Endocrine Abstracts

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...

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...

Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise various genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. Some of these conditions are associated with hypoparathyroidism and therefore hypocalcaemia. There are no established guidelines on the management and prevention of hypocalcaemia during the transplant period.<p ...

Background: The severe neurodevelopmental phenotype of untreated congenital hypothyroidism exemplifies the critical role of thyroid hormones (TH) in CNS development, acting via thyroid hormone receptor α1 (TRα1) on cortical neurogenesis, cerebellar development and oligodendrocyte differentiation. We have identified the first humans with defective TRα1 and investigated neurocognitive phenotype and CNS abnormalities in this disorder.Methods:...

The pituitary gland, is a small midline organ situated at the base of the brain, that acts as a master regulator of multiple physiological functions: such as growth, puberty, metabolism, stress response, reproduction and lactation. The pituitary gland is composed of three lobes: the anterior and intermediate, which form the anterior pituitary (AP and contains hormone producing cells), and the posterior lobe which constitutes the posterior pituitary (PP contains axonal inputs)....

Introduction: Mutations affecting hypothalamic development in humans have been identified in genes that affect isolated domains of hypothalamic function leading to restricted phenotypes, such as obesity or hypogonadotrophic hypogonadism. We describe the first human cases of diabetes insipidus and combined pituitary hormone deficiency due to a mutation in a gene regulating hypothalamic development.Results: Six affected individuals from a highly consanguin...

Introduction: Loss-of-function mutations in PROK2 and PROKR2 in humans have been associated with Kallmann syndrome (KS), characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that both are critical for GnRH neuronal development.Objective: KS has overlapping phenotypes and genotypes through FGF8 and FGFR1 with congenital hypopituitarism including septo-optic dysplasia (SOD) and thus we aime...

Background: SOX2 is an early developmental transcription factor implicated in pituitary development. It consists of a N-terminal domain, a high mobility group (HMG)-DNA binding domain and a carboxyl-terminal domain. Heterozygous SOX2 mutations have been described in patients with a severe ocular phenotype and hypogonadotrophic hypogonadism (HH) with/without associated abnormalities. In vitro SOX2 interacts with β-catenin, a member of the Wnt signalling pathway, and...

P450 oxidoreductase (POR) transfers electrons to all microsomal P450 enzymes including CYP21A2 and CYP17A1, key enzymes of glucocorticoid and andogen synthesis, respectively. Mutant POR results P450 oxidoreductase deficiency (ORD) manifesting with glucocorticoid deficiency and disordered sex development in both sexes. Neonatal presentation with undervirilisation in boys and virilisation in girls is well described. However, there is a paucity of data on the pubertal phenotype i...