Health behaviour changes in partners of women with recent gestational diabetes: a phase IIa trial.

BACKGROUND: We recently demonstrated that a gestational diabetes history in mothers is associated with higher postpartum incident diabetes not only in mothers but also in fathers. In the present study, we examined changes in health behaviours and cardiometabolic profiles in both mothers and partners who participated in a diabetes prevention program within 5 years of a gestational diabetes pregnancy. METHODS: Couples were enrolled into a 13-week program that included 5 half-day group sessions and web/telephone-based support between sessions. It was designed in consultation with patients and previously studied in mothers. We computed mean changes from baseline (95% CI) for physical activity, eating, and sleep measures, and cardiometabolic parameters (fasting and 2-h post glucose load plasma glucose, BMI, blood pressure) in both partners and mothers. RESULTS: Among 59 couples enrolled, 45 partners (76%) and 47 mothers (80%) completed final evaluations. Baseline cardiometabolic measures averaged within normal limits. Similar to mothers, partners increased physical activity (+ 1645 steps/day, 95%CI 730, 2561; accelerometer assessed moderate-to-vigorous physical activity + 36.4 min/week, 95% CI 1.4, 71.4) and sleep duration (+ 0.5 h/night, 95% CI 0.1, 0.9) and reduced the sodium-to-potassium ratio of food intake (- 0.09 95% CI -0.19, - 0.001). No conclusive changes were observed in glucose measures or insulin resistance; in analyses combining mothers and partners, systolic blood pressure decreased (- 2.7 mmHg, 95% CI -4.4, - 1.0). CONCLUSIONS: Partners and mothers demonstrated improved physical activity, sleep, and dietary quality. Baseline cardiometabolic profiles averaged at normal values and there were no changes in glucose or insulin resistance; some blood pressure impact was observed. While strategies need to be developed to attract participants at higher cardiometabolic risk, this study demonstrates that partners of women within 5 years of a gestational diabetes diagnosis can be recruited and do achieve health behaviour change. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02343354 (date of registration: January 22, 2015).

Fertility and Pregnancy in Turner Syndrome.

Turner syndrome (TS) occurs in one in 2500 live female births and is one of the most common chromosomal abnormalities in women. Pregnancies in women with TS, conceived with either autologous or donated oocytes, are considered high risk because of the associated miscarriages and life-threatening cardiovascular complications (aortic dissection, severe hypertension). Therefore, it is imperative to conduct a full preconception evaluation and counselling that includes cardiac assessment with Holter blood pressure monitoring, echocardiography, and thoracic MRI. Abnormal findings, such an aortic dilatation, mandate close monitoring throughout the pregnancy and the immediate postpartum period and could possibly contraindicate pregnancy. When in vitro fertilization using donated oocytes is performed in these women, only a single embryo should be transferred. Women with a Turner mosaic karyotype appear to have a lower risk of obstetrical and cardiovascular complications but should nevertheless undergo the full preconception evaluation. In this article, we offer guidelines on the management of women with TS in the preconception period, during pregnancy, and postpartum.

Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes.

AIMS: Glycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. METHODS: We reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1-5.2 mmol/L, 1 h PG 10.0-10.5 mmol/L, or 2 h PG 8.5-8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. RESULTS: There were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. CONCLUSION: The diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.

Improved Glycemic Control Through the Use of a Telehomecare Program in Patients with Diabetes Treated with Insulin.

