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Dive into the research topics where Paul V. Carroll is active.

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Featured researches published by Paul V. Carroll.


The Journal of Clinical Endocrinology and Metabolism | 2010

Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients.

Wiebke Arlt; Debbie Willis; Sarah H. Wild; Nils Krone; Emma J. Doherty; Stefanie Hahner; Thang S. Han; Paul V. Carroll; G. S. Conway; D. Aled Rees; Roland H. Stimson; Brian R. Walker; John M. Connell; Richard Ross

Context: No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size. Objective: Our objective was to establish the health status of adults with CAH. Design and Setting: We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine centers across the United Kingdom. Patients: Participants included 203 CAH patients (199 with 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18–69) years. Main Outcome Measures: Anthropometric, metabolic, and subjective health status was evaluated. Anthropometric measurements were compared with Health Survey for England data, and psychometric data were compared with appropriate reference cohorts. Results: Glucocorticoid treatment consisted of hydrocortisone (26%), prednisolone (43%), dexamethasone (19%), or a combination (10%), with reverse circadian administration in 41% of patients. Control of androgens was highly variable with a normal serum androstenedione found in only 36% of patients, whereas 38% had suppressed levels suggesting glucocorticoid overtreatment. In comparison with Health Survey for England participants, CAH patients were significantly shorter and had a higher body mass index, and women with classic CAH had increased diastolic blood pressure. Metabolic abnormalities were common, including obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised. Conclusions: Currently, a minority of adult United Kingdom CAH patients appear to be under endocrine specialist care. In the patients studied, glucocorticoid replacement was generally nonphysiological, and androgen levels were poorly controlled. This was associated with an adverse metabolic profile and impaired fertility and quality of life. Improvements in the clinical management of adults with CAH are required.


American Journal of Physiology-endocrinology and Metabolism | 1999

The metabolic consequences of critical illness: acute effects on glutamine and protein metabolism

N. C. Jackson; Paul V. Carroll; David Russell-Jones; P. H. Sönksen; David F. Treacher; A. M. Umpleby

Net protein loss and large decreases in plasma glutamine concentration are characteristics of critical illness. We have used [2-15N]glutamine and [1-13C]leucine to investigate whole body glutamine and leucine kinetics in a group of critically ill patients and matched healthy controls. Glutamine appearance rate (Ra,Gln) was similar in both groups. However, in the patients, the proportion of Ra,Gln arising from protein breakdown was higher than in the control group (43 +/- 3 vs. 32 +/- 2%, P < 0.05). Glutamine metabolic clearance rate (MCR) was 92 +/- 8% higher (P < 0.001), whereas plasma glutamine concentration was 38 +/- 5% lower (P < 0.001) than in the control group. Leucine appearance rate (whole body proteolysis) and nonoxidative leucine disposal (whole body protein synthesis) were 59 +/- 14 and 49 +/- 15% higher in the patients (P < 0.001). Leucine oxidation and MCR were increased in the patients by 104 +/- 37 and 129 +/- 39%, respectively (P < 0.05). These results demonstrate that critical illness is associated with a major increase in protein turnover. The acute decrease in plasma glutamine concentration and the unaltered plasma Ra,Gln suggest that the increase in proteolysis is insufficient to meet increased demand for glutamine in this severe catabolic state.Net protein loss and large decreases in plasma glutamine concentration are characteristics of critical illness. We have used [2-15N]glutamine and [1-13C]leucine to investigate whole body glutamine and leucine kinetics in a group of critically ill patients and matched healthy controls. Glutamine appearance rate (Ra,Gln) was similar in both groups. However, in the patients, the proportion of Ra,Gln arising from protein breakdown was higher than in the control group (43 ± 3 vs. 32 ± 2%, P < 0.05). Glutamine metabolic clearance rate (MCR) was 92 ± 8% higher ( P < 0.001), whereas plasma glutamine concentration was 38 ± 5% lower ( P < 0.001) than in the control group. Leucine appearance rate (whole body proteolysis) and nonoxidative leucine disposal (whole body protein synthesis) were 59 ± 14 and 49 ± 15% higher in the patients ( P < 0.001). Leucine oxidation and MCR were increased in the patients by 104 ± 37 and 129 ± 39%, respectively ( P < 0.05). These results demonstrate that critical illness is associated with a major increase in protein turnover. The acute decrease in plasma glutamine concentration and the unaltered plasma Ra,Gln suggest that the increase in proteolysis is insufficient to meet increased demand for glutamine in this severe catabolic state.


