Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Abstract

The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.

The Biochemical Diagnosis of Acromegaly

“…Paradoxical GH response after OGTT may reflect the pathophysiological severity of acromegaly and may predict the effectiveness of treatment with somatostatin receptor ligand [19]. The paradoxical response of GH to OGTT was also reported in patients with impaired glucose tolerance or diabetes, anorexia nervosa, puberty, renal or liver failure, or malnutrition [20] (Table 1).…”

“…Severe obesity, malnutrition, and prolonged fasting can reduce IGF-1 levels in patients with and without acromegaly [18,19]. High GH with low IGF-1 can be observed in states of GH resistance such as systemic inflammation, chronic liver disease, cirrhosis, and anorexia nervosa [20,21]. Oral estrogen and selective estrogen receptor modulators (SERM) can also render the liver less responsive to GH, resulting in lower IGF-1 levels.…”

“…Elevated basal GH levels are not specific for acromegaly, and levels may be significantly elevated in poorly controlled diabetes mellitus secondary to reduction in somatostatin release, renal failure associated with increased GH release and reduced GH clearance, malnutrition, in the setting of stress or during exercise and sleep [20,26]. In pregnancy, measurement of GH is challenging due to homology between GH and placental GH [28] (Table 1).…”

MANAGEMENT OF ENDOCRINE DISEASE: Etiology and outcome of acromegaly in patients with a paradoxical GH response to glucose

“…The influence of glucose on GH secretion has been shown since the early 1960s (22). However, to date, the precise mechanisms of GH suppression by oral glucose are not completely understood and are hindered by species disparities in the physiological response of GH to glucose overload as previously reviewed in detail (23). GH suppression seems to be most likely related to a glucose mediated increase in somatostatin release (24,25).…”

The role of glucose and insulin in the metabolic regulation of growth hormone secretion

“…Несмотря на недостаточное изучение патофизиологических основ этого процесса, недавно появилось предположение о нарушении взаимодействия между соматостатином и ГРРГ, а также была показана связь между эктопической гипофизарной экспрессией рецептора глюкозозависимого инсулинотропного полипептида и парадоксальной реакцией гормона роста на ПГТТ [67]. Наименее выраженное подавление ГР в ПГТТ наблюдается в подростковом возрасте [68].…”