Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumours, is due to mutations of a tumour suppressor gene, MEN1. MEN1 mutations have also been reported to cause familial isolated primary hyperparathyroidism (FIHP). Moreover, 15 identical MEN1 mutations have been reported to cause MEN1 or FIHP in unrelated families; thereby implicating a r...

Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to early onset pituitary adenoma, with a preponderance of somatotrophinomas. Patients harbouring an AIP mutation respond poorly to somatostatin analogue (SSA) treatment. On the other hand, a subset of sporadic somatotrophinomas with no AIP mutations show low AIP protein expression and exhibit a decreased response to SSA treatment as well. microRNAs are small...

Pituitary non-functioning adenomas (NFAs), arising mostly from gonadotroph cells, represent the second most common type of pituitary tumour, after prolactinomas. NFAs are monoclonal in origin, but mutations of genes associated with hereditary pituitary syndromes (e.g. MEN1, AIP, CDKN1B, and PRKAR1A), classic oncogenes or tumour suppressor genes are rarely found. We therefore performed whole-exome sequence analysis to determine the tumourigenic events in pituitary NFAs using DN...

Background: Thyrotropinomas (TSHomas) are traditionally considered a rare albeit important cause of thyrotoxicosis, accounting for ∼1% of all pituitary adenomas. Although early case series reported a preponderance of macroadenomas, emerging evidence suggests microadenomas are being increasingly diagnosed. In addition, the clinical/biochemical phenotype appears to be more variable than previously suspected. We therefore examined the clinical, metabolic, biochemical and ra...

Somatotroph adenomas causing acromegaly are histologically classified into densely and sparsely granulated subtypes and an intermediate, mixed type. Although the different subtypes are not currently taken into account when making decisions about the management of acromegaly, there is growing evidence that the subtypes represent clinically different entities.In a cohort (n=52) of somatostatin-naïve patients with acromegaly, sparsely granulat...

The clinical effectiveness of ablative radioiodine treatment is limited by the ability of the sodium iodide symporter (NIS) to uptake 131I. A significant proportion of well-differentiated thyroid tumours are unable to concentrate sufficient radioiodine for effective therapy, and in other tumour models such as breast, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient. Pituitary tumor-transforming gene-binding factor (PBF/ PTTG...

Mutations of the cell division cycle 73 (CDC73) gene, which encodes the 531 amino acid protein parafibromin, are associated with the Hyperparathyroidism-Jaw Tumour (HPT-JT) syndrome, an autosomal dominant disorder characterised by parathyroid tumours and ossifying jaw fibromas. In addition, ∼75% of women with HPT-JT develop benign and malignant uterine tumours, which include endometrial hyperplasia, adenosarcomas, adenofibromas, and leiomyomas. To explore the role of <em...

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:...