Ezio Ghigo

Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults

OBJECTIVE To define the appropriate diagnostic cut-off limits for the GH response to GHRH+arginine (ARG) test and IGF-I levels, using receiver operating characteristics (ROC) curve analysis, in late adolescents and young adults. DESIGN AND METHODS We studied 152 patients with childhood-onset organic hypothalamic-pituitary disease (85 males, age (mean+/-s.e.m.): 19.2+/-0.2 years) and 201 normal adolescents as controls (96 males, age: 20.7+/-0.2 years). Patients were divided into three subgroups on the basis of the number of the other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A consisted of 35 panhypopituitary patients (17 males, age: 21.2+/-0.4 years), subgroup B consisted of 18 patients with only one or with no more than two pituitary hormone deficits (7 males, age: 20.2+/-0.9 years); and subgroup C consisted of 99 patients without any known hormonal pituitary deficits (60 males, age: 18.2+/-0.2 years). Both patients and controls were lean (body mass index, BMI<25 kg/m(2)). Patients in subgroup A were assumed to be GHD, whereas in patients belonging to subgroups B and C the presence of GHD had to be verified. RESULTS For the GHRH+ARG test, the best pair of highest sensitivity (Se; 100%) and specificity (Sp; 97%) was found choosing a peak GH of 19.0 microg/l. For IGF-I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a cut-off point of 160 microg/l (SDS: -1.3). Assuming 19.0 microg/l to be the cut-off point established for GHRH+ARG test, 72.2% of patients in subgroup B and 39.4% in subgroup C were defined as GHD. In patients belonging to group B and C and with a peak GH response <19 microg/l to the test, IGF-I levels were lower than 160 microg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients respectively predicting severe GHD in 85.7% of panhypopituitary patients (subgroup A). CONCLUSIONS In late adolescent and early adulthood patients, a GH cut-off limit using the GHRH+ARG test lower than 19.0 microg/l is able to discriminate patients with a suspicion of GHD and does not vary from infancy to early adulthood.

The activation of somatostatinergic receptors by either somatostatin-14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing's disease.

OBJECT Somatostatin (SS) is known to inhibit GH and insulin, while its effect on corticotrope secretion is controversial: inhibition of ACTH secretion by agonists activating somatostatinergic receptors (sst)-2 and sst-5 was reported in vitro. Cortistatin (CST) not only binds all sst receptor subtypes but also possesses central actions that are not shared by SS. DESIGN In nine patients with Cushings disease (CD), ACTH, cortisol, GH, insulin, and glucose levels were studied during 120-min i.v. infusion of SS-14 (2.0 microg/kg per h), CST-17 (2.0 microg/kg per h) or saline. RESULTS Both SS or CST significantly affected the hypothalamic-pituitary-adrenal axis. Cortisol was decreased to the same extent by either SS or CST (P < 0.05). Both SS and CST decreased ACTH, although statistical difference was reached only during CST (P < 0.05). Analyzing the individual responses as areas under curve (AUCs), a clear and consensual inhibition of ACTH and cortisol under either SS or CST was recorded in five out of nine patients. Both SS or CST inhibited (P < 0.05) insulin, that even showed a rebound (P < 0.01) at the end of infusion. GH was not modified by either peptide. CONCLUSION SS and CST often display similar inhibitory effects on the HPA axis in CD. The activation of sst receptors by both peptides is followed in almost 50% of patients by a remarkable inhibition of ACTH and cortisol hypersecretion. These findings reinforce the view that sst receptors are involved in the control of the secretory activity of tumoral corticotropic cells.

Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to snort-term fasting in acromegaly

Starvation exerts critical influence on somatotroph and leptin secretion. Fasting enhances GH levels in normal subjects, but not in GH hyposecretory states, while it always inhibits leptin secretion. We aimed to clarify the GH/IGF-I and metabolic response to short-term fasting in a GH hypersecretory state such as acromegaly. To this goal, in 8 active acromegalic (ACRO) and in 7 normal women (NS) we evaluated mean GH (mGHc), leptin (mLEPc), insulin (mINSc), glucose (mGLUc) concentrations as well as IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and free fatty acid (FFA) levels before and after 36-h fasting. Before fasting, mGHc, IGF-I, mINSc, mGLUc, and FFA levels in ACRO were higher (p<0.01) than in NS. IGFBP-3, IGFBP-1, and mLEPc were similar in ACRO and in NS. Fasting clearly (p<0.02) increased mGHc in NS only. After 36-h fasting, significant IGF-I reduction was recorded in NS only (p<0.03). IGFBP-3 did not change both in ACRO and NS. IGFBP-1 significantly increased (p<0.05) after fasting in both groups but in ACRO were lower (p<0.03) than in NS. Fasting decreased (p<0.03) mLEPc, mGLUc, and mINSc in ACRO as well as in NS; mINSc and mGLUc after fasting in ACRO persisted higher (p<0.005) than in NS. FFA levels were increased by fasting in NS (p<0.02), but not in ACRO. This study shows that GH/IGF-I axis, glucose metabolism, and lypolisis but not leptin display some degree of refractoriness to short-term fasting in acromegaly. The lack of any GH response to fasting in acromegaly would likely reflect neuroendocrine alterations secondary to the GH hypersecretory state. On the other hand, the lack of somatotropic response and the peculiarly blunted metabolic reaction to short-term fasting would partially reflect the delayed adaptation of insulin resistance to starvation.

The GH-releasing effect of acylated ghrelin in normal subjects is refractory to GH acute auto-feedback but is inhibited after short-term GH administration inducing IGF1 increase.

OBJECTIVE GH secretion is regulated by an interplay between GH-releasing hormone (GHRH), somatostatin (SST), and other central and peripheral signals. Acylated ghrelin (AG) amplifies GH pulsatility acting, at least partially, independently from GHRH and SST. The GH response to GHRH is inhibited by recombinant human GH (rhGH), likely due to a SST-mediated negative GH auto-feedback. The effect of exogenous rhGH on the GH-releasing effect of AG has never been tested. DESIGN AND METHODS In six healthy volunteers, we studied the GH response to acute AG administration (1.0 μg/kg i.v.) during saline or rhGH infusion (4.0 μg/kg per h i.v.) or after 4-day rhGH (10.0 μg/kg s.c.) administration. RESULTS Compared with saline, rhGH infusion increased GH levels (P<0.01). During saline, acute i.v. AG induced a marked increase (P<0.01) in GH levels similar to those observed after AG administration during rhGH infusion. During s.c. rhGH, IGF1 levels rose from day 0 to day 5 (P<0.01). After 4-day s.c. rhGH, i.v. AG increased (P<0.01) GH levels, though significantly (P<0.05) less than on day 0. CONCLUSIONS The marked somatotroph-releasing effect of AG is refractory to a direct GH auto-feedback whereas is markedly inhibited after 4-day rhGH administration, suggesting the possibility of a selective IGF1-mediated inhibitory feedback.

Preoperative medical treatment in Cushing’s syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN

BACKGROUND Surgery is the definitive treatment of Cushings syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. OBJECTIVE (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). PATIENTS AND METHODS 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). RESULTS Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. CONCLUSIONS PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.

Long-term follow-up in adrenal incidentalomas: an Italian Multicentre Study

Department of Clinical Sciences and Community Health (V.M., S.P., A.D., M.A., P.B.-P., I.C.), University of Milan, 20122 Milan, Italy; Unit of Endocrinology and Diabetology (V.M., S.P., P.B.-P., I.C.), Fondazione IRCCS Ca Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy; Division of Internal Medicine I (G.R., M.T.), Ospedale San Luigi, 10043 Orbassano, Italy; Department of Biological and Clinical Sciences (G.R., R.G., M.T.), University of Turin, 10124 Turin, Italy; Catholic University (S.D.C., C.P.), Unit of Endocrinology and Metabolism, 00168 Rome, Italy; Unit of Endocrinology (A.S.S., A.S.), Ospedale “Casa Sollievo della Sofferenza,” IRCCS, 71013 San Giovanni Rotondo, Foggia, Italy; Unit of Endocrine Diseases and Diabetology (A.D., M.A.), Ospedale San Giuseppe, Gruppo Multimedica, 20123 Milan, Italy; Department of Biomedical Sciences for Health (M.M., B.A.), University of Milan, Unit of Endocrinology and Diabetology, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Milan, Italy; and Division of Endocrinology, Diabetology, and Metabolism (E.G.), Department of Medical Sciences, University of Turin, 10124 Turin, Italy

