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1.
Aging Clin Exp Res ; 36(1): 38, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345765

RESUMEN

BACKGROUND: Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS: In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS: A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION: This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.


Asunto(s)
Citrato de Calcio , Osteoporosis , Humanos , Femenino , Anciano , Masculino , Citrato de Calcio/efectos adversos , Calcio , Estudios Prospectivos , Osteoporosis/tratamiento farmacológico , Calcio de la Dieta , Suplementos Dietéticos/efectos adversos
2.
Endocr Pract ; 30(1): 11-18, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37805100

RESUMEN

OBJECTIVE: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate-corrected QT interval (QTc). METHODS: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. RESULTS: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. CONCLUSION: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.


Asunto(s)
Síndrome de Cushing , Síndrome de QT Prolongado , Humanos , Estudios Cruzados , Síndrome de Cushing/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electrocardiografía , Voluntarios Sanos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/tratamiento farmacológico , Moxifloxacino , Receptores de Glucocorticoides , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto
3.
Front Endocrinol (Lausanne) ; 12: 634415, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790864

RESUMEN

Traumatic brain injury (TBI)-related hypopituitarism has been recognized as a clinical entity for more than a century, with the first case being reported in 1918. However, during the 20th century hypopituitarism was considered only a rare sequela of TBI. Since 2000 several studies strongly suggest that TBI-mediated pituitary hormones deficiency may be more frequent than previously thought. Growth hormone deficiency (GHD) is the most common abnormality, followed by hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The pathophysiological mechanisms underlying pituitary damage in TBI patients include a primary injury that may lead to the direct trauma of the hypothalamus or pituitary gland; on the other hand, secondary injuries are mainly related to an interplay of a complex and ongoing cascade of specific molecular/biochemical events. The available data describe the importance of GHD after TBI and its influence in promoting neurocognitive and behavioral deficits. The poor outcomes that are seen with long standing GHD in post TBI patients could be improved by GH treatment, but to date literature data on the possible beneficial effects of GH replacement therapy in post-TBI GHD patients are currently scarce and fragmented. More studies are needed to further characterize this clinical syndrome with the purpose of establishing appropriate standards of care. The purpose of this review is to summarize the current state of knowledge about post-traumatic GH deficiency.


Asunto(s)
Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Hormona del Crecimiento/deficiencia , Hormona de Crecimiento Humana/deficiencia , Hipopituitarismo/complicaciones , Hipófisis/metabolismo , Animales , Composición Corporal , Densidad Ósea , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/tratamiento farmacológico , Enfermedades Cardiovasculares/complicaciones , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Hipotálamo/metabolismo , Hipotiroidismo/complicaciones , Factor I del Crecimiento Similar a la Insulina/metabolismo , Calidad de Vida , Factores de Riesgo
4.
Rev Endocr Metab Disord ; 21(3): 411-420, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32418064

RESUMEN

The use of hypnosis can generate hallucinatory phenomena, which ranged from vivid/auditory imagery to fully developed "hallucinations" in selected people. The aim of this pilot trial was investigating the acute effects of a hypnosis-induced hallucinated breakfast (HB) compared to those of a real breakfast (RB) on subjective appetite and appetite-regulating hormones in highly hypnotizable individuals. Eight healthy post-menopausal women were recruited to consume two meals: the HB and the RB in a randomized crossover design. Participants underwent appetite sensations measurements (before meal and each 30-min until 270-min) and blood sample collection (at 0, 20, 60, 90, 180-min). A 3-day food-record was filled after each meal. The adjusted repeated measures ANCOVA did not show any meal×time interactions on subjective appetite postprandially. As expected, significantly higher glucose (p < 0.001), insulin (p < 0.001), and lower free fatty acid (p < 0.001) concentrations were found after the RB, but not following HB. Furthermore, RB significantly increased postprandial levels of glucagon-like-peptide-1 and peptide-YY at 20, 60, 90 and 180-min, whereas acylated-ghrelin and leptin levels did not differ. Postprandial neuropeptide-Y and orexin-A values significantly increased at different time-points after RB, but not following HB, while α-melanocyte-stimulating hormone levels enhanced after HB only. Energy intakes were significantly lower after HB on the test-day only (HB = 1146.6 ± 343.8 vs RB = 1634.7 ± 274.2 kcal/d; p = 0.003). Appetite sensation might be modulated by fully developed meal "hallucination" induced by hypnosis, likely affecting brain-peptides implicated in the appetite regulation. However, further studies are needed to verify these results obtained in a highly selected group of individuals. NCT03934580.


