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PURPOSE: Testosterone therapy represents the cornerstone of gender affirming hormone therapy (GAHT) among t-AFAB (transgender Assigned Female At Birth) people. Minoxidil is a vasodilator drug approved for topical use for the treatment of androgenetic alopecia. The aim of the present study was to evaluate the efficacy of topical minoxidil in enhancing beard growth in a group of t-AFAB people on GAHT. METHODS: Sixteen t-AFAB individuals with an incomplete beard development, on GAHT for at least 6 months, were enrolled. Topical minoxidil was applied to the interested facial areas. Before starting (T0), after 3 (T3) and 6 (T6) months, we evaluated facial hair growth using the Ferriman-Gallwey modified score (FGm). RESULTS: Subjects were 26 (2.7) years old and on GAHT for 18.5 [15-54] months; using a paired match evaluation, a statistically significant facial hair growth was observed over time, in particular at T6 (median upper lip FGm 3.5 [3-4] vs 2 [1-2] at T0 and chin FGm 4 [3.25-4] vs 1 [1-2] at T0; p ≤ 0.002). Comparing the minoxidil group with a control group (n = 16) matched for age and BMI who developed a full-grown beard only with GAHT, a logistic multivariable analysis identified hirsutism before GAHT was independently positively associated with the development of a full beard [OR 15.22 (95% CI 1.46-158.82); p = 0.023]. CONCLUSIONS: This is the first study demonstrating the efficacy of topical minoxidil in enhancing facial hair growth among t-AFAB people on GAHT. Further studies will be necessary to assess whether the obtained improvements will persist after discontinuing the medication.
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BACKGROUND: Patients with non-functioning pituitary adenoma (NFPA) often present with a variety of clinical manifestations and comorbidities, mainly determined by the local mass effect of the tumor and by hypopituitarism. Whether this has an impact on overall mortality, however, is still unclear. METHODS: PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until May 2023 for studies reporting data either about standardized mortality ratios (SMRs) or about predictors of mortality in patients with NFPA. Effect sizes were pooled through a random-effect model. This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, #CRD42023417782). RESULTS: Eleven studies were eligible for inclusion in the systematic review; among these, five studies reported data on SMRs, with a total follow-up time of approximately 130,000 person-years. Patients with NFPA showed an increased mortality risk compared to the general population (SMR = 1.57 [95%CI: 1.20-1.99], p < 0.01). Age and sex appeared to act as effect modifiers, with a trend towards higher SMRs in females (SMR = 1.57 [95%CI: 0.91-2.41], p = 0.10) than in males (SMR = 1.00 [95%CI: 0.89-1.11], p = 0.97), and in patients diagnosed at age 40 years or younger (SMR = 3.19 [95%CI: 2.50-3.97], p < 0.01) compared to those with later onset of the disease (SMR = 1.26 [95%CI: 0.93-1.65], p = 0.13). The trend towards excess mortality was similar in patients with normal (SMR = 1.22 [95%CI: 0.94-1.53], p = 0.13) or deficient (SMR = 1.26 [95%CI: 0.82-1.79], p = 0.27) pituitary function. CONCLUSIONS: Excess mortality is observed in patients with NFPA, regardless of pituitary function, especially in women and in patients with a younger age at diagnosis.
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PURPOSE: The clinical features of adult GH deficiency (GHD) are nonspecific, and its diagnosis is established through GH stimulation testing, which is often complex, expensive, time-consuming and may be associated with adverse side effects. Moreover, diagnosing adult GHD can be challenging due to the influence of age, gender, and body mass index on GH peak at each test. The insulin tolerance test (ITT), GHRH + arginine test, glucagon stimulation test (GST), and, more recently, testing with macimorelin are all recognized as useful in diagnosing adult GHD. To date GST is still little used, but due to the unavailability of the GHRH all over the world and the high cost of macimorelin, in the next future it will probably become the most widely used test when ITT is contraindicated. The aim of the present review is to describe the current knowledge on GST. METHODS: Narrative review. RESULTS: In the last years several studies have suggested some changes in the original GST protocol and have questioned its diagnostic accuracy when the classic GH cut-point of 3 µg/L is used, suggesting to use a lower GH cut-point to improve its sensitivity and specificity in overweight/obese patients and in those with lower pretest GHD probability. CONCLUSION: This document provides an update on the utility of GST, summarizes how to perform the test, shows which cut-points should be used in interpreting the results, and discusses its drawbacks and caveats referring to the most recent studies.
