The 2011 update to The Endocrine Society Clinical Practice Guideline on the evaluation and treatment of growth hormone deficiency (GHD) in adults offers recommendations on the definition and diagnosis of GHD, weighs the risks and benefits of growth hormone (GH) replacement, and offers recommendations on individualizing treatment. Below is a summary of key recommendations.
Definition and Evaluation of GHD in Adults
In adults, the causes of GHD are divided into 3 subgroups:
Diagnosis of GHD in Adults
Benefits of GH Treatment in GH-Deficient Adults
Side Effects and Risks of GHD Treatment
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML; Endocrine Society. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.
Commentary by Tamara L Wexler MD, PhD
Tamara L. Wexler, MD, PhD, is an endocrinologist specializing in neuroendocrinology and reproductive endocrinology. She is the Director of the NYU Langone Medical Center Pituitary Center in New York, NY, as well as an Attending in Medicine at Massachusetts General Hospital, Boston, MA.
This 2011 update to the 2006 Endocrine Society stance on the evaluation of, and treatment for adult growth hormone deficiency (AGHD) provides guidelines for diagnosis, the role of treatment, and appropriate monitoring. In addition, evidence to support the guidelines is summarized. The article also discusses those patients who were treated with GH as children, addressing when to re-test and when to treat that particular cohort.
The article also may serve as a useful practical guide for clinicians deciding when and how to test for GHD, and ties monitoring recommendations to evidence of the impact of GH in different areas of the body (eg, bone, cardiovascular). Available diagnostic tests are discussed with recommended prioritization and interpretations. For example, while the ITT is referred to as the gold standard for diagnosis of GHD, given the potential contraindications and need for careful monitoring during administration, GHRH-arginine stimulation is recommended as one first-line option (unless a hypothalamic cause is suspected). The glucagon stimulation test is recommended as an alternate to GHRH-arginine stimulation testing when the latter is not available; as discussed in the Introduction to this issue of EndoScan, as of July 2008, recombinant GHRH was no longer commercially available in the United States. The potential for future use of ghrelin-mimetic GH secretagogues in diagnosing GHD is mentioned. Since the publication of the guidelines, at least one such option concluded phase 3 trials, with an NDA submitted to the FDA (NDA not approved in present form).1
The article also alludes to the impact of body mass index (BMI) on thresholds used in dynamic testing; we later review a recent article by Dichtel and colleagues suggesting new glucagon stimulation testing cutoffs in obese patients.
While the focus of this EndoScan is adults (children will be discussed in a future EndoScan), the article touches on two important factors for endocrinologists: 1) the need to retest GH in cases in which a congenital GHD is not present, underscoring that not all children for whom GHR is indicated and approved will meet criteria for adult GHD and replacement, and 2) the importance of continuing GH replacement (GHR) in some patients who received it as children (as well as particular considerations in monitoring and treating this cohort).
Discussion of the potential benefits (and risks) of GHR in adults, and reference to the related evidence, is particularly useful in understanding why it is important to consider testing and replacement in addition to offering guidance for appropriate monitoring.
1. Garcia JM, Swerdloff R, Wang C, et al. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2013;98(6):2422-2429.