Endocrine Abstracts

Background: SGPL1 carries out the final degradative step of the sphingolipid pathway, irreversible cleavage of sphingosine-1-phopshate. SGPL1 deficiency is associated with a pathological accumulation of sphingolipid species and a multi-systemic condition incorporating primary adrenal insufficiency (PAI). Sphingolipid intermediates, ceramide and sphingosine are postulated to act as modulators of the steroidogenic pathway, acting as second messengers altering downstream expressi...

Background: Our Paediatric Diabetes service has a challenging rise in proportion of patients with Type 2 Diabetes Mellitus (T2DM); 8.5% of our current cohort; compared to 3.5% regionally and 2.5% nationally (NPDA 2017–2018).Objectives: Establish a T2DM New Diagnosis Pathway and T2DM clinics aiming to achieve HbA1c < 48 mmol/mol for all new patients at 3 months and a year, with 10% weight loss.Methods: Patients diagnosed wi...

Congenital adrenal hyperplasia (CAH) has an estimated prevalence of one in 10 000–20 000 live births. Patients are described as salt wasting (SW), simple virilising (SV), or non-classical (NC). The CAH genotype is usually compound heterozygous.Aims: To characterise the cohort of CAH patients presenting to a regional centre 1994–2014, to quantify the allelic frequency of CYP21A2 mutations and to examine genotype–phenotype associations.<...

Familial glucocorticoid deficiency (FGD) results from the inability of the adrenal cortex to produce cortisol in response to ACTH stimulation and can be fatal if unrecognised. The disease manifests clinically with increased ACTH and reduced cortisol levels. Our group has recently demonstrated that oxidative stress is implicated in the pathogenesis of this disorder.We previously identified mutations in nicotinamide nucleotide transhydrogenase (NNT) in pat...

Introduction: Loss of function mutations in SGPL1, a key component of sphingolipid metabolism, are associated with accumulation of sphingolipid intermediates giving rise to a multisystemic disease incorporating primary adrenal insufficiency (PAI) and progressive renal and neurological disease. Sphingolipid accumulation is implicated in mitochondrial pathology.Objective: To investigate the impact of SGPL1 deficiency on mitochondrial morphology/ f...

Familial glucocorticoid deficiency (FGD, OMIM#202200) is a rare autosomal recessive disorder characterised by adrenal resistance to the action of ACTH, with isolated glucocorticoid deficiency. Recently, mutations in NNT, encoding the mitochondrial anti-oxidant nicotinamide nucleotide transhydrogenase have been reported to cause FGD.Our index case, from a highly consanguineous Kashmiri family, was diagnosed with adrenal insufficiency during a sep...

Hypobaric hypoxia, an environmental condition arising due to the reduced partial pressure of oxygen on ascent to high altitude, is known to cause memory impairment. The mechanism underlying the cognitive dysfunction has been attributed to oxidative stress, glutamate excitotoxicity and Ca2+ mediated death cascade. Though the role of corticosterone in higher order brain function including cognition has been well documented in restrained stress, social stress and other...

An underlying genetic/endocrine cause for severe hypospadias is found in up to 20% of affected boys as described in the literature, with environmental and epigenetic factors also believed to play a role. We conducted a retrospective analysis of 65 boys with severe hypospadias (penoscrotal, scrotal, perineal) managed by Paediatric Urology at Barts Health NHS Trust, born between January 2010 and 2021 (38% white caucasian, 28% asian, 22% black and 12% other/undefined). Boys with ...

Background: Thyroid hormones are essential for the adequate growth and development of the kidney and also target changes in glomerular and tubular functions and electrolyte and water homeostasis. Hyperthyroidism leads to an increase in glomerular filtration rate (GFR) and renal blood flow with converse effects seen in hypothyroidism. In turn, the kidneys are responsible for the metabolism and elimination of thyroid hormones and thus renal disease can lead to s...

Case: A 43-year-old Caucasian lady presented with an acutely painful, cold left leg to the vascular surgeons. She was being treated for respiratory tract infection in the community. She has been investigated for palpitations 7 years ago with no cause identified and headache 3 years ago with normal CT head. Her peripheral vascular examination was unremarkable, including a normal ankle brachial pressure index. She was admitted for further investigations to rule out an underlying...