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Primary aldosteronism (PA) is the most common endocrine cause of arterial hypertension. Despite the increasing incidence of hypertension worldwide, the true prevalence of PA in hypertension was only recently recognized. The objective of the work was to estimate the prevalence of PA in patients at different stages of hypertension based on a newly developed screening-diagnostic overnight test. This is a prospective study with hypertensive patients (n=265) at stage I (n=100), II (n=88), and III (n=77) of hypertension. A group of 103 patients with essential hypertension without PA was used as controls. PA diagnosis was based on a combined screening-diagnostic overnight test, the Dexamethasone-Captopril-Valsartan Test (DCVT) that evaluates aldosterone secretion after pharmaceutical blockade of angiotensin-II and adrenocorticotropic hormone. DCVT was performed in all participants independently of the basal aldosterone to renin ratio (ARR). The calculated upper normal limits for post-DCVT aldosterone levels [3 ng/dl (85 pmol/l)] and post-DCVT ARR [0.32 ng/dl/μU/ml (9 pmol/IU)] from controls, were applied together to establish PA diagnosis. Using these criteria PA was confirmed in 80 of 265 (30%) hypertensives. The prevalence of PA was: 21% (21/100) in stage I, 33% (29/88) in stage II, and 39% (30/77) in stage III. Serum K+ levels were negatively correlated and urinary K+ was positively correlated in PA patients with post-DCVT ARR (r=–0.349, p

Neuroendocrine neoplasms (NENs) are rare tumours that arise mainly in the gastrointestinal or pulmonary system. Most NENs are well-differentiated and may obtain prolonged survival besides the presence of metastatic disease; however, a subset (poorly differentiated NENs) may display a truly aggressive behaviour exhibiting a poor prognosis. The recently developed classification systems along with advances in functional imaging have helped stratify patients to the administration of appropriate therapeutic options. Surgery is the mainstay of treatment of NENs, but in recent decades there has been a considerable evolution of medical treatments that are used for locally advanced or metastatic disease not amenable to surgical resection. Long acting somatostatin analogues are the main therapeutic modality for patients with functioning and well-differentiated low grade NENs exhibiting symptomatic control and mainly stabilisation of tumour growth. Other systemic treatments include chemotherapy, molecular targeted agents, interferon-α, peptide receptor radionuclide therapy (PRRT), and immunotherapy. In addition, new agents such as telotristat may be used for the control of symptoms of carcinoid syndrome. The choice and/or sequence of therapeutic agents should be individualized according to tumour origin and differentiation, disease burden, presence of clinical symptoms and patients’ performance status in the context of a multidisciplinary approach. Recent advances in the molecular pathogenesis of NENs set the field for a more personalised treatment approach.

With the advent of modern imaging modalities, endocrine incidentalomas are increasingly being discovered. We aimed to investigate the presence of pituitary incidentalomas (PI) in patients with adrenal incidentalomas (AI), and identify potential metabolic correlates in this cohort. 26 patients (18 females) with AI discovered on abdominal computerized tomography were studied. All patients underwent pituitary magnetic resonance imaging (MRI) and endocrine investigations to evaluate functional adrenal pathology, anterior pituitary hormonal status, insulin-resistance indices and presence of metabolic syndrome. Pituitary MRI revealed a microadenoma and a 4×5 mm cyst in 1 patient respectively, and an empty sella in 4 (2 partial) patients. Overall, 6/26 (23%) patients with an AI had evidence of pituitary imaging pathology but only 8% had a PI; none had any evidence of abnormalities in pituitary function. Subclinical hypercortisolism was the only hyperfunctional status detected in 4 patients with AI but was unrelated to the pituitary findings. No abnormality of insulin secretion and action was found between patients with or without pituitary pathology. In the present study 23% of patients with AI had some alteration in pituitary morphology, and 2 a PI without accompanying pituitary hormonal deficit or metabolic derangement. Further studies are required to address this issue and identify a potential pathogenetic mechanism.

Phaeochromocytoma and paraganglioma are rare neuroendocrine tumours (NETS). They may be benign or malignant but the pathological distinction is mainly made when metastases are present. Available treatments in the form of surgery, chemotherapy, and radionuclide therapy may improve symptoms and biochemical markers, but the results for the control of tumour bulk are less favourable. Furthermore, responses to treatment are frequently short-lived. This short review outlines the main molecular and histological features of malignant phaeochromocytoma and the difficulties in differentiating between benign and malignant disease. We list current therapies used for malignant pheochromocytoma; however, these generally achieve relatively low success rates. Hence, there is a need for new and more effective therapies. In vitro studies have implicated the PI3/Akt/mTOR pathway in the pathogenesis of malignant NETS, including phaeochromocytoma. Everolimus (RAD001, Novartis UK) is a compound that inhibits mTOR (mammalian Target Of Rapamycin) signalling. We have used RAD001 in four patients with progressive malignant paraganglioma/phaeochromocytoma in addition to other therapies (with institutional approval for compassionate use), and evaluated the effects of this treatment. We outline these four cases and review the theoretical background for this therapy, although the outcomes were relatively disappointing.

Since the adrenal cortex and medulla are intimately interrelated, the effects of anticonvulsant drugs may affect both of these hormonal systems. Anticonvulsants are commonly used long-term for the treatment of epilepsy, chronic pain syndromes and affective disorders. In patients where adrenal function needs to be evaluated, the clinician should be aware of the potential interactions between anticonvulsant medication and the hypothalamo-pituitary-adrenal axis. Carbamazepine, phenytoin and phenobarbitone induce the liver P450 cytochrome enzyme system and stimulate steroid clearance. Therefore, patients investigated for Cushing's syndrome may show a falsely positive dexamethasone suppression test, and patients with adrenal insufficiency on steroid replacement may require increased doses of steroids; furthermore, increased corticosteroid-binding-globulin levels are also associated with chronic anticonvulsant administration. In addition, concomitant treatment with benzodiazepines, probably acting via the GABA pathway, can also alter the ACTH/cortisol response to stressful stimuli. Direct and indirect evidence suggest that benzodiazepines, acetazolamide and magnesium sulphate can also interfere with the renin-angiotensin-aldosterone system. Finally, to our knowledge, no systemic data are yet available in the human on the effect of antiepileptics on the function of the adrenal medulla and/or catecholamine metabolism; however, as the adrenal medulla receives part of its blood supply from the cortex, it is possible that alterations of cortical hormonal composition might affect adrenal medulla function overall.

This letter is a short response to Dr Funder's recent commentary on primary aldosteronism under the title "Primary aldosteronism: are we missing the wood for the trees?". We briefly discuss recent data from our department on autonomous aldosterone secretion (AAS) and the efficacy of mineralocorticoid receptor antagonists in a group of patients with AAS, that would otherwise remain undiagnosed.