scholarly journals Phosphodiesterase 8B Gene Polymorphism Is Associated with Subclinical Hypothyroidism in Pregnancy

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5191-5191
Author(s):  
Beverley M. Shields ◽  
Rachel M. Freathy ◽  
Bridget A. Knight ◽  
Anita Hill ◽  
Michael N. Weedon ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Subclinical Hypothyroidism ◽  
Reference Range ◽  
Adverse Outcomes ◽  
Thyroid Peroxidase ◽  
Intention To Treat ◽  
Recommended Treatment ◽  
Normal Ranges ◽  
Serum Tsh ◽  
In Pregnancy

ABSTRACT Background: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society’s recent consensus guidelines have recommended treatment with T4 for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy. Methods: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women. Results: TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery. Conclusion: Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy.

scholarly journals Phosphodiesterase 8B Gene Polymorphism Is Associated with Subclinical Hypothyroidism in Pregnancy

2009 ◽  
Vol 94 (11) ◽  
pp. 4608-4612 ◽  
Author(s):  
Beverley M. Shields ◽  
Rachel M. Freathy ◽  
Bridget A. Knight ◽  
Anita Hill ◽  
Michael N. Weedon ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Subclinical Hypothyroidism ◽  
Reference Range ◽  
Adverse Outcomes ◽  
Thyroid Peroxidase ◽  
Intention To Treat ◽  
Recommended Treatment ◽  
Normal Ranges ◽  
Serum Tsh ◽  
In Pregnancy

Background: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society’s recent consensus guidelines have recommended treatment with T4 for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy. Methods: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women. Results: TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery. Conclusion: Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy. Variation in the PDE8B gene leads to alteration in serum TSH concentration and different proportions of women picked up with subclinical hypothyroidism in pregnancy.

scholarly journals Does foetal gender influence maternal thyroid parameters in pregnancy?

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgiana Sitoris ◽  
Flora Veltri ◽  
Pierre Kleynen ◽  
Malika Ichiche ◽  
Serge Rozenberg ◽  
...  
Keyword(s):  
Reference Range ◽  
Thyroid Autoimmunity ◽  
First Trimester ◽  
Thyroid Peroxidase ◽  
Reference Ranges ◽  
Free T4 ◽  
Cross Sectional ◽  
Maternal Thyroid ◽  
Serum Tsh ◽  
Tsh Levels

Objective It is unknown if foetal gender influences maternal thyroid function during pregnancy. We therefore investigated the prevalence of thyroid disorders and determined first-trimester TSH reference ranges according to gender. Methods A cross-sectional study involving 1663 women with an ongoing pregnancy was conducted. Twin and assisted pregnancies and l-thyroxine or antithyroid treatment before pregnancy were exclusion criteria. Serum TSH, free T4 (FT4) and thyroid peroxidase antibodies (TPOAb) were measured at median (interquartile range; IQR) 13 (11–17) weeks of gestation. Subclinical hypothyroidism (SCH) was present when serum TSH levels were >3.74 mIU/L with normal FT4 levels (10.29–18.02 pmol/L), and thyroid autoimmunity (TAI) was present when TPOAb were ≥60 kIU/L. Results Eight hundred and forty-seven women were pregnant with a female foetus (FF) and 816 with a male foetus (MF). In women without TAI and during the gestational age period between 9 and 13 weeks (with presumed high-serum hCG levels), median (IQR range) serum TSH in the FF group was lower than that in the MF group: 1.13 (0.72–1.74) vs 1.24 (0.71–1.98) mIU/L; P = 0.021. First-trimester gender-specific TSH reference range was 0.03–3.53 mIU/L in the FF group and 0.03–3.89 mIU/L in the MF group. The prevalence of SCH and TAI was comparable between the FF and MF group: 4.4% vs 5.4%; P = 0.345 and 4.9% vs 7.5%; P = 0.079, respectively. Conclusions Women pregnant with an MF have slightly but significantly higher TSH levels and a higher upper limit of the first-trimester TSH reference range, compared with pregnancies with a FF. We hypothesise that this difference may be related to higher hCG levels in women pregnant with a FF, although we were unable to measure hCG in this study. Further studies are required to investigate if this difference has any clinical relevance.

