Subclinical hypothyroidism worsens cardiometabolic profile

Subclinical hypothyroidism and cardiometabolic biomarkersSubclinical hypothyroidism (SCH), poor thyroid effect throughout the body in the presence of ‘normal’ thyroid serum tests, is a widespread yet under-appreciated clinical challenge. A recent study published in the Journal of the Endocrine Society documents adverse cardiometabolic biomarkers in the presence of subclinical hypothyroidism. Additionally, practitioners must bear in mind that more than adequate iodine intake can worsen the condition.

Clarifying the definition of normal thyroid function

The authors note that uncertainty around the definition of normal thyroid function can go beyond contention involving different opinions on laboratory reference ranges by examining the effect of suboptimal thyroid function on the entire organism.

“As thyroid function has multisystemic effects, its derangement could affect a broad range of cardiometabolic pathways potentially related to clinical manifestations. However, the definition of normal thyroid function has been intensely debated, with some experts advocating for lowering the upper limit of normal for thyroid stimulating hormone (TSH) and others for maintaining the current standard. In this regard, thyroid-related risk for incident type 2 diabetes (T2D) and cardiovascular disease (CVD) may impact the definition of TSH normality.”

They note some of the mechanisms by which SCH can adversely affect cardiovascular and metabolic function:

“The potential relationship of thyroid hypofunction with T2D and CVD may be mediated by abnormalities in lipids, lipoprotein subclasses, endothelial function, coagulation, inflammatory pathways, and insulin resistance.”

This hardly exhausts the list of adverse physiological effects since every part of the body, including the brain, requires the stimulus of thyroid hormone to produce energy and function. The public health implications are enormous.

“Detailed assessment of thyroid function effects on these mediators/markers may have high population health implications, especially along the milder hypofunction spectrum within euthyroidism and SCH. Understanding the role of thyroid function in cardiometabolic pathways may guide the clinically relevant definition of thyroid function and unveil potential targets for controlling related morbidity.”

Subclinical hypothyroidism increases cardiometabolic risk

Thus the authors set out to…

“…examine thyroid function across the spectrum of euthyroid to HT in relationship to cardiometabolic pathways represented by lipids, lipoproteins, inflammation, coagulation, glycemic, and insulin resistance biomarkers.”

They examined data for 28,024 apparently healthy middle-aged and older women, and indeed found that cardiometabolic health worsens on a gradient from normal thyroid (euthyroid) function, through subclinical hypothyroidism, to full-blown hypothyroid:

Going from euthyroid to HT, the lipoprotein subclass profiles were indicative of insulin resistance: larger very-low-density lipoprotein size (nm); higher low-density lipoprotein (LDL) particle concentration (nmol/L), and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid to SCH and HT. Of the other biomarkers, SCH and HT were associated with higher high-sensitivity C-reactive protein and hemoglobin A1c. For increasing TSH quintiles, results were overall similar.”

TSH, total and LDL cholesterol not so useful

They note that it was other biomarkers that revealed the actual progressive risk:

“In this population of apparently healthy middle-aged and older women, individuals with SCH and HT had differences in the lipid and lipoprotein subclass profile that indicated worsening insulin resistance and higher cardiometabolic risk compared with euthyroid individuals, despite having similar LDL cholesterol and total cholesterol. Of the other biomarkers, only hs-CRP and HbA1c were associated with SCH and HT. For TSH quintiles mostly within the normal range, lipid and lipoprotein results for TSH quintiles were generally similar but null for other biomarkers. Hence, progressive thyroid hypofunction was associated with insulin-resistant and proatherogenic lipids and lipoproteins profile in a graded manner, with potential clinical consequences.”


Besides thyroid as a driver of metabolic activity, insulin resistance appears to play a key role. They point out that insulin resistance appears to affect lipoprotein metabolism before glucose metabolism, an observation important for clinicians to bear in mind.

