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Author: John A H Wass (72)


Feb
2018

Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial.
1) Evaluate how frequently PMT is given to CS patients across Europe 2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery; 3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS).

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Dec
1969

To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines.
We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS).

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Jun
2017

Despite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking.
To assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment.
Retrospective cohort study of 237 patients with regrown CNFA managed in two UK centers.

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Feb
2017

Acromegaly is a rare condition necessitating large population studies for the generation of reliable epidemiological data. In this review, we systematically analysed the epidemiological profile of this condition based on recently published population studies from various geographical areas. The total prevalence ranges between 2.

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May
2016

Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized.
This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR).
A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.

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Feb
2016

Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors.

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Aug
2015

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly.

J Endocrinol 2015 Aug 1;226(2):T141-60. Epub 2015 Jul 1.
Cristina Capatina, John A H Wass
Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease.

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Nov
2015

Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11OHD appears to be a rare condition. Our study assessed the residual CYP11B1 function of detected mutations, adding to the spectrum of mild 11OHD, and illustrates the variability of the clinical presentation of 11OHD.

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Mar
2015

Hypopituitarism: growth hormone and corticotropin deficiency.

Endocrinol Metab Clin North Am 2015 Mar 6;44(1):127-41. Epub 2014 Nov 6.
Cristina Capatina, John A H Wass
This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI.

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May
2015

Pituitary tumour apoplexy (PA) is a rare clinical syndrome that occurs as a result of acute haemorrhage and/or infarction within a frequently undiagnosed pituitary tumour. The sudden enlargement of the pituitary mass undergoing PA is responsible for a wide range of acute symptoms/signs (severe headache, visual loss, diplopia, hypopituitarism, impaired consciousness) which, together with the radiological evidence of a pituitary lesion, establish the diagnosis. The optimal care of PA requires involvement of a multidisciplinary team including endocrinologist, neurosurgeon, neuroophthalmologist and the management strategy that depends on the clinical manifestations, as well as the presence of co-morbidities.

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Nov
2014

The aim was to formulate clinical practice guidelines for acromegaly.
The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration.

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Aug
2014

Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life.
Month of birth effects were investigated in three independent European Caucasian AITD datasets.

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Nov
2013

We investigated the control of GH and IGF1 in acromegaly in routine clinical practice in the UK on and off medical treatment.
The UK Acromegaly Register collected routine biochemical and clinical data on patients with acromegaly from 31 UK centres with GH data covering >30y.
We identified 2572 patients.

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Dec
1969

Acute adrenal crisis is an important condition to consider in any shocked patient presenting to the acute medical unit. This article aims to highlight the key aspects of initial management, focussing on the importance of rapid recognition and prompt initiation of steroid treatment.

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Apr
2013

The tumorigenic role of genetic abnormalities in sporadic pituitary nonfunctioning adenomas (NFAs), which usually originate from gonadotroph cells, is unknown.
The objective of the study was to identify somatic genetic abnormalities in sporadic pituitary NFAs.
Whole-exome sequencing was performed using DNA from 7 pituitary NFAs and leukocyte samples obtained from the same patients.

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Aug
2013

The frequency and the degree of recovery of anterior pituitary hormone deficits in patients with macroprolactinoma responsive to cabergoline are not clear. Our aim was to evaluate pituitary function in these patients with particular reference to an assessment of the possible restoration of pituitary deficits.
The records of all subjects prospectively presenting to our Department with macroprolactinomas treated with cabergoline over a 2-year period were reviewed.

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Oct
2012


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Aug
2012

Somatotroph adenomas harboring aryl hydrocarbon receptor interacting protein (AIP) mutations respond less well to somatostatin analogs, suggesting that the effects of somatostatin analogs may be mediated by AIP.
The objective of the investigation was to study the involvement of AIP in the mechanism of effect of somatostatin analogs.
In the human study, a 16-wk somatostatin analog pretreatment compared with no pretreatment.

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Aug
2012

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry.