scholarly journals Nutrition in pregnancy: Basic principles and recommendations

2014 ◽  
Vol 142 (1-2) ◽  
pp. 125-130 ◽  
Author(s):  
Draga Plecas ◽  
Snezana Plesinac ◽  
Olivera Kontic-Vucinic
Keyword(s):  
Adult Life ◽  
Adverse Outcomes ◽  
Adaptive Responses ◽  
Normal Ranges ◽  
Energy Needs ◽  
Wide Range ◽  
Short And Long Term ◽  
Adverse Pregnancy ◽  
In Pregnancy

Healthy diet in pregnancy should guarantee proper fetal growth and development, maintain (and promote) maternal health and enable lactation. Nutritional counseling and interventions need to be an integral part of antenatal care and continue during pregnancy in order to reduce the risk of maternal, fetal and neonatal complications, as well as the short- and long-term adverse outcomes. Adverse pregnancy outcomes are more common in women who begin the gestation as undernourished or obese in comparison to pregnant women whose weight is within normal ranges. Increased nutritional and energy needs in pregnancy are met through numerous metabolic adaptations; pregnancy is successfully achieved within wide range of variations in energy supply and weight gain. However, if nutrient restriction exceeds the limits of adaptive responses, evidence indicates that fetus will develop the alternative metabolic competence that might emerge as a disease (type 2 diabetes, hypertension, coronary heart disease and stroke) in adult life.

Subclinical hypothyroidism: treat or watch?

2021 ◽  
pp. 98-108
Author(s):  
I. A. Tsanava ◽  
S. V. Bulgakova ◽  
A. V. Melikova
Keyword(s):  
Thyroid Hormones ◽  
Subclinical Hypothyroidism ◽  
Metabolic Disorders ◽  
Reference Range ◽  
Cognitive Disorders ◽  
The Body ◽  
Relationship Of ◽  
The Relationship ◽  
Serum Tsh ◽  
Tsh Levels

Manifest hypothyroidism occurs in more than 5 % of the population, while prevalence of subclinical hypothyroidism is much higher and reaches 15 %. In the practice of an endocrinologist, in most cases, the diagnosis and treatment of manifest hypothyroidism does not raise questions, while subclinical changes in thyroid hormones quite often generate a lot of discussions. The generally accepted reference range for TSH up to 4.50 μIU / ml is in conflict with data showing that more than 95 % of healthy people with euthyroidism have serum TSH levels up to 2.5 μIU / ml. At the same time, a lot of data has been accumulated on the effect of even slightly altered levels of thyroid hormones and TSH on various tissues, organs and systems of the body, especially on the cardiovascular, nervous and reproductive systems. This review analyzes the results of studies aimed at studying the relationship of subclinical hypothyroidism with cardiovascular and metabolic disorders, cognitive disorders, pathology of pregnant women.

scholarly journals The sequelae of untreated maternal hypothyroidism

2004 ◽  
pp. U45-U48 ◽  
Author(s):  
ML Mitchell ◽  
RZ Klein
Keyword(s):  
Pregnant Women ◽  
Subclinical Hypothyroidism ◽  
Reference Range ◽  
Critical Time ◽  
Normal Reference Range ◽  
Screening Programs ◽  
Normal Reference ◽  
Significant Difference ◽  
The Mean ◽  
In Pregnancy