Thyroid hormones act as modulators of cholesterol synthesis and degradation through key enzymes. One of the main mechanisms is the stimulus of thyroid hormones over sterol regulatory element–binding protein 2, which in turn induces LDL receptor gene expression. However, it was shown that the association of HT and higher LDL cholesterol levels is present only in insulin-resistant subjects. Indeed, the lack of LDL cholesterol differences could be explained by our insulin-sensitive study population (low HbA1c levels). HT has also been associated with lower catabolism of lipid-rich lipoproteins by lipoprotein lipase, hepatic lipase, and decreased activity of cholesterol ester transfer proteinthat mediates exchanges of cholesteryl esters of HDL particles with triglyceride-rich LDL and VLDL particles. These mechanisms might explain the relationship of thyroid hypofunction with atherogenic and insulin-resistant lipid and lipoprotein abnormalities. Finally, the milder differences noted in HbA1c compared with LPIR across thyroid categories may be explained by the earlier effects of insulin resistance on lipoprotein metabolism than on glucose metabolism.”

Practitioners should be attentive to the authors’ conclusion:

“In this large population of apparently healthy women, individuals with SCH had differences in their biomarker profile that indicated worsening lipoprotein insulin resistance and higher cardiometabolic risk compared with euthyroid individuals, despite having similar LDL cholesterol and total cholesterol levels. These findings suggest that cardiometabolic risk may increase early in the progression toward SCH and overt HT.

Iodine supplementation reminder

More than adequate iodine increases autoimmune thyroiditisClinicians who may be tempted to reflexively offer iodine supplementation for thyroid disorders including subclinical hypothyroidism should remember the body of evidence showing this can fire up autoimmune thyroiditis. One example by way of a reminder is a study published in the European Journal of Endocrinology showing that more thanequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis. The authors describe their intent:

“With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200–300 μg/l) or excessive iodine intake levels (MUI >300 μg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations.”

They examined thyroid hormones, thyroid autoantibodies in serum, iodine levels in urine were measured. and B-mode ultrasonography of the thyroid for 3813 individuals, in two areas with differing levels of iodine exposure. The levels of iodine intake were: Rongxing, MUI 261 μg/l; and Chengshan, MUI 145 μg/l. (MUI =median urinary iodine excretion.) They found a blatant difference in thyroid biomarkers:

“The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan. The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan. The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: ≥500 IU/ml) and low concentrations of TgAb (TgAb: 40–99 IU/ml) in Rongxing.”

Their results suggest there is a discrete window for thyroid intake:

“Compared with the adequate iodine intake level recommended by WHO/UNICEF/ICCIDD MUI (100–200 μg/l), our data indicated that MUI 200–300 μg/l might be related to potentially increased risk of developing subclinical hypothyroidism or autoimmune thyroiditis. This result differs from the WHO’s suggestion that MUI >300 μg/l may increase the risk of developing autoimmune thyroid diseases.”

Practitioners should be cautious with dosing of supplemental iodine in keeping with the authors’ conclusion:

“In conclusion, compared with the population with MUI 145 μg/l in Chengshan, the population with MUI 261 μg/l in Rongxing had a higher risk to develop autoimmune thyroiditis and subclinical hypothyroidism. Thus, more than adequate iodine intake might not be recommended for the general population in terms of keeping a normal function of thyroid.”

Readers may wish to also see the earlier post Hypothyroidism can be provoked by small amounts of supplemental iodine.

Iodine deficiency, pregnancy, and autoimmunity

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Iodine deficiency is still a serious concern, especially for pregnant women in North America, as reported in a review just published in the journal Thyroid. Despite global improvements since 1990, iodine sufficiency has actually been declining in US adults. As the authors state, the consequences can be severe:

Thyroid“Dietary iodine intake is required for the production of thyroid hormone. Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality. Thyroid hormone is particularly crucial for fetal and infant neurodevelopment in utero and in early life, and insufficient iodine during pregnancy and infancy results in neurological and psychological deficits in children…Iodine deficiency remains the leading cause of preventable mental retardation worldwide. In adults, mild-to-moderate iodine deficiency increases the incidence of hyperthyroidism due to toxic goiter.”

