SFEBES2023 Poster Presentations Neuroendocrinology and Pituitary (74 abstracts)
A first report of pituitary Neuro-Endocrine-Tumour in a young patient with Coffin-Siris syndrome. Is there a link between the ARID1B c.6157dup gene and pituitary tumourigenesis?
James Macfarlane 2 , Nyan Lin 1 , Laura Serban 2 , Devesh Sennik 1 , Jian Ping Jen 2 , Steven Mes 2 , Andrew Dean 2 , Olympia Koulouri 2 , Neil Donelly 2 , Richard Mannion 2 , Mark Gurnell 2 & Eleftheria Panteliou 1
1Princess Alexandra Hospital NHS Trust, Harlow, Essex, United Kingdom. 2Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom
A 19-year-old gentleman, with Coffin-Siris-Syndrome(CSS)(ARID1B:c.6157dup gene-mutation), was referred to our endocrinology clinic, with rapid weight-gain and recent onset of Type-2-Diabetes. He was of short stature, he had central-adiposity, facial plethora, proximal myopathy and gynaecomastia. Endocrine testing revealed ACTH:61ng/l, Cortisol:772nmol/l, Total-Testosterone:2.8nmol/l, FSH:6.3U/l, LH:2.2U/l, Prolactin:87mU/l, IGF-1:61ug/l, TSH:0.18mU/l, T4:10.3 pmol/l, HbA1C:84mmol/mol. Overnight-Dexamethasone-Suppression-Test(ONDST) showed a cortisol of 907nmol/l, a Low-Dose-Dexamethasone-Suppression-Test cortisol was 708nmol/l and 24-h Urine-Free-Cortisol(UFC) was 1383.5nmol/l/24hrs. Pituitary-Magnetic-Resonance-Imaging(MRI) showed a 2.6cm pituitary-macroadenoma with suprasellar-extension, in contact with the optic-chiasm, lack of sphenoid-sinus pneumatisation and dysgenesis of the Corpus-Callosum. Z-score was -4.9 on Dual-Energy-X-ray-Absorptiometry(DEXA) scan. Access to the sella, for transsphenoidal pituitary-surgery, was achieved via drilling though a thick layer of sphenoid-bone, which was complicated by significant haemorrhage and an intra-operative ischaemic-cardiac-event. Post-operatively cortisol-levels were 56 and 60nmol/l, ODST-Cortisol<28nmol/l, 24hr-UFC was 36nmol/l/24hrs and late salivary-cortisol levels were 41.5/1.2(<2.6nmol/l). Pituitary histology showed a corticotroph adenoma/Pituitary-Neuroendocrine-Tumour(PitNET) with some very atypical features[ACTH, Steroidogenic-Factor-1(SF-1) and Neuronal-nuclear-antigen(NeuN) expression and mutant BRAF]. This is the first case to demonstrate Cushing’s disease in a patient with CSS. Endocrine disorders associated with CSS, include pituitary hypoplasia, Growth-Hormone(GH) deficiency, idiopathic short stature, hyperinsulinism, obesity and cryptorchidism. CSS is a rare (200 cases world-wide), autosomal-dominant, usually de-novo, genetic syndrome characterised by intellectual disability, aplasia/hypoplasia of the fifth finger/toe, coarse facial features, and multiple anatomical abnormalities. “AT-Rich-Interactive-Domain-1B”(ARID1B)-gene mutation, the one that our patient had, is the commonest. ARID1B encodes a protein in the “SWItch/Sucrose Non-Fermentable”(SWI/SNF) complex, thought to act as a tumour suppressor. Somatic ARID1B-gene variants are involved in breast cancer, neuroblastoma and diffuse large B-cell lymphoma. In recent years, our knowledge on pituitary tumourigenesis has exponentially expanded(germline/somatic mutations and epigenetic-mechanisms). ARID1B:c.6157dup gene’s potential role in pituitary tumourigenesis remains to be elucidated.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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