Endocrine Society Hypercalcemia of Malignancy Guidelines.

This guideline synopsis summarizes the Endocrine Society guidelines for hypercalcemia of malignancy in adults.

Denosumab Discontinuation in Patients Treated for Low Bone Density and Osteoporosis.

Denosumab (DMAB) is a potent antiresorptive treatment used for treatment of osteoporosis and low bone mineral density (BMD) in those at high risk for fracture. In postmenopausal women with osteoporosis, DMAB treatment for 10 years has been studied, with results showing continued gains in BMD, sustained fracture risk reduction, and low risk of adverse events. However, upon discontinuation of DMAB, there is a rapid reversal of effect, with increase in bone turnover, loss of BMD, and in a subset of patients, a greater risk for multiple vertebral fractures.

Updates in Gestational Diabetes Prevalence, Treatment, and Health Policy.

PURPOSE OF REVIEW: Gestational diabetes (GDM) is associated with adverse pregnancy and neonatal outcomes and increased maternal risk for subsequent type 2 diabetes. The best diagnostic strategy for GDM is debated and the role of oral antidiabetic medications (OAD) for treatment is unclear. In this paper, we review methods of GDM diagnosis, updates in GDM therapy, and interventions to reduce future type 2 diabetes in women with a history of GDM. RECENT FINDINGS: A "one-step" screening protocol for GDM using 75-g, 2-h oral glucose tolerance testing at 24-28 weeks gestation is recommended by the International Association of the Diabetes and Pregnancy Study Groups, the American Diabetes Association, and the Endocrine Society. This strategy identifies a milder degree of hyperglycemia and thus increases GDM prevalence. Studies indicate that in these cases of mild hyperglycemia, treatment decreases pregnancy and neonatal complications. Insulin analogues including detemir, aspart, and lispro have been shown to be safe in pregnancy with a pregnancy category B classification. Growing literature suggests that sulfonylureas cross the placenta and are associated with increased incidence of macrosomia and neonatal hypoglycemia. Telephone or online diabetes prevention program (DPP)-based interventions for women with GDM have shown encouraging results in pilot studies. Insurance coverage remains a barrier. Additional studies are needed to determine the safety of OAD in pregnancy. Public policy supporting DPP could help improve patient access to these proven interventions.

Management and pregnancy outcomes of women with GCK-MODY enrolled in the US Monogenic Diabetes Registry.

AIMS: GCK-MODY is characterized by mild hyperglycemia. Treatment is not required outside of pregnancy. During pregnancy, insulin treatment is recommended if second trimester fetal ultrasound monitoring shows macrosomia, suggesting the fetus has not inherited the GCK gene. There are limited data about GCK-MODY management in pregnancy. The aim of this study was to examine clinical management and pregnancy outcomes amongst women with a known diagnosis of GCK-MODY. METHODS: In this observational, cross-sectional study, a survey was distributed via Redcap to women ≥ 18 years enrolled in the University of Chicago Monogenic Diabetes Registry (n = 94). All or part of the survey was completed by 54 women (128 pregnancies). RESULTS: There were 78 term births (61%), 15 pre-term births (12%), and 24 miscarriages (19%). Of the 39 pregnancies where insulin was given, 22 (56%) had occasional or frequent hypoglycemia including 9 with severe hypoglycemia. Average birth weight for full-term GCK-affected infants was significantly less in cases of maternal insulin treatment versus no treatment (2967 and 3725 g, p = 0.005). For GCK-unaffected infants, conclusions are limited by small sample size but large for gestational age (LGA) was common with maternal insulin treatment (56%) and no treatment (33%), p = 0.590. CONCLUSIONS: The observed miscarriage rate was comparable to the background US population rate (15-20%). Patients treated with insulin experienced a 23% incidence of severe hypoglycemia and lower birth weights were observed in the insulin-treated, GCK-affected neonates. These data support published guidelines of no treatment if the fetus is suspected to have inherited GCK-MODY and highlight the importance of additional studies to determine optimal pregnancy management for GCK-MODY, particularly among unaffected fetuses.

Clinical Management of Women with Monogenic Diabetes During Pregnancy.

PURPOSE OF REVIEW: Monogenic diabetes accounts for 1-2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for KATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management. Here, we discuss the key issues in pregnancy affected by monogenic diabetes. RECENT FINDINGS: General recommendations for pregnancy affected by GCK-MODY determine need for maternal insulin treatment based on fetal mutation status. However, a recent study suggests macrosomia and miscarriage rates may be increased with this strategy. Recent demonstration of transplacental transfer of sulfonylureas also raises questions as to when insulin should be initiated in sulfonylurea-responsive forms of monogenic diabetes. Pregnancy represents a challenge in management of monogenic diabetes, where factors of maternal glycemic control, fetal mutation status, and transplacental transfer of medication must all be taken into consideration. Guidelines for pregnancy affected by monogenic diabetes will benefit from large, prospective studies to better define the need for and timing of initiation of insulin treatment.