The concept that gestational subclinical hypothyroidism could have deleterious effects on the intellectual outcome of progeny was championed more than three decades ago by Evelyn Man in a series of publications. Her studies lay fallow until the Spanish group directed by Morreale de Escobar and the Dutch group headed by Vulsma provided the rationale for her results. Although the findings of the Spanish and Dutch groups elucidated the pathophysiologic basis for Man's conclusions, questions remained regarding the reliability of her biochemical measurements and possible bias in patient selection. In view of the uncertainty surrounding the validity of Man's work, we decided to try to confirm her findings. Our initial goal was to obtain an estimate of the prevalence of subclinical hypothyroidism in an unselected population living in New England. We accomplished this with two separate prospective studies involving 12 000 pregnant women residing in Maine. We found that 2.3% had TSH concentrations of >6.0 mU/l and 0.3% had TSH values of >12 mU/l at 17 weeks' gestation. We next did a retrospective study, utilizing sera that had been stored at -20 degrees C for 8 years, obtained in week 17 of gestation from 25 000 women. We identified 62 women with subclinical hypothyroidism and 124 matched controls. Fourteen of the hypothyroid mothers had been diagnosed and treated before and during pregnancy on a dosage of thyroxine that was unchanged. WISC IQs of the offspring of the 124 control and 62 hypothyroid mothers were determined at 8+/-0.5 years. The mean and s.d. of IQs of the children of the 124 control and of the 14 treated hypothyroid mothers were significantly higher than those of the children of the 48 untreated hypothyroid women. More than twice as many children of the untreated mothers had IQs of >1 s.d. below the control mean, and four times as many of the children had IQs 2 s.d. below the control mean, as did the children of the controls. A comparison of the mean hormonal values of the treated and untreated mothers at 17 weeks showed no significant difference in any of the biochemical markers. We surmise that the circulating level of thyroxine was normal in the treated mothers at a critical time before 17 weeks' gestation, but by 17 weeks it was insufficient to meet the growing demands of pregnancy. Treatment should begin as early as possible in pregnancy with the goal of maintaining free thyroxine (FT(4)) in the upper half of the normal reference range and TSH in the lower half of the normal reference range. In view of these data, we believe that all pregnant women should be screened for hypothyroidism as early in pregnancy as possible (or even before conception). To be cost-effective, screening programs should be based on those designed for congenital hypothyroidism, in which filter-paper blood specimens are forwarded to regional laboratories for thyroid function determinations.

scholarly journals Serum TSH and serum thyroid peroxidase antibody fluctuate in parallel and high urinary iodine excretion predicts subsequent thyroid failure in a 1-year study of patients with untreated subclinical hypothyroidism

2008 ◽  
Vol 158 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Jesper Karmisholt ◽  
Peter Laurberg
Keyword(s):  
Thyroid Function ◽  
Subclinical Hypothyroidism ◽  
Urinary Iodine ◽  
Time Shift ◽  
Urinary Iodine Excretion ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibody ◽  
Iodine Excretion ◽  
Symptoms And Signs ◽  
Serum Tsh

ObjectiveTo explore the possibility of predicting decline or improvement in thyroid function over 1 year, and to investigate the correlations of serum TSH (s-TSH) with hypothyroidism-related symptoms and signs, serum thyroid peroxidase antibody (s-TPO-Ab) and urinary iodine excretion in individual patients with untreated subclinical hypothyroidism (SH).DesignMonthly repeated measurement study without intervention.MethodsTwenty-one patients without former thyroid disease who had been identified with s-TSH between 5 and 12 mU/l and normal serum thyroxine (s-T4) at two occasions were enrolled. Subsequently, 13 monthly measurements of s-TSH, hypothyroidism-related symptoms and signs, serum free T4, s-TPO-Ab and urinary iodine excretion were performed.ResultsOver the study year, s-TSH increased significantly in 5 patients, 16 had unchanged s-TSH, whereas none improved. From clinical and biochemical inclusion data, it was not possible to predict who would later increase in s-TSH. In individual patients, a highly significant correlation between s-TSH and s-TPO-Ab was found (r=0.37, P<0.0001) and also between s-TSH and urinary iodine excretion (r=0.14, P=0.034). No correlation between s-TSH and clinical symptoms and signs was observed. Time shift showed best correlation between s-TSH and s-TPO-Ab measured at the same time point, whereas urinary iodine excretion correlated best to s-TSH and s-TPO-Ab obtained 1 month later.ConclusionAt the time of inclusion, it was not possible to identify the 24% of SH patients who would show deterioration in thyroid function over the following year. Impairment in thyroid function varied in parallel with thyroid autoimmunity, whereas high urinary iodine excretion predicted high s-TSH and s-TPO-Ab 1 month later.

