Karen Mullan

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

Backround  Peroxisomal proliferator‐activated receptors (PPAR)‐ γ 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.

Endocrine clinical update: where are we in the therapeutic management of pituitary-dependent hypercortisolism?

As we approach the centenary of the discovery of Cushing’s disease (CD) (pituitary-dependent hypercortisolism), it may seem surprising that its management has remained such a challenge. The initial therapy for most patients with the condition remains transsphenoidal hypophysectomy. However, authors, including ourselves, studying long-term outcomes of patients achieving apparent early remission have highlighted late relapse rates of up to 25%. 1–5 Some late recurrences manifest classically while others present as cyclical or episodic hypercortisolism, which can be particularly challenging to diagnose and to treat. This imperfect record with transsphenoidal microsurgery has spurred new interest in alternative therapies. This article reviews these new therapies as well as pre-existing therapies and discusses their place in treatment algorithms.

100 cases of primary aldosteronism: careful choice of patients for surgery using adrenal venous sampling and CT imaging results in excellent blood pressure and potassium outcomes

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.

Cyclical Cushing's syndrome: an update.

Purpose of reviewThis article reviews the features of cyclical hypercortisolism. This syndrome was once considered to be very rare but is now being increasingly recognized. Recent findingsEither true cycles or the variant of episodic and fluctuating levels of hypercortisolism can lead to considerable clinical dilemmas, which are discussed. The review details possible pathophysiological mechanisms and the effects of centrally acting drugs. SummaryCyclical Cushings 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. This type of case was initially thought to be rare. It has, however, recently been recognized as occurring much more frequently. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. All of these can have very serious clinical consequences. Clinical researchers, including ourselves, have developed criteria, protocols and dynamic biochemical tools to detect cycling in patients with hypercortisolism. Unfortunately, the mechanisms causing the abnormal pathophysiology have not been well elucidated but some recent insights have been gained. The review discusses strategies for diagnosing and managing this important subgroup of patients with hypercortisolism.

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. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. The techniques and criteria, protocols and dynamic biochemical tools to detect cycling in patients with hypercortisolism are discussed as are the strategies for diagnosing and managing this important subgroup of patients with hypercortisolism.

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

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.

Stewart PM and Allolio B. Adrenal vein sampling for primary aldosteronism: time for a reality check Response

Stewart and Allolio raised an important clinical question regarding the use of adrenal venous sampling (AVS) in the subtype differentiation of primary aldosteronism (PA). We agree that AVS is a technically difficult procedure with variability in bilateral cannulation rates outside of large centres of excellence. However, although bilateral cannulation is the recommended standard, unilateral cannulation of the unaffected gland, although not ideal, may be able to guide treatment decisions. This is because its aldosterone/ cortisol ratio will be suppressed in between 93 and 100% of cases with unilateral disease. Stewart and Allolio argue that AVS has not been found to improve clinical outcome in patients with PA. To highlight this, they describe a study by Zarnegar et al. A significant number of the patients in this study who underwent adrenalectomy had a histological diagnosis of diffuse hyperplasia (25/102, 24Æ5%). This reduced specificity was possibly related to the reliance on CT alone for adenomas greater than 1 cm in size. They also found that cure of hypertension occurred most frequently in patients with a histological diagnosis of adenoma. Therefore, the key to improving outcome post-adrenalectomy is to avoid surgery in patients with bilateral aldosterone hypersecretion as these patients are less likely to benefit from surgery. The weaknesses of CT imaging in are well recognized. In a large series of 203 patients with PA, 25% of patients with bilateral hypersecretion would have had unnecessary surgery if CT alone had been used. Therefore, AVS is necessary to correctly identify those patients with bilateral disease, thus preventing unnecessary surgery in this group. A major benefit of AVS is in identifying patients who would have been missed by CT imaging as potential candidates for adrenalectomy. In the series of 203 patients by Young et al., 22% of patients with unilateral disease would have been incorrectly excluded as adrenalectomy candidates on the basis of CT results alone. This is in keeping with the rather low sensitivity of CT. Indeed, in centres which employ AVS along with CT, aldosterone producing adenoma (APA) make up approximately 28–50% of patients with PA. However, in a centre that used CT imaging alone, only 9% of patients with PA had an APA. Therefore, another major benefit of AVS is the improved identification of patients with unilateral disease when compared to CT alone. Stewart and Allolio also discuss the cost impact of AVS and give an estimate for the European budget. However, we also need to consider the cost of treatment of patients with APA who fail to get diagnosed because of the poor sensitivity of CT. Such patients require lifelong aldosterone blockade and often multiple other antihypertensive agents. Patients may experience a number of side effects of medication, particularly when spironolactone is used. Adrenalectomy in appropriately chosen patients results in cure or improvement in hypertension. It has also recently been found to significantly improve quality of life. Missing a unilateral diagnosis by using a less sensitive test denies patients with unilateral disease potential cure and almost certainly improved blood pressure control and quality of life. Stewart and Allolio have highlighted a number of very important issues relating to AVS including the inconsistencies of protocols between centres. These include the use of ACTH stimulation, the dose of ACTH used and the optimal ratios for definition of successful cannulation and also for lateralization. Recent studies are now trying to address these issues, and it is hoped that further work will enable a standardized optimal protocol to be devised. This will certainly improve the utility and interpretation of this test between centres. The suggestion that AVS should no longer be the gold standard test for lateralization implies that CT imaging is a better diagnostic tool, and this is clearly not the case. This is demonstrated by the study of Kempers et al., which showed that CT alone gives inappropriate results in 37Æ8% when compared to AVS. We suggest that whilst CT remains of value this is only when considered alongside AVS findings. We conclude that AVS remains the best available differentiating test, and by this definition, the gold standard investigation to accurately detect those patients with unilateral production of excess aldosterone.

Twenty-four-hour growth hormone profiling in the assessment of acromegaly

Recent guidelines recommend insulin‐like growth factor (IGF‐1), random growth hormone (GH) and nadir GH on an oral glucose tolerance test (OGTT) for assessment of acromegaly. At this Regional Centre, the 24‐hour GH profile has also been used.

Neonatal TSH levels in Northern Ireland from 2003 to 2014 as a measure of population iodine status: XXXX

The re‐emergence of iodine deficiency in the UK has recently been reported in a large cohort of teenage girls including from Northern Ireland (NI) using the gold standard spot urinary iodine concentration. We wished to explore and confirm this by analysing neonatal thyroid‐stimulating hormone (nTSH) levels in the NI population.

A cross sectional survey of dietary iodine intake in pregnant women living in Northern Ireland

Introduction Adequate iodine intake during pregnancy is required for the production of thyroid hormones and is essential for brain development in the foetus. Recent evidence has suggested a re-emergence of mild iodine deficiency in the UK1 and during pregnancy this has been associated with lower IQ and reading ability in offspring in a dose dependent manner2. Currently there are few studies that have specifically looked at dietary iodine intake during this crucial time.