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      Impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in premenopausal HIV infected females at NAUTH, Nnewi, Nigeria

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          Abstract

          Background

          This was a prospective study designed to evaluate the impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in HIV infected females at Nnamdi Azikiwe University Teaching Hospital Nnewi, South-East Nigeria.

          Methods

          The study randomly recruited 35 Symptomatic HIV infected females and 35 Symptomatic HIV infected females on antiretroviral therapy (HAART) for not less than six weeks from an HIV clinic and 40 apparently heathy control females among the hospital staff of NAUTH Nnewi. They were all premenopausal females with regular menstrual cycle and aged between 15–45 years. Blood samples were collected at follicular and luteal phases of their menstrual cycle for assay of Thyroid indices (FT3, FT4 and TSH) and Reproductive indices (FSH, LH, Estrogen, Progesterone, Prolactin and Testosterone) using ELISA method.

          Results

          The result showed significantly higher FSH and LH but significantly lower progesterone (prog) and estrogen (E2) in the test females compared to control females at both phases of menstrual cycle (P<0.05). There was significantly lower FT3 but significantly higher TSH value in Symptomatic HIV females (P<0.05). FSH, LH and TSH values were significantly lowered while prog and FT3 were significantly higher in Symptomatic HIV on ART compared to Symptomatic HIV females (P<0.05). FT3, FT4, Prog and E2 were inversely correlated while FSH and LH were positively correlated with duration of HIV infection in HIV females (P<0.05 respectively). There was a direct correlation between CD4+ count and FT3 while inverse correlation was found between CD4+ count and TSH levels (P<0.05).

          Discussion

          The present study demonstrated hypothyroidism with a significant degree of primary hypogonadism in Symptomatic HIV infected females at both follicular and luteal phases of menstrual cycle which tends to normalize on treatments.

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          Most cited references45

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          A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors.

          To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. Cross-sectional study. Outpatient clinic of a university teaching hospital. HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47). Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.
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            The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.

            The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
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              Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review.

              Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy. Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register. From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Project administrationRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Resources
                Role: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Resources
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Resources
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Resources
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 July 2017
                2017
                : 12
                : 7
                : e0176361
                Affiliations
                [1 ] Department of Medical Laboratory Science, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria
                [2 ] Department of Prosthesis and Orthotics, School of Health Technology, Federal University of Technology Owerri, Imo State, Nigeria
                [3 ] Depatment of Community Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Anambra, State Nigeria
                [4 ] Department of Chemical pathology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria
                [5 ] Department of Obstetrics and Gynecology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria
                [6 ] Department of Medical Services, Federal Polytechnic, Oko, Anambra State, Nigeria
                Universite Clermont Auvergne, FRANCE
                Author notes

                Competing Interests: The authors have declared no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-4244-4892
                Article
                PONE-D-16-00326
                10.1371/journal.pone.0176361
                5516981
                28723963
                17bc9646-9484-4717-8581-89736c76e096
                © 2017 Ukibe et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 February 2016
                : 10 April 2017
                Page count
                Figures: 3, Tables: 4, Pages: 15
                Funding
                Funded by: TETFUND
                Award Recipient :
                This work was funded by TETFUND through Nnamdi Azikiwe University, Awka, Nigeria. ETF/ES/NAUNIV/AWKA/VOL.1.
                Categories
                Research Article
                Medicine and health sciences
                Diagnostic medicine
                HIV clinical manifestations
                Medicine and health sciences
                Infectious diseases
                Viral diseases
                HIV infections
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Menstrual Cycle
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Menstrual Cycle
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Menstrual Cycle
                Biology and Life Sciences
                Physiology
                Reproductive Physiology
                Menstrual Cycle
                Medicine and Health Sciences
                Physiology
                Reproductive Physiology
                Menstrual Cycle
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Highly-Active Antiretroviral Therapy
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Highly-Active Antiretroviral Therapy
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Highly-Active Antiretroviral Therapy
                Biology and Life Sciences
                Anatomy
                Endocrine System
                Thyroid
                Medicine and Health Sciences
                Anatomy
                Endocrine System
                Thyroid
                Biology and Life Sciences
                Biochemistry
                Hormones
                Lipid Hormones
                Progesterone
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Thyroid-Stimulating Hormone
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Hypothyroidism
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                All relevant data are within the paper and its Supporting Information files.

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