Subclinical hypothyroidism: an audit of management

2003 ◽  
Vol 40 (6) ◽  
pp. 694-696
Author(s):  
PK Prakash ◽  
H Bolusani ◽  
A Hameed ◽  
LDKE Premawardhana
Keyword(s):  
Subclinical Hypothyroidism ◽  
Thyroid Disease ◽  
Treatment Guidelines ◽  
Thyroid Stimulating Hormone ◽  
Overt Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Amiodarone Therapy ◽  
Retrospective Case ◽  
General Physicians ◽  
Serum Tsh

Background: Subclinical hypothyroidism (SH) is a marker for overt hypothyroidism and vascular disease. Treatment guidelines are not universally followed. Thyroxine is recommended if serum thyroid-stimulating hormone (TSH) concentration is 10 mU/L or more, or if serum TSH is 5-9.9 mU/L (mild SH) with other risk factors, such as thyroid peroxidase antibodies (TPOAb). Methods: We examined the management of mild SH in a retrospective case note audit of 150 consecutive subjects. Twenty-seven subjects with a serum TSH concentration above 10 mU/L were excluded from analysis. Of the group with mild SH, 27 were also excluded because of previous thyroid disease or amiodarone therapy. Results: The prevalence of previous thyroid disease was similar in subjects with TSH 10 mU/L or more, compared to those with mild SH. Overall, both TPOAb and goitre status were determined in only 39% of subjects with mild SH, but in more by endocrinologists compared with general physicians (63% versus 22% for TPOAb; 47% versus 17% for goitre) ( P = 0.001). Endocrinologists treated a greater number of subjects with mild SH who were eligible for thyroxine therapy compared to nonendocrine colleagues (96% versus 67%) ( P = 0.024). Both groups treated subjects in whom TPOAb status was not determined (endocrinologists 21% versus general physicians 40%) ( P = 0.21). Conclusion: In subjects with mild SH, evaluation is incomplete, a large percentage who were TPOAb positive were on appropriate therapy, thyroxine was prescribed when TPOAb status was unknown and, on the whole, endocrinologists performed better than general physicians.

Thyroid Disease II: Hypothyroidism in Pregnancy

2020 ◽  
Author(s):  
Robert B. Martin ◽  
Brian Casey
Keyword(s):  
Thyroid Disease ◽  
Elevated Serum ◽  
Disease Diagnosis ◽  
Small Subset ◽  
Overt Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Postpartum Thyroiditis ◽  
Increased Risk ◽  
Serum Tsh ◽  
In Pregnancy

Hypothyroidism affects between 2 and 12 per 1000 pregnancies.  Symptoms in pregnancy are similar those encountered in the nonpregnant population, but may be attributed to the pregnancy itself. Thyroxine-binding globulin increases in pregnancy, leading to increased thyroxine levels in order to meet the metabolic needs of normal pregnancy.  Routine screening is not recommended, and testing should be done using a targeted approach in women with symptoms or history of thyroid disease. Diagnosis is based upon the finding of an elevated serum TSH using population and trimester-specific ranges. Overt hypothyroidism, identified by high serum TSH and low free thyroxine, is associated with increased risk of pregnancy-related complications, and is treated with maternal thyroxine supplementation.  Adequate iodine is necessary for fetal neurodevelopment, and women with iodine deficiency may present with a goiter, though it is important to distinguish it from other causes of thyroid enlargement, including malignancy.  Postpartum thyroiditis is diagnosed infrequently, as only a small subset of women will demonstrate the classic biphasic presentation,  Additionally, symptoms are often vague, nonspecific, and self-limited.  Importantly, many women are at risk of eventually developing permanent hypothyroidism. This review contains 6 tables, and 48 references.  Key words: euthyroid, goiter, overt hypothyroidism, postpartum thyroiditis, thyroixine binding globulin, thyroid peroxidase, thryroid nodules

scholarly journals Application of a Multi-Marker Approach to Assess Vitamin B12 Status at the End of the First Trimester of Pregnancy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4804-4804
Author(s):  
Alesia Abigael Khan ◽  
Ashwenia Krishnan ◽  
Dominic Jon Harrington ◽  
Susan Robinson
Keyword(s):  
Renal Function ◽  
Vitamin B12 ◽  
Binding Proteins ◽  
Reference Range ◽  
First Trimester ◽  
Adverse Outcomes ◽  
Reference Ranges ◽  
Available N ◽  
Dynamic Assay ◽  
In Pregnancy

