Prevalence of Thyroid Dysfunction in Postpartum Women With Suboptimal Iodine and Selenium and Adequate Iron Status

Ying Jin; Jane Coad; Shao J. Zhou; Sheila Skeaff; Thiagarajah Ramilan; Louise Brough

Disclosures

Clin Endocrinol. 2021;95(6):873-881. 

In This Article

Discussion

This cross-sectional study of 78 women at six months postpartum found thyroid dysfunction in 18%, including 3% with overt hypothyroidism (higher than the normal TSH concentration), and 15% with subclinical hyperthyroidism (lower than the normal TSH concentration). This was higher than a previous study of Australian women (n = 748) which detected 11.5% with thyroid dysfunction at six months postpartum.[24] In New Zealand (2006/2007), 4.8% of adults aged from 18 to 80 years old registered with General Practices had thyroid dysfunction;[25] however, the prevalence in postpartum women was not determined. Median thyroid volume (6.1 ml) in the MINI study was similar to that estimated in a study of Cuban women (6.4 ml) aged 18–50 years who lived in iodine-sufficient areas.[26] There was no obvious thyroid enlargement observed in the current study; however, ultrasound echogenicity of the thyroid gland was not examined, which has been suggested as a predictor in thyroid dysfunction development.[27]

In the MINI study, low selenium status was the only significant predictor of the likelihood that women had thyroid dysfunction. Women with a plasma selenium concentration below 95 μg/L had a higher likelihood of experiencing thyroid dysfunction (46.7%), compared with only 10.7% in women with a plasma selenium concentration above 95 μg/L. This aligns with the results of a large Chinese observational study (n = 6152) which reported a higher prevalence of thyroid disease in people living in a low selenium region compared with those living in an adequate selenium region (31% vs 18%, p <.001), and higher serum selenium was associated with a reduced risk of having autoimmune thyroiditis.[28] However, the major thyroid dysfunction reported in the Chinese study was subclinical hypothyroidism, while subclinical hyperthyroidism was the predominant type in the MINI study. There might be a number of reasons for the differences between the Chinese study and the findings presented here: firstly, subclinical hyperthyroidism may be due to Graves' disease, which has TSH receptor antibodies present to stimulate thyroid hormone secretion but lower TSH from the pituitary gland;[29] secondly, women who experienced biphasic postpartum thyroid dysfunction might have been missed out during this postpartum period;[29] and thirdly, the plasma concentration reported in the Chinese study (57.4μg/L) was much lower than that found in the current study (105.8 μg/L). In addition, low selenium status has been reported in patients with Graves' disease,[7] and selenoproteins play anti-inflammatory and protective effects from oxidative stress which are suggested as the reason for Graves' disease.[30] Many women in the current study did not meet the plasma selenium concentrations required for maximum expression of selenoprotein p (>110 μg/L), which is suggested to reduce inflammatory cytokines.[7] In a randomized placebo-controlled Italian study, women with positive TPOAb in the first trimester had a lower incidence of PPT (28.6%) in the selenium supplemented group (200 μg/day during pregnancy and postpartum) compared with 48.6% in the non-supplemented group; however, the adverse effect after supplementation ceased were not ascertained.[31] Of interest, study subjects were advised to use iodised salt, but iodine status was not measured and remains unconfirmed.

In the current study, women with a plasma selenium concentration below 95 μg/L had a significantly higher serum Tg and lower TSH, compared to women with adequate plasma selenium concentrations. There were only 15 women whose plasma selenium concentration was lower than 95 μg/L, with 56 women with a plasma selenium concentration higher than 95 μg/L. However, median serum Tg in women with low selenium status was double the suggested normal concentration of 10 μg/L, indicative of iodine deficiency. The co-existence of inadequate selenium and iodine intake in this cohort may be due to the main food groups contributing to their intakes being similar, for example fish, eggs and breads, based on the 2016 New Zealand Total Diet Study.[32] In 2009, mandatory fortification of bread with iodised salt was introduced, bread is now one of the major contributions of iodine in the New Zealand adult diet.[32] In the MINI study, an increased TSH was observed in women with a higher plasma selenium concentration (≥ 95 μg/L), although median TSH concentrations in the low versus high selenium status groups were significantly different; these were still within the normal range. The possible mechanism of this phenomenon is difficult to explain. We also found a high prevalence of hyperthyroidism, possibly due to Graves' disease (having low TSH concentrations).[29] Similarly, one of the main findings in this cohort is that women with low plasma selenium concentration were more likely to have abnormal TSH concentrations (predominately < 0.4 mIU/L). A similar result was also reported in an observational study of pregnant Netherlands (n = 2041) at 12-week gestation,[33] and the authors suggested human gonadotropin hormone may interfere with the role selenium plays in synthesising thyroid hormones. In contrast, a secondary analysis of the effects of antenatal selenium (60 μg/day) supplementation among UK pregnant women (n = 114) living in an area of mild-to-moderate iodine-deficient area reported decreased TSH in the selenium supplementation group. The authors of the UK study stated that this phenomenon might be due to the anti-inflammatory function of selenium and its modulation of the immune response; however, this effect was only observed in women with positive TPOAb.[34] Future research is needed to investigate the impact of selenium on postnatal thyroid function.

