Rogerio Silicani Ribeiro

Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment

CONTEXT Persistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis. OBJECTIVE To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. DESIGN Open label, single-arm, prospective trial. PATIENTS Fourteen adult hypogonadal males (testosterone <300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 microg/l; median: 101 microg/l) despite maximal doses of DA. INTERVENTION Clomiphene (50 mg/day orally) for 12 weeks. MEASURES Testosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene. RESULTS Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone >300 ng/dl). Testosterone levels increased from 201+/-22 to 457+/-37 ng/dl, 436+/-52, and 440+/-47 ng/dl at 4, 8, and 12 weeks respectively (0.001<P<0.01). Estradiol increased significantly and peaked at 12 weeks. LH increased from 1.7+/-0.4 to 6.2+/-2.0 IU/l, 4.5+/-0.7, and 4.6+/-0.7 IU/l at 4, 8, and 12 weeks respectively (0.001<P<0.05). FSH levels increased in a similar fashion. Prolactin levels remained unchanged. Erectile function improved (P<0.05) and sperm motility increased (P<0.05) in all six patients with asthenospermia before clomiphene. CONCLUSIONS Clomiphene restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under DA therapy. Recovery of gonadal function by clomiphene is independent of prolactin levels.

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas

OBJECTIVE To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.

Síndrome de Kallmann: uma revisão histórica, clínica e molecular

Kallmann syndrome (KS), the association of hypogonadotropic hypogonadism and anosmia, was described by Maestre de San Juan in 1856 and characterized as a hereditary condition by Franz Josef Kallmann in 1944. Many aspects such as pathogeny, phenotype and genotype in KS were described in the last fifteen years. The knowledge of this condition has grown fast, making it difficult to update. Here we review historical aspects of this condition and its discoverers and describe new findings regarding the embryogenesis of the olfactory bulb and GnRH secreting neuronal tracts that are important for understanding the association of hypogonadism and anosmia. Additionally, we describe the phenotypic and genotypic heterogeneity of KS, including five related genes (KAL-1, FGFR1, PROKR2, PROK2 e NELF), and discuss the function of each codified protein in migration and maturation of the olfactory and GnRH neurons, with data from in vitro and in vivo studies. Finally we describe the clinical phenotype of patients carrying these mutations.ABSTRACT Kallmann Syndrome: a Hystorical, Clinical and Molecular Review.Kallmann syndrome (KS), the association of hypogonadotropic hypogonad-ism and anosmia, was described by Maestre de San Juan in 1856 and charac-terized as a hereditary condition by Franz Josef Kallmann in 1944. Many aspects such as pathogeny, phenotype and genotype in KS were described in the last fifteen years. The knowledge of this condition has grown fast, making it difficult to update. Here we review historical aspects of this condition and its discoverers and describe new findings regarding the embryogenesis of the olfactory bulb and GnRH secreting neuronal tracts that are important for understanding the association of hypogonadism and anosmia. Additionally, we describe the phenotypic and genotypic heterogeneity of KS, including five related genes ( KAL-1 , FGFR1 , PROKR2 , PROK2 e NELF) , and discuss the function of each codified protein in migration and maturation of the olfactory and GnRHneurons, with data from in vitro

Terapia de reposição hormonal no hipopituitarismo

This article brings an updated review of hypopituitarism with emphasis in hormone replacement therapy. The physiological basis of hormone replacement therapy and practical aspects of treating hypopituitary patients were both taken into account to provide a rational strategy for treatment. The review is organized by individual pituitary hormone deficiency and covers epidemiology, etiology, clinical presentation, and diagnosis of hypopituitarism, as well as the most relevant hormone preparations currently available for treating each hormone deficiency. Practical guidelines to hormone dosing, routes of administration, side effects and clinical and laboratory monitoring during the entire lifespan are given for each individual hormone replacement therapy: growth hormone in GH-deficient children and adults, thyroid hormone in central hypothyroidism, glucocorticoid in central hypoadrenalism, vasopressin analogs in diabetes insipidus, sex hormones in man and women from puberty to senescence, and gonadotropins for treating infertility. In addition to the literature review, we took into account our own experience of more than two decades in investigating, diagnosing, and treating hypopituitary patients at the Universidade Federal de Sao Paulo.