Clinical Endocrinology | 2007

The influence of the route of oestrogen administration on serum levels of cortisol‐binding globulin and total cortisol

Ayesha C. Qureshi; Aman Bahri; Louise Breen; Sophie C. Barnes; Jake Powrie; Stephen Thomas; Paul V. Carroll

Objectives  Oral oestrogen preparations increase total cortisol concentration by increasing circulating cortisol‐binding globulin (CBG) levels. Transdermal oestrogen treatments are being used increasingly in clinical practice. These topical preparations may have less of an effect on CBG and hence on total serum cortisol levels by reducing hepatic oestrogen exposure. The purpose of this study was to compare the effects of oral and topical oestrogen treatments on CBG, total serum cortisol and salivary cortisol levels.


European Journal of Endocrinology | 2015

The epidemiology of pituitary adenomas in Iceland, 1955–2012: a nationwide population-based study

Tomas Thor Agustsson; Tinna Baldvinsdottir; Jon G. Jonasson; Elinborg J Olafsdottir; Valgerdur Steinthorsdottir; Gunnar Sigurdsson; Arni V Thorsson; Paul V. Carroll; Márta Korbonits; Rafn Benediktsson

OBJECTIVE Pituitary adenomas (PA) are among the most common human neoplasms. To describe the epidemiology and assess the disease burden of clinically significant PAs, population-based studies are needed. Iceland has a small well-defined population. The aim of this study is to describe the epidemiology of PAs in Iceland over an expanded period of time. DESIGN This is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012. METHODS Extensive clinical information was gathered in a database. Prevalence rates for all PA subtypes were calculated along with standardized incidence rates (SIR). Sex ratios and relationships with adenoma size, age, and symptoms were assessed. RESULTS We identified 471 individuals: 190 men and 281 women. Total prevalence in 2012 was 115.57/100, 000, prolactinomas were most prevalent (54.37/100, 000) followed by non-functioning adenomas (NFPAs) (42.32/100 ,000). Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas (39.9%) and 11.3% had acromegaly and 5.7% Cushings disease. Women are diagnosed younger with smaller adenomas. Total SIR has increased significantly and is now 5.8/100 000 per year. CONCLUSION In this nationwide study spanning six decades, we have confirmed PAs rising prevalence and incidence rates noted in recent studies. We demonstrated higher overall prevalence and incidence rates than ever previously recorded with an increasing predominance of NFPAs, which is not explained by incidental findings alone. There is a relationship with the introduction of imaging modalities, but the vast majority of patients are symptomatic at diagnosis. This underlines the importance of increased awareness, education, and appropriate allocation of resources for this growing group of patients.


Diabetes | 1997

rhIGF-I Administration Reduces Insulin Requirements, Decreases Growth Hormone Secretion, and Improves the Lipid Profile in Adults With IDDM

Paul V. Carroll; Margot Umpleby; Gill S Ward; Stephen Imuere; Elaine L. Alexander; David B. Dunger; P. H. Sönksen; David Russell-Jones

IDDM is associated with elevated circulating levels of growth hormone (GH) and reduced insulin-like growth factor I (IGF-I). GH antagonizes the action of insulin-increasing insulin requirements in IDDM. The effects of subcutaneously administered rhIGF-I on glycemie control, insulin requirements, and GH secretion were studied in eight adults with IDDM. Patients received either placebo or rhIGF-I (50 pg/kg b.i.d.) for 19 days in a randomized, double-blind, parallel-design, placebo-controlled trial. Overnight GH, plasma glucose, free insulin, IGF-I, fructosamine, and lipid profiles were assessed during this period. rhIGF-I therapy increased IGF-I concentration from 117.1 ± 14.2 (mean ± SE) ng/ml (baseline) to 310.5 ± 40.6 and 257.1 ± 41.2 ng/ml on day 5 (P < 0.01 vs. baseline) and day 20 (P < 0.01 vs. baseline), respectively. After 19 days of rhIGF-I treatment, fructosamine concentrations were unchanged compared with baseline (439 ± 32 vs. 429 ± 35 μmol/l, day –1 vs. day 20, respectively), yet insulin requirements were decreased by ∼45% (0.67 ± 0.08 vs. 0.36 ± 0.07 U · kg−1 · day−1, day –1 vs. day 19, respectively, P < 0.005). After 4 days of rhIGF-I therapy, there was a decrease in free insulin levels (8.38 ± 1.47 vs. 4.98 ± 0.84 mU/l, P < 0.05), mean overnight GH concentration (12.6 ± 3.3 vs. 3.8 ± 2.1 mU/l, P = 0.05), and total cholesterol and triglycerides (4.68 ± 0.31 vs. 4.25 ± 0.35 mmol/l, P < 0.05, 1.27 ± 0.19 vs. 0.95 ± 0.21 mmol/l, P < 0.001, respectively). There was no change in any variable in the placebo-treated patients. This study demonstrates that subcutaneous administration of rhIGF-I decreases insulin requirements and improves the plasma lipid profile while maintaining glycemie control in adults with IDDM. The excess nocturnal release of GH, characteristic of IDDM, is also decreased by rhIGF-I therapy. Exogenous rhIGF-I therapy may have a role in the treatment of adults with IDDM, particularly in the setting of abnormal lipids and a high insulin requirement.


