RESUMO
It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat-to-beat mean arterial pressure, heart rate and efferent post-ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30 min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.
Assuntos
Acromegalia/fisiopatologia , Neurônios Adrenérgicos/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Sistema Nervoso Periférico/fisiopatologia , Adeno-Hipófise/inervação , Sistema Nervoso Simpático/fisiopatologia , Acromegalia/sangue , Acromegalia/etiologia , Acromegalia/metabolismo , Adenoma/fisiopatologia , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/fisiopatologia , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Inibição Neural , Adeno-Hipófise/fisiopatologia , Índice de Gravidade de Doença , Pele/inervação , Pele/fisiopatologia , Transmissão SinápticaRESUMO
BACKGROUND: Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy. OBJECTIVE: The aim of this study was to retrospectively evaluate (years 2004-2007) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected by type 1 diabetes mellitus (T1DM) during pregnancy. METHODS: The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within 8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM were treated with conventional basal-bolus insulin therapy (aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant women were used as controls for fetal and neonatal parameters. Patients were consecutively enrolled. In all women, metabolic status was determined daily by mean glycemic values (2-hour postprandial blood glucose) and glycosylated hemoglobin (HbA1c) values (at 3-month intervals). Fetal measurements (<50th and >90th centiles of the head circumference, abdomen circumference, and femoral length) were evaluated by ultrasound at second and third trimesters. Weight and femoral length were assessed at birth, and neonates were classified according to the fetal growth curve for the Italian population (<10th centile = small for gestational age; and >90th centile = large for gestational age (LGA). RESULTS: A total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included in the study. Of the 30 diabetic pregnant women included in the study, 15 (mean [SD] age, 27.4 [5.2] years; mean pregravidic weight, 59.7 [11.7] kg) maintained their preconception therapy with glargine, and 15 (mean age, 30.1 [2.4] years; mean pregravidic weight, 60.7 [8.7] kg) with NPH. No significant difference was observed between the glargine-treated group and the NPH-treated group with regard to pregravidic hypertension, third-trimester preeclampsia, maternal complications and/or their progression during pregnancy (diabetic retinopathy, micro- or macroalbuminuria) and episodes of mild hypoglycemia, severe hypoglycemia, and ketosis. There were no significant between group differences in insulin requirements (IU/kg of body weight) and glycemic profile, with the exception of better fasting and 2 hours after breakfast glycemic values in the glargine group during the first (P = 0.008 and P < 0.001, respectively) and the second (P = 0.015 and P = 0.016) trimesters, confirmed by the lower HbA1c levels in the first trimester (P = 0.037). The frequency of femoral length <50th centile at both second and third trimesters was 4/15 (26.7%) in the glargine-treated group (P = 0.033 and P = 0.013, respectively, vs control), 3/15 (20.0%) and 1/15 (6.7%), respectively, in the NPH-treated group (both, P = NS vs control), and 2/43 (4.7%) and 1/43 (2.3%), respectively, in the control group. The prevalence of LGA was 7/15 (46.7%) in the glargine group (P < 0.001 vs control), 4/15 (27.6%) in the NPH group (P = 0.033 vs control), and 2/43 (4.7%) in the control group. CONCLUSIONS: Although our retrospective study involved only a small number of participants, no significant difference was found in glycemic control between glargine and NPH treatments. Use of glargine was associated with a significantly higher frequency of femoral length <50th centile. Further larger prospective studies are necessary to assess the safety profile of glargine in T1DM during pregnancy.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Glicemia , Pesos e Medidas Corporais , Estudos de Casos e Controles , Feminino , Fêmur , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Aspart , Insulina Glargina , Insulina Lispro , Insulina Isófana/uso terapêutico , Insulina de Ação Prolongada , Gravidez , Resultado da Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. METHODS: Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. RESULTS: The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). CONCLUSIONS: The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Mutação , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Testes Genéticos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/genética , Linhagem , Sistema de Registros , Avaliação de Sintomas , Adulto JovemRESUMO
Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C-terminal telopeptide of type I collagen (CTx), and urinary cross-linked N-telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the pathophysiology of bone demineralization in this disease. In particular, the contribution of GHD to femoral osteoporosis appears to be likely mediated by locally produced rather than circulating IGF-I.
Assuntos
Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Osteoporose/diagnóstico por imagem , Talassemia/sangue , Absorciometria de Fóton , Adulto , Biomarcadores/sangue , Colágeno Tipo I/sangue , Feminino , Fêmur/diagnóstico por imagem , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/complicações , Peptídeos/sangue , Talassemia/complicações , Talassemia/diagnóstico por imagemRESUMO
A case of hemolytic uremic syndrome is reported in a female patient affected by metastatic breast carcinoma receiving chemotherapy with gemcitabine and docetaxel. Up to now this is the first case that has been reported in the medical literature in patients treated with docetaxel (taxotere)and gemcitabine. The patient developed hemolytic uremic syndrome after the third cycle of chemotherapy. She was treated with diuretics, steroids, antibiotics, antifungal drugs, erythropoietin and fluid replacement. The patient underwest dialysis, and survived the hemolytic uremic syndrome. It was not possible to ascertain if the hemolytic uremic syndrome was related to the chemotheraputic treatment or the cancer itself.