Asunto(s)
Apetito/fisiología , Hormonas/sangre , Hipnosis , Glucemia/metabolismo , Desayuno , Estudios Cruzados , Femenino , Ghrelina/sangre , Péptido 1 Similar al Glucagón/sangre , Alucinaciones/sangre , Humanos , Hipnosis/métodos , Insulina/sangre , Italia , Leptina/sangre , Comidas , Persona de Mediana Edad , Orexinas/sangre , Péptido YY/sangre , Proyectos Piloto , Periodo Posprandial , alfa-MSH/sangre
5.
Pituitary ; 20(6): 692-701, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28887782

RESUMEN

PURPOSE: Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. METHODS: An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. RESULTS: From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. CONCLUSION: The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.


Asunto(s)
Acromegalia/diagnóstico , Programas Informáticos , Humanos
6.
Eur J Endocrinol ; 162(6): 1067-74, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20219855

RESUMEN

CONTEXT: Mineralocorticoid receptors (MRs) in the hippocampus display an important role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, mediating the proactive feedback of glucocorticoids, which maintains the basal HPA activity. The systemic administration of MR antagonists enhances spontaneous and CRH-stimulated ACTH, cortisol, and DHEA secretion, while the effects of chronic treatment with MR antagonists are scanty. Our study was performed in order to clarify this point. DESIGN: ACTH, cortisol, and DHEA levels were studied during the infusion of placebo, canrenoate, a MR antagonist (CAN, 200 mg i.v. bolus at 1600 h followed by 200 mg infused over 4 h), and human CRH (hCRH; 2.0 microg/kg i.v. bolus at 1800 h) before and during the last week of 28-day treatment with CAN (200 mg/day p.o.) in eight young women. RESULTS: Pre-treatment sessions: CAN and hCRH administration increased ACTH, cortisol, and DHEA levels versus placebo (P<0.05). Post-treatment sessions: during placebo infusion, cortisol and DHEA were significantly amplified versus pre-treatment session (P<0.05), while ACTH levels were not modified; CAN infusion, differently from pre-treatment session, was not able to significantly increase ACTH, cortisol, and DHEA levels; ACTH, cortisol, and DHEA responses to hCRH were amplified with respect to pre-treatment session, although statistical significance was obtained for cortisol and DHEA only. CONCLUSIONS: MR blockade by acute CAN administration significantly enhances the HPA activity in the afternoon, during the quiescent phase of the circadian rhythm. At the same period, prolonged treatment with CAN amplifies both spontaneous and CRH-stimulated activities of the HPA axis, while it blunts the HPA responsiveness to a further MR-mediated stimulation.


Asunto(s)
Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Antagonistas de Receptores de Mineralocorticoides , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Receptores de Mineralocorticoides/fisiología , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/fisiología , Hormona Adrenocorticotrópica/metabolismo , Adulto , Análisis de Varianza , Ácido Canrenoico/farmacología , Hormona Liberadora de Corticotropina/farmacología , Deshidroepiandrosterona/metabolismo , Femenino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Hipófisis/efectos de los fármacos , Hipófisis/fisiología , Sistema Hipófiso-Suprarrenal/fisiología
7.
Fertil Steril ; 94(3): 841-9, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19524226

RESUMEN

OBJECTIVE: To determine the effect of the GHRH antagonist JV-1-36 on proliferation and survival of primary ectopic human endometriotic stromal cells (ESCs) and the T HESC cell line. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): 22 women with endometriosis (aged 34.8+/-5.7 years) undergoing therapeutic laparoscopy. INTERVENTION(S): Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV). MAIN OUTCOME MEASURE(S): Expression of GHRH, GHRH receptor (GHRH-R) and GHRH-R splice variant (SV) 1 mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR). The ESC proliferation was assessed by 5-bromo-2-deoxyuridine incorporation, cell survival by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Trypan blue assay. The T HESC survival was evaluated by MTT, cyclic adenosine monophosphate (cAMP) levels by ELISA, extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation by Western blot, and insulin-like growth factor (IGF)-2 mRNA by real-time PCR. RESULT(S): The ESCs and T HESCs, but not normal endometrial tissues, expressed GHRH-R mRNA; SV1 mRNA was determined in normal endometrial tissues, ESCs, and T HESCs; GHRH mRNAwas found in T HESCs; JV-1-36 inhibited ESC proliferation and ESC and T HESC survival. In T HESCs, JV-1-36 reduced cAMP production and ERK1/2 phosphorylation but had no effect on IGF-2 mRNA expression. CONCLUSION(S): The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Coristoma/patología , Endometriosis/patología , Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Células del Estroma/efectos de los fármacos , Enfermedades Uterinas/patología , Adulto , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Coristoma/genética , Coristoma/metabolismo , Evaluación Preclínica de Medicamentos , Endometriosis/genética , Endometriosis/metabolismo , Endometrio , Femenino , Hormona Liberadora de Hormona del Crecimiento/antagonistas & inhibidores , Hormona Liberadora de Hormona del Crecimiento/genética , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Antagonistas de Hormonas/farmacología , Humanos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Neuropéptido/genética , Receptores de Neuropéptido/metabolismo , Receptores de Hormona Reguladora de Hormona Hipofisaria/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/metabolismo , Células del Estroma/metabolismo , Células del Estroma/patología , Células del Estroma/fisiología , Enfermedades Uterinas/genética , Enfermedades Uterinas/metabolismo
8.
Lancet Oncol ; 9(6): 543-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18495537