Background: With the drastic surge in the prevalence of diabetes, the use of medical resources for management of diabetic patients increased markedly. This study aimed to evaluate the impact of telehomecare (THC) use on clinical efficacy, nursing interventions, and medical visits compared with the standard care in insulin-treated diabetic patients. Materials and Methods: A prospective noninferiority clinical trial was designed. Participants were assigned to either an intervention group provided with a THC system during 3 months or to a control group. Main outcome was the difference in A1c at 3 months compared with baseline. Secondary outcomes were the difference in A1c at 6 months compared with baseline, the number of medical visits during the 6-month period of the study, and nursing interventions during the 3 months on THC. Results: A total of 92 participants completed the study. A significant decrease in A1c levels was observed in the THC group (n = 45) compared with the control group (n = 47) at 3 months (-0.61% vs. -0.06%, respectively, P = 0.048) and at 6 months (-0.37% vs. -0.10%, respectively, P = 0.036). The THC group had an average of 0.6 medical visit compared with 1.0 in the control group (P < 0.001). An increase in nursing interventions (mainly e-mails) was noted in THC group (n = 14.7) compared with control group (n = 1.1). Conclusions: This THC program demonstrates improvement in glycemic control and a decrease in the number of medical visits. However, it is important to consider an additional burden in nursing interventions when implementing a THC program.

Demonstrated Cost-Effectiveness of a Telehomecare Program for Gestational Diabetes Mellitus Management.

Background: Prevalence of gestational diabetes mellitus (GDM) has increased steadily in recent years. Pregnant women with GDM are at risk for obstetrical and neonatal complications and require close multidisciplinary follow-up, which implies a significant use of hospital resources. Methods: A prospective noninferiority and controlled clinical trial was designed. The telehomecare (THCa) initiative is a clinical remote patient management project in women with GDM. The main objective was to evaluate the cost-effectiveness of THCa by assessing the direct costs, including the related reduction in medical visits. Secondary outcomes were to evaluate the impact of THCa on diabetes control, GDM-related complications, and patient satisfaction. Results: A total of 161 women were assigned to either an intervention group provided with a THCa system for transmission and online analysis of capillary glucose data (n = 80) or a control group receiving usual care in the clinic (n = 81). A decrease in medical visits by 56% (P < 0.001) in the THCa group was observed. There was no difference between the two groups in diabetes control or maternal and fetal complications. However, results showed a 10-fold increase in nursing interventions in THCa group (mainly by phone calls and e-mails). Satisfaction with care was high. Direct cost analysis revealed savings of 16% in patients followed by THCa compared with the control group. Conclusion: THCa monitoring significantly decreases medical visits and direct costs in GDM women without compromising pregnancy outcomes, quality of care, or patient satisfaction. THCa was shown to be cost-effective despite placing an additional burden on nursing time.

Obesity and Infertility: A Metabolic Assessment Strategy to Improve Pregnancy Rate.

BACKGROUND: The metabolic global approach is a multidisciplinary intervention for obese women before undergoing assisted reproductive techniques, with the goal of improving fertility and decreasing adverse pregnancy outcomes. The objective of this study was to evaluate the impact of the metabolic global approach on pregnancy rate. METHODS: This retrospective cohort study included 127 women and was conducted at the Centre hospitalier de l'Université de Montréal fertility center. Eligibility included BMI at initial consultation of ≥30 kg/m 2. Fertility treatments were considered when a weight loss of minimum 5% and normal metabolic indices were achieved. The p<0.05 was considered statistically significant. RESULTS: Median baseline and last clinical assessment BMIs were 38.2 kg/m 2 and 35.8 kg/m 2 respectively (p<0.001), representing a median weight loss of 5.1%. At baseline, at least one metabolic parameter was abnormal in 66% of women. Total pregnancy rate was 53%. The majority of women (63%) who achieved pregnancy did so with weight loss and metabolic stabilization alone (11%) or combined with metformin (36%) and/or oral ovulation drugs (16%). Normal vitamin D (p<0.001) and triglyceride levels (p<0.05) as well as lower BMI after weight loss (p<0.05) were associated with an increased relative risk of pregnancy. CONCLUSION: Replete vitamin D status, weight loss of 5% and lower BMI as well as normal triglyceride level are significant and independent predictors of pregnancy in obese women presenting to our fertility center. The metabolic global approach is an effective program to detect metabolic abnormalities and improve obese women's pregnancy rate.

Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment.

Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with the classic triad of headache, palpitations and generalized sweating. Although not described as a typical symptom of pheochromocytoma, anxiety is the fourth most common symptom reported by patients suffering of pheochromocytoma. We report the case of a 64 year old man who had severe anxiety and panic disorder as presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up, the patient was diagnosed with malignant pheochromocytoma. After surgical resection of his pheochromocytoma and his hepatic metastases, the major panic attacks completely disappeared, the anxiety symptoms improved significantly and the psychiatric medications were stopped except for a very low maintenance dose of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2 others cases of apparently benign tumors with severe anxiety that resolved after pheochromocytoma resection. These cases highlight that pheochromocytoma should be included in the differential diagnosis of refractory anxiety disorder. LEARNING POINTS: Anxiety and panic disorder may be the main presenting symptoms of pheochromocytoma.The diagnosis of pheochromocytoma should be excluded in cases of long-term panic disorder refractory to medications since the anxiety may be secondary to a catecholamine-secreting tumor.Surgical treatment of pheochromocytoma leads to significant improvement of anxiety disorders.

Are There Benefits for Gestational Diabetes Mellitus in Treating Lower Levels of Hyperglycemia Than Standard Recommendations?

OBJECTIVES: The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosis of gestational diabetes mellitus (GDM) are generating discussion regarding their universal adoption. Our centre is currently using stricter GDM diagnostic criteria than those proposed by the IADPSG. Evaluation of complication rates and their predictors in our cohort may provide insight for the care of this high-risk population. Therefore, we determined complication rates and identified antepartum maternal predictors of adverse outcomes in our cohort with mild GDM. METHODS: A retrospective cohort study was performed between 2005 and 2011. It included women with and without GDM, which was diagnosed if fasting plasma glucose levels were 5.0 or above or 2-hour post 75 gram oral glucose tolerance test (OGTT) were 7.8 mmol/L or higher. RESULTS: A total of 3712 women, with and without diabetes, were included. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM but were lower than the rates usually reported. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included prepregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found. CONCLUSIONS: This study provides insight into GDM-related complications rates and the benefits of intervention in a large cohort of women with levels of hyperglycemia lower than those currently recommended for diagnosis of GDM. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment.

Pituitary apoplexy in pregnancy: A case series and literature review.

BACKGROUND: Severe headache during pregnancy is a challenging condition that may rarely imply endocrine disturbances. Rapid recognition of pituitary apoplexy is needed to improve pregnancy outcome. OBJECTIVE: To review and compare maternal and fetal outcomes after pituitary apoplexy. METHODS: Four cases of pituitary apoplexy during pregnancy in our centre are reported and literature review covering the past 54 years was performed. RESULTS: In the four cases presented and the 33 reported in the literature, most women presented with severe headaches and systemic symptoms. Overall, 42% were treated surgically, 31% received bromocriptine or cabergoline and 61% were given hormone replacement. No major obstetrical complication was reported and all babies were healthy. CONCLUSION: Pituitary apoplexy is a rare cause of sudden and severe headache during pregnancy. Rapid identification of this condition with potentially associated endocrine disturbances is important to ensure maternal and fetal well-being. A multidisciplinary team approach seems to reduce morbidity and mortality.

Transition from pediatric to adult healthcare: assessment of specific needs of patients with chronic endocrine conditions.

