Endocrine Abstracts

Background: Plasma normetanephrine levels are an annual screening tool for detecting paragangliomas in SDHB mutation carriers. Sensitivity is increased when patients are fasting and recumbent prior to phlebotomy, to allow use of age-adjusted reference ranges rather than the 1180 pmol/l upper limit for ambulatory patients of any age. We present our clinic’s results of samples taken after 30 minutes of recumbency to determine if applying age-adjusted ranges...

Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Conventional therapy (calcium and active vitamin D) worsens hypercalciuria, which may result in renal complications. Calcilytics, such as encaleret, are negative allosteric modulators of the calcium-sensing receptor (CaSR). T...

Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR ) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Conventional therapy (calcium and active vitamin D) can exacerbate hypercalciuria, which may result in renal complications. Calcilytics that act as negative allosteric modulators of the calcium-sensing receptor (CaSR), like ...

Autosomal dominant hypocalcemia type 1 (ADH1), caused by pathogenic gain-of-function calcium-sensing receptor gene (CASR ) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Current standard-of-care (SoC) (calcium and active vitamin D) can exacerbate hypercalciuria, which may result in renal complications. Encaleret is an investigational oral calcilytic, functioning as a negative allo...

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

The global prevalence of obesity continues to rise, creating a growing need for new effective medicines. Selective targeting of visceral obesity (fat around the internal organs) would be particularly advantageous because it carries a greater risk for cardiometabolic diseases. The ectonucleotide pyrophosphatase (ENPP) enzyme family participates in several pathological conditions including diabetes (ENPP1, and ENPP2, also known as autotaxin) and vascular dysfunction (ENPP3-4). O...

Case history: Pre pregnancy: A 31-year-old female with no family history of thyroid disease presented with clinical hyperthyroidism and large goitre with bruit. Graves’ Disease was confirmed: TSH <0.01 (0.35–5.0 mU/l), free T4 53.4 (9.0–21.0 pmol/l), TSH Receptor Antibodies (TRAB) >40 (0–1.9 U/l), TPO 32.2 (<6 U/ml). She started on carbimazole (CBZ: 20 mg BD) and propranolol. She then switched to propylthiouracil (PTU: 150 mg BD) at 2 months due...

Background: Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion causing persistent hypoglycaemia. In around 50% of the patients with CHI, the underlying molecular genetic etiology is unknown. Ca2+/calmodulin-dependent protein kinase 2 (CaMKK2) belongs to the Serine/Threonine protein kinase family. Alternative splicing results in multiple transcripts encoding distinct isoforms. We report, for the first time, CaMKK2 mutati...

A 26-year-old Caucasian female presented at 14 weeks gestation with a 6-week history of lethargy, nausea and vomiting during her first pregnancy. Her adjusted Calcium was 4.12 mmol/l and parathyroid hormone (PTH) 26 pmol/l, consistent with possible primary hyperparathyroidism. She was previously well apart from occasional migraines. There was no known history of familial hypercalcaemia or MEN. Other biochemistry results revealed hypokalaemia of 3.2 mmol/l, low vitamin D at 16 ...

We present the case history of a 62 year old male, who was recently diagnosed with sarcoidosis which was confirmed on biopsy of a calf nodule. CT scan revealed pulmonary involvement. Our patient had low vitamin D 12 nmol/l (nr 50–100) and initial adjusted calcium was 2.48 mmol/l (2.13–2.63). DEXA bone density scan revealed osteopenia. He was commenced on loading dose of colecalciferol 40,000 units weekly and received 3 doses. He presented 1 month later with polydipsi...