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Glucagon , Hormônio do Crescimento Humano , Humanos , Hormônio do Crescimento Humano/deficiência , AdultoRESUMO
PURPOSE: Cabergoline (CAB) has shown to have benefic effects on the metabolism in different clinical settings but its metabolic role in acromegaly disease has not been studied yet. Aim of our study was to evaluate the impact of CAB on glucose metabolism and weight in patients with acromegaly. METHODS: All patients with acromegaly undergoing continuous treatment with CAB for at least 6 months were retrospectively screened. Exclusion criteria were discontinuation of CAB for more than one month, change of antidiabetic or other therapy for acromegaly, concomitant untreated hormonal deficiency, initiation of pregnancy and/or breastfeeding. All patients were evaluated in terms of biochemical disease control, glucose metabolism and weight at baseline (T0) and after the introduction of CAB therapy at 6 (T6) and 12 months (T12). RESULTS: Twenty-six patients (15 females and 11 males) were evaluated at T0 and T6 and 19 patients (12 females and 7 males) were also evaluated at T12. Insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were significantly lower at T6 and T12 compared to baseline (p < 0.001 for IGF-I, p < 0.05 for PRL) even if no further differences were observed between T12 and T6. Considering the entire cohort, no differences were appreciated regarding the metabolic parameters but a significant reduction in weight and body mass index (BMI) was observed at both T6 (p = 0.009 for weight, p = 0.021 for BMI) and T12 (p = 0.014 for weight, p = 0.017 for BMI) compared to baseline. CONCLUSION: Our results confirm the efficacy of CAB in providing a significant improvement in the biochemical disease control but do not demonstrate a marked benefit on glucose metabolism of acromegaly patients. In such patients, CAB appears to have a rapid effect on weight and BMI, with significant changes noticeable as early as 6 months and persisting for at least 12 months.
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PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. METHODS: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. RESULTS: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role. CONCLUSION: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.
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Glucagonoma , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas , Adulto , Feminino , Humanos , Glucagonoma/genética , Glucagonoma/diagnóstico , Glucagonoma/patologia , Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação , Neoplasias Pancreáticas/genética , Linhagem , Proteínas Proto-Oncogênicas/genéticaRESUMO
PURPOSE: Patients with secondary adrenal insufficiency (SAI) have an increased morbidity and an impaired health-related quality of life (HRQoL), which seems to primarily depend on the sub-optimal replacement of hypoadrenalism with standard glucocorticoid (GC) therapy, and on the inadequate correction of other associated pituitary deficiencies. A dual-release hydrocortisone (DR-HC) formulation has shown to exert positive effects on morbidity and HRQoL, mainly in patients with primary adrenal insufficiency. We assessed the variations of anthropometric and metabolic parameters and HRQoL in patients with SAI after switching from cortisone acetate (CA) or hydrocortisone (HC) to DR-HC. METHODS: Twenty-one patients (17 M, 4 F) treated with CA (n = 16; 25 mg/day twice a day) or HC (n = 5; 20 mg/day three times a day), were evaluated for waist circumference, BMI, fasting glucose, HbA1c, insulin, HOMA-IR index, serum lipids, electrolytes, blood pressure and HRQoL at baseline, at 3, 6 and 12 months after switching from CA/HC to DR-HC. RESULTS: The study showed a significant reduction of waist circumference and BMI (p = 0.04, for both), after 3 and 6months of DR-HC treatment, respectively. No significant changes were observed for fasting glucose, insulin, HOMA-IR index, HbA1c, total cholesterol, triglycerides, LDL cholesterol, electrolytes, and blood pressure. However, HDL cholesterol significantly decreased (p = 0.003). An improvement of AddiQoL total score was observed during DR-HC treatment (p = 0.01), mainly for the category "emotions". No predictors resulted for these changes. CONCLUSION: DR-HC treatment provides some benefits in patients with SAI, reducing central adiposity and improving HRQoL; however, worsening of HDL cholesterol is observed during treatment with DR-HC.
