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Management can be difficult and delayed due to their location and extension. Macroprolactinomas are uncommon and can often pursue an aggressive clinical course, including invasion into the nasopharynx. We describe three cases of prolactinomas that initially presented to the ENT Department as nasal polyps. We describe their clinical features and response to treatment. Recurrence of nasal polyps (patient 1) and radiological evidence of a pituitary mass (patients 2 & 3) prompted testing for a prolactinoma. None of the patients had any signs of hyperprolactinaemia. All have significant residual tumour at follow up, despite prolactin levels approaching the normal range on dopaminergic therapy. Pituitary tumours that invade the nasal cavity are rare and clinicians should be aware of their existence. Measurement of serum prolactin and immuno-histochemistry for prolactin secreting cells in intranasal tumours should be considered if there is clinical evidence of hyperprolactinaemia or if there is recurrence of the nasal tumour/polyp. This can expedite a diagnosis and prevent delay of treatment with dopamine agonists. Dopaminergic therapy controls excessive prolactin secretion and results in tumour shrinkage in most patients, but treatment may be complicated by dopamine resistance, extensive tumour necrosis and CSF rhinorrhoea. [ABSTRACT FROM AUTHOR]

A 2 yr old boy presented initially with hypoglycaemia following a 6h fast prior to an elective surgical procedure. Investigations demonstrated low plasma glucose (1.6mmol/l), undetectable serum insulin, elevated beta hydroxybutyrate (5.2mmol/l) and normal lactate. Plasma amino-acid profile was normal. The dorsum of his hands were pigmented, however a synacthen test demonstrated a normal cortisol response. Ketotic hypoglycaemia was diagnosed, and his parents were given dietary advice. At age 11, he was referred to medical genetics with poor coordination, delayed fine motor skills and a dysmorphic appearance. Chromosomal analysis revealed a normal male karyotype, and no specific diagnosis was made. He presented at age 18 to our unit with recurrent hypoglycaemia. A 72h fast was terminated after 10 h as the patient was symptomatic with plasma glucose 1.6mmol/l. A synacthen test demonstrated an absent cortisol response and elevated ACTH level. Serum electrolytes were normal, adrenal autoantibodies were absent and very long chain fatty acids were normal. He was commenced on both glucocorticoid and mineralocorticoid replacement and had no further hypoglycaemic episodes. Later the patient's brother also presented at age 16 with hypoglycaemia when he was unwell with nausea and vomiting. A diagnosis of primary adrenal insufficiency was confirmed - also with normal serum electrolytes and absent adrenal autoantibodies. Further genetic analysis revealed that both brothers were homozygous for the S74I mutation of the MC2 (melanocortin 2) receptor and a diagnosis of Familial Glucocorticoid Deficiency (FGD) was made. This rare autosomal recessive ACTH insensitivity syndrome responds to glucocorticoid replacement alone. [ABSTRACT FROM AUTHOR]

Summary Objective Patients with primary aldosteronism (PA) who are suitable for surgery should undergo adrenal computerised tomography (CT) and adrenal venous sampling (AVS). A retrospective study was performed of 100 patients with PA. We determined the optimal AVS lateralisation ratio for unilateral disease and reviewed adrenalectomy outcomes evaluating which characteristics predicted hypertension cure. Methods AVS was performed in 93 patients. Lateralisation criteria were assessed using ROC curve analysis. The outcome of adrenalectomy was reviewed in 39 patients and predictive factors for cure determined using univariate and multivariate analysis. Results Of previously published criteria, ROC curve analysis found a cortisol corrected aldosterone affected to unaffected (Aldo/Cort A:U) cut-off of 2·0 was the best predictor of adenoma identifying 80·4% of patients. A novel ratio calculated by dividing the affected to unaffected ratio by the unaffected to peripheral ratio [(Aldo/Cort A:U)/(Aldo/Cort U:IVC)] was successful in identifying 87·0% of patients. Cure rate for blood pressure after adrenalectomy was 38·5% with improvement in 59·0%. On univariate analysis, predictors of post-operative hypertension were increased weight, raised creatinine, left ventricular hypertrophy (LVH) and male sex. On multivariate analysis, male sex and higher pre-operative systolic blood pressure were predictive. Conclusions Patients with PA should have CT scanning and AVS. Aldo/Cort A:U >2·0 is the most accurate of previously published ratios in predicting unilateral disease. When patients were carefully selected for surgery, 97% had cure or improvement in blood pressure control. Further confirmatory work is required on a novel ratio which was even more predictive in our series. [ABSTRACT FROM AUTHOR]

Presents information on insulin action and insulin resistance among patients with diabetes. When the insulin radioimmunoassay was developed; Effects of insulin on diabetes; Insight into the syndromes of severe insulin resistance; Reference to the glucose transport effector system; Details on type 2 diabetes mellitus and the insulin resistance syndrome.

A letter to the editor is presented in response to the study presented by P. M. Stewart and B. Allolio on the adrenal vein sampling (AVS) in the subtype differentiation of primary aldosteronism (PA).

Aims KCNJ11-related diabetes is the most common form of permanent neonatal diabetes and has been associated with a spectrum of neurodevelopmental problems. We compared neurodevelopmental outcomes in patients with KCNJ11 mutations and their sibling controls. Methods Through our Monogenic Diabetes Registry (), we evaluated 23 patients with KCNJ11 mutations with ( n = 9) and without ( n = 14) global developmental delay successfully treated with sulfonylurea and 20 healthy sibling controls, using a battery of targeted neuropsychological and behavioural assessments with scaled scores that are comparable across a wide range of ages. Results Patients with KCNJ11-related diabetes without global developmental delay had significant differences compared with sibling controls on a range of assessments including IQ, measures of academic achievement and executive function. KCNJ11 patients with global delay exhibited significant differences in behavioural symptoms with a tendency to avoid social contact and displayed a reduced ability to adapt to new circumstances. Parents reported more immature behaviour, gross mood swings, bizarre thoughts, other unusual and severe behaviours, and there were also significant deficits in all subdomains of daily living skills. Conclusions This series represents the largest and most comprehensive study of neuropsychological and behavioural dysfunction of individuals with KCNJ11 diabetes and is the first to compare outcome with sibling controls. Our data demonstrate the variety of neurodevelopmental problems seen in those with KCNJ11 mutations, even in those without recognized global developmental delays. These data can be used to counsel families and guide structured neurodevelopmental assessments and treatments based on the initial genetic diagnosis in patients with neonatal diabetes. [ABSTRACT FROM AUTHOR]

An association exists between hyperaldosteronism, hypertension and impaired insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action. The aim of this study was to determine the effect of eplerenone on insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either eplerenone 25 mg twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting glucose, or fasting insulin between treatment with eplerenone or doxazosin. The measure of overall insulin sensitivity, exogenous glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg−1 min−1 after eplerenone and 23.3 (3.6) μmol kg−1 min−1 after doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production rates were similar after both treatments (eplerenone 9.4 (0.6) μmol kg−1 min−1 vs doxazosin 10.6 (0.7) μmol kg−1 min−1). There was a trend for lower endogenous glucose production rates during hyperinsulinaemia following eplerenone compared with doxazosin (2.0 (0.8) μmol kg−1 min−1 vs 4.1 (0.9) μmol kg−1 min−1). There was no difference in insulin stimulated peripheral glucose utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) μmol kg−1 min−1 vs 27.0 (3.9) μmol kg−1 min−1). This study gives reassuring evidence of the neutral effect of eplerenone on insulin action in hypertensive, non-diabetic patients. [ABSTRACT FROM AUTHOR]