RESUMEN

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.


Asunto(s)
Galectina 3/análisis , Selección de Paciente , Neoplasias de la Tiroides/química , Nódulo Tiroideo/química , Tiroidectomía , Adulto , Anciano , Biopsia con Aguja Fina , Femenino , Humanos , Inmunohistoquímica , Italia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , Procedimientos Innecesarios
9.
Clin Endocrinol (Oxf) ; 64(3): 260-4, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16487434

RESUMEN

OBJECTIVE: Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. STUDY DESIGN AND METHODS: Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. RESULTS: At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. CONCLUSIONS: This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1 and LDL cholesterol levels as well as an increase in testosterone and E(2) levels. These findings, therefore, suggest that chronic DHEA supplementation would exert antiatherogenic effects, particularly in elderly subjects who display low circulating levels of this hormone.


Asunto(s)
Plaquetas/efectos de los fármacos , GMP Cíclico/sangre , Deshidroepiandrosterona/administración & dosificación , Vasodilatadores/administración & dosificación , Anciano , Aterosclerosis/prevención & control , Biomarcadores/análisis , Análisis Químico de la Sangre/métodos , Plaquetas/metabolismo , Deshidroepiandrosterona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/biosíntesis
10.
Eur J Endocrinol ; 152(4): 589-96, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15817915

RESUMEN

OBJECTIVE: A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 microg/l based on a cohort of subjects with a mean age of 45 years. DESIGN AND METHODS: By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic-pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8 +/- 2.3 years, range 17-25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2 +/- 4.4 years, range 15.1-30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals. RESULTS: Mean peak GH response to ITT was significantly lower in the 26 patients (1.8+/-2.0 microg/l, range 0.1-6.1 microg/l) compared with the 39 controls (18.5 +/- 15.5 microg/l, range 6.1-84.0 microg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 microg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 microg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of -1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I < or = - 2.0 SDS showed a sensitivity of 62%. CONCLUSION: Our data show that the cut-off value of the peak GH response to ITT of less than 3 microg/l or 5 microg/l and of IGF-I of less than -2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic-pituitary abnormalities.


Asunto(s)
Hormona de Crecimiento Humana/deficiencia , Factor I del Crecimiento Similar a la Insulina/análisis , Insulina , Adolescente , Adulto , Envejecimiento , Glucemia/análisis , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Hipotálamo/patología , Imagen por Resonancia Magnética , Masculino , Hipófisis/patología , Hormonas Hipofisarias/deficiencia , Sensibilidad y Especificidad
11.
Endocrinology ; 143(5): 1968-71, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11956180

RESUMEN

Ghrelin is an acylated peptide recently isolated from rat stomach that potently stimulates GH release in vitro and in vivo in rat and man. Ghrelin specifically activates the receptor for the growth hormone secretagogues (GHS-Rla), and it has been proposed as the endogenous ligand mimicked by these synthetic compounds. Very recently, it was shown in cells transfected with the GHS-Rla that short acylated peptides encompassing the first 4-5 residues of ghrelin were capable of increasing intracellular calcium almost as efficiently as the full-length ghrelin. In the present study, we demonstrate that truncated analogs of ghrelin are ineffective in stimulating GH release in neonatal rats and do not displace radiolabelled ghrelin from binding sites in membranes from human hypothalamus and pituitary. In conclusion, our data demonstrate that the ability of short ghrelins to stimulate the GHS-Rla in transfected cells is not predictive of their capability to stimulate GH secretion in vivo.


Asunto(s)
Hormona del Crecimiento/metabolismo , Hormonas Peptídicas , Péptidos/metabolismo , Péptidos/farmacología , Adulto , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Unión Competitiva/efectos de los fármacos , Ghrelina , Humanos , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Masculino , Membranas/efectos de los fármacos , Membranas/metabolismo , Persona de Mediana Edad , Datos de Secuencia Molecular , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Ratas
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