Hormone Use and Abuse by Athletes

Hormone use and abuse by athlete , Hormone use and abuse by athlete , کتابخانه دیجیتال جندی شاپور اهواز

Motor Performance and Muscle Mass as a Function of Hormonal Responses to Exercise

Hormones, motoneurons, and skeletal muscle fibers represent the main actors in regulating the motor performance during acute physical exercise. Moreover, muscle growth in response to exercise conditioning is related to direct actions of hormones and autocrine/paracrine factors on skeletal muscle fibers. The aim of this chapter is to illustrate the main interactions that take place between the neuro-endocrine and neuro-muscular systems in response to acute exercise and to review the main hormonal mechanisms that underlie the structural growth and remodeling of skeletal muscle fibers in response to chronic exercise training.

Il trauma cranico e l’emorragia subaracnoidea sono condizioni ad alto rischio di ipopituitarismo: valutazione a 3 mesi dopo danno cerebrale

RiassuntoL’ipopituitarismo acquisito nei soggetti adulti è ovviamente sospettato in pazienti con patologia primitiva della regione ipotalamo-ipofisaria, particolarmente dopo neurochirurgia e/o radioterapia. Il trauma cranio-encefalico è inserito tra le cause di ipopituitarismo. Tuttavia la valutazione neuroendocrina non è inclusa di routine nel monitoraggio di questi pazienti. Scopo di questo studio è quello di chiarire la prevalenza di ipopituitarismo dopo trauma cranico (TBI) o emorragia subaracnoidea (SAH) a 3 mesi dall’evento acuto. A tale scopo sono stati arruolati in uno studio multicentrico 140 soggetti a 3 mesi dall’evento acuto [TBI, n=100, 31 donne, 69 uomini; età: 37,1±1,8 anni; indice di massa corporea (BMI) 23,7±0,4 kg/m2; Glasgow Coma Scale (GCS) 3–15;SAH, n=40, 14 uomini, 26 donne, età: 51,0±2,0 anni; BMI: 25,0±0,6 kg/m2; Fisher’s scale 1–4]. Tutti i pazienti sono stati sottoposti ad un’ampia valutazione ormonale basale; l’asse GH/IGF-I è stato valutato mediante test al GHRH+Arginina e dosaggio dell’IGF-I. Il 25–30% dei pazienti traumatizzati in età adulta presentava gradi diversi di ipopituitarismo. In particolare il 4, 6 ed il 25% dei pazienti presentava un deficit totale, multiplo ed isolato, rispettivamente. Il diabete insipido era presente nel 4%. Ipocorticosolismo, ipotiroidismo ed ipogonadismo secondari erano presenti nell’ 8,5 e 17%, rispettivamente. Il deficit di GH grave (GHD) era il più frequente dei deficit ipofisari (25%). Nel 37,5% dei pazienti con SAH erano presenti gradi diversi di ipopituitarismo. Benché nessun caso di ipopituitarismo totale era presente in questa popolazione, deficit multipli ed isolati erano presenti nel 10 e 27,5%, rispettivamente. Il diabete insipido era presente nel 7,5%. Ipocorticosolismo, ipotiroidismo ed ipogonadismo secondari erano presenti nel 2,5, 7,5 e 12,5%, rispettivamente. Anche in questa popolazione il deficit di GH grave era il più frequente (25%). Il TBI e la SAH sono condizioni associate ad un alto rischio di ipopituitarismo acquisito. L’ipopituitarismo è spesso multiplo ed il deficit di GH grave è quello più frequente. Pertanto una valutazione neuroendocrina è sempre necessaria in pazienti dopo danno cerebrale.