BACKGROUND/AIM: Transition from pediatric to adult care is a challenging turning point. The aim was to evaluate the transition process and needs expressed by patients with chronic endocrine conditions at transition in order to ensure program optimization. METHODS: Prospective assessment of the transition period was conducted through completion of standardized questionnaires given to targeted patients. Two types were created: (1) a general questionnaire (GQ) addressing universal aspects of transition, and (2) a specific questionnaire (SQ) exploring concerns related to each endocrine condition. Three endocrinopathies (congenital adrenal hyperplasia, hypogonadotropic hypogonadism and growth hormone deficiency) were selected for assessment since they present specific challenges requiring characterization. RESULTS: Over the last decade, 244 patients in transition were registered in our department and 153 were included since they presented one of the endocrinopathies selected. A total of 73 subjects completed both the GQ and the SQ. Over 80% of the patients were satisfied with the transition process in terms of organization, accessibility and medical care. The actual age of transition corresponded for most to the age considered by patients as ideal for transition. SQs identified psychosexual issues that must be addressed more systematically. CONCLUSION: This study identified key elements allowing the creation of an improved transition program tailored for our center and for each endocrine condition studied.

Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients.

CONTEXT: Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE: The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS: Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS: A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS: Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor.

Cabergoline monotherapy in the long-term treatment of Cushing's disease.

BACKGROUND: Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D(2) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD). OBJECTIVE: To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD. METHODS: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1-3 months interval; partial response was defined as a decrease of UFC to <125% of the upper limit of normal, and treatment failure as UFC ≥ 125% of it. RESULTS: Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 patients (13.3%). After long-term therapy, nine patients (30%) remain with a complete response after a mean of 37 months (range from 12 to 60 months) with a mean dose of 2.1 mg/week of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one patient transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in four initial partial responders. CONCLUSIONS: Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.

Regulation of aldosterone secretion by several aberrant receptors including for glucose-dependent insulinotropic peptide in a patient with an aldosteronoma.

CONTEXT: Primary adrenal Cushing's syndrome can result from the aberrant adrenal expression of several hormone receptors; this mechanism has not been explored in detail in aldosterone-producing tumors. OBJECTIVE: The objective of the study was to evaluate a 56-yr-old male patient with an aldosteronoma for the regulation of aldosterone secretion by aberrant hormone receptors. RESULTS: Renin-independent stimulation of aldosterone secretion was observed in vivo after a mixed meal, oral glucose, or administration of glucose-dependent insulinotropic peptide (GIP), vasopressin, and tegaserod. The mixed meal-mediated stimulation of aldosterone was not present in five other cases of aldosteronoma. A smaller response of aldosterone after GIP infusion was observed in a normal subject. Aldosterone secretion was stimulated by GIP in primary cultures of this patient's aldosteronoma. Increased expression of GIP receptor was found in this aldosteronoma by real-time RT-PCR and immunohistochemistry. The GIP receptor protein was also found at lower levels in zona glomerulosa cells of the normal adjacent adrenal gland. Increased expression of serotonin 4 and ACTH receptors was also present in this aldosteronoma. CONCLUSIONS: This case report provides new evidence of the implication of aberrant hormone receptors in the regulation of this aldosteronoma and suggests that further detailed studies of the role of aberrant hormone receptors in this frequent pathology should be undertaken.

Who should benefit from the use of alpha-glucosidase inhibitors?

Although most commonly used drugs such as biguanides, sulfonylureas, and more recently, thiazolidinediones, are effective in controlling fasting hyperglycemia, a high percentage of patients have sustained elevated hemoglobin A(1c) because of persistent elevation of postprandial plasma glucose (PPPG). alpha-Glucosidase inhibitors (AGIs) specifically target PPPG. AGIs have been shown in several randomized controlled trials to be effective in controlling blood glucose, whether they are used as monotherapy or in combination with other antidiabetic medications. Among the AGIs, acarbose has also been shown to decrease the risk of progressing to diabetes in subjects with impaired glucose tolerance (IGT). Studies have also suggested that acarbose could decrease the risk of cardiovascular disease, both in IGT and in diabetes. Furthermore, AGIs are very safe and are nontoxic drugs. Their only side effects are gastrointestinal, such as flatulence and diarrhea; however, these can be minimized by the "start low, go slow" approach. AGIs should be considered whenever postprandial hyperglycemia is the dominant metabolic abnormality.