Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism

Background Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long‐term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. Objective To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long‐term hypothyroidism. Design Case–control with follow‐up. Patients A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. Measurements Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12‐year follow‐up. Results At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH < 0·4 mU/l 130·0 μg/l (82·0, 170·0); for TSH 0·4–4·0 mU/l 123·0 μg/l (80·5, 168·0); for TSH > 4·0 mU/l 85·0 μg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC < 50 μg/l, OR 4·22, (95%CI: 1·54, 11·55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12‐year follow‐up (P = 0·002); as did UIC < 100 μg/l (P = 0·03) and UIC < 50 μg/l (P = 0·02). The association was independent of antibody status. Conclusion Low UIC measured at 6 months postpartum is associated with hypothyroid PPTD and independently predicts long‐term hypothyroidism. We believe that it results from more severe preceding destructive thyroiditis, with discharge of thyroidal iodine, and thereby predicts a greater risk of long‐term hypothyroidism.     

Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity

Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.     

The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision

OBJECTIVE: To follow the clinical and biochemical course of a cohort of women who had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine the treatment practices of general practitioners and endocrinologists in the setting of PPTD. DESIGN: Prospective longitudinal study. SETTING: Metropolitan, Perth, Australia. PARTICIPANTS: Eighty-six Caucasian women who were identified to have PPTD at 6 months postpartum in a cross-sectional study of 748 women. MAIN OUTCOME MEASURES: Characteristics of the clinical and biochemical course of PPTD and documentation of the treatment practices and factors influencing treatment of PPTD by general practitioners and endocrinologists. RESULTS: Sixteen of 86 women (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum 27% of women had received treatment for PPTD. Fifty-one percent of those not treated were biochemically euthyroid at 9 months, although, for those with hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the upper limit of the reference range. Thyroid peroxidase antibody titre fell over the 2 years of follow-up. There was no significant change in clinical parameters over the study. Forty-nine percent of endocrinologists and 73% of general practitioners reported that they required clinical signs or symptoms before initiating treatment for hypothyroid PPTD. CONCLUSIONS: In a cohort of women with postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in untreated women does not completely return to the normal median. The role of clinical assessment in treatment decision-making differs between primary care physicians and endocrinologists. A case is made for the early Institution of permanent thyroxine replacement in women with postpartum thyroid dysfunction, elevated TSH and positive thyroid antibodies.     

Age as a predictor of recurrent hypothyroidism in patients with post-partum thyroid dysfunction

The long term effect of post-partum thyroid dysfunction (PPTD) is not well established. This study was conducted to evaluate the outcome of permanent hypothyroidism and factors predictive of thyroid dysfunction in a large cohort of women with PPTD. In 164 women, treated with levothyroxine for moderate and severe post- partum hypothyroidism, the treatment was discontinued and subjects were followed-up for the recurrence of hypothyroidism. Factors such as thyroid function tests, tyroid peroxidase antibodies (TPOAb) titers, multiparity, history of autoimmune disorders, smoking habits, use of oral contraceptives, family history of thyroid disease, goiter size and age at active phase of PPTD were assessed. Seventy-one post-partum women without PPTD were considered as control group. One hundred forty-eight women (90%) returned for follow-up, and 93 subjects (63%) developed hypothyroidism with a median of 2 months after T4 withdrawal. Of factors predicting recurrence of hypothyroidism, only age, and serum TSH and T3 concentrations at the time of occurrence of PPTD entered the model in multiple stepwise regression analysis. Hypothyroidism occurred earlier and more frequently in women aged 30 and over, as compared to younger ones (p < 0.01), hazard ratio 1.69. In 55 euthyroid subjects with history of PPTD, serum TSH was significantly increased as compared to the control group (3.0 +/- 1.6 vs 0.8 +/- 0.5 mU/l, p < 0.001). These data, representing the largest cohort of women with PPTD who have been followed, show that a significant proportion of women with moderate and severe PPTD, in particular those aged 30 yr and over, develop recurrent hypothyroidism. Proper follow-up of all women with PPTD, the older ones in particular, is recommended.     

