Endocrine Abstracts

Wnt/beta-catenin signalling pathway is required during embryonic development for normal cell proliferation, differentiation and for organ homeostasis in adulthood. Over-activation of this pathway has been implicated in human cancers such as colon or skin cancers. Here, we demonstrate that enhancement of the Wnt pathway in the embryonic Rathke’s pouch causes over-proliferation of progenitor cells and severe differentiation defects in the Pit1-lineage, which results ...

Background and aim: Achondroplasia (ACH) is one of the commonest skeletal dysplasias affecting 1:15 000–1:40 000 live births. The average attained adult height is 131±5.6 cm for men and 124±5.9 cm for women. Previous studies have shown that the use of rhGH may result in transient increase in the growth rate, but there have been no long-term data regarding adult height. We aimed to study a cohort of patients with ACH and other skeletal dysplasias who have been tr...

The superfamily of ~25 human selenoproteins includes antioxidant and oxidoreductase enzymes together with other proteins of unknown function. We describe a child with a multisystem disorder involving deficiencies of several selenoproteins, identified on the basis of abnormal thyroid function.A 3.6-year-old male was referred with elevated free thyroxine (FT4 – 44.4 pmol/l (N 12–22)), low free triiodothyronine (FT3 &#...

Background: SOX2 is a member of the SOX family of transcription factors (SRY-related high-mobility group (HMG) box). Heterozygous, de novo, loss-of-function mutations were initially reported in patients with bilateral anophthalmia/microphthalmia, developmental delay, male genital tract abnormalities, oesophageal atresia and sensorineural hearing loss. We have recently reported a number of SOX2 mutations in patients with anterior pituitary hypoplasia and hy...

Background: The most common cause of death in patients with Multiple Endocrine Neoplasia type 2 is medullary thyroid carcinoma. All patients with MEN2 develop this cancer and Prophylactic Thyroidectomy (PT) is recommended to prevent malignant transformation.Method: This study reviews our experience of treating children identified as carriers of a RET mutation diagnostic of MEN-2A. Data was collected by reviewing patient notes and hospital electronic data...

Background: SOX2 is a member of the SOX family of transcription factors (SRY-related high-mobility group (HMG) box). Heterozygous, de novo, loss-of-function mutations were initially reported in patients with bilateral anophthalmia/microphthalmia, developmental delay, male genital tract abnormalities, oesophageal atresia and sensorineural hearing loss. We have recently reported a number of SOX2 mutations in patients with anterior pituitary hypoplasia and hy...

The paired-like homeodomain transcriptional repressor HESX1 is implicated in forebrain and pituitary embryogenesis. A homozygous mutation (R160C) was identified in two siblings with septo-optic dysplasia (SOD), with consequent loss of DNA-binding. We have now identified a second homozygous mutation (I26T) within the highly conserved engrailed homology domain (eh-1) of HESX1 that is crucial for the repressor function of HESX1. We aimed to investigate the functional consequences...

Somatic activating mutations in BRAF, encoding B-Raf, have been described in tumours and recently craniopharyngiomas. Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include endocrine deficiencies but not craniopharyngiomas. We report three BRAF mutations (two of which are novel) in four children with congenital hypopituitarism. To demonstrate the functional role of the three variants w...

Adamantinomatous craniopharyngiomas (ACPs) are among the most common intracranial tumours in children and they originate from undifferentiated pituitary progenitors. Mutations in the gene encoding for β-catenin (CTNNB1), which lead to the constitutive activation of the Wnt/β-catenin signalling pathway, have been associated with ACP. These tumours can invade adjacent structures, such as the hypothalamus, which makes comp...

Somatic activating mutations in BRAF, encoding B-Raf, have been described in tumours and recently craniopharyngiomas. Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include endocrine deficiencies but not craniopharyngiomas. We report three BRAF mutations (two of which are novel) in four children with congenital hypopituitarism. To demonstrate the functional role of the three variants w...