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Open access

Verônica Carneiro Borges Mioto, Ana Carolina de Castro Nassif Gomes Monteiro, Rosalinda Yossie Asato de Camargo, Andréia Rodrigues Borel, Regina Maria Catarino, Sergio Kobayashi, Maria Cristina Chammas, and Suemi Marui

Objectives

Iodine deficiency during pregnancy is associated with obstetric and neonatal adverse outcomes. Serum thyroglobulin (sTg) and thyroid volume (TV) are optional tools to urinary iodine concentration (UIC) for defining iodine status. This cross-sectional study aims to evaluate the iodine status of pregnant women living in iodine-adequate area by spot UIC and correlation with sTg, TV and thyroid function.

Methods

Two hundred and seventy-three pregnant women were evaluated at three trimesters. All had no previous thyroid disease, no iodine supplementation and negative thyroperoxidase and thyroglobulin antibodies. Thyroid function and sTg were measured using electrochemiluminescence immunoassays. TV was determined by ultrasonography; UIC was determined using a modified Sandell–Kolthoff method.

Results

Median UIC was 146 µg/L, being 52% iodine deficient and only 4% excessive. TSH values were 1.50 ± 0.92, 1.50 ± 0.92 and 1.91 ± 0.96 mIU/L, respectively, in each trimester (P = 0.001). sTg did not change significantly during trimesters with median 11.2 ng/mL and only 3.3% had above 40 ng/mL. Mean TV was 9.3 ± 3.4 mL, which positively correlated with body mass index, but not with sTg. Only 4.5% presented with goitre.

When pregnant women were categorized as iodine deficient (UIC < 150 µg/L), adequate (≥150 and <250 µg/L) and excessive (≥250 µg/L), sTg, thyroid hormones and TV at each trimester showed no statistical differences.

Conclusions

Iodine deficiency was detected frequently in pregnant women living in iodine-adequate area. sTg concentration and TV did not correlate to UIC. Our observation also demonstrated that the Brazilian salt-iodization programme prevents deficiency, but does not maintain iodine status within adequate and recommended ranges for pregnant women.

Open access

Dimitra Argyro Vassiliadi, Ioannis Ilias, Maria Pratikaki, Edison Jahaj, Alice G Vassiliou, Maria Detsika, Kleio Ampelakiotou, Marina Koulenti, Konstantinos N Manolopoulos, Stamatis Tsipilis, Evdokia Gavrielatou, Aristidis Diamantopoulos, Alexandros Zacharis, Nicolaos Athanasiou, Stylianos Orfanos, Anastasia Kotanidou, Stylianos Tsagarakis, and Ioanna Dimopoulou

Objective

Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients.

Design

Cohort observational study.

Methods

We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism.

Results

A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of negative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare.

Conclusions

NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients.

Open access

Xiujuan Su, Yan Zhao, Zhijuan Cao, Yingying Yang, Tony Duan, and Jing Hua

Background

The effect of isolated maternal hypothyroxinaemia (IMH) on pregnancy complications and neonatal outcomes in human beings is still controversial.

Methods

This was a retrospective cohort study based on the electronic medical register system. The records of women with a singleton pregnancy who sought antenatal examination between January 2014 and December 2015 at Shanghai First Maternity and Infant Hospital were extracted from the electronic medical records system. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab) was measured before 20 gestational weeks, and a multiple logistic regression model was used to estimate the odds ratios of pregnancy complications and neonatal outcomes between euthyroid women and those with isolated hypothyroxinaemia.

Results

A total of 8173 women were included in this study, of whom 342 (4.18%) were diagnosed with IMH. Regression analysis showed that IMH diagnosed in the second trimester (13–20 weeks) was associated with an increased risk of hypertensive disorders of pregnancy (OR = 2.66, 95% CI: 1.38–5.10) and placenta abruption (OR = 3.64, 95% CI: 1.07–12.41), but not with preterm delivery (OR = 1.09, 95% CI: 0.50–2.40), small or large gestational age of infant (OR = 0.91, 95% CI: 0.39–2.12; OR = 1.16, 95% CI: 0.72–1.86), macrosomia (OR = 1.71, 95% CI: 0.95–3.07), gestational diabetes mellitus (OR = 1.36, 95% CI: 0.86–2.15) and placenta previa (OR = 1.62, 95% CI: 0.39–7.37).

