Endocrine Abstracts

Background: G3 NETs are a recently recognized entity and although the treatment recommendations largely follow those for grade 1 and 2 NETs, the outcomes of therapy are inferior. Little is known about the optimal therapy sequencing but small studies have suggested a benefit of multikinase inhibitors. Somatostatin analogs, PRRT and chemotherapy have all been reported to have activity but later lines of therapy are needed. In this study, we sought to evaluate the activity of cab...

A 51 year old presented with headaches, fatigue and generalised weakness. She had a background history of hypertension diagnosed one year prior to presentation. Initial laboratory evaluation demonstrated life-threatening hypokalaemia, potassium 0.9mmol/l(R.I. 3.5-5.3). This profound hypokalaemia required ICU admission for replacement of potassium and monitoring. Management of subsequent fluid overload necessitated a brief period of hemofiltration. During the course of evaluati...

Background: Hypothalamic obesity (HO) is an acquired form of severe obesity that can occur following surgical resection of or radiotherapy for brain tumors and is often unresponsive to lifestyle modifications or traditional obesity pharmacotherapies. Here, we report weight- and body composition–related findings from a Phase 2 trial of setmelanotide, a melanocortin-4 receptor agonist, in patients with HO.Methods: A Phase 2, open-label, 16-week trial ...

Background: Hypothalamic injury and impaired melanocortin-4 receptor (MC4R) pathway signaling, often a result of surgery or radiation for a benign tumor, may lead to hypothalamic obesity (HO). After injury, sudden weight gain and appetite changes unresponsive to existing therapies develop. Setmelanotide, an MC4R agonist, is approved for chronic weight management in patients with certain MC4R pathway–associated diseases. We report interim results of a Phase 2 study of setm...

Objective: To report hunger-related results from a Phase 2 trial of setmelanotide in patients with hypothalamic obesity (HO).Methods: A Phase 2, open-label, 16-week trial of setmelanotide in patients aged ≥6 to ≤ 40 years with body mass index (BMI) ≥95th percentile (aged <18 years) or ≥35 kg/m2 (aged ≥18 years) and HO caused by hypothalamic damage secondary to brain tumor, surgical resection, and/or chemothera...

Background : Adrenocortical cancer (ACC) is a very rare but aggressive tumour with annual incidence of 2 cases per million populations. Hypercalcaemia is a commonly encountered paraneoplastic manifestation of certain cancers such as lung, breast, kidney, gynaecological and neuroendocrine tumours but very rare in ACC. So far, there are only two cases of ACC and PTHrP-related hypercalcaemia reported in the literature.Case report: 32-year-old man presented ...

Efficacy of rhGH for treatment of pediatric GH deficiency (PGHD) may depend on several variables at treatment initiation (age, body weight, height velocity (HV), IGF-I SDS, skeletal maturation, GHmax), but may be compromised by poor adherence to required daily injections. Somavaratan is a novel, long-acting rhGH fusion protein that demonstrated clinically meaningful improvements in HV and IGF-I concentration in PGHD patients. Over 200 pre-pubertal GHD subjects have enrolled in...

RANK and RANKL are essential for mammary gland development in mice. We demonstrated that RANK signalling promotes proliferation and impairs mammary epithelial differentiation in mice. RANK and RANKL expression is detected in breast cancer cells. MMTV-RANK acini show hallmarks of transformation in a RANKL dependent manner. After multiple pregnancies MMTV-RANK females spontaneously develop adenocarcinomas, and after DMBA (dimethylbenz(a)anthracene) and MPA (medroxiprogesterone) ...

Aim: To assess the effects of a continuous overnight infusion of two doses of UAG (3&10 μg UAG/kg.hr-1) versus placebo in a double blind cross-over study on AG levels, as well on glucose and insulin response to a standard breakfast meal (SBM) in 8 overweight patients with type 2 diabetes (HbA1c 6.5-7.5%).Methods: During these 3 admissions, in randomized order, all subjects received either placebo, or UAG 3 μg/kg.hr-1 or UAG 10 μg/kg.hr...

Up to 15% of unselected patients with hypertension have evidence of inappropriate aldosterone production, identified by a raised ratio of plasma aldosterone to renin (ARR), suggesting that altered regulation of aldosterone synthesis is a key intermediate phenotype in essential hypertension. We previously described an association between the -344C/T 5'UTR polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with raised ARR; the same genetic variation associa...