Case Presentation

A 54-year-old white man with obstructive sleep apnea was referred for coarsening of the facial features. The patient complained of increasing fatigue, weakness, heat intolerance, and a tendency to sweat. Review of systems was remarkable for arthralgias, increasing shoe size, deepening voice, and debilitating symptoms of sleep apnea. The patient stated that sexual function was diminished but libido was unaffected. The past medical history was remarkable for type 2 diabetes mellitus diagnosed 2 years previously and a history of colon polyps. The physical examination revealed an obese man (BMI 35 kg/m2) with coarse facial features, prognathism, and a large tongue (Figure 1). The patient's hands were enlarged and felt "doughy," warm, and moist (Figure 2).

Patient's face. Note the coarse facial features, including frontal bossing, prominent supra- and suborbital ridges, enlarged nose and lips, and widened jaw.

Patient's enlarged hands. Note the increased width of the hands.

What tests are necessary to confirm the diagnosis of acromegaly?

  1. Although the clinical presentation of this patient is highly suggestive of acromegaly, the definitive diagnosis requires documented elevation of serum concentrations of growth hormone (GH) and/or insulin-like growth factor 1 (IGF-1). GH is secreted in a pulsatile manner every 2-4 hours, and serum levels vary throughout the day. The serum concentration of IGF-1 is relatively constant throughout the day and reliably reflects integrated GH secretion over 24 hours, establishing IGF-1 as a convenient initial test in the evaluation of acromegaly.Once the elevation of IGF-1 has been documented, or if equivocal results are obtained, the presence of GH excess should be confirmed with a standardized oral glucose suppression test. In normal subjects, serum GH concentrations fall to 2 ng/mL or less within 2 hours of ingesting 75 grams of glucose. The failure of GH to suppress to less than 2 ng/mL is seen in most individuals with acromegaly (85%).After confirmation of GH elevation, radiologic images of the pituitary gland should be done to establish the etiology of acromegaly. Magnetic resonance imaging (MRI) is the preferred technique, because it can detect small tumors and delineate surrounding soft-tissue structures.

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What is the differential diagnosis in a patient with acral enlargement?

  1. In the vast majority of cases (95%), acromegaly is caused by a pituitary somatotroph adenoma. Overproduction of growth hormone-releasing hormone (GHRH) by certain hypothalamic tumors (hamartomas, choristomas, gliomas, and gangliocytomas) can cause acromegaly by inducing hyperplasia of GH-secreting pituitary cells. Rarely, acromegaly may be caused by ectopic production of GHRH in a variety of endocrine tumors, such as bronchial or intestinal carcinoid tumors, pancreatic islet cell carcinomas, and pheochromocytomas. Ectopic GH-secreting tumors are extremely rare. GH-secreting pituitary adenomas may be associated with multiple endocrine neoplasia type 1 (MEN-1), so a measurement of serum calcium should be obtained to screen for coexisting hyperparathyroidism. Some persons have physical features very suggestive of acromegaly but have no increase in basal or stimulated serum GH concentrations. This condition, termed "acromegaloidism," is sometimes associated with marked insulin resistance.

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What additional studies are needed to evaluate pituitary function?

  1. GH-producing pituitary adenomas are very slow-growing tumors, and the progression of clinical symptoms and signs may be quite insidious. Hence, there is often a considerable delay (7-10 years) between the onset of acromegaly and the diagnosis. A macroadenoma (pituitary tumor ≥ 1 cm) is present at the time of diagnosis in 75% of persons with acromegaly. The large tumor compresses normal pituitary cells, occasionally resulting in pituitary hypofunction. As part of the hormonal evaluation of patients with acromegaly, it is necessary to measure serum levels of thyroid-stimulating hormone (TSH), leuteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, adrenocorticotropin (ACTH), and cortisol (8 AM sample). An ACTH stimulation test should be performed if there is a clinical suspicion of adrenal insufficiency. Formal visual field testing is indicated in individuals with macroadenomas, or if there is a suggestion of optic chiasm impingement.

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