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Insuficiência Adrenal , Hidrocortisona , Humanos , Adiposidade , Hemoglobinas Glicadas , Qualidade de Vida , HDL-Colesterol/metabolismo , Insuficiência Adrenal/induzido quimicamente , Obesidade , Obesidade Abdominal , Insulina , GlucoseRESUMO
BACKGROUND: When evaluating a patient for central adrenal insufficiency (CAI), there is a wide range of morning cortisol values for which no definite conclusion on hypothalamus-pituitary-adrenal (HPA) axis function can be drawn; in these cases, a stimulation test is required. Aim of this study was to develop an integrated model for CAI prediction when morning cortisol is in the grey zone, here defined as 40.0-160.0 µg/L. METHODS: Overall, 119 patients with history of sellar tumour which underwent insulin tolerance test (ITT) for the evaluation of HPA axis were enrolled. Supervised regression techniques were used for model development. RESULTS: An integrated predictive model was developed and internally validated, and showed a significantly better diagnostic performance than morning cortisol alone (AUC 0.811 vs 0.699, p = 0.003). A novel predictive score (CAI-score) was retrieved, on a 5.5-point scale, by considering morning cortisol (0 points if 130.1-160.0 µg/L, 1 point if 100.1-130.0 µg/L, 1.5 points if 70.1-100.0 µg/L, 2.5 points if 40.0-70.0 µg/L), other pituitary deficits (2 points if ≥ 3 deficits), and sex (1 point if male). A diagnostic algorithm integrating CAI-score and ITT was finally proposed, with an overall accuracy of 99%, and the possibility to avoid the execution of stimulation tests in 25% of patients. CONCLUSIONS: This was the first study that proposed an integrated score for the prediction of CAI when morning cortisol is in the grey zone. This score might be helpful to reduce the number of patients who need a stimulation test for the assessment of HPA axis function.
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Insuficiência Adrenal , Hidrocortisona , Humanos , Masculino , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Insuficiência Adrenal/diagnóstico , HipófiseRESUMO
INTRODUCTION: The proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH stimulation tests may be unnecessary to diagnose GH deficiency (GHD) PURPOSE: To re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients' pituitary function as the gold standard for the diagnosis of GHD. METHODS: The GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%. RESULTS: The best GH cut-off was 8.0 µg/l (SE 95%, SP 100%) in lean, 7.0 µg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 µg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 µg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 µg/l (SE 70.0%, SP 97.2%) in obese subjects. CONCLUSIONS: This is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.
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Nanismo Hipofisário , Hormônio do Crescimento Humano , Doenças da Hipófise , Humanos , Índice de Massa Corporal , Sobrepeso/complicações , Hormônio Liberador de Hormônio do Crescimento , ArgininaRESUMO
PURPOSE: Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety. METHODS: A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events. RESULTS: Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits' number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups. CONCLUSION: Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.
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PURPOSE: The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. METHODS: For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. RESULTS: No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p < 0.00001), especially in extracellular fluid (ECF) (16.47 ± 1.65 vs 15.67 ± 1.84, p < 0.001). Salivary cortisol and cortisone tended to increase only the night after placebo administration (p = 0.054 cortisol; p = 0.021 cortisone). CONCLUSION: Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.
