Endocrine Abstracts

Neuroendocrine tumours (NETs) have an age-adjusted incidence of 1.2-2.1 per 100,000. We have studied 36 such patients with NETs who are being followed up in our multidisciplinary clinic. Of these 36 patients, there are 17 males (median age 71, range 55-88) and 19 females (median age 66, range 36-79). The presenting features were highly variable; only three patients (8.3 percent) presented with the carcinoid syndrome, eight patients (22.2 percent) presented with small bowel obs...

Parathyroid tumours occurring in association with ossifying fibromas of the jaw are the hallmarks of the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is inherited as an autosomal dominant trait. The HPT-JT gene, which is located on chromosome 1q25, consists of 17 exons and encodes a 531 amino acid protein named PARAFIBROMIN (Nature Genetics, in press). The observation of loss of heterozygosity (LOH) involving 1q25 in HPT-JT parathyroid tumours and the detection of i...

Disorders of calcium metabolism may occur as hereditary traits eg. the Multiple Endocrine Neoplasia type 1 (MEN1) or type 2 (MEN2) syndromes, Familial isolated hyperparathyroidism (FIHP), neonatal severe primary hyperparathyroidism (NSHPT), Familial benign hypocalciuric hypercalcaemia (FBHH), the autoimmune poly- endocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and DiGeorge syndromes, isolated hypoparathyroidism and the autosomal dominant hypocalcaemic hypercalciuria (...

The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder that is due to mutations of the dual zinc-finger transcription factor, GATA3. The C-terminal zinc finger (ZF2) is crucial for DNA binding, whilst the N-terminal finger (ZF1) stabilizes the DNA binding by ZF2 and interacts with other multi-type zinc finger proteins, referred to as Friends of GATA (FOG), which modulate GATA3 function. The majority of GATA3 mutations causing HDR ...

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. Over 95% of MEN1 patients will have developed a manifestation of MEN1 by the age of forty years, and in >85% of patients, parathyroid tumours are the first to occur. In a previously reported Men1 knockout mouse model, parathyroid tumours occurred in less than 50% of Men1 heterozygous (Men1+/−...

Pituitary tumours occur in more than 40% of multiple endocrine neoplasia type 1 (MEN1) patients, and these are more aggressive and difficult to treat than those in non-MEN1 patients. Assessments of in vivo proliferation rates will be of importance in evaluating emerging treatments. We have used the uptake of the DNA nucleotide precursor, 5-bromo-2-deoxyuridine (BrdU), to assess proliferation rates of pituitary tumours in our Men1 knockout mouse model, which devel...

Mutations of parafibromin, which is a 531 amino acid protein, are associated with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome. HPT-JT is an autosomal dominant disease that is characterised by the occurrence of parathyroid tumours, which are commonly malignant, and ossifying fibromas of the jaw bones. To date 13 different inactivating germline mutations (3 nonsense, 9 frameshift and one missense altering the initiation codon) of PARAFIBROMIN have been identified in HPT...

Carcinoid tumours are neuroendocrine tumours that may arise as isolated non-familial cancers or in association with multiple endocrine neoplasia type 1 (MEN1), which is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, the anterior pituitary and the pancreatic islets. The molecular mechanisms underlying carcinoid tumourogenesis have not been fully defined and in order to further characterise these, we undertook 2 approaches...

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterised by hypoparathyroidism, adrenocortical failure, and mucocutaneous candidiasis. The gene causing APS1 is the autoimmune regulator (AIRE-1) gene, which maps to 21q22.3 and consists of 14 exons. The AIRE-1 protein, comprising of 545 amino acids, contains two PHD zinc-finger motifs, a proline rich region and four LXXLL motifs, consistent with its role as a transcription factor. Over 25 diff...

GATA3 mutations cause the congenital autosomal dominant Hypoparathyroidism, Deafness and Renal dysplasia (HDR) syndrome. GATA3 belongs to a family of dual zinc-finger transcription factors that recognise the consensus (A/T)GATA(A/G) motif and are involved in vertebrate embryonic development. We investigated a HDR proband for GATA3 abnormalities. Venous blood was obtained after informed consent, as approved by the local ethical committee, and leukocyte DNA extract...