Roberto Peino

Serum leptin concentrations in patients with anorexia nervosa, bulimia nervosa and non‐specific eating disorders correlate with the body mass index but are independent of the respective disease

OBJECTIVE Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but little else is known about the physiological actions of leptin in humans. The aim of this study was to determine the role of leptin in severe eating disorders, and whether its levels are correlated with the specific disease or exclusively with body weight.

Effect of combined administration of growth hormone (GH)-releasing hormone, GH-releasing peptide-6, and pyridostigmine in normal and obese subjects

Growth hormone (GH) secretion in response to all provocative stimuli is decreased in patients with obesity. Recently, we found that the combined administration of GH-releasing hormone (GHRH) and the hexapeptide GH-releasing peptide-6 (GHRP-6) induced a large increase in plasma GH levels. To gain further insight into the disrupted mechanism of GH regulation in obesity, we investigated whether the inhibition of somatostatinergic tone with pyridostigmine could further increase the GH response to combined administration of GHRH and GHRP-6. In normal subjects, administration of GHRH plus GHRP-6 induced a marked increase in plasma GH with a peak at 30 minutes (mean +/- SEM, 76.7 +/- 9.7 micrograms/L), which was similar to that obtained after pretreatment with pyridostigmine (74.7 +/- 9.4 micrograms/L). In obese patients, combined administration of GHRH plus GHRP-6 induced a clear increase in GH secretion with a peak at 15 minutes of 42.2 +/- 10.0 micrograms/L, which was also unaffected after pretreatment with pyridostigmine (38.4 +/- 5.8 micrograms/L). The GH response was lower in obese patients than in controls as assessed by the area under the curve after administration of both GHRH plus GHRP-6 (1,846 +/- 396 v 4,773 +/- 653, P < .01) and pyridostigmine plus GHRH plus GHRP-6 (1,989 +/- 372 v 5,098 +/- 679, P < .005). In conclusion, these data suggest that GHRP-6 can behave as a functional somatostatin antagonist, and that somatotrope responsiveness to the combined administration of GHRH plus GHRP-6 is largely independent of somatostatinergic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypopituitarism and Growth Hormone Deficiency in Adult Subjects after Traumatic Brain Injury: Who and When to Test

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.

Pituitary Stalk Dysgenesis-Induced Hypopituitarism in Adult Patients: Prevalence, Evolution of Hormone Dysfunction and Genetic Analysis

Objectives: To investigate the prevalence of pituitary stalk dysgenesis (PSD) in adult hypopituitary patients by describing the chronology of hormone deficiencies and their potential correlation with traumatic delivery, mutations in genes required for pituitary development and function and pituitary stalk visibility on MRI. Design: Retrospective and prospective study involving 231 hypopituitary patients, including 26 diagnosed with PSD. Clinical, biochemical and radiological studies were reviewed. Molecular analyses of HESX1, LHX4,PROP1 and POU1F1 genes were performed prospectively. Results: PSD was present in 11.2% of hypopituitary patients. PSD was diagnosed before 14 years of age in 46.2% of cases, between 14 and 18 years of age in 23%, and in adulthood in 30.8%. Perinatal complications or gene mutations were present in 26.9 and 4.3% of patients, respectively. At first assessment, 92.3% of patients had growth hormone (GH) deficiency. 26.9% presented as combined pituitary deficiencies and 7.6% as panhypopituitarism. Hormone deficiencies were progressive during follow-up in 84.6%. 96% progressed to multiple deficiencies and 46% to panhypopituitarism. No significant association was found between hormonal dysfunction and previous perinatal damage or breech delivery (p = 0.17), PROP1 mutations (p = 0.26) or pituitary stalk visibility on MRI (p = 0.52). No mutations in POU1F1, HESX1 and LHX-4 genes were detected. Conclusion: In this study, PSD prevalence in adult hypopituitary patients was 11.2%. Typical clinical presentation includes isolated or combined pituitary hormone deficiencies during the pediatric age, which usually progress to combined or complete hypopituitarism in adulthood. Phenotype is highly variable depending on hormone profile and age at onset.

The sequential administration of growth hormone‐releasing hormone followed 120 minutes later by hexarelin, as an effective test to assess the pituitary GH reserve in man

OBJECTIVE GH deficiency, either in children or in adults, is a clinically relevant problem. The diagnosis is based on dynamic tests of GH secretion, which are clear cut on a group basis but highly problematic for individual diagnosis. The controversy surrounding the diagnosis of GH deficiency reflects the absence of a gold standard dynamic test. The synthetic hexapeptide hexarelin and GHRH stimulate GH secretion using different mechanisms. A sequential test has been devised using the administration of GHRH as first stimulus followed 120 minutes later by hexarelin. The two aims of the study were (a) to evaluate the interaction of GHRH and hexarelin, and (b) to devise a sequential test of GH reserve.

Effect of acute reduction of free fatty acids by acipimox on growth hormone‐releasing hormone‐induced GH secretion in type 1 diabetic patients

background  In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1.