Abstract Background : During pregnancy, vitamin B12 (B12) utilisation increases, with deficiency being associated with adverse outcomes (Murphy 2007, VanderJagt 2011). It remains unclear however at what level vitamin B12 status becomes detrimental, and the correlation with fetal harm. Establishing B12 status during pregnancy is complicated by physiological changes such as haemodilution due to expanded blood volume, altered renal function, alterations in the vitamin B12 -binding proteins and transfer of materno-fetal B12 yet laboratories typically rely on the total abundance of B12 in serum (serum B12) asthe sole laboratory status indicator, interpreting results against reference range cut offs derived from non-pregnant populations, including men. Serum B12 assays measure the sum of holohaptocorrin and holotranscobalamin (holoTC). Other markers of B12 status are also available and are increasingly being adopted: holoTC (active B12) accounts 6-20% of bound B12, which is the only form of B12 presented for cellular uptake and used to satisfy metabolic demand; methylmalonic acid (MMA) is a by-product of methylmalonyl-CoA metabolism, the concentration of which in serum correlates inversely with tissue B12 utilisation. Methods: Over a 2 monthperiod in 2015 we used an extended panel of laboratory tests consisting of serum B12, holoTC, and MMA to determine B12 status, and assess appropriateness of our assay reference ranges, in 100 pregnant women with normal renal function at the end of the first trimester. Laboratory Analysis Serum B12 and holoTC were determined by an Abbott Architect analyzer. The serum B12 assay has a reference range of 187 - 883 ng/L. The holoTC assay has ²10% cross-reactivity from B12-binding proteins haptocorrin and apotranscobalamin. Values >128 pmol/L are above the dynamic assay range. In our laboratory holoTC results <25 pmol/L are defined as deficient and those >70 pmol/L as replete. Results 25-70 pmol/L are classified as indeterminate and a serum MMA assay subsequently performed (Sobczyńska-Malefora A et al 2014). We determined serum MMA using a Gerstel Multipurpose Sampler coupled to a liquid chromatography tandem mass spectrometer with electrospray ionization with results >270 nmol/L considered indicative of suboptimal B12 status (Harrington DJ 2016). Results: All three assays, figure 3, were performed for 92 women (insufficient sample available n=8).HoloTCand MMA results are shown in Table 1. The distribution ofholoTCand MMA concentrations are shown in Figure 1. One woman had a serum B12 below the reference range with a corresponding indeterminate holoTC and normal MMA. This set of results suggests questionable abundance of B12 that has not translated to functional deficiency. One woman had a holoTCconcentration <25pmol/L, however the corresponding serum B12 and MMA were not indicative of sub optimal B12 status. Fourteen women had aholoTC result above the dynamic assay range. Two women had an elevated MMA concentration with corresponding holoTCresults indicating questionable abundance of B12 but serum B12 within our reference limit. This triad of values indicates possible emerging suboptimal B12 status that would have been overlooked if serum B12 had been used in isolation. Discussion: B12 requirement increases in pregnancy and diet alone is unlikely to meet requirements (Murphy et al 2007). Deficiency has a detrimental impact on maternal and infant development and therefore it is useful to explore the relationship between different laboratory markers of B12 status in pregnancy (Ramirez-Velez et al 2016, Siddiqua et al 2014). The comparison of serum B12,holoTC and MMA levels at the end of the first trimester with reference ranges derived from non-pregnant adults suggests that they are broadly applicable. Serum B12 is the least sensitive marker and its use in isolation to assess B12 status is limiting. The application of holoTC and MMA in tandem can reveal previously missed deficient states. Using these markers two women in this small study were identified as possibly deficient although the true significance of a mildly elevated MMA in pregnancy requires further investigation. These data highlight the benefit of adopting a panel of markers ahead of a single test to assess B12 status. Identifying women at the end of the first trimester that may benefit from B12 replacement potentially protects from deficient states. Disclosures Robinson: Pharmacosmos: Honoraria; Amgen: Honoraria; Novartis: Honoraria.

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