Diagnosing Adult Growth Hormone Deficiency
by Lewis Chase, M.D.
Diagnosing isolated adult growth hormone deficiency is difficult and controversial. Growth hormone deficiency in adults causes a variety of metabolic abnormalities, including muscle mass loss, fat redistribution, abnormal lipid levels, abnormal cardiac function, decreased bone density, low energy and a reduced sense of well-being. Treatment with recombinant human growth hormone can result in improvement of these abnormalities. However, it is not easy to separate uncertain responses from the concurrent treatment of other pituitary hormone deficiencies. Growth hormone deficiency in patients having hypothalamic or pituitary disease and multiple other hormonal deficiencies (TSH, ACTH, gonadotropins, vasopressin) provides a better diagnosis than isolated growth hormone deficiency in an adult.
The anterior pituitary secretes growth hormone episodically. Growth hormone releasing hormone (GHRH) stimulates secretion; and somatostatin and feedback inhibition from insulin-like growth factor-1 (IGF-1) inhibit it. The pulsatile nature of growth hormone secretion can result in undetectable serum concentrations between pulses making random measurement of growth hormone useless in diagnosis. Secretion rates of growth hormone fall with age, decreasing up to six-fold between puberty and older adulthood, further complicating diagnosis. In obese and older adults, random growth hormone measurements are usually undetectable.
Principally IGF-1, which is secreted mainly by the liver, mediates the actions of growth hormone. Serum concentrations of IGF-1 do not fluctuate and generally reflect the overall secretion rate of growth hormone. Serum concentrations of IGF-1 vary with age and sex and require reference to age and gender specific normal values. In obese patients, both growth hormone and IGF-1 concentrations are reduced and increase with significant weight loss without hormonal therapy.
In patients with known hypothalamic or pituitary disease, doctors can establish the diagnosis of growth hormone deficiency with high sensitivity and specificity when there are 3 or 4 additional pituitary hormonal deficiencies or an IGF-1 less than 84 mcg/liter. To establish the diagnosis in patients without these criteria requires provocative growth hormone stimulation. Adults diagnosed in childhood with isolated growth hormone deficiency often have normal growth hormone secretion after puberty and need retesting before continuing replacement therapy into adulthood. The “gold standard,” an insulin tolerance test, is time consuming, expensive and potentially dangerous. The next best test combines stimulation with arginine and GHRH. Stimulation with arginine or L-Dopa alone or serum IGF-1 concentrations alone are not considered adequate to establish the diagnosis.
Treating a patient with recombinant human growth hormone is expensive and has significant side-effects including edema, arthralgias, carpal tunnel syndrome and glucose intolerance. Most of the symptoms of adult growth hormone deficiency can be treated successfully with weight loss and medications directed at specific abnormalities such as hyperlipidemia and decreased bone mineral density. Treatment with recombinant human growth hormone should be considered only in adults with well established growth hormone deficiency.