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Cortisona , Diclofenaco , Humanos , Feminino , Masculino , Projetos Piloto , Voluntários Saudáveis , Hidrocortisona/urina , Estudos Cross-Over , Solução Salina , SódioRESUMO
BACKGROUND AND AIMS: HIV-associated lipodystrophy syndrome (HALS) contributes to the increased cardiovascular risk connoting people living with HIV (PLHIV). HALS recognition, based on clinical ground, may be inaccurate urging an objective instrumental diagnosis. The aim of this study is to search for the DXA-derived fat mass ratio (FMR) threshold, among those suggested for the diagnosis of HALS, able to identify PLHIV at high cardiovascular risk. METHODS AND RESULTS: In a cross-sectional analysis of 101 PLHIV (age 53 ± 11 years, men 55%) and 101 age- and sex-matched uninfected controls, DXA-derived FMR and anthropometric as well as cardio-metabolic parameters were assessed. PLHIV showed a higher FMR (1.15 ± 0.42 vs 0.95 ± 0.18, p < 0.01) together with a greater cardio-metabolic derangement than controls, in spite of lower BMI (24.3 ± 4.3 vs 26.9 ± 4.0 kg/m2, p < 0.01) and fat mass index (FMI, 6.6 ± 3.0 vs 9.2 ± 3.1 kg/m2, p < 0.01). Particularly, PLHIV with HALS (n = 28), defined as those with a FMR above 1.260 and 1.329 for men and women, respectively, had a greater prevalence of type 2 diabetes mellitus (18% vs 1%), insulin resistance (68% vs 27%), hypertriglyceridemia (50% vs 29%), hypertension (61% vs 30%) and metabolic syndrome (32% vs 10%) than those without HALS (p < 0.05 for all comparisons) and controls. At multivariate analyses, FMR in PLHIV was significantly associated (p < 0.05) with fasting glucose (ß [95%CI] = 0.5, [0.1-0.9]), insulin (44.6, [14.9-74.2]), HOMA-IR (1.6, [0.5-2.7]), triglycerides (1.0, [ 0.2-1.8]) and HDL-cholesterol (-2.1, [-3.9/-0.4]) levels. CONCLUSION: Sex-specific FMR thresholds, proposed for diagnosis of HALS, could represent new indices of cardio-metabolic derangement in PLHIV.
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Diabetes Mellitus Tipo 2 , Síndrome de Lipodistrofia Associada ao HIV , Doenças Metabólicas , Adulto , Composição Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30') from baseline to +120' or +180'. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate. METHODS: Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression. RESULTS: The sampling at 90' was the one in which a GH level < 1 µg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90' and +150' and achieved 95.6% accuracy; the best combination of 3 time-points was +60', +90' and +150' and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60', +90', +120' and +150'. CONCLUSION: A subset of 4 time-points (60' - 90' - 120' - 150') was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.
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Acromegalia , Hormônio do Crescimento Humano , Acromegalia/diagnóstico , Coleta de Amostras Sanguíneas , Estudos de Coortes , Teste de Tolerância a Glucose , Humanos , Fator de Crescimento Insulin-Like IRESUMO
PURPOSE: This study aims to compare the accuracy of mean GH profile (GHP) < 2.5 ng/ml and single fasting GH (SGH) < 1 ng/ml in the evaluation of disease control in acromegaly patients during somatostatin receptor ligands (SRLs) therapy. METHODS: We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated. RESULTS: Median GHP levels (1.2 ng/ml, IQR 0.5-2.3 ng/ml) were lower (p = 0.001) than SGH (1.9 ng/ml, IQR 1.0-3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (p = 0.002) and IGFBP-3 (p = 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver-operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones. CONCLUSIONS: GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.
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Acromegalia , Hormônio do Crescimento Humano , Acromegalia/tratamento farmacológico , Jejum , Hormônio do Crescimento Humano/metabolismo , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Receptores de Somatostatina , Estudos RetrospectivosRESUMO
PURPOSE: Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). METHODS: 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. RESULTS: 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. CONCLUSION: Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.
