title: Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters.
abstract: OBJECTIVE
  Subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy have been associated with an increased risk of gestational diabetes. We aimed to ascertain if these women have a worse metabolic phenotype than euthyroid pregnant women.
  
  
  METHODS
  We recruited 956 healthy Caucasian women with singleton, non-diabetic pregnancies from routine antenatal clinics. Detailed anthropometric measurements (including BMI and skinfold thickness) and fasting blood samples (for TSH, free thyroxine (FT4), free triiodothyronine (FT3), HbA1c, lipid profile, plasma glucose and insulin resistance (HOMA-IR) analysis) were obtained at 28 weeks gestation.
  
  
  RESULTS
  In comparison to euthyroid women (n=741), women with isolated hypothyroxinaemia (n=82) had significantly increased BMI (29.5 vs 27.5 kg/m(2), P<0.001), sum of skinfolds (57.5 vs 51.3 mm, P=0.002), fasting plasma glucose (4.5 vs 4.3 mmol/l, P=0.01), triglycerides (2.3 vs 2.0 mmol/l, P<0.001) and HOMA-IR (2.0 vs 1.3, P=0.001). Metabolic parameters in women with subclinical hypothyroidism (n=133) were similar to those in euthyroid women. Maternal FT4 was negatively associated with BMI (r=-0.22), HbA1c (r=-0.14), triglycerides (r=-0.17), HOMA-IR (r=-0.15) but not total/HDL cholesterol ratio (r=-0.03). Maternal FT3:FT4 ratio was positively associated with BMI (r=0.4), HbA1c (r=0.21), triglycerides (r=0.2), HOMA-IR (r=0.33) and total/HDL cholesterol ratio (r=0.07). TSH was not associated with the metabolic parameters assessed.
  
  
  CONCLUSIONS
  Isolated hypothyroxinaemia, but not subclinical hypothyroidism, is associated with adverse metabolic phenotype in pregnancy, as is decreasing maternal FT4 and increasing FT3:FT4 ratio. These associations may be a reflection of changes in the thyroid hormone levels secondary to increase in BMI rather than changes in thyroid hormone levels affecting body weight and related metabolic parameters.
authors.affiliation: NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Knight
authors.affiliation: NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK.
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.affiliation: NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.affiliation: NIHR Exeter Clinical Research FacilityUniversity of Exeter Medical School, University of Exeter, Exeter, UKDepartment of EndocrinologyRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter, EX2 5DW, UKResearch and Development DepartmentRoyal Devon and Exeter Hospital NHS Foundation Trust, Exeter UK b.vaidya@exeter.ac.uk.
authors.forename: Bijay
authors.initials: B
authors.lastname: Vaidya
mesh_terms: D000328:Adult; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005865:Gestational Age; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007037:Hypothyroidism / Q000150:complications*; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications*; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D012307:Risk Factors; D012885:Skinfold Thickness; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D013972:Thyrotropin; D013974:Thyroxine; D014280:Triglycerides; D014284:Triiodothyronine