Clinical Endocrinology | 2016

Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review.

Mamta Joshi; Benjamin C Whitelaw; Maria Teresa Pacheca Palomar; Yin Wu; Paul V. Carroll

Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs’ mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5–36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and ‘high‐dose’ glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine‐related consequences of this novel class of immunotherapies.


The Journal of Clinical Endocrinology and Metabolism | 2013

Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

Nils Krone; Ian T. Rose; Debbie Willis; James Hodson; Sarah H. Wild; Emma J. Doherty; Stefanie Hahner; Silvia Parajes; Roland H. Stimson; Thang S. Han; Paul V. Carroll; G. S. Conway; Brian R. Walker; Fiona MacDonald; Richard Ross; Wiebke Arlt

CONTEXT In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. OBJECTIVE The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. RESEARCH DESIGN AND METHODS We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. RESULTS CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. CONCLUSIONS In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment.


Clinical Endocrinology | 2004

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion

Paul V. Carroll; J. P. Monson; Ashley B. Grossman; G. M. Besser; P.N. Plowman; F. Afshar; Martin O. Savage

objective  Although Cushings disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH‐deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established.


Hormone Research in Paediatrics | 2002

Growth in Disorders of Adrenal Hyperfunction

Martin O. Savage; S. Scommegna; Paul V. Carroll; J.T.F. Ho; John P. Monson; G. M. Besser; Ashley B. Grossman

Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.23 ± 0.42 and 1.3 ± 0.37 SDS respectively. In poorly controlled CAH, excess androgens cause early epiphyseal fusion and adult short stature. Increased growth occurs only after 18 months of age, even in untreated CAH, i.e. hydrocortisone >10 mg/m2/day is not generally required and may suppress infantile growth, affecting childhood and adult height. Growth was studied in 19 patients, aged 6.4–17.8 years, with Cushing’s disease (CD). At diagnosis, mean height SDS was –1.81 (1.2 to –4.17), 53% < –1.8 SDS, height velocity in 6 was 0.9–3.8 cm/year and mean BMI SDS 2.29 (0.7–5.06). From 1983 to 2001, CD was cured in 18 patients (61%) by transsphenoidal surgery (TSS) alone and 39% by TSS plus pituitary irradiation (RT). In 13 patients, growth hormone (GH) was assessed by ITT/glucagons at 1–108 months after cure. Four had severe GH deficiency (<9 mU/l), 7 subnormal (10–29 mU/l) and 2 normal (>30 mU/l) GH status. Subnormal GH was present in 7 subjects >2 years after TSS or RT cure. In 10 subjects, aged 12.9 ± 3.4 years, growth after cure was studied for 9.1 ± 5.0 years. Nine had no catch-up growth in the interval of 0.3–1.1 years after cure (mean HV 5.3 ± 2.4 cm/year). All these had GH deficiency peak GH 0.5–20.9 mU/l, and received hGH 2.7 mg/m2/week, 3 with GnRHa. All 10 showed long-term catch-up growth with mean delta SDS at diagnosis (Ht SDS–target Ht SDS) –1.72 ± 1.26 improving to –0.83 ± 1.08 (p = 0.0005) at latest of final Ht. At diagnosis, virilization was present in 82% of 17 patients with CD. Mean SDS values of serum androstenedione, DHEA-S and testosterone were normal, i.e. 0.72 (–2.9 to 3.0), –0.8 (6.0 to 2.2), 0.7 (–7.9 to 9.5) respectively, whereas SHBG was reduced at –2.1 (–5.3 to 1.2), increasing free androgen levels. Bone age (BA) was delayed (mean 1.46 years) in 14/16 patients, suggesting cortisol excess contributed more then androgen effect to skeletal maturation. In conclusion, most paediatric patients with CD had subnormal linear growth with delayed BA. After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height.


Clinical Endocrinology | 2011

Cardiac valve disease and low-dose dopamine agonist therapy: an artefact of reporting bias?

Haotian Gu; Sara Luck; Paul V. Carroll; Jake Powrie; John Chambers

Introduction  Chronic low‐dose cabergoline treatment for microprolactinoma may cause cardiac valve pathology, but the evidence is contradictory. We investigated whether the expectation of the echocardiographer could influence the report.

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P. H. Sönksen

University of Southampton

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David Russell-Jones

Royal Surrey County Hospital

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Emanuel Christ

University Hospital of Bern

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Stephen Thomas

Guy's and St Thomas' NHS Foundation Trust

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