Paulo Augusto Carvalho Miranda

Previous gestational diabetes is independently associated with increased carotid intima-media thickness, similarly to metabolic syndrome - a case control study

BackgroundWomen with previous gestational diabetes mellitus (pGDM) face a higher risk of developing type 2 diabetes and, consequently, a higher cardiovascular risk. This study aimed to compare the carotid intima-media thickness (cIMT) from young women with pGDM to those with metabolic syndrome (MS) and to healthy controls (CG) to verify whether a past history of pGDM could be independently associated with increased cIMT.MethodsThis is a cross-sectional study performed in two academic referral centers. Seventy-nine women with pGDM, 30 women with MS, and 60 CG aged between 18 and 47 years were enrolled. They all underwent physical examination and had blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDLc), and triglycerides determined. The cIMT was measured by ultrasound in several carotid segments. The primary endpoint was cIMT and clinically relevant parameters included as predictors were: age, systolic blood pressure, waist, BMI, total cholesterol, LDLc, triglycerides, fasting glucose, previous history of GDM as a whole group, previous history of GDM without MS, presence of DM, presence of MS, and parity.ResultscIMT was significantly higher in pGDM when compared to CG in all sites of measurements (P < 0.05) except for the right common carotid. The pGDM women showed similar cIMT measurements to MS in all sites of measurements, except for the left carotid bifurcation, where it was significantly higher than MS (P < 0.001). In a multivariate analysis which included classical cardiovascular risk factors and was adjusted for confounders, pGDM was shown to be independently associated with increased composite cIMT (P < 0.01). The pGDM without risk factors further showed similar cIMT to MS (P > 0.05) and an increased cIMT when compared to controls (P < 0.05).ConclusionsPrevious GDM was independently associated with increased composite cIMT in this young population, similarly to those with MS and regardless the presence of established cardiovascular risk factors.

THE BRAZILIAN VERSION OF THE QUALITY OF LIFE ASSESSMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS (QOL-AGHDA) – FOUR- STAGE TRANSLATION AND VALIDATION

OBJECTIVE This study reports on the Brazilian Portuguese adaptation of the QoL-AGHDA (Quality of Life Assessment of Growth Hormone Deficiency in Adults) for use in adult growth hormone deficient (GHD) patients. MATERIALS AND METHODS The translation process adopted the dual panel methodology. The questionnaire was tested through field-test interviews (16 GHD patients). In the final stage, data from 120 GHD patients (81 included in a test-retest analysis) were analyzed for internal consistency, test-retest reliability, convergent validity and validity among known groups. RESULTS The translation panels were successful and the draft version was amended to improve the wording as a result of the field-test interviews. Cronbachs alpha was 0.90 and test-retest reliability 0.88. QoL-AGHDA scores had the expected pattern of association with NHP scale scores and QoL-AGHDA was able to differentiate significantly between patients based on patient-reported general health (p < 0.01) and QoL (p < 0.01). CONCLUSIONS The adaptation of the QoL-AGHDA for a Brazilian population was successful and the adapted questionnaire was shown to be reliable and valid.

Increased tissue kallikrein amidase activity in urine of patients with type 1 diabetes under insulin therapy, and in those with gestational diabetes mellitus not under insulin therapy.

Human tissue kallikrein (hK1) is reduced in hypertension, cardiovascular and renal diseases. There is little information on the participation of hK1 in type 1 diabetes mellitus (DM), type 2 DM, and gestational diabetes mellitus (GDM), respectively. The aim of this study was to evaluate the roles of insulin and hyperglycemia on urinary hK1 activity in type 1 DM and in GDM. Forty-three type 1 DM patients (5-35 years, disease duration ≤ 5years, receiving insulin, HbA(1c)>7.6%) were selected. Forty-three healthy individuals, paired according to gender and age, were used as controls. Thirty GDM patients (18-42 years, between the 24th and 37th week of pregnancy, recently diagnosed, not under insulin therapy) were also selected. Thirty healthy pregnant (18-42years, between the 24th and 37th week of pregnancy) and 30 healthy non-pregnant women (18-42years) were selected as controls. Random midstream urine was used. hK1 amidase activity was estimated with D-Val-Leu-Arg-Nan substrate. Creatinine was determined by Jaffes method. hK1 specific amidase activity was expressed as μM/(minmg creatinine) to correct for differences in urine flow rate. hK1 specific amidase activity was significantly higher in the urine of type 1 DM than in controls, and in the urine of GDM patients than in healthy pregnant women and healthy non-pregnant women, respectively. The data suggest that hyperglycemia, rather than insulin, is involved in the mechanism of increased hK1 specific amidase activity in both type 1 DM and GDM patients, respectively.

