AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: UPDATE ON GROWTH HORMONE STIMULATION TESTING AND PROPOSED REVISED CUT-POINT FOR THE GLUCAGON STIMULATION TEST IN THE DIAGNOSIS OF ADULT GROWTH HORMONE DEFICIENCY.

OBJECTIVE: The clinical features of adult GH deficiency (GHD) are nonspecific, and GH stimulation testing is often required to confirm the diagnosis. However, diagnosing adult GHD can be challenging due to the episodic and pulsatile GH secretion, concurrently modified by age, gender, and body mass index (BMI).

METHODS: PubMed searches were conducted to identify published data since 2009 on GH stimulation tests used to diagnose adult GHD. Relevant articles in English language were identified and considered for inclusion in the present document.

RESULTS: Testing for confirmation of adult GHD should only be considered if there is a high pretest probability, and the intent to treat if the diagnosis is confirmed. The insulin tolerance test (ITT) and glucagon stimulation test (GST) are the two main tests used in the United States. While the ITT has been accepted as the gold-standard test, its safety concerns hamper wider use. Previously, the GH-releasing hormone-arginine test, and more recently the GST, are accepted alternatives to the ITT. However, several recent studies have questioned the diagnostic accuracy of the GST when the GH cut-point of 3 μg/L is used and have suggested that a lower GH cut-point of 1 μg/L improved the sensitivity and specificity of this test in overweight/obese patients and in those with glucose intolerance.

CONCLUSION: Until a potent, safe, and reliable test becomes available, the GST should remain as the alternative to the ITT in the United States. In order to reduce over-diagnosing adult GHD in overweight/obese patients with the GST, we propose utilizing a lower GH cut-point of 1 μg/L in these subjects. However, this lower GH cut-point still needs further evaluation for diagnostic accuracy in larger patient populations with varying BMIs and degrees of glucose tolerance.

ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists BMI = body mass index GH = growth hormone GHD = GH deficiency GHRH = GH-releasing hormone GHS = GH secretagogue GST = glucagon stimulation test IGF = insulin-like growth factor IGFBP-3 = IGF-binding protein 3 ITT = insulin tolerance test ROC = receiver operating characteristic WB-GST = weight-based GST.