Conclusion

IMH could be a risk factor for hypertensive disorders of pregnancy.

Open access

Ulla Schmidt, Birte Nygaard, Ebbe Winther Jensen, Jan Kvetny, Anne Jarløv, and Jens Faber

Background

A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.

Hypothesis

Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy.

Methods

Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.

Results

TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.

Conclusions

T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.

Open access

Enrique Soto-Pedre, Paul J Newey, John S Bevan, and Graham P Leese

Purpose

High serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia.

Methods

A population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014 was performed. Record-linkage technology was used to identify patients with hyperprolactinaemia that were compared to an age–sex-matched cohort of patients free of hyperprolactinaemia. The number of deaths and incident admissions with diabetes mellitus, cardiovascular disease, cancer, breast cancer, bone fractures and infectious conditions were compared by the survival analysis.

Results

Patients with hyperprolactinaemia related to pituitary tumours had no increased risk of diabetes, cardiovascular disease, bone fractures, all-cause cancer or breast cancer. Whilst no increased mortality was observed in patients with pituitary microadenomas (HR = 1.65, 95% CI: 0.79–3.44), other subgroups including those with pituitary macroadenomas and drug-induced and idiopathic hyperprolactinaemia demonstrated an increased risk of death. Individuals with drug-induced hyperprolactinaemia also demonstrated increased risks of diabetes, cardiovascular disease, infectious disease and bone fracture. However, these increased risks were not associated with the degree of serum prolactin elevation (P trend > 0.3). No increased risk of cancer was observed in any subgroup.

Conclusions

No excess morbidity was observed in patients with raised prolactin due to pituitary tumours. Although the increased morbidity and mortality associated with defined patient subgroups are unlikely to be directly related to the elevation in serum prolactin, hyperprolactinaemia might act as a biomarker for the presence of some increased disease risk in these patients.

Open access

Sarah Byberg, Jesper Futtrup, Mikkel Andreassen, and Jesper Krogh

Objectives

Recent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to systematically assess the effect of reducing prolactin with dopamine agonist on established cardiovascular risk factors in patients with prolactinomas.

Design

Bibliographical search was done until February 2019 searching the following databases: PubMed, EMBASE, WHO and LILAC. Eligible studies had to include participants with verified prolactinomas where metabolic variables were assessed before and after at least 2 weeks treatment with dopamine agonists.

Methods

Baseline data and outcomes were independently collected by two investigators. The study was registered with PROSPERO (registration number CRD42016046525).

Results

Fourteen observational studies enrolling 387 participants were included. The pooled standardized mean difference of the primary outcome revealed a reduction of BMI and weight of −0.21 (95% CI −0.37 to −0.05; P = 0.01; I 2 = 71%), after treatment. Subgroup analysis suggested that the reduction of weight was primarily driven by studies with high prolactin levels at baseline (P = 0.04). Secondary outcomes suggested a small decrease in waist circumference, a small-to-moderate decrease in triglycerides, fasting glucose levels, HOMA-IR, HbA1c and hsCRP, and a moderate decrease in LDL, total cholesterol and insulin.

Conclusion

This systematic review suggests a reduction of weight as well as an improved lipid profile and glucose tolerance after treatment with dopamine agonist in patients with prolactinomas. These data are based on low-quality evidence.

Open access

Lijin Ji, Na Yi, Qi Zhang, Shuo Zhang, Xiaoxia Liu, Hongli Shi, and Bin Lu

Objective

To assess the current management of prolactinoma among endocrinologists in China.

Methods

An online survey of a large sample of endocrinologists was conducted in China. The questionnaire included 21 questions related to controversial issues about the management of prolactinomas. Doctors in the endocrinology department of a university-affiliated hospital or a comprehensive secondary hospital in 12 cities from East, West, South, North and Middle China were surveyed.

