Sandro Loche

Interaction of free fatty acids and arginine on growth hormone secretion in man.

We studied the interaction between free fatty acids (FFAs) and arginine (ARG) on basal and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in 14 normal subjects. Compared with placebo, ARG induced a significant increase of GH secretion (334.0 +/- 157.5 v 36.9 +/- 27.6 micrograms/L/h, P < .05). The increased levels of FFAs (1.9 +/- 0.4 mEq/L), obtained by the infusion of a lipid-heparin emulsion, abolished the effect of ARG (55.8 +/- 45.6 v 334.0 +/- 157.5 micrograms/L/h, P < .05). GHRH-induced GH secretion was potentiated by ARG (2,009.9 +/- 463.2 v 922.0 +/- 244.4 micrograms/L/h, P < .05) and suppressed by lipid-heparin infusion (106.2 +/- 28.3 v 922.0 +/- 244.4 micrograms/L/h, P < .01). Moreover, the lipid-heparin infusion inhibited the potentiating effect of ARG on the GHRH-induced GH increase (527.9 +/- 113.6 v 2,009.9 +/- 463.2 micrograms/L/h, P < .01). These results confirm the strong inhibitory effect of FFAs on GH secretion, showing that they are even able to inhibit the potentiating effect of ARG on the GH response to GHRH. Since ARG likely acts via inhibition of hypothalamic somatostatin release, the inhibitory effect of FFAs on GH secretion could take place directly at the pituitary level and/or at the hypothalamic level, counteracting the effect of ARG.

Effects of Hexarelin on Growth Hormone Secretion in Short Normal Children, in Obese Children, and in Subjects with Growth Hormone Deficiency

A series of small peptides [growth hormone releasing peptides (GHRPs)], analogues of enkephalin, have been recently synthesized that selectively stimulate growth hormone (GH) secretion (1). These peptides have potent GH releasing activity in all species tested so far, and are effective also after oral administration (2-4). One of these peptides, GHRP-6, has been extensively studied in vitro and in vivo. In vitro, GHRP-6 stimulates GH secretion from pituitary cells by a mechanism not mediated by either growth hormone releasing hormone (GHRH) or opioid receptors (5–9), and via signaling mechanisms distinct from those of GHRH (5,10). In vivo, GHRP- 6 stimulates GH secretion in animals (11–13) and in humans (2, 3,14–18). Interestingly, the GH releasing activity of GHRP-6 in vivo is more potent than that observed in in vitro experiments, indicating that the peptide may also have a hypothalamic site of action, a view supported by the observation that GHRP-6 activity is enhanced when the experiments are carried out on hypothalamic-pituitary incubates (12), and by the evidence of specific hypothalamic binding sites for the peptide (7, 8). Furthermore, GHRP-6 acts synergistically with GHRH to release GH both in vitro (5, 10, 12) and in vivo (3,15).

Growth Hormone Deficiency in the Transition Age

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations.

Sindrome di Down ed endocrinopatie

SommarioLa Sindrome di Down ha un’incidenza di 1/400–1500 nati vivi ed è la causa più frequente di disabilità intellettiva di origine genetica. È caratterizzata da un insieme di manifestazioni fenotipiche variabili riscontrabili sin dalla nascita, legate alla presenza, parziale o completa, di un cromosoma 21 sovrannumerario. Oltre alle caratteristiche fisiche che la contraddistinguono, la Sindrome di Down può presentare complicanze a livello sistemico. Le complicanze endocrine più frequenti della sindrome di Down sono a carico della tiroide, dell’osso, del sistema metabolico, delle gonadi e del pancreas.

PO2-15: Insulin tolerance test and GHRH plus arginine in the reassessment of pituitary function at adult height achievement

N . Di Iorgi1, M .C . Salerno2, M . Cappa3, S . Loche4, G . Radetti5, D . Capaldo6, A . Allegri7, F . Napoli8, A . Calcagno7, O .B . Iovovich9, S . Noli7, S . Parodi10, M . Maghnie1 . 1DINOGMI, Endocrine Unit, IRCCS G Gaslini, University of Genova, Genova, Italy, 2Traslational Medical Sciences, Pediatric Endocrinology Unit, University Federico II, Naples, Italy, 3Unit of Endocrinology and Diabetology, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy, 4Pediatric Endocrine Unit, Ospedale Microcitemico, Cagliari, Italy, 5Pediatrics, Regional Hospital, Bolzano, Italy, 6Traslational Medical Sciences, Pediatric Endocrinology Unit, Federico II, Naples, Italy, 7DINOGMI, Endocrine Unit, University of Genova, Genova, Italy, 8Endocrine Unit, IRCCS, G Gaslini, Genova, Italy, 9Divisione di Laboratorio, IRCCS, G Gaslini, Genova, Italy, 10Institute of Electronics, Computer and Telecommunication Engineering, National Research Council of Italy, Genova, Italy

Tiroidite di Hashimoto in età pediatrica: diagnosi e terapia

RiassuntoLa tiroidite di Hashimoto è la più comune malattia della tiroide nonché la causa più frequente di gozzo e di ipotiroidismo acquisito in età pediatrica in presenza di un normale apporto iodico. La tiroidite di Hashimoto è una malattia cronica autoimmune, spesso asintomatica e per tale motivo viene diagnosticata, nei bambini enegli adolescenti, solo occasionalmente o in corso di screening familiari o scolastici. La diagnosi è basata sulle indagini di laboratorio e sull’ecografia tiroidea. Alla diagnosi la funzionalità tiroidea può essere normale o alterata con ipotiroidismo subclinico o conclamato oppure, occasionalmente, con transitorio ipertiroidismo. La terapia sostitutiva con levotiroxina, che trova accordo unanime in caso di ipotiroidismo conclam ato, è invece molto discussa in caso di ipotiroidismo subclinico