The occurrence of permanent thyroid failure in patients with subclinical postpartum thyroiditis

OBJECTIVE: The long-term effect of the subclinical form of postpartum thyroid dysfunction (PPTD) has not been well established. This study was conducted to evaluate the outcome of permanent hypothyroidism in a large cohort of women with PPTD. DESIGN AND METHODS: Of 213 women with PPTD, 172 (81%) returned for follow-up. There were 27 (16%) with subclinical (group 1) and 145 (84%) with overt hypothyroidism (group 2). They were all treated with levothyroxine for 23 +/- 16 months and followed-up for thyroid function after thyroxine (T(4)) withdrawal. RESULTS: In group 1, the time of occurrence of PPTD was longer, serum T(4) was higher and TSH was lower than in group 2. After T(4) withdrawal, 59 and 64% of patients became hypothyroid in groups 1 and 2 respectively; however, serum TSH was increased in group 2 as compared with group 1 (29.7 +/- 8.4 vs 16.4 +/- 15.4 mU/l, P < 0.002). The duration of euthyroidism, serum free T(4) and triiodothyronine indices and thyroperoxidase antibodies were not significantly different between the two groups. CONCLUSION: It was concluded that a high percentage of patients with the subclinical form of PPTD proceed to permanent thyroid failure. The timely recognition of mild to severe cases of PPTD is important for the improvement of life for mothers and infants.     

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.     

Postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) refers to the syndromes of transient hyperthyroidism, transient hypothyroidism, or both, occurring sequentially in the first 12 months postpartum. Approximately 5 to 9% of women develop the disorder in this period. PPTD is most often subclinical but some women will experience symptoms such as lack of energy and depression in the hypothyroid phase. The thyroid gland, which normally enlarges during pregnancy, will remain enlarged or enlarge further in the postpartum period in a significant number of affected women, instead of returning to the prepregnancy size as in unaffected women. The gland is painless and histologically demonstrates lymphocytic infiltration. PPTD is strongly associated with the presence of antimicrosomal and/or antithyroglobulin antibodies, which occur in up to 76% of cases. Antibody activity tends to increase in the postpartum period and to peak at the time of onset of the disorder. TSH receptor antibodies are not seen and the gland has low radioiodine uptake, distinguishing PPTD from Graves' disease. The HLA associations are controversial, as is the role of dietary iodine. The etiology of PPTD is almost certainly immunological, reflecting the phenomenon of rebound from the relative immune tolerance of pregnancy. Detection of the disorder is important in order to reassure or treat those who are symptomatic and because PPTD may recur in subsequent pregnancies. In addition, up to one third of affected women will go on to develop permanent hypothyroidism 2 to 4 years later. The role of screening for PPTD remains to be clarified.     

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity

OBJECTIVE: Postpartum thyroid dysfunction (PPTD), diagnosed using biochemical criteria, is usually transient with a wide range of reported prevalence rates. The specific clinical and psychiatric morbidity associated with PPTD is still uncertain. The aims of the study were to determine the point prevalence of PPTD in Australian women at 6 months postpartum and to assess the specific clinical and psychiatric morbidity in these women. DESIGN: Women who were Caucasian, aged 20-45 years and 4.5-5.5 months postpartum, were randomly selected and invited into the study. The respondents were assessed for biochemical and psychiatric morbidity. PPTD for this study was defined as TSH or free T4 outside the adult reference range. A double blind clinical assessment of PPTD women and their matched controls used standardized clinical hypo- and hyperthyroid clinical indices. PATIENTS: From the total randomly selected sample size of 1816 women, 748 participated. MEASUREMENTS: Biochemical measurements were serum TSH, free T4, microsomal antibody (MsAb) and thyroid peroxidase antibody (TPOAb), and thyroid receptor antibodies (only in women with low TSH). Psychiatric assessment involved screening all participants using the General Health Questionnaire 28, followed by classifying and quantifying severity of cases using DSM-III-R categories for depression and anxiety. Clinical signs and symptoms of hypo- and hyper-thyroidism were measured using weighted standardized indices. Thyroid size was assessed by palpation. Achilles tendon reflex time was measured by photomotograph. RESULTS: The prevalence of PPTD in the participants was 11.5% (95% CI 9.2-13. 8%), giving a minimum prevalence for the randomly selected sample of 4.7% (95% CI 3.7-5.7%). In the PPTD women, 54% had an elevated TSH, 30% had a suppressed TSH and the remainder had a low fT4 and normal TSH. Positive thyroid autoantibody titres in the PPTD group were 46. 5% for microsomal antibody (MsAb) and 63.9% for thyroid peroxidase antibody (TPOAb), and in the non-PPTD group were 1.7% and 4.9%, respectively. The 6 month point prevalence rates of depression, generalized anxiety disorder and panic disorder and/or agoraphobia were 9.4%, 1.4% and 3.1%, respectively. No relationship was found between PPTD status and the diagnosis of current depression or between thyroid antibody status and current depression. In women who were diagnosed as anxious at the time of assessment, the number of anxiety symptoms was higher in the PPTD group (P < 0.05). There was no difference in signs and symptom scores for the hypo- and hyper-thyroid clinical indices between PPTD women and their controls. CONCLUSION: This study has shown a high prevalence of postpartum thyroid dysfunction but there was no difference in the clinical and psychiatric signs and symptoms between cases and controls. In the social, psychological, physical and endocrine setting of the postpartum period, women with postpartum thyroid dysfunction are identifiable by the attending physician only by their abnormal thyroid function tests.     

