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Purpose of Review: This article summarizes recent advances in testing for growth hormone deficiency (GHD) in adults, focusing on critical appraisal of existing growth hormone (GH) provocative tests as well as newer tests in development., Recent Findings: The diagnosis of GHD can be challenging and often requires the use of GH provocative testing. The most widely validated of these is insulin-induced hypoglycemia (ITT), which requires close supervision and has significant contraindications and side-effects. The arginine-growth hormone-releasing hormone (GHRH) test had become widely used as a safe and accurate alternative to the ITT, but GHRH is currently unavailable for clinical use in the USA. On the basis of review of recent literature we recommend that in the absence of GHRH, glucagon stimulation testing should be the preferred alternative to ITT. Several synthetic GH secretagogues that mimic the gastric peptide ghrelin are currently in development and may become available for use in the diagnosis of GHD in the near future. Other GH provocative tests suitable for use in children lack adequate specificity for the diagnosis of GHD in adults., Summary: Due to the current unavailability of the arginine-GHRH test in the USA, when ITT is contraindicated or impractical we recommend the glucagon stimulation testing as the GH provocative test of choice. There remains a need for a simple, safe and accurate test for the diagnosis of GHD.

The decline in the function of the growth hormone-releasing hormone, growth hormone, insulin-like growth factor (GHRH-GH-IGF) axis has been termed the somatopause. Many of the catabolic sequelae seen in normal aging has been attributed to this decrease in circulating GH and IGF-I. In order to provide hormone replacement therapy for the somatopause, elderly subjects have been treated with GH, IGF-I, or both hormones together. Whereas numerous beneficial effects on body composition, strength, and quality of life have been reported in some studies, other studies have reported only marginal functional improvements. Moreover, it is clear that both hormones can cause significant morbidity.

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.

The growth hormone (GH)-insulin-like growth factor type I (IGF-I) axis is subject to exquisite regulation by multiple internal physiological variables and external cues. This review and update summarizes the impact of age, obesity, gonadal function and sleep on the control of GH secretion by the pituitary gland, as regulated by the dominant hypothalamic regulatory peptides, GH-releasing hormone (GHRH) and somatostatin. Available studies show an exponential decline in the calculated daily GH-secretion rate as a function of age in healthy men, such that every 7 years of advancing age beyond age 18-21 results in an approximately 50% decline. There are also strongly negative correlations between the daily GH-secretion rate and indices of obesity, such as the body mass index (BMI). For each increase in BMI of 1.5 kg/m2, there is a 50% decrease in the amount of GH secreted per day. At puberty, and across a span of adult ages, gonadal steroid-hormone concentrations in blood positively determine GH release. In particular, serum estradiol and testosterone concentrations are proportionate to GH-secretory burst mass and mean serum GH concentrations. Deep sleep (stages 3 and 4) is accompanied by markedly increased pulsatile GH secretion that can be accounted for mechanistically by presumptive somatostatin withdrawal combined with hypothalamic GHRH release. Lastly, body composition (especially visceral adiposity) appears to be a dominant negative determinant of GH production, since the relationships between GH secretion and age, testosterone, or sleep are all attenuated or abolished by adiposity. Recent data using pulsatile GHRH treatment or pharmacological methods to reduce somatostatin secretion point to combined defects in GHRH release and somatostatin excess as the most plausible pathophysiology of hyposomatotropism accompanying obesity.