Endocrine Abstracts

Introduction: Pituitary gigantism is a rare disorder caused by GH-secreting lesions.Aim: We studied gigantism for genetic defects.Methods: We performed genome-wide analyses in 46 patients with gigantism and 248 patients with acromegaly.Results: We detected a novel microduplication at chromosome Xq26.3 in two unrelated kindreds and 13 sporadic cases de novo. All patients had disease onset before five ...

We have recently reported that somatic mutations in the ubiquitin-specific protease 8 (USP8) are present in corticotropinomas of patients with Cushing’s disease and that these mutations reduced the interaction with 14-3-3. Mutant USP8 exhibited higher deubiquitination activity and potentiated EGFR-induced POMC expression (Reincke et al., Nat Genet 2014). To further study the prevalence of these mutations, we have analyzed 134 ACTH-producing corticotropin...

X-linked acro-gigantism (X-LAG) is a rare novel genomic syndrome of pituitary gigantism that has a typical onset within the first year of life in children of normal or even low birth weight. X-LAG patients have a microduplications on chromosome Xq26.3 that includes a gene GPR101, which is highly upregulated in pituitary tumor tissue of affected patients. We performed a study of all 18 known X-LAG syndrome patients currently in the NICHD-University of Liège databa...

Background and Methods: Corticotropin-independent Cushing’s syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol producing adrenal adenomas is not well understood. Therefore, exome sequencing was performed in 10 cortisol-producing adenomas and recurrent mutations in candidate genes were evaluated in additional 171 patients with adrenocortical tumors. In addition, genome-wide copy number analysis was performed in 35 pati...

Aim: To analyse a large series of patients with pituitary gigantism.Materials and methods: We included in this multicentre study 158 patients (129 males) with pituitary adenoma (PA) or hyperplasia and current/previous abnormal, excessively rapid growth velocity for age or a final height greater than 2 SD above normal for their population. Data of patients were systematically recorded in case report forms.Results: The...

IntroductionPrimary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of adrenal Cushing’s syndrome due to bilateral adrenal tumors, is an heterogenous disease with various clinical, hormonal and morphological characteristics. ARMC5 inactivating mutations is the most frequent genetic cause of PBMAH and variants of PDE11A4 have been associated with the disease. In order to better understand the heterogeneity ...

During the last two decades attention has been focused on the role of different neuropeptides in hypothalamic control of feeding behavior. Se-veral hypothalamic peptides that participate in the control of ingestive behavior are produced in neuronal cell bodies of the arcuate nucleus and/or the lateral hypothalamic area. Apart from producing orexigenic or anorexigenic compounds of peptidergic nature, it has recently become apparent that these neurons also produce several classi...

Introduction: In Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH), cortisol secretion may be consecutive to physiological stimuli, through the illegitimate expression of G-protein coupled receptors (GPCR) in adrenocortical cells. The most characterized is the overexpression of GIP receptor (GIPR) leading to food-dependent Cushing syndrome (FDCS) but it has not been associated with the consecutive inactivation of ARMC5 responsible for 25% of PBMAH. This work aimed to ...

Pituitary adenomas and phaeochromocytoma/paragangliomas (PHAEO/PGL) can very rarely occur in the same patient or in the same family. Together, they are not known to be part of any classical endocrine neoplasia syndromes. In some caes the pathogenetic mechanism may be secondary to a PHAEO secreting GHRH leading to somatotroph hyperplasia and clinical acromegaly. However, we suggest several other mechanisms which could lead to the development of pituitary and PHAEO/PGL together:...

Case: A 20 year old female was referred for further evaluation of ovarian function. She has a history of beta thalassemia and bone marrow transplant in 2009 at age 11. Her menarche started in 2008 and she continued having regular periods until shortly after her bone marrow transplant. She was subsequently started on Loestrin oral contraceptive pill. Examination showed a height of 164 cm and weight of 57 kg. She had well developed secondary sexual characteristics. Her OCPs was ...