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Acromegalia/tratamento farmacológico , Receptores de Somatostatina/metabolismo , Acromegalia/sangue , Adulto , Feminino , Cálculos Biliares/sangue , Cálculos Biliares/tratamento farmacológico , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Ácido UrsodesoxicólicoRESUMO
PURPOSE: Hypovitaminosis D has been associated with many cardio-metabolic disorders, although their pathogenetic link still remains unclear. Our aim was to evaluate whether 1-year vitamin D (D) supplementation could improve glycemic control, lipid profile, systolic (SBP) and diastolic (DBP) blood pressure levels and body composition. METHODS: In an open-label randomized-controlled pilot study, thirty poor-controlled (HbA1c > 59 mmol/mol) type 2 diabetic patients (age 71.5 ± 3.2 years, M/F 21/9, BMI 29.8 ± 3.6 kg/m2) with hypovitaminosis D (25OHD 22.0 ± 11.3 nmol/l) were randomized to cholecalciferol supplementation (500 UI/kg p.o. weekly, + D) or observation (- D) for one year. Changes in parameters of glucose, lipid and blood pressure control at 3, 6, 9 and 12 months vs. baseline were assessed. RESULTS: One-year D supplementation restored D status and had a beneficial effect on fasting glucose (FG, mean percentage changes ± SD, - 1.8% ± 23.1 vs. + 18.8% ± 30.0), glycosylated haemoglobin (HbA1c, - 13.7% ± 14.5 vs. - 4.2% ± 14.1), SBP (- 13.4% ± 8.5 vs. - 2.4% ± 12.6) and HDL-cholesterol levels (- 2.1% ± 14.0 vs. - 10.9% ± 12.9; p < 0.05 for all comparisons) in + D vs. - D patients, respectively. In the former, a reduction in HBA1c, SBP and DBP levels, BMI, fat mass index (FMI) and ratio (FMR) was observed after 1 year (p < 0.05 for all comparisons vs. baseline). We noticed a relationship between 1-year mean percentage changes of serum 25OHD and SBP levels (R = - 0.36, p < 0.05). CONCLUSION: One-year cholecalciferol supplementation, able to restore D status, significantly improves FG, HbA1c, SBP and HDL-cholesterol levels in patients with poor-controlled type 2 diabetes mellitus and D deficiency.
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Pressão Sanguínea/efeitos dos fármacos , Colecalciferol , Diabetes Mellitus Tipo 2 , Metabolismo dos Lipídeos/efeitos dos fármacos , Deficiência de Vitamina D , Vitamina D , Idoso , Índice de Massa Corporal , Hormônios e Agentes Reguladores de Cálcio/administração & dosagem , Hormônios e Agentes Reguladores de Cálcio/farmacocinética , Colecalciferol/administração & dosagem , Colecalciferol/farmacocinética , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/metabolismoRESUMO
PURPOSE: Postoperative assessment of acromegaly activity is typically performed at least 3 months after neurosurgery (NS). Few studies have evaluated the use of early postoperative growth hormone (GH) levels as a test to predict short- and long-term remission of acromegaly. Our objective was to evaluate the diagnostic performance of serum random GH on a postoperative day one (D1-rGH) and two (D2-rGH), particularly in predicting long-term disease persistence. MATERIALS AND METHODS: Forty-one subjects with acromegaly who were undergoing NS were enrolled (mean age ± SD 47.4 ± 13.1 years at diagnosis; women 54%; macroadenomas 71%). The final assessment of disease activity was performed one year after NS. ROC curves were used to evaluate the diagnostic performance of D1-rGH and D2-rGH. RESULTS: After a 1-year follow-up, the overall remission rate was 55%. ROC analysis identified an optimal D1-rGH cut-off value of 2.1 ng/mL for diagnosing long-term disease persistence (55.6% SE; 90.9% SP). The cut-off point became 2.5 ng/mL after maximizing specificity for disease persistence (yielding a 100% positive predictive value) and 0.3 ng/mL after maximizing sensitivity for disease remission. The optimal D2-rGH cut-off value was 0.6 ng/mL (81.8% SE; 50% SP); the cut-off point became 2.9 ng/mL after maximizing specificity and 0.1 ng/mL after maximizing sensitivity, with no clinical utility. CONCLUSIONS: D1-rGH could be a highly specific test for the early diagnosis of long-term acromegaly persistence, which is predicted by a value > 2.5 ng/mL with a great degree of certainty. The diagnostic performance of D2-rGH was insufficient. Further research is required to validate these preliminary results prior to modifying the postoperative management of acromegaly.