The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies

CONTEXT: Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis. OBJECTIVE: We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function. DESIGN: This was a prospective, randomized, placebo-controlled study. SETTING: The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology. PATIENTS: A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+). INTERVENTIONS: During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C). MAIN OUTCOME MEASURES: We measured the prevalence of PPTD and hypothyroidism. RESULTS: PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01). CONCLUSION: Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.     

Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months

Objective To examine the relationship between specific thyroid abnormalities (subclinical hypothyroidism, hypothyroxinaemia or elevated thyroid peroxidase antibody titres) in women during pregnancy and the subsequent neuropsychological development of their offspring. Design/Patients Serum was collected from 1268 women at 16–20 weeks of gestation and thyroid stimulating hormone (TSH), total thyroxine (tT₄), free thyroxine (fT₄), and Thyroid peroxidase antibodies (TPOAb) levels were measured. Thyroid function reference ranges specific for pregnancy were used to screen for thyroid abnormalities. Patients with isolated subclinical hypothyroidism (18 cases), hypothyroxinaemia (19 cases), and those who were euthyroid patients with elevated titres of TPOAb (34 cases) were identified. One hundred and forty‐two euthyroid and TPOAb‐negative women matched for gestational age from the same cohort were selected as controls. Measurements Intellectual and motor development score evaluations were performed on the children from the pregnancies at 25–30 months of age. Results Children of women with subclinical hypothyroidism, hypothyroxinemia and elevated TPOAb titres had mean intelligence scores 8·88, 9·30 and 10·56 points lower than those of the control group (P = 0·008, P = 0·004 and P = 0·001, respectively); mean motor scores were 9·98, 7·57 and 9·03 points lower than those of the controls [P < 0·001, P = 0·007 and P < 0·001, respectively (t‐test)]. Unconditional multivariate logistic regression analysis showed that increased maternal serum TSH, decreased maternal serum tT₄, and elevated maternal TPOAb titres were separately associated with lower intelligence scores (ORs 15·63, 12·98, and 6·69, respectively) and poorer motor scores (ORs 9·23, 5·52, and 8·25, respectively). Conclusions Intellectual and motor development of children at 25–30 months of age is separately associated with abnormalities of maternal thyroid at 16–20 weeks gestation. Maternal subclinical hypothyroidism, hypothyroxinaemia or euthyroidism with elevated TPOAb titres were all statistically significant predictors of lower motor and intellectual development at 25–30 months.     

Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes

Postpartum thyroid dysfunction (PPTD) develops during the first 9 months in up to 50% of women who have thyroid peroxidase antibodies (anti-TPOAb +ve). Humoral immunity in PPTD has been well documented, but the cellular immunological events accompanying the Th2 to Th1 state postpartum are less clear. Peripheral blood lymphocyte cytokine secretion was examined in 48 TPOAb +ve and 33 TPOAb -ve women at 36 wk gestation and at 6, 12, and 24 wk postpartum. Eighteen women with PPTD had significantly greater secretion of interferon gamma and IL-4 than euthyroid women at 36 wk gestation with no significant differences in cytokine secretion at other time points. Also, at 36 wk gestation, the median plasma cortisol concentration in the PPTD group was significantly lower than the euthyroid group (442 nmol/liter vs. 567 nmol/liter, P < 0.02). There were no differences between the groups in levels of prolactin, progesterone, or estradiol. These data suggest that there may be less immunological suppression at 36 wk in TPOAb +ve women destined to develop PPTD possibly because of lower levels of cortisol. Thus, the immunological determinants of PPTD may in part occur antenatally, although the mechanism(s) for this is still unclear.     

