Endocrine Abstracts

Background: Primary adrenal insufficiency (PAI) can be associated with significant morbidity in children of all ages, the most common cause being Congenital Adrenal Hyperplasia (CAH). Several other rare inherited causes of PAI have been identified over the years which lack diagnostic phenotypic or biochemical signs, leaving genetic testing as the only approach to make a definitive diagnosis. Our cohort involves >440 patients who presented with features of PAI – hypogl...

Adrenal insufficiency (AI) is life-threatening and can present alone or in combination with other co-morbidities. Here we describe families with a novel association of AI with porphyria caused by biallelic mutations in protoporphyrinogen oxidase (PPOX) or coproporphyrinogen oxidase (CPOX). The porphyrias are a group of disorders caused by defects in one of eight enzymes within the haem biosynthetic pathway, divided into acute porphyrias, resulting in mainly n...

Introduction: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a rare autosomal recessive disorder characterized by deficiency of cortisol and oftentimes aldosterone, with elevated adrenocorticotropic hormone (ACTH) and steroid precursors that are shunted toward excess androgen production. A phase 2 study of adults with classic 21OHD demonstrated that crinecerfont–an oral, non-steroidal, selective corticotropin-releasing factor type...

Primary adrenal insufficiency (PAI) in children is usually congenital with more than 25 causal genes leading to overlapping phenotypes. A genetic diagnosis is helpful to guide management and genetic counselling but can be challenging in resource limited settings where facilities for antibodies and genetic testing may be unavailable. Studies from Africa are rare but, in Sudan, the most common genetic aetiologies for PAI are congenital adrenal hyperplasia (CAH; mostly CYP21A...

Objectives: The activating mutation (L206R) in PRKACA has been reported in more than 30–50% of cases with cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and gene expression profiling between PRKACA L206R mutant and wild type CPAs.Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA w...

Background: TSH suppression therapy has been associated with hip and vertebral fracture. However, the relationship between TSH suppression and bone mineral density (BMD) remains controversial. The aim of this study was to evaluate the effect of TSH suppression therapy on cortical bone geometry in differentiated thyroid cancer (DTC) patients.Methods: This study included 122 subjects (19 men, 27 premenopausal women, and 75 postmenopausal women) who have be...

Background: Novel pathogenic mechanisms involving replicative and oxidative stress have recently been described in familial glucocorticoid deficiency (FGD); including mutations in NNT. NNT supplies high concentrations of NADPH needed by the glutathione and thioredoxin anti-oxidant systems to detoxify mitochondrial H2O2.Six patients, from a consanguineous Kashmiri family, were diagnosed with glucocorticoid deficiency between...

Investigations of bone disorders which are often inherited have yielded important insights in the molecular mechanisms of bone development, osteoporosis and osteoarthritis. However, these studies have been hampered by the lack of available patients and affected families. To overcome this limitation, we have investigated mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) for hereditary bone disorders. Mice were kept in accordance with national welf...

Cushing’s disease (CD) is very rare in prepubertal children, and remains a challenge to diagnose and manage. We review the diagnostic features and therapeutic outcome of prepubertal (defined as testicular volume <4 ml (M) and breast stage <2 (F)) CD patients treated in a single centre. Fifteen prepubertal patients (median age 9.4 years; range 5.8–13.7) fulfilled standard diagnostic criteria for CD and there was male preponderance (12 M (80%), median age 9.1 y...

BACKGROUD: Parathyroid hormone (PTH) is normally secreted in a circadian rhythm and modulates bone turnover through the differential stimulation of receptor activator for nuclear factor kappa-B ligand (RANKL) and suppression of osteoprotegerin (OPG), both of which are fundamental factors in regulating bone turnover. We have studied the relationship between PTH and OPG over a 24-hour period.METHODS: Hourly peripheral venous blood samples were obtained fro...