A Brazilian Experience with a Diabetes Program for Patient Safety in a Tertiary Hospital

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Under-recording of diabetes on medical record may be associated with adverse in-hospital outcomes

Materials and methods This is a retrospective analysis including 62136 adults (> 18 yrs.) admissions in groups NL (69%), DM (17%), DMNR (5%), and SH (9%), hospitalized between 2010 and 2013. Patients were classified according to five coded discharge diagnoses registered in electronic medical record. The inclusion criteria for DMNR were registration of DM in previous admissions and omission of diagnosis in consecutive readmission. Inclusion criteria were length of stay between 2 and 120 days, availability of capillary glucose (at least one measurement for NL patients and two measurements for DM, DMNR and SH patients). Exclusion criteria were pregnancy. In hospital outcomes included in the retrospective analysis were nosocomial infection, sepsis, intensive care unit admission and death. To compare the proportion of adverse outcomes we perform chi-square test. Results Average age was 54,8 yrs., the proportion of females was 52%. The proportion of hospitalizations with surgical interventions was 44%. The average length of stay among NL, DM, DMNR and SH, were 4,7; 7,3; 13,9 and 17,1 days respectively. The incidence of nosocomial infection were 0,4%; 0,9%; 2,3% and 3,9% and the incidence of sepsis were 1,5%; 4.0%; 13,7% and 16% in NL, DM, DMNR and SH, respectively. The mortality rate were 0,8%, 1,4%, 10,2% and 12,7%, respectively. P values were < 0.05 for every outcome described.

Assessment of inpatient diabetes education throughout a structured questionnaire

Materials and methods From January to May 2015, 92 patients were educated during hospitalization and were included in this pilot study. Since inclusion is ongoing, here we present partial Results. On average, age was 63+17 yrs. and time of diagnosis was 13+2 yrs. and 80 patients were on insulin. The average number of sessions were 2,8 (range 1-8). Previous A1c were available for 62 patients (average: 8,1%) and were above 7% in 46 cases. Patients were evaluated using questionnaire concerning the perceived importance of diabetes care and the knowledge about DM, nutrition, physical activity, glycemic control and medications. For those on insulin, there were additional questions concerning insulin administration and storage, glucose monitoring, response to hypo and hyperglycemia and foot care. For each question, patients scored from 0 (no knowledge) to 10 (full knowledge). After intervention, 64 (66%) were

The reduction of hypoglycemia among inpatients through a multidisciplinary team work using a PDCA approach

Background Hypoglycemia is associated with transient cognitive deficits and can result in cardiac arrhythmia, neurological damage, falls or aspiration. Among critical and noncritical inpatients, hypoglycemia increases the risk of death. Since 2012, we had kept the rate of hypoglycemia (proportion of capillary glucose episodes bellow 60 mg/dL per 100 glucose measurements) well controlled. During the first 3 months of 2014 we were aiming to keep the rate under 0,46%. However, there was an average of 149 episodes/month, which was equivalent to the rate of 0,57%.

Impacto do rastreamento e monitoramento de glicemia capilar na detecção de hiperglicemia e hipoglicemia em pacientes não graves internados

RESUMO Objetivo: Analisar o impacto do rastreamento de hiper e hipoglicemia mensurada por glicemia capilar e da monitorizacao padronizada em pacientes hiperglicemicos internados em unidades nao graves do Hospital Israelita Albert Einstein. Metodos: A glicemia capilar foi mensurada com glucosimetro Precision PCx (Abbott), rastreada com software PrecisionWeb (Abbott). A deteccao de hiper e hipoglicemia no bimestre Maio/Junho foi comparada ao bimestre Marco/Abril de 2009 e ainda quanto a frequencia de diagnosticos relacionados ao diabetes no ano de 2007. Resultados: Houve [...]

Impact of screening and monitoring of capillary blood glucose in the detection of hyperglycemia and hypoglycemia in non-critical inpatients.

OBJECTIVE To evaluate the impact of screening hyper and hypoglycemia measured by capillary glycemia and standard monitorization of hyperglycemic patients hospitalized in regular care units of Hospital Israelita Albert Einstein. METHODS The capillary glycemia was measured by the Precision PCx (Abbott) glucosimeter, using the PrecisionWeb (Abbott) software. The detection of hyper and hypoglycemia during the months of May/June were compared to those of March/April in 2009 and to the frequency of the diagnosis of diabetes in 2007. RESULTS There was an increase in the glycemia screening from 27.7 to 77.5% of hospitalized patients (p < 0.001), of hyperglycemia detection (from 9.3 to 12.2%; p < 0.001) and of hypoglycemia (from 1.5 to 3.3%; p < 0.001) during the months of May/June 2009. According to this action 14 patients for each additional case of hyperglycemia and 26 cases for each case of hypoglycemia were identified. The detection of hyperglycemia was significantly higher (p < 0.001) than the frequency of registered diagnosis related do diabetes in the year of 2007. CONCLUSIONS the adoption of an institutional program of glycemia monitorization improves the detection of hyper and hypoglycemia and glycemia control in hospitalized patients in regular care units.