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Jan
2013

Non-functioning pituitary adenomas (NFA) may be associated with significant morbidity. Published data on the quality of life (QoL) of patients with NFA are scarce and conflicting. In view of the discordant findings and the advances in the management of these subjects, we aimed to evaluate the QoL in patients with NFA followed up in a tertiary endocrine UK referral centre.

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Feb
2012

Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Although a common finding in routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic RCC do not require surgical intervention, and their natural history is not clear.

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Nov
2011

Non-functioning pituitary adenomas (NFAs) are slow-growing tumours with reported re-growth rates following surgical resection alone of up to 50% at 10 years. Currently, the desired length of follow-up surveillance imaging in un-irradiated patients is unclear.
To clarify the timing of re-growth in patients with NFAs, treated solely by surgery without post-operative pituitary radiotherapy, and also to clarify whether continued imaging is necessary in these patients.

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Sep
2011

The European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS).
Baseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.

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Dec
2011

The optimal duration of dopamine agonist (DA) therapy in prolactinoma is unknown. There are concerns that despite low recurrence rates in highly selected groups, high recurrence rates after DA withdrawal may occur in routine practice.
To explore recurrence of hyperprolactinaemia and predictive factors following DA withdrawal in patients with microprolactinoma and macroprolactinoma.

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Oct
2011

Aggressive pituitary tumours are associated with substantial morbidity and mortality. Treatment options are often limited, and chemotherapy has been reserved as salvage therapy although historically results have often been disappointing. However, temozolomide, an oral alkylating agent, has recently demonstrated significant activity against these tumours.

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Apr
2011

Clinically nonfunctioning pituitary tumors are common in tertiary endocrine practice. Although it is widely accepted that patients with these adenomas require long-term surveillance after surgery-particularly those with macroadenomas, which grow much more frequently than microadenomas-a consensus on postoperative monitoring and treatment strategies is lacking. The indications for radiotherapy, which has seen a decline in use over the past decade, are not clear, although most experts would agree that residual tumor mass after surgery, as well as tumor expansion into the cavernous sinus, indicate the need to consider postoperative radiotherapy.

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Feb
2011

The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia.
The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer.
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence.

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Aug
2010


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Nov
2010

Growth hormone and memory.

J Endocrinol 2010 Nov 9;207(2):125-6. Epub 2010 Aug 9.
John A H Wass, Raghava Reddy
Growth hormone (GH) replacement unequivocally benefits growth, body composition, cardiovascular risk factors and quality of life. Less is known about the effects of GH on learning and memory. The recent paper on 'early onset - GH deficiency (GHD) results in spatial memory impairment in mid life - and is prevented by GH supplementation' by Nieves-Martinez importantly adds to this literature.

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Oct
2009

Non-adenomatous pituitary tumours.

Best Pract Res Clin Endocrinol Metab 2009 Oct;23(5):651-65
Niki Karavitaki, John A H Wass
Apart from pituitary adenomas, a number of tumours may arise from within the sella presenting a diagnostic and therapeutic challenge at a multidisciplinary specialist level. This article focus on the most commonly diagnosed non-adenomatous pituitary tumours (craniopharyngiomas, Rathke's cleft cysts and meningiomas) and provides data on their pathogenesis, diagnosis and treatment.

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May
2010

To evaluate and compare MRI-based ovarian morphology in groups of women with polycystic ovary syndrome (PCOS) and controls.
All PCOS cases (n = 44) had oligo-amenorrhoea and hyperandrogenism irrespective of ovarian morphology, and fulfilled NIH/Rotterdam diagnostic criteria for PCOS. All control women (n = 40) had normal menses and normoandrogenaemia.

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Dec
1969

Nonfunctioning adenomas are the second most common type of pituitary tumor. Over the past few years, our knowledge of the epidemiology, natural history, diagnosis, treatment, and recurrence rates of these tumors has improved. Here, we highlight some of these advances and speculate on future avenues of research.