Results

A total of 290 valid questionnaires were collected, and the response rate was 40%. When hyperprolactinemia occurred, 97% of the respondents would test thyroid-stimulating hormone routinely. 22% of the respondents considered that prolactin levels <100 ng/mL exclude the presence of a prolactinoma. Only 9% of the respondents believed that prolactin >250 ng/mL could occur in all the following situations as macroprolactinoma, mircoprolactinoma, macroprolactinemia and drug-induced hyperprolactinemia. Surgery was not recommended by 272 (94%) endocrinologists as the first choice for treating microprolactinomas. 58% and 92% of endocrinologists would start drug treatment for microprolactinomas and macroprolactinomas at diagnosis. 70% and 40% chose to withdraw treatment after 2–3 years of prolactin normalization in microprolactinomas and macroprolactinomas. In case of pregnancy, 57% of the respondents considered bromocriptine as choice for women patients. Drug discontinuation after pregnancy was advocated in 63% and 27% for microprolactinoma and macroprolactinoma. Moreover, 44% of endocrinologists believed that breastfeeding was allowable in both micro- and macroprolactinoma.

Conclusion

This is the first study to investigate the management of prolactinomas among endocrinologists in China. We found that the current clinical treatment was not uniform. Therefore, it is necessary to strengthen the training of endocrinologists to improve clinical diagnosis and treatment practices.

Open access

Shruti Khare, Anurag R Lila, Hiren Patt, Chaitanya Yerawar, Manjunath Goroshi, Tushar Bandgar, and Nalini S Shah

Macroprolactinomas are the most common functional pituitary tumours. Hypotheses proposed to explain predominance of large tumours in males are: i) diagnostic delay, as hyperprolactinaemia remains under recognised in males and ii) gender-specific difference in tumour proliferation indices. Our study objectives are to compare gender differences in clinical, biochemical, radiological features, management outcomes and cabergoline responsiveness in macroprolactinomas. Drug resistance was defined as failure to achieve prolactin normalisation and >50% reduction in tumour volume with cabergoline (3.5 mg/week dose for minimum 6 months duration). The baseline characteristics of 100 patients (56 females and 44 males) with macroprolactinoma were analysed. Drug responsiveness was analysed in 88 treatment naive patients, excluding 12 post-primary trans-sphenoidal surgery cases. We found that females (30.29±10.39 years) presented at younger mean age than males (35.23±9.91 years) (P<0.01). The most common presenting symptom was hypogonadism (oligo-amenorrhoea/infertility) in females (96.15%) and symptoms of mass effect (headache and visual field defects) in males (93.18%). Baseline mean prolactin levels were significantly lower in females (3094.36±6863.01 ng/ml) than males (7927.07±16 748.1 ng/ml) (P<0.001). Maximal tumour dimension in females (2.49±1.48 cm) was smaller than males (3.93±1.53 cm) (P<0.001). In 88 treatment naïve patients, 27.77% females and 35.29% males had resistant tumours (P=0.48). On subgrouping as per maximum tumour dimension (1.1–2 cm, 2.1–4 cm and >4 cm), gender difference in response rate was insignificant. In conclusion, macroprolactinomas are equally prevalent in both sexes. Macroprolactinomas in males predominantly present with symptoms of mass effects, as against females who present with symptoms of hypogonadism. Males harbor larger tumours but are equally cabergoline responsive as those in females.

Open access

Tao Mei, Jianhe Zhang, Liangfeng Wei, Xingfeng Qi, Yiming Ma, Xianhua Liu, Shaohua Chen, Songyuan Li, Jianwu Wu, and Shousen Wang

Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.

Open access

Jia Liu, Lin Zhang, Jing Fu, Qiu Wang, and Guang Wang

Objective

Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes.

Methods

A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured.

Results

In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: β = −0.263, P < 0.05; adipo-IR: β = −0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01).

Conclusion

The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.