Lavin Chapter 12

130   Section 2 • Hypothalamic-Pituitary Dysfunction

III. CONTROL OF GH SECRETION Two hypothalamic hormones and one hormone produced in the stomach control GH release and secretion (Table 12-1). A. Growth hormone–releasing hormone (GHRH) from the hypothalamus stimulates the synthesis and secretion of GH from the pituitary gland. B. Somatostatin is a peptide produced by several tissues in the hypothalamus and elsewhere, which inhibits the release of GH. C. Ghrelin is a peptide hormone secreted from the stomach that binds to receptors on somatotrophs in the pituitary gland and stimulates secretion of GH. D. GH secretion is part of a negative feedback system: High levels of IGF-1 lead to suppression of GH by directly suppressing the somatotroph and also stimulating release of somatostatin from the hypothalamus. GH also inhibits GHRH secretion. IV. ADULT GROWTH HORMONE DEFICIENCY SYNDROME AGHDS is a clinical entity characterized by decreased lean body mass and decrease in BMD as well as increased visceral adiposity and an abnormal lipid profile. There is also decreased muscle strength, exercise endurance, and a diminished quality of life. Some data indicate increased morbidity and mortality associated with GHD secondary to cerebral or cardiovascular disease as well as bone fractures. GH replacement has been shown to reverse many of these abnormalities. V. EVALUATION A. IGF-1. Because GH is secreted in an episodic manner, random sampling has little validity in the diagnosis of GHD. A random IGF-1 level, however, can be obtained at any time of the day and is a strong surrogate marker for the level of GH in the absence of catabolic conditions and/or liver disease. Contrariwise, a normal IGF-1 level does not exclude a diagnosis of GHD. Therefore, if it is clinically indicated, GH-stimulation tests should be performed. Additionally, the presence of low levels of three or more pituitary hormones other than GH strongly suggests the presence of GHD, and therefore, stimulation testing may not be required in this situation. B. Stimulation tests 1. Current diagnostic testing involves provocation of GH secretion, including the insulin-tolerance test, which is considered to be the “gold standard.”This test is

Control of Growth Hormone Secretion

TABLE 12-1

Stimulators

Inhibitors

1.  GHRH 2.  Stage III and stage IV sleep 3.  Stressors 4. a -Adrenergic stimuli 5.  Fasting

1.  Somatostatin 2.  Elevated IGF-1 levels 3.  Hyperglycemia 4.  Elevated free fatty acid levels 5.  Serotonin antagonists 6.  Corticotropin-releasing factor 7. b -Adrenergic stimuli 8.  Progesterone

6.  Melatonin 7.  Estrogens 8.  Dopaminergic stimuli 9.  Exercise 10.  Serotonin 11.  Hypoglycemia 12.  Interleukin 1, 2, and 6

9.  ACTH deficiency 10.  Hyperthyroidism 11.  Hypothyroidism 12.  Obesity 13.  Depression 14.  Corticosteroids

13.  Levodopa 14.  Clonidine

15.  Bromocriptine 16.  Arginine/lysine 17.  Ghrelin

15.  Amitriptyline 16.  Substance P

ACTH, adrenocorticotropic hormone; GHRH, growth hormone–releasing hormone; IGF-1, insulin-like growth factor 1.