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Mar
2010

Pituitary adenomas (PAs) are associated with increased morbidity and mortality. The optimal delivery of services and the provision of care for patients with PAs require distribution of the resources proportionate to the impact of these conditions on the community. Currently, the resource allocation for PAs in the health care system is lacking a reliable and an up-to-date epidemiological background that would reflect the recent advances in the diagnostic technologies, leading to the earlier recognition of these tumours.

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Dec
1969

We report a patient presenting with ALS in whom acromegaly was later confirmed. Insulin-like growth factor-1 (IGF-1) has been tried in the treatment of ALS and despite equivocal results from clinical trials, efforts have continued to try to harness the significant positive effects on motor neuron growth observed in vitro and in survival of mouse models of the disease. One subsequent study has reported an association between higher circulating serum IGF-1 levels and longer disease duration in ALS patients.

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Jul
2009

Addison's disease.

BMJ 2009 Jul 2;339:b2384. Epub 2009 Jul 2.
Sarah J K Baker, John A H Wass

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Sep
2009

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity.
The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls.

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Sep
2009

Radiation-induced hypopituitarism.

Endocr Relat Cancer 2009 Sep 4;16(3):733-72. Epub 2009 Jun 4.
Alberto Fernandez, Michael Brada, Lina Zabuliene, Niki Karavitaki, John A H Wass
The hypothalamic-pituitary unit is a particularly radiosensitive region in the central nervous system. As a consequence, hypopituitarism commonly develops after radiation treatments for sellar and parasellar neoplasms, extrasellar brain tumours, head and neck tumours, and following whole body irradiation for systemic malignancies. Increasing tumour-related survival rates provide an expanding population at risk of developing hypopituitarism.

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May
2009

Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease.

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Jan
2009

The use of high doses of the ergot-derived dopamine agonist cabergoline (> 3 mg/day), especially with cumulative doses > 4000 mg, has been associated with an increase in cardiac valvular thickening and significant (moderate to severe) regurgitation. Whether lower doses commonly used in the treatment of prolactinomas (0.25-3 mg/week) are also associated with significant valvulopathy is controversial.

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Jul
2008

Insulin resistance, which associates with levels of retinol-binding protein 4 (RBP4) and adiponectin, is implicated in the development of polycystic ovary syndrome (PCOS).
The objective of the study was to explore the potential contribution of RBP4 and adiponectin in the etiology of PCOS and their relationships with specific fat depot measurements.
This was a cross-sectional study.

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Jun
2008

Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis.
AIP sequence changes and expression were studied in FIPA and sporadic adenomas.

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Apr
2008

Abnormal ghrelin regulation may influence the development of obesity-associated conditions including polycystic ovary syndrome (PCOS). Our aim was to compare ghrelin regulation between PCOS cases and controls.
We compared serum ghrelin (total) levels, fasting and 30-min post-oral (75 g) glucose load, between 50 PCOS cases and 28 female controls, including 22 body mass index (BMI)/fat mass-matched pairs.

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Mar
2008

Craniopharyngiomas.

Endocrinol Metab Clin North Am 2008 Mar;37(1):173-93, ix-x
Niki Karavitaki, John A H Wass
Craniopharyngiomas are epithelial tumors arising along the path of the craniopharyngeal duct and presenting with a variety of manifestations. Their optimal management remains a subject of debate. Currently, surgical excision followed by external beam irradiation is the main treatment option.

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Nov
2007

Silent corticotroph adenomas.

Arq Bras Endocrinol Metabol 2007 Nov;51(8):1314-8
Niki Karavitaki, Olaf Ansorge, John A H Wass
Silent corticotroph pituitary adenomas (SCA) are defined as pituitary adenomas showing positive staining for adrenocorticotrophic hormone in immunohistochemical studies, but not associated with perioperative clinical or laboratory features of hypercortisolaemia. They account for 1.1-6% of surgically removed pituitary adenomas.

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Mar
2008

Obesity-related predisposition to polycystic ovary syndrome (PCOS) could reflect overall adiposity and/or regional accumulation of abdominal visceral fat.
The objective of the study was to compare distributions of visceral, abdominal sc, and gluteofemoral sc adipose tissue in PCOS cases vs. control women.

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