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Zheng Chen Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Haixia Zeng Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Qiulan Huang Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Cuiping Lin Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Xuan Li Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Shaohua Sun Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Jian-ping Liu Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 µg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.

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Jorge Gabriel Ruiz-Sánchez Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Hospital Universitario Fundación Jiménez Díaz, Madrid, España
Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España

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Alfonso Luis Calle-Pascual Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, España

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Miguel Ángel Rubio-Herrera Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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María Paz De Miguel Novoa Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Emilia Gómez-Hoyos Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, España

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Isabelle Runkle Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Introduction

Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease’s spectrum.

Methods

In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia.

Results

Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+.

Conclusion

Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity.

Significance statement

Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

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Mireille N M van Poppel Institute of Human Movement Sciences, Sport and Health, University of Graz, Graz, Austria

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Christopher J Nolan Department of Endocrinology at The Canberra Hospital and the Australian National University School of Medicine and Psychology, Canberra, ACT, Australia

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Gernot Desoye Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria

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Pancreas agenesis is a rare condition underlying a variant of permanent neonatal diabetes mellitus. Neonates with this condition are born small for gestational age, but less is known about which components of growth are impacted, the timing of the growth restriction and potential sex differences. Our objective was to assess in which periods in gestation complete pancreas agenesis restricts fetal growth and possible sex differences in susceptibility. Published cases (n = 49) with pancreas agenesis providing relevant data (gestational age, fetal sex, birth weight, birth length, head circumference, placental weight) were identified by MEDLINE and secondary literature search covering the years 1950–January 2023. Semiquantitative analysis of these case reports used centiles based on Intergrowth-21 reference charts. Neonates with pancreas agenesis were severely growth restricted; however, median centiles for birth weight, birth length, and head circumference of those born before week 36 were significantly higher compared to those born from 36 weeks. Similar results were found when data were separated by before and from 38 weeks. Head circumference was less affected than birth weight or birth length. No sex differences were found. In conclusion, pancreas agenesis severely restricts fetal length and head circumference in addition to weight growth, with stronger effects evident from 36 weeks of gestation. In addition to the well-known effects of insulin on growth of fetal fat mass, the pronounced effect on birth length and head circumference indicates effects of insulin on fetal lean body growth as well. Lack of power may account for failure to find sex differences.

Significance statement

Neonates with complete pancreas agenesis are born small, but the details of their growth deviation, timing, and potential sex differences remain uncertain. All neonates with pancreas agenesis in our study had reduced birth weight, length, and head circumference, with milder effects in those born before 36 weeks compared to after 36 weeks. This trend persisted when data were separated into before and after 38 weeks, with no discernible sex differences. The absence of the pancreas, and therefore insulin, significantly reduces fetal growth, especially after 36 weeks of gestation. In addition to insulin’s known role in fetal fat mass, our findings suggest it has a substantial influence on birth length and head circumference, underscoring its impact on fetal lean body growth.

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Bogumila Urgatz Merck Healthcare KGaA, Darmstadt, Germany

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Kris G Poppe University Hospital CHU Saint Pierre, Free University of Brussels, Brussels, Belgium

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Hypothyroidism is a relatively common finding during pregnancy. This may be due either to the presence of existing thyroid disease and/or to the increased demands that pregnancy places the thyroid gland to provide thyroid hormones for the mother and the developing fetus. There is no doubt that overt hypothyroidism is associated strongly with adverse pregnancy outcomes, including miscarriage. Meta-analyses show that thyroid hormone replacement with levothyroxine (LT4) reduces the risk of adverse pregnancy outcomes in the setting of overt hypothyroidism. Accordingly, management guidelines in this area are unanimous in recommending intervention with to control the level of thyrotropin (TSH) to below 2.5 μIU/mL. The evidence for an adverse impact of subclinical hypothyroidism (SCH) on pregnancy outcomes is less clear, although meta-analyses suggest that SCH reduces the chance of a successful pregnancy outcome. Guidelines also support intervention for some patients with SCH, particularly where TSH is high (>10 μIU/mL), or where TSH is above its trimester-specific reference range in a woman with thyroid autoimmunity (giving LT4 to euthyroid women with thyroid autoimmunity is not supported). Real-world evidence suggests that hypothyroidism in pregnancy is often overlooked or that LT4 is not given appropriately to gain tight control of TSH. More research is needed to identify the barriers to optimal thyroid care with LT4 at this crucial time.

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Behnaz Abiri Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Majid Valizadeh Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Amirhossein Ramezani Ahmadi Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

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Shirin Amini Department of Nutrition, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran

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Mohammad Nikoohemmat Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Faeze Abbaspour Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Farhad Hosseinpanah Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Objectives

It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages.

Methods

Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle–Ottawa criteria.