Iodine status (UIC or BMIC) was not a predictor of thyroid dysfunction in the current study, which was not entirely unexpected as UIC has high intraindividual variation (10 −15 urine samples are suggested for assessing habitual status).[35] This could also be due to a small number of women who had abnormal thyroid hormones, and that thyroid hormones may remain in the normal range even in a mild-to-moderate iodine-deficient population.[36] The current study found women using iodine-containing supplements (9/74) presented with normal TSH concentrations, while 20% (13/65) of women not using iodine-containing supplements were found to have abnormal TSH concentrations. The protective effect of iodine supplementation on maternal thyroid function in this iodine-deficient population cannot be concluded, since the numbers of participants using iodine-containing supplements were too small decreasing the statistical power of the finding. A Swedish study (n = 58) investigating the effectiveness of using L-T4 (100 μg/day) or iodine (150 μg/day) for 40 weekspostpartum on thyroid dysfunction, found extra iodine during the postpartum period may aggravate autoimmune thyroid dysfunction, such as Graves' disease (commonly present in the postpartum population); however, baseline iodine status of women was not assessed.[37] In contrast, in a moderately iodine-deficient area in Denmark, euthyroid pregnant women (n = 72) were assigned to three groups: 1) a 150 μg/day iodine supplementation during both pregnancy and postpartum, 2) only during pregnancy and 3) given a placebo (supplement without iodine). No significant differences in PPT prevalence, severity or duration among the three groups were reported. The Danish authors suggested both prenatal and postpartum iodine supplementation of 150 μg/day were considered safe in that setting.[38]

Iron status in the current study was not associated with thyroid hormone concentrations. A low iron status blunts the activity of the haem-dependent enzyme (thyroid peroxidase) which results in a reduction in thyroid hormone synthesis.[39] However, in this study cohort, only two women were classified with hypothyroidism (having low fT4); thus, the association between ID and low fT4 observed in other studies[39,40] was not observed in this cohort of postpartum women. It was unexpected that most women at six months postpartum achieved adequate iron status, with only 4% being iron deficient (ID). The low rate of ID in the current study could be due to the protective effect of six months of lactational amenorrhoea. However, a previous study of American women up to six months postpartum (n = 220) reported that 12.7% were ID, and women up to six months postpartum from low-income groups had a fourfold increased risk of ID compared with their non-pregnant counterparts.[41] In the current study, 62% reported a household income above the median New Zealand household income.[42] Although iron status in the current cohort was mostly adequate, further research is required to ascertain the iron status of low-income postpartum women in New Zealand, who are known to consume a diet having lower iron bioavailability.[43]

To the best of our knowledge, the MINI study was the first study to examine iodine, selenium and iron concurrently in relation to thyroid function of postpartum women. It is one of a few studies to investigate the prevalence of thyroid dysfunction in a New Zealand postpartum cohort. One of the strengths of this study is the comprehensive range of biomarkers used to measure iron, iodine and selenium status. Measuring SF is a well-established method to assess iron storage,[44] but it does not indicate the severity of iron depletion. Increased serum sTfR would indicate functional iron deficiency without being confounded by inflammation. Changes in the reciprocal relationship between these measures would provide a better understanding of iron status and allow early detection of ID before the occurrence of IDA.[23] Iodine status was determined using triangular measures including UIC, BMIC and serum Tg.[13] Plasma selenium concentration reflects short-term status and was used because it is the most used biomarker in other published research which would allow comparison. Measuring selenium in nail clippings may be another useful assessment of selenium status over a long-term exposure time (up to 52 weeks).[45] Iodine concentrations measured in non-fasting spot urine samples can vary considerably due to the variations of daily and seasonal iodine intake. However, previous research also suggested iodine status may be underestimated when measuring iodine concentrations in fasting morning urine samples.[46] It has been suggested to use ten repeat spot urine samples to minimize dietary variations of iodine intake, when evaluating individual iodine intake.[35] However, this large number of repeat samples is a high burden for participants and has limited use in population studies. UIC measured in spot urine samples has been recommended to estimate population iodine status.[20] Other limitations of the study include the small sample size, and the participants were predominantly well educated and may not have been representative of the wider New Zealand population. Less educated women are under-represented; thus, their thyroid function, and their iodine, selenium and iron status may be inadequate which require further investigation. Few participants reported the use of selenium-containing supplements; therefore, this study has insufficient statistical power to examine the effects of such supplementation on thyroid function.

A high prevalence of thyroid dysfunction (especially subclinical hyperthyroidism) was observed, and low plasma selenium concentration significantly increased the risk of thyroid dysfunction within this group of iodine-deficient postpartum women who predominantly had adequate iron status. Iodine supplementation may potentially provide a beneficial effect on maternal thyroid function. Measuring long-term selenium status via nail clippings could identify the risk of selenium deficiency and its impacts on thyroid function. Strategies are required to improve both iodine and selenium status, which may support optimal thyroid function for women during perinatal period.

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