Growth hormone-secreting pituitary adenomas From molecular basis to treatment options in acromegaly

Acromegaly is a disease of exaggerated somatic growth and distorted proportion arising from hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although almost never malignant, somatotropinomas may cause significant morbidity and the uncontrolled excess of GH is related to mortality 2 to 4 times higher than the expected rate. Recently, clinicians treating acromegalic patients have been aware of the importance of trying to normalize IGF-1 while GH values may differ depending on assay. Despite the significant efforts made over the last decade, little is known about the genetic causes of somatotropinomas and even less of this knowledge is applied therapeutically. In this review, we attempt to address the genetic and molecular knowledge regarding somatotropinomas and their therapeutic aspects.

Seventy two-hour glucose monitoring profiles in mild gestational diabetes mellitus: differences from healthy pregnancies and influence of diet counseling

OBJECTIVE To study glucose profiles of gestational diabetes (GDM) patients with 72 h of continuous glucose monitoring (CGM) either before (GDM1) or after (GDM2) dietary counseling, comparing them with nondiabetic (NDM) controls. DESIGN AND METHODS We performed CGM on 22 GDM patients; 11 before and 11 after dietary counseling and compared them to 11 healthy controls. Several physiological and clinical characteristics of the glucose profiles were compared across the groups, including comparisons for pooled 24-h measures and hourly median values, summary measures representing glucose exposure (area under the median curves) and variability (amplitude, standard deviation, interquartile range), and time points related to meals. RESULTS Most women (81.8%) in the GDM groups had fasting glucose <95mg/dL, suggesting mild GDM. Variability, glucose levels 1 and 2h after breakfast and dinner, peak values after dinner and glucose levels between breakfast and lunch, were all significantly higher in GDM1 than NDM (P<0.05 for all comparisons). The GDM2 results were similar to NDM in all aforementioned comparisons (P>0.05). Both GDM groups spent more time with glucose levels above 140mg/dL when compared with the NDM group. No differences among the groups were found for: pooled measurements and hourly comparisons, exposure, nocturnal, fasting, between lunch and dinner and before meals, as well as after lunch (P>0.05 for all). CONCLUSION The main differences between the mild GDM1 group and healthy controls were related to glucose variability and excursions above 140mg/dL, while glucose exposure was similar. Glucose levels after breakfast and dinner also discerned the GDM1 group. Dietary counseling was able to keep glucose levels to those of healthy patients.

Recommendations of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism for the diagnosis of Cushing's disease in Brazil.

Although it is a rare condition, the accurate diagnosis and treatment of Cushings disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushings syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushings syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushings disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86.

Angiotensin-converting enzyme inhibition changes the metabolic response to neuroglucopenic stress

Neuroglucopenia induced by 2-deoxy-D-glucose (2DG) activates hypothalamic glucoreceptors leading to increased hepatic glucose production and insulin inhibition. This response is similar to what is observed with intravenous injection of angiotensin II (Ang II). However, the involvement of an angiotensin-converting enzyme inhibitor on neuroglucopenia has not been investigated. The aim of this study was to determine the effects of chronic enalapril treatment on plasma glucose, insulin and lipid levels in response to neuroglucopenia. Male Holtzman rats (120—170 g) were chronically treated with enalapril (10 mg/kg per day) in the drinking water for two weeks. On the day of experiment the animals received an i.v. enalapril final dose one hour before the neuroglucopenic stress by 2DG infusion (500 mg/kg), and blood samples were drawn before and 5, 10, 20, 30 and 60 minutes following infusion. The hyperglycaemic response to 2DG was not significantly changed by enalapril treatment. The enalapril-treated group exhibited a peak of plasma insulin higher than controls. Plasma triglyceride showed a significant increase only in the enalapril group after neuroglucopenic stress (p < 0.05).These data show that chronic enalapril treatment changes insulin and triglyceride responses to neuroglucopenia, suggesting an effect on glucose-induced insulin secretion and the storage of triglycerides.

Histiocitose cutânea não-Langerhans como causa de diabetes insípido central

The histiocytoses are rare diseases caused by alterations in the monocyte-histiocytic series with several clinical findings. Among the cutaneous syndromes of non-Langerhans cells, xanthoma disseminatum is the only disease of this group that has been classically associated to the central diabetes insipidus (CDI). The case reported describes a 30-year-old man that two years after presenting with CDI developed non confluent disseminated cutaneous brown papular lesions throughout the body. The histopathology, immunohistochemistry, and electronic microscopy were compatible with the diagnosis of non-Langerhans histiocytoses, suggesting the diagnosis of juvenile xanthogranuloma. The endocrine-metabolic evaluation did not show other alterations besides CDI in a 10-year follow up. The magnetic resonance of hypophysis showed absence of the pituitary hyperintense sign (bright spot). The radiologic and scinthigraphic evaluation of the bones did not show the presence of osteolytic lesions. This case prints out the importance of skin examination in cases of CDI and its association with cutaneous non-Langerhans histiocytoses in a broader spectrum, rather then restricted to the cases of xanthoma disseminatum.

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

The treatment objectives for a patient with Cushings disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.