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Acromegalia , Diagnóstico Precoce , Hormônio do Crescimento Humano/sangue , Efeitos Adversos de Longa Duração/diagnóstico , Procedimentos Neurocirúrgicos/métodos , Cuidados Pós-Operatórios , Acromegalia/sangue , Acromegalia/diagnóstico , Acromegalia/cirurgia , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/normas , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Indução de Remissão/métodos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Bariatric surgery (BS) has been recognized as an effective treatment for most patients with morbid obesity, but a variable range of patients failed to achieve a successful weight-loss. Controversial data are available about predictors of unsuccess. We aimed to retrospectively assess whether clinical baseline characteristics of patients submitted to sleeve gastrectomy (SL) or gastric bypass (GBP) were associated with unsuccessful weight-loss after 12 and 24-month follow-up. METHODS: Three hundred patients who underwent BS from the 1st January 2016, with at least 24-months follow-up, were enrolled. Patients were divided according to their percentage of excess weight-loss (%EWL) either < 50% or ≥ 50% after 12 and 24-month follow-up. RESULTS: None of the patients was lost at follow-up; 56 (18.7%) patients showed a %EWL < 50% at 24 months. Age, neck circumference, obstructive sleep apnea (OSA) were significantly higher, while total cholesterol and %EWL 6-months lower in those with %EWL < 50% at 12-months. Age, neck circumference, male and OSA rates were increased, while %EWL at 6-months lower in patients with %EWL < 50% at 24-months. In a multiple regression model, age (OR = 1.076; 95% CI 1.029-1.125; p = 0.001; OR = 1.066; 1.027-1.107; p < 0.001) and %EWL at 6-months (OR = 0.876; 0.840-0.913; p < 0.001; OR = 0.950; 0.928-0.972; p < 0.001) were associated with %EWL < 50% both at 12- and 24-months, respectively, and neck circumference (OR = 1.142; 1.011-1.289; p = 0.032) with %EWL < 50% at 24-months. CONCLUSION: Older age, larger neck circumference, and %EWL at 6-months were significantly associated with BS unsuccess, showing almost 90% of those patients an unsuccessful weight-loss early after surgery. Further larger studies with longer follow-up are needed to confirm these results.
Assuntos
Gastrectomia , Derivação Gástrica , Obesidade Mórbida , Complicações Pós-Operatórias , Falha de Tratamento , Fatores Etários , Índice de Massa Corporal , Tamanho Corporal , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/etiologia , Redução de PesoRESUMO
INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.
Assuntos
Sintomas Comportamentais/diagnóstico , Transtornos Disruptivos, de Controle do Impulso e da Conduta , Agonistas de Dopamina , Doenças da Hipófise , Sintomas Comportamentais/sangue , Sintomas Comportamentais/etiologia , Cabergolina/administração & dosagem , Cabergolina/efeitos adversos , Estudos Transversais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Feminino , Humanos , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/etiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
PURPOSE: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. METHODS: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. RESULTS: High IGF-I levels (ULN 1.01-1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma. CONCLUSION: The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.
Assuntos
Acromegalia/epidemiologia , Prolactinoma/fisiopatologia , Acromegalia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.