Tests of pituitary function: acromegaly

From Dr. Lewis Blevins.  Growth Hormone is secreted in pulses, usually 9-12 per 24-hour period, and most of these occur at night while we are sleeping. In normal adults, growth hormone levels are undetectable 50% of the time during the day. In patients with acromegaly, growth hormone levels are typically elevated but may actually be in the normal range for a normal pulse of hormone secretion. Thus, growth hormone levels, themselves, do not constitute a diagnostic test for acromegaly. They can, however, be useful to follow disease activity and are somewhat predictive of the likelihood of successful surgery.

IGF-I is a protein made by the liver and response to growth hormone secretion. IGF-I, and its principal binding protein, IGF BP-3, both serve as reasonable tests of integrated growth hormone secretion in patient’s with suspected acromegaly. In fact, an elevated IGF-I in the clinical context of acromegaly with a documented pituitary lesion is essentially diagnostic of a growth hormone producing pituitary adenoma. It is important to evaluate IGF-I levels in the context of an age- and sex-matched reference range. A lack of clinical features and absence of a pituitary tumor usually suggests that an elevated IGF one might be a false positive test. False positive tests can occur due to certain conditions, like uncontrolled diabetes mellitus, and due to poorly performing assays. The best IGF-I assay at this time is the GC/MS assay by Quest diagnostics.

When the diagnosis is unclear, an oral glucose suppression test is often employed to diagnose acromegaly. This involves administration of 100 g oral glucose followed by growth hormone levels at 30 minute intervals for 2 hours. Growth hormone levels are expected to go to less than 1 ng/mL during the test and in many assays a true separation of normal from the diseased individuals is obtained by using a cutoff of 0.4 ng/mL.

If results are equivocal there is nothing wrong with waiting a few months and repeating the investigations. Patients with true acromegaly will have some worsening of their disease state and their biochemical tests but not sufficient so to result in any significant adverse health effects. The best thing is to not rush into a diagnosis because the consequences and costs of an erroneous diagnosis are great.

Reasonable goals of surgery or other treatments for acromegaly are to normalize the IGF-I level, more towards the middle of the normal range is best, and to achieve a random growth hormone level less than 1 ng/mL. Disparate results, such as a normal IGF-I but elevated growth hormone level, or vice versa, can be sorted out with the oral glucose suppression test and careful review of an MRI for evidence of residual tumor.

Patients who achieve a normal growth hormone and IGF-I levels after surgery should probably have these levels checked at 6 month intervals for 2 years after surgery and then annually thereafter because the recurrence risk of acromegaly is not insignificant.

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