Generation of TWO iPSC lines (CRICKi009-A; CRICKi010-A) from patients with type 1 von Hippel-Lindau (VHL) and histopathologically confirmed renal cell carcinoma (RCC).

VHL disease is an inherited and autosomal dominant disorder affecting 1 in 36,0000 individuals worldwide. It is caused by von Hippel-Lindau (VHL) gene mutations and can affect both genders and all ethnic backgrounds (Nordstrom-O'Brien et al., 2009; Maher, 2004).

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1).

Resolution of dysglycaemia after treatment of monoclonal gammopathy of endocrine significance.

In very rare cases of monoclonal gammopathy, insulin-binding paraprotein can cause disabling hypoglycaemia. We report a 67-year-old man re-evaluated for hyperinsulinaemic hypoglycaemia that persisted despite distal pancreatectomy. He had no medical history of diabetes mellitus or autoimmune disease but was being monitored for an IgG kappa monoclonal gammopathy of undetermined significance.

Primary aldosteronism: molecular medicine meets public health.

Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s.

Radiofrequency Ablation in Primary Aldosteronism.

The radiofrequency ablation (RFA) technique has been extensively used in the treatment of primary malignancies and metastases and has been recently deployed for the treatment of unilateral primary aldosteronism (PA) as an alternative to whole unilateral adrenalectomy.Current evidence comparing RFA with unilateral adrenalectomy in the treatment of PA so far has been variable, with studies being retrospective and small-scale, but it remains a very attractive option as a potentially less invasive treatment option compared to adrenalectomy.This review article describes the procedure, and provides evidence and the possible future direction of RFA in the treatment of unilateral PA.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1.

The clinical outcomes of imaging modalities for surgical management Cushing's disease - A systematic review and meta-analysis.

Introduction: Cushing's disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing's disease.

The road to systemic therapy in von Hippel-Lindau (VHL) disease: Are we there yet?

Pathogenic germline mutations in VHL gene cause von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary cancer syndrome associated with high penetrance of benign and malignant neoplasms, including clear cell renal cell carcinoma (ccRCC), central nervous system haemangioblastomas (CNS-HB), retinal angiomas, phaeochromocytomas and pancreatic neuroendocrine tumours (pNET). Management of VHL disease involves lifelong radiological and biochemical surveillance, often leading to repeat surgical intervention causing significant morbidity and mortality. Systemic therapy that prevents or reduces the need for surgical intervention could improve clinical outcomes and quality of life for affected individuals.

A study of acromegaly-associated headache with somatostatin analgesia.

The aim of this study is to characterise somatostatin analogue-responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria.

The metabolic phenotype of patients with primary aldosteronism: impact of subtype and sex - a multicenter-study of 3566 Caucasian and Asian subjects.

Background: Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics.

A novel variant of fructose-1,6-bisphosphatase gene identified in an adult with newly diagnosed hepatitis C.

Hepatic fructose-1,6-bisphosphatase (FBPase) deficiency commonly presents with acute crises during infancy when glycogen stores are depleted. In these patients, dependence on glycogenolysis means that the duration of normoglycaemia is related to liver glycogen stores. Clinical hallmarks of FBPase deficiency include hypoglycaemia and lactic acidosis with or without ketosis.

Postradioiodine Graves' management: The PRAGMA study.

Objective: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies.

Design: Retrospective, multicentre and observational study.

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs.

Performance evaluation of scoring systems for predicting post-operative hypertension cure in primary aldosteronism.

Objective: Hypertension cure following adrenalectomy in unilateral primary aldosteronism is not guaranteed. Its likelihood is associated with pre-operative parameters, which have been variably combined in six different predictive scoring systems. The relative performance of these systems is currently unknown.

Incidence of Cabergoline-Associated Valvulopathy in Primary Care Patients With Prolactinoma Using Hard Cardiac Endpoints.

Background: Controversy exists as to whether low-dose cabergoline is associated with clinically significant valvulopathy. Few studies examine hard cardiac endpoint data, most relying on echocardiographic findings.

Objectives: To determine the prevalence of valve surgery or heart failure in patients taking cabergoline for prolactinoma against a matched nonexposed population.

Adrenal Venous Sampling-Guided Adrenalectomy Rates in Primary Aldosteronism: Results of an International Cohort (AVSTAT).

Context: Adrenal venous sampling (AVS) is the current criterion standard lateralization technique in primary aldosteronism (PA). Japanese registry data found that 30% of patients with unilateral PA did not undergo adrenalectomy, but the reasons for this and whether the same pattern is seen internationally are unknown.

Objective: To assess the rate of AVS-guided adrenalectomy across an international cohort and identify factors that resulted in adrenalectomy not being performed in otherwise eligible patients.

Low-grade Cortisol Cosecretion Has Limited Impact on ACTH-stimulated AVS Parameters in Primary Aldosteronism.

Context: In primary aldosteronism, cosecretion of cortisol may alter cortisol-derived adrenal venous sampling indices.

Objective: To identify whether cortisol cosecretion in primary aldosteronism alters adrenal venous sampling parameters and interpretation.

Design: Retrospective case-control study.

Induced Lactation in a Mother Through Surrogacy With Complete Androgen Insensitivity Syndrome (CAIS).

Introduction: Breastfeeding offers the optimal feeding option for newborns in terms of nutritional content and reinforces mother-infant bonding. As a physiological process intrinsically linked to parturition, breastfeeding is no longer reserved for puerperal mothers. Progress in understanding the intricacies of lactogenesis and breastfeeding has further paved the way for artificially induced lactation in recent years.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

Context: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era.

Objective: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS.

Patients, Design, And Setting: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis.

Flipped learning: Turning medical education upside down.

Background: Flipped learning is an approach in which core teaching is delivered using online material viewed prior to face-to-face learning, applying knowledge gained from online material. Core teaching in a module for third-year undergraduate medical students was based around a 1-week course comprising 32 hours of lectures. Feedback suggested that students were poorly engaged and attendance was poor.

DLK1/PREF1 marks a novel cell population in the human adrenal cortex.

The adrenal cortex governs fundamental metabolic processes though synthesis of glucocorticoid, mineralocorticoids and androgens. Studies in rodents have demonstrated that the cortex undergoes a self-renewal process and that capsular/subcapsular stem/progenitor cell pools differentiate towards functional steroidogenic cells supporting the dynamic centripetal streaming of adrenocortical cells throughout life. We previously demonstrated that the Notch atypical ligand Delta-like homologue 1 (DLK1)/preadipocyte factor 1 (PREF1) is expressed in subcapsular Sf1 and Shh-positive, CYP11B1-negative and CYP11B2-partially positive cortical progenitor cells in rat adrenals, and that secreted DLK1 can modulate GLI1 expression in H295R cells.