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Anorexia nervosa is a syndrome with multifactorial etiology in which several genetic, biologic, psychological and social factors are involved. Patients affected by anorexia nervosa (AN) may develop multiple endocrine abnormalities, e.g. amenorrhea, hypothalamus-pituitary-adrenal axis hyperactivity, low T3 syndrome and peculiar changes of somatotroph axis function. These endocrine abnormalities are also found after prolonged starvation and may represent an adaptive response developed in order to save energy and proteins. It is still a matter of debate whether these endocrine changes are etiologic or secondary. In fact, several evidences suggest the existence in AN of hypothalamus functional alterations, which may be involved in the development and maintenance of the food intake disorder; on the other hand, the increased CRH secretion seems to be secondary to malnutrition as well as GH hypersecretion coupled to low IGF-I levels; the latter is a common finding in AN, as well as in other undernutrition and malabsorption conditions, type 1 diabetes mellitus, liver cirrhosis and catabolic states. Hypothalamic amenorrhea, which is one of the diagnostic criteria for AN, is not linked only to the reduction of body weight but reflects also deep alterations of gonadotropin secretory pattern. Low T3 syndrome is frequently found in AN; on the other hand, an iodide-induced hypothyroidism is quite uncommon. T3 reduction in AN seems to be an adaptive response to prolonged starvation; however the presence of a simultaneous central dysregulation cannot be excluded. Finally, AN patients frequently show defects in urinary concentration or dilution with inappropriate secretion of antidiuretic hormone, which may be due to intrinsic defects in the neurohypophysis or to abnormalities of its regulatory afferent neurons.

Background: Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli < 3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status., Methods: We aimed to verify the GH response to GHRH (1 mg/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS)., Results: IGF-I levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 mg/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS, the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH., Conclusions: Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.

Background: It is widely accepted that IGF-I synthesis and release depend on GH secretion as well as on the nutritional status and vary with age. Based on these premises, after the definition of normal IGF-I levels during lifespan, in a large population of normal subjects of both sexes, our aim was to verify IGF-I levels in large groups of adult patients with GH deficiency or obesity, a condition in which a reduced somatotrope secretion is well known., Methods: To this goal, IGF-I levels were assayed after acid-ethanol extraction, in 326 normal subjects (NS, 98 men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH deficiency (GHD, 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and 195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9 kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive decrease with age. No correlation was present between IGF-I and BMI in NS. Median IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230 and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and 41.6; VIII) 82 and 24.7 micrograms/l. In GHD, IGF-I levels were independent on sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were lower than that in NS (64.5 +/- 5.9 vs 171.3 +/- 4.8 micrograms/l, p < 0.01) and did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In OB, IGF-I levels were independent on sex but, like in NS, showed a progressive decrease with age and were independently, negatively correlated with BMI but not with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd centile in 10/77 patients in the III and IV decade and in only 8/108 patients up to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9 micrograms/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9 micrograms/l) while only in the IV decade IGF-I levels in OB group were lower (p < 0.02) than those in NS (184.7 +/- 12.6 micrograms/l vs 224.0 +/- 9.2 micrograms/l)., Conclusions: In conclusion, present data confirm that IGF-I levels depends on GH secretion as well as on nutritional status, being negatively and independently correlated with age and BMI. IGF-I assay is not a reliable test for the diagnosis of GH deficiency in adulthood though it gives good discrimination between GHD and normal subjects up to 40 yrs of age. In spite of low GH secretion, IGF-I levels are only slightly reduced in obesity, probably as consequence of hyperinsulinism.

Growth hormone (GH), Insulin Growth Factor-I (IGF-I) and lipids are linked by important reciprocal influences. Their knowledge allowed relevant pathophysiological and clinical acquisitions more and more interesting in scientific research and in medical practice. In this survey the influence of (GH) on lipid metabolism, particularly on free fatty acids (FFA) and lypoprotein metabolism has been analysed. Attention has been given to the disorders of the lipid-metabolism in GH hypo- and hyper-secretory states. On the other hand the role of lipids in the control of GH secretion has been extensively considered with particular attention to the role of exaggerated FFA levels in the pathogenesis of GH insufficiency in obesity.

The effect of propranolol on certain insulin-induced metabolic changes in man. The effects of 0.2 mg/kg/body weight propranolol perfused in 10' on insulin-induced (0.15 I.U./Kg i.v.)changes in blood glucose, pyruvate, lactic acid, phosphorus, and potassium levels were examined in 12 normal volunteers. The blood glucose curve was substantially unaffected. Insulin-induced increases in lactate and pyruvate were inhibited to a varying degree, namely 78% (61-93%) and 44% (0.94%) respectively. The fall in phosphorus was reduced in a more constant manner (mean 48; range 37-57%) in all subjects, while that of potassium was not altered. The data indicate that these insulin-induced changes are significantly, though variably, attributable to beta-adrenergic activity on the part of endogenous catecholamines released during insulin-induced hypoglycaemia.