Determinants and outcome of amiodarone-associated thyroid dysfunction

Objective Amiodarone is frequently associated with thyroid dysfunction. Identifying predictors for amiodarone‐associated thyroid dysfunction and assessing treatment outcome may aid clinicians in daily practice. Methods We included 303 consecutive patients with amiodarone therapy for cardiac arrhythmias (260 with atrial fibrillation and 43 with ventricular arrhythmias). Thyroid function tests were performed every 6 months. Results Mean age was 63 ± 12 years and 66% was male. After median follow‐up of 3·3 (0·1–24) years, 23 (8%) patients developed amiodarone‐associated thyrotoxicosis (incidence rate 1·9 per 100 person years) and 18 (6%) hypothyroidism (incidence rate 1·1 per 100 person years). The only predictor for amiodarone‐associated thyrotoxicosis was age <62 years [HR = 2·4 (95% CI 1·0–5·7), P = 0·05]. Predictors for amiodarone‐associated hypothyroidism were thyroid stimulating hormone >1·4 mU/l at baseline [HR = 5·1 (95% CI 1·1–22·4), P = 0·03], left ventricular ejection fraction <45% [HR = 3·8 (95% CI 1·1–13·3), P = 0·04] and diabetes mellitus at baseline [HR = 3·3 (95% CI 1·1–10·3), P = 0·04]. Gender was not a predictor for amiodarone‐associated thyroid dysfunction. Five out of 12 (42%) patients with thyrotoxicosis exhibited spontaneous normalization of thyroid function on continuation of amiodarone therapy. Mean time to normalization in the total group was 6·2 ± 3·3 months, with no difference between continuing or discontinuing amiodarone (6·6 ± 3·8 vs 5·8 ± 2·8 months, P = 0·5). Conclusions During median follow‐up of 3·3 years, the incidence of amiodarone‐associated thyrotoxicosis was higher compared to hypothyroidism. Only general predictors for amiodarone‐associated thyroid dysfunction were observed. Discontinuation of amiodarone did not influence treatment outcome.     

Postpartum thyroid dysfunction in an Italian population residing in an area of mild iodine deficiency.

We have evaluated the occurrence of postpartum thyroid dysfunction (PPTD) in a group of 372 women residing in area of mild iodine deficiency. Thyroid function and autoimmune status were evaluated by means serum T4, T3, TSH measurement and detecting the presence of positive antithyroglobulin antibodies (AbTg), antimicrosomal antibodies (AbM) and thyroid-peroxidase antibodies (AbTPO) titers in women at parturition, at 1, 3, 6 and 12 months postpartum. New onset transient hypothyroidism occurred in 6.4% of women whereas transient thyrotoxicosis in only 1.8% of women. Transient hypothyroidism was not preceded by thyrotoxicosis as indicated by thyroid function tests and serum Tg concentrations. At parturition, the positivity of AbM and AbTPO titers and the presence of goiter appeared to be a risk factors for the development of PPTD.     

The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto's thyroiditis and isolated hyperthyrotropinaemia: a 3-year follow-up

Objective The natural history of Hashimoto’s thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. Design This is retrospective cross‐sectional study. Patients Three hundred and twenty‐three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. Results HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty‐six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0‐, 3·4‐ and 3·5‐fold, respectively. The increase in TSH levels during follow‐up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. Conclusions Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients.     

Serum TSH related to measures of body mass: longitudinal data from the HUNT Study, Norway

Objective Thyroid function and body mass are related, but the causal relationship remains unclear. Our objective was to investigate the longitudinal relationship between thyroid stimulating hormone (TSH) and body mass measures [body weight, body mass index (BMI), waist circumference (WC) and waist‐hip‐ratio (WHR)]. Design We used data from two waves of a population‐based study: HUNT 2 (1995–1997) and 3 (2006–2008). Average follow‐up time was 10·5 years. Multivariable general linear and logistic regression models were used to assess the relation between TSH and the body mass measures. Participants In total 9954 women and 5066 men without self‐reported thyroid disease and TSH within the reference range (0·5–3·5 mU/l) at baseline and <10 mU/l at follow‐up. Results For each mU/l increase in TSH among women, weight increased 0·9 kg (95% CI 0·8, 1·1), BMI 0·3 kg/m² (95% CI 0·3, 0·4) and WC 0·6 cm (95% CI 0·3, 0·8). In men, the corresponding figures were 0·8 kg (95% CI 0·5, 1·0), 0·2 kg/m² (95% CI 0·2, 0·3) and 0·5 cm (95% CI 0·2, 0·8). In line with this, a weight gain of more than 5 kg was associated with a TSH increase of 0·08 mU/l (95% CI 0·06, 0·11) in women and 0·15 mU/l (95% CI 0·12, 0·18) in men. Women who lost more than 5 kg decreased their TSH by 0·12 mU/l (95% CI 0·09, 0·16) and men by 0·03 mU/l (95% CI ?0.02, 0·09). Conclusion Weight gain is accompanied by increasing TSH, and weight loss in women is related to decreasing TSH.     

Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT)

OBJECTIVE: To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmunity in Norway. MATERIALS AND METHODS: All inhabitants 20 years and older (94009) in Nord-Trondelag were invited to participate in a health survey with a questionnaire and blood samples. RESULTS: The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49-5.70 for females and 1. 50 and 0.56-4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (>200U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3. 40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH >/=10mU/l 0.90% and 0.37%; TSH 4.1-9. 9mU/l 5.1% and 3.7%; and TSH200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2-1.9mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH>10mU/l (85% TPOAb positive). CONCLUSIONS: In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb.     

Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals

Objective The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester‐ and method‐specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer’s methodology, euthyroid definition and iodine status. Design Cross‐sectional dataset analysis. Subjects Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Measurements Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti‐TPOAb and anti‐TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. Results All participants had long‐term consumption of iodized salt and median urinary iodine of 150–200 μg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03–4·51, 0·05–4·50 and 0·47–4·54 mIU/l and FT4 11·8–21·0, 10·6–17·6 and 9·2–16·7 pmol/l. The manufacturer’s method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. Conclusions The trimester‐ and method‐based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.     

Prevalence of thyroid deficiency in pregnant women

OBJECTIVE: The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring. DESIGN: TSH concentrations were measured in the sera of women at 15-18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest in order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyroid antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and/or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women. PATIENTS: The sera were from 2000 consecutive women in Maine being tested for alpha-fetoprotein concentration at 15-18 weeks of gestation. RESULTS: TSH concentrations above 6 mU/l were found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9-54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty-eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls. CONCLUSIONS: Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data indicate a sufficiently high prevalence of thyroid dysfunction to demand investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.     

Hyperthyrotropinemia at 2 weeks of age indicates thyroid dysfunction and predicts the occurrence of delayed elevation of thyrotropin in very low birth weight infants

Background For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important. Methods To address the above two issues, we performed thyrotropin‐releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less. Results For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10–15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10–15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later. Conclusions Thyrotropin‐releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic–pituitary–thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation.     

Five‐year incidence and progression of thyroid dysfunction in an older population

Background: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population‐based cohort. In this study, we aimed to assess the 5‐year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population. Methods: The Blue Mountains Eye Study is a longitudinal population‐based cohort study. During 1997–1999, 1768 participants (≥55 years) had thyroid function assessed. After excluding participants reporting any form of treatment for their thyroid condition at baseline, 951 participants (91.4%) without thyroid dysfunction and 54 (5.4%) with thyroid dysfunction were re‐examined 5 years later. Thyroid dysfunction was defined using serum thyrotropin (thyroid stimulating hormone (TSH)) screen, followed by serum free T4 assessment. Results: The overall 5‐year incidence of thyroid dysfunction was 4.7% (95% confidence interval (CI) 3.4–6.1). Obesity (body mass index ≥ 30 kg/m²) and serum TSH > 2 mIU/L at baseline predicted incident overt hypothyroidism (odds ratio (OR) 4.05, CI 1.74–9.41) and (OR 5.46, CI 1.16–25.67) respectively. The 5‐year incidence of subclinical hypothyroidism was significantly higher in women than in men, 2.5% versus 0.7% (P= 0.03). Progression to overt hypothyroidism was observed in 17.9% of subjects with subclinical hypothyroidism over 5 years. Conclusions: The 5‐year incidence of thyroid dysfunction in this older population was relatively low, and was associated with obesity and serum TSH level > 2 mIU/L at baseline. Over one in six persons with subclinical hypothyroidism progressed to overt thyroid dysfunction over the 5‐year period. Our findings highlight the need for appropriate management of subclinical hypothyroidism among older people.