Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304 (or p.R304 ; NM_003977.3:c.

Recurrence of Phaeochromocytoma and Abdominal Paraganglioma After Initial Surgical Intervention.

Background: Clinical and biochemical follow up after surgery for phaeochromocytoma is essential with long term studies demonstrating recurrence frequencies between 6% and 23%.

Aim: To examine the characteristics and frequency of tumour recurrence in a regional endocrine referral centre, in patients with surgical resection of phaeochromocytoma (P) and abdominal paraganglioma (AP).

Methods: We identified a cohort of 52 consecutive patients who attended our Regional Endocrinology & Diabetes Centre and retrospectively reviewed their clinical, biochemical and radiological data (between 2002 and 2013).

The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.

Aims: Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus.

Methods: Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or atorvastatin 10mg daily followed by the alternate drug in the second period. Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution.

Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation.

Context: Germline AIP mutations usually cause young-onset acromegaly with low penetrance in a subset of familial isolated pituitary adenoma families. We describe our experience with a large family with R304* AIP mutation and discuss some of the diagnostic dilemmas and management issues.

Objective: The aim of the study was to identify and screen mutation carriers in the family.

Outcome of 131I therapy in hyperthyroidism using a 550MBq fixed dose regimen.

Background: Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary.

Aim: To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome.

Effects on insulin action of adding low-dose thiazide to angiotensin-converting enzyme inhibitor in essential hypertension.

Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme (ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients.

Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma.

Objectives: Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts of patients with non-syndromic PPGL and head and neck paraganglioma (HNPGL).

Design: Prospective, observational evaluation of NHS practice.

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study.

Objective: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism.

What is the best approach to suspected cyclical Cushing syndrome? Strategies for managing Cushing's syndrome with variable laboratory data.

Cyclical Cushing's syndrome is a pattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. This syndrome is often associated with fluctuating symptoms and signs. It is now being increasingly recognized.

AIP mutation in pituitary adenomas in the 18th century and today.

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP).

Advances in the genetics of familial renal cancer.

We discuss recent advances in the diagnosis and management of renal cell cancer (RCC) given the enhanced molecular genetics knowledge in this area. A number of hereditary renal cancer syndromes have been described, including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary leiomyomatosis/RCC syndrome, and hereditary papillary renal cancer. Early molecular diagnosis now facilitates the management and prevention of RCC in families.

Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD.

Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal and extraadrenal pheochromocytomas, head and neck paragangliomas (HNPGL), and other tumor types. We report tumor risks in 358 patients with SDHB (n=295) and SDHD (n=63) mutations. Risks of HNPGL and pheochromocytoma in SDHB mutation carriers were 29% and 52%, respectively, at age 60 years and 71% and 29%, respectively, in SDHD mutation carriers.

Genetic aspects of familial thyroid cancer.

Familial thyroid cancer is rare, accounting for <10% of thyroid cancer cases. Activating germline point mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia types 2A, 2B, and familial medullary thyroid cancer (FMTC)-around 3% of thyroid cancer cases. Familial papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) have been identified as a distinct group of familial thyroid cancers.

Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.

Context: The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial.

Objective: Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI.

Data Sources: We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators.

All patients with 'idiopathic' hypopituitarism should be screened for hemochromatosis.

Hypopituitarism usually occurs as the result of a pituitary tumour or as a consequence of its treatment. If, however, pituitary imaging is negative then an alternative diagnosis should be sought. Patients are often diagnosed as having idiopathic hypopituitarism when imaging is normal.

Cyclical Cushing's syndrome: an update.

Purpose Of Review: This article reviews the features of cyclical hypercortisolism. This syndrome was once considered to be very rare but is now being increasingly recognized.

Recent Findings: Either true cycles or the variant of episodic and fluctuating levels of hypercortisolism can lead to considerable clinical dilemmas, which are discussed.

Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus.

Background: Diabetics have a significantly higher percentage of sperm with nuclear DNA (nDNA) fragmentation and increased levels of advanced glycation end products (AGEs), in their testis, epididymis and sperm. As the receptor for AGEs (RAGE) is important to oxidative stress and cell dysfunction, we hypothesise, that it may be involved in sperm nDNA damage.

Methods: Immunohistochemistry was performed to determine the presence of RAGE in the human testis and epididymis.

The PPAR-gamma activator rosiglitazone fails to lower plasma ACTH levels in patients with Nelson's syndrome.

Background: Peroxisomal proliferator-activated receptors (PPAR)- gamma are expressed abundantly in ACTH-secreting pituitary tumours. The PPAR-gamma activator rosiglitazone has been shown to suppress ACTH secretion in human adrenocorticotroph tumour cells in vitro, and prevent and reduce adrenocorticotroph tumour development in mouse models in vivo.

Objective: To evaluate the effect of rosiglitazone in patients with persistently elevated plasma ACTH levels postbilateral adrenalectomy for Cushing's disease.