Results

Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered.

Conclusion

Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

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Marianna Viukari Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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Helena Leijon Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland

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Tiina Vesterinen Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland

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Sanni Söderlund Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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Päivi Hämäläinen Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Iina Yliaska Medical Research Center Oulu, Oulu University Hospital and Research Unit of Internal Medicine, University of Oulu, Oulu, Finland

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Päivi Rautiainen Joint Municipal Authority for North Karelia Social and Health Services (Siun Sote), Joensuu, Finland

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Reeta Rintamäki Department of Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland

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Minna Soinio Department of Endocrinology, Turku University Hospital, Turku, Finland

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Ilkka Pörsti Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

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Pasi I Nevalainen Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Niina Matikainen Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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Objective

The associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping.

Design

A retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures.

Results

Re-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies.

Conclusions

Incorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.

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Xinge Tao Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China

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Yanbin Xue Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Rui Niu Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China

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Wenjing Lu Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China

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Huayan Yao Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Chunmei He Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China

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Bin Cui Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Changqin Liu Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Xiamen Key Laboratory for Clinical Efficacy and Evidence-Based Research of Traditional Chinese Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
Fujian Province Key Laboratory of Diabetes Translational Medicine, The First Affiliated Hospital of Xiamen University, School of medicine, Xiamen University, Xiamen, China

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Objective

The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice.

Methods

This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18–40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65–80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups.

Results

There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital.

Conclusions

Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

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Signe Kirkegaard Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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Stine Linding Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The disorders share a link to female reproduction and infertility; however, divergent effects on menstrual cycle, related hormones, and body composition have been proposed. Disorders of the thyroid gland including abnormal thyroid dysfunction (hyperthyroidism or hypothyroidism) and/or markers of thyroid autoimmunity similarly show a female predominance and onset in younger age groups. We reviewed the literature on the association between endometriosis, PCOS, and thyroid disease up until July 1, 2023, and identified 8 original studies on endometriosis and thyroid disease and 30 original studies on PCOS and thyroid disease. The studies were observational and heterogeneous regarding the design, sample size, and definitions of exposure and outcome; however, a tendency was seen toward an association between hyperthyroidism and endometriosis. Especially an association between endometriosis and slightly elevated levels of thyroid-stimulating hormone receptor antibodies has been found and corroborated in studies from different populations. On the other hand, the literature review turned a focus toward an association between hypothyroidism and PCOS, however, with uncertainties as to whether the association is caused by hypothyroidism per se and/or the thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies). More evidence is needed to substantiate an association between endometriosis, PCOS, and thyroid disease, and to differentiate between the role of thyroid function and thyroid autoimmunity. Furthermore, studies are warranted to extend knowledge on the different disease characteristics and underlying mechanisms.

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Deirdre Green Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Rosemary Dineen Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Michael W O’Reilly Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Mark Sherlock Academic Department of Endocrinology, Beaumont Hospital and the Royal College of Surgeons in Ireland, Dublin

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Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic–pituitary–adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

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Timothy J Morris Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK
Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK

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Andrew Whatmore Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Laura Hamilton Pathology Department, Clinical Biochemistry, Huddersfield Royal Infirmary, Lindley, Huddersfield, UK

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Beverly Hird Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Eric S Kilpatrick Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Lesley Tetlow Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Peter Clayton Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Children with salt-wasting adrenal insufficiency are managed with glucocorticoid and mineralocorticoid replacement. Measurement of renin activity or concentration alongside blood electrolyte levels is used to monitor the adequacy of mineralocorticoid replacement. Our unit changed from using renin activity to renin concentration and carried out a service review to assess whether this influenced decision-making for fludrocortisone dosing. In total, 50 measurements of plasma renin activity and 50 of renin concentration were analysed on separate cohorts before and after the assay change, with values standardised to multiples of the upper limit of normal (MoU) to allow comparison between assays. We were more likely to increase the fludrocortisone dose for a raised renin concentration than a raised renin activity. The renin concentration MoU was more strongly related to plasma sodium (negatively) and 17α-hydroxyprogesterone (17α-OHP) (positively) than the renin activity MoU. Using a MoU cut-off of 1.5, a decision to increase the dose of fludrocortisone was more likely to be made when using the renin concentration assay compared with the activity assay. Using a cut-off of 40 nmol/L for 17α-OHP, a decision not to change the fludrocortisone dose when 17α-OHP was <40 was more likely when using the renin concentration assay. For both assays, a plasma sodium <140 mmol/L was more likely to lead to a fludrocortisone dose increase, and most likely for the renin concentration assay. Overall, the decision to adjust fludrocortisone dose in this cohort of children with adrenal insufficiency was better supported by the biochemical parameters when based on renin concentration results and clinical status.

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