Endocrine Abstracts

Olfactory neuroblastoma (ONB) is a rare neuroendocrine tumour arising within the sino-nasal cavity. It occurs world wide, affecting both sexes, all ages and all races with no underlying predilection having yet been identified. ONB exhibits a range of phenotypes from indolent to very aggressive, and up to 5% cases are associated with ectopic hormone secretion. Despite current gold-standard treatment of surgical resection (either endoscopic or craniofacial resection) followed by...

Introduction: Acromegaly is usually not a difficult condition to diagnose if the possibility of this diagnosis has been raised. However, there are a few conditions presenting with some aspects of acromegaly or gigantism but without growth hormone excess. Such cases are described as ‘pseudoacromegaly’ (acromegaloidism).Methods: A female patient was first investigated for GH excess at 10 y for tall stature since infancy (over 97th perc...

Introduction: Chromosome Xq26.3 microduplications have recently been identified, and explained this 11-year-old girl’s marked tall stature. Her severe phenotype illustrates X-linked acrogigantism (X-LAG) and demonstrates therapeutic benefit from growth hormone receptor blockade.Case: A 5.6-year-old girl presented with growth acceleration from 3 years and appearance of secondary dentition, greasy skin and blackheads from age 4. Past medical and famil...

A 31-year-old female was referred to Endocrinology clinic for review of her hypergonadotrophic-hypogonadism. She had cleft palate operation at age 3. At age 15y lack of pubertal signs prompted investigations showing XX genotype, FSH:120 IU/L, LH:32 IU/L and low E2. She was started on cyclo-progynova (elsewhere). She has tall stature, span 2.5 cm longer than height, bifid uvula, arachnodactyly with positive ‘wrist sign’, mild scoliosis, pectus excavatum and reduced mu...

Background: Heterozygote germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) gene play a role in the pathogenesis of pituitary adenoma development in familial isolated pituitary adenoma as well as simplex pituitary adenoma cases. AIP mutation positive patients develop often aggressively growing tumours in early teenage years.Aims: The aim of this study was to perform comparative gene expression analysis of AIP mutation-positive ...

Background: AIP mutations cause sporadic and familial pituitary adenomas, but establishing the pathogenic role of missense AIP variants with unknown significance is difficult. The AIP interaction partner AHR – a xenobiotic-activated transcription factor – regulates transcription of xenobiotic-metabolising enzymes, mediates xenobiotic toxicity, and has been implicated in tumorigenesis.Aim: To describe the effect of AIP...

Background: Heterozygous germline AIP mutations can lead to young-onset invasive GH-secreting adenomas. There are no data available to explain the proliferative and invasive nature of AIP-mutation positive somatotrophinomas.Methods: Cell viability (MTS assay), invasion (single cell fluorescence invasion assay) and migration assays (Boyden chambers) were used to further characterise the phenotype of AIP-silenced GH3 cells. Affymetrix gen...

: AIP mutation-positive familial isolated pituitary adenoma is commonly diagnosed in young patients who have a poor prognosis due to large, treatment-resistant tumours. Microarray analysis carried out on AIP knockdown pituitary (GH3) cells and control cells, identified CDC42 as one of the genes that was up-regulated by loss of AIP protein. This small Rho GTPase activates MAPK signalling, suggesting it may contribute to the proliferative phenotype of AIP knock...

Introduction: Pituitary adenomas (PAs) account for <3% of all paediatric supratentorial tumours. Despite being benign, they can cause significant tumour- and treatment-related neuroendocrine and visual morbidity. Patients may be the index case for syndromes such as multiple endocrine neoplasia type 1 (MEN1).Case report: Patient R was referred at 11.9 years with longstanding headaches and bilateral visual deterioration to the point of near-blindness. ...

Introduction: Heterozygote loss-of-function mutations in AIP (Aryl hydrocarbon receptor interacting protein) predispose to young-onset pituitary adenomas. Homozygote murine knockout model of AIP leads to lethality. While the majority of the 75 published AIP mutations result in truncated or missing proteins, missense mutations are more difficult to characterise and to establish their pathogenic role. We have identified the orthologue of AIP, CG1847, in Drosophila melanogaster. ...