by ectopic secretion of growth hormone–releasing hormone or GH secreted by a neuroendocrine tumor or lymphoma.

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 manifestations of acromegaly usually present insidiously; median time to diagnosis after symptom onset is 10 years. 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. 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.)

Macroglossia occurs, as does hypertrophy of pharyngeal and laryngeal tissue; this causes a deep, coarse voice and sometimes makes intubation difficult. Snoring and obstructive sleep apnea are common. A goiter may be noted. Hypertension (50%) and cardiomegaly are common. At diagnosis, about 10% of acromegalic patients have a dilated LV and heart failure with reduced EF. Weight gain is typical, particularly of muscle and bone. Insulin ...

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