The authors defined population iodine sufficiency as a median urinary iodine concentrations of 100–299 μg/L in school-aged children and equal to or more than 150 μg/L in pregnant women, with these serious implications for pregnant women and their children in the US:

“Based on National Health and Nutrition Examination Surveys (NHANES), the median UIC in U.S. adults decreased by >50% between the early 1970s and the late 1990s. Of particular concern, the prevalence of UICs <50 μg/L among women of childbearing age increased by almost fourfold, from 4% to 15%, over this period. The most recent NHANES survey (2009–2010) demonstrated that the overall U.S. population remains iodine-sufficient, with a median UIC of 144 μg/L among individuals aged six years and older. However, aggregate NHANES data from 2001 to 2006 showed that U.S. pregnant women sampled were only marginally iodine-sufficient (median UIC, 153 μg/L) and the most recent NHANES data from 2007 to 2010 demonstrated that the median UIC among pregnant U.S. women had dropped to <150 μg/L, indicating mild iodine deficiency.”

Considering possible causes for this growing insufficiency they note…

“Reductions in U.S. dietary iodine over the last several decades have been variously ascribed to a possible reduction in the iodine content of dairy products, the removal of iodate dough conditioners in commercially produced bread, new recommendations for reduced salt intake for blood-pressure control, and the increasing use of noniodized salt by the food industry.”

Processed food producers in the US typically do not use iodized salt. Iodate dough conditioners have been largely replaced by bromate which competes with iodine (as does fluoride). Iodizing salt is the tried and true method for preventing iodine deficiency in the general population, but considering the shortfall lead author Dr. Elizabeth Pearce commented for Medscape:

“That leaves public-health recommendations for groups at risk and the recommendation for women who are pregnant, planning a pregnancy, or breast-feeding is to take an iodine-containing supplement of 150 µg of iodine daily in the form of potassium iodide.”

But the authors note caution must be taken when supplementing iodine:

“Following exposure to high iodine levels, the synthesis of thyroid hormone is normally inhibited via the acute Wolff–Chaikoff effect. If excessive iodine exposure persists, the thyroid is able to “escape” from the acute Wolff–Chaikoff effect within a few days…Conversely, individuals with subtle defects in thyroid hormone synthesis, such as those with Hashimoto’s thyroiditis, may be unable to escape from the acute Wolff–Chaikoff effect, and can develop iodine-induced hypothyroidism. In addition, even small increases in population iodine intake are associated with an increased prevalence of thyroid autoimmunity.”

Bear in mind that by far the most common form of hypothyroid in developed countries is Hashimoto’s thyroiditis (autoimmune thyroiditis). The authors conclude:

“Although substantial progress has been made over the last several decades, iodine deficiency remains a significant public health problem worldwide, including in developed nations. The ongoing monitoring of the population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations. There is also a need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition. Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines.”

The LancetA paper just published in the prestigious medical journal The Lancet documented the serious effects of even mild iodine deficiency during pregnancy. The authors state:

“As a component of thyroid hormones, iodine is essential for fetal brain development. Although the UK has long been considered iodine replete, increasing evidence suggests that it might now be mildly iodine deficient. We assessed whether mild iodine deficiency during early pregnancy was associated with an adverse effect on child cognitive development.”

They examined data for measured urinary iodine concentration for 1040 first-trimester pregnant women andlater the intelligence quotient (IQ) in their children at age 8 years and reading ability at 9 years of age. To define iodine deficiency they used the WHO criteria of 150 μg/g in pregnancy. Their data revealed a growing public health problem:

The group was classified as having mild-to-moderate iodine deficiency on the basis of a median urinary iodine concentration of 91·1 μg/L. After adjustment for confounders, children of women with an iodine-to-creatinine ratio of less than 150 μg/g were more likely to have scores in the lowest quartile for verbal IQ, reading accuracy, and reading comprehension than were those of mothers with ratios of 150 μg/g or more. When the less than 150 μg/g group was subdivided, scores worsened ongoing from 150 μg/g or more, to 50—150 μg/g, to less than 50 μg/g.”

For the authors, this is an issue that demands attention:

“Our results show the importance of adequate iodine status during early gestation and emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient. Iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention.”

NIH Office of Dietary SupplementsHow do we go about testing for iodine deficiency when a single spot collection is only accurate for large populations studies and doesn’t reliably apply to the individual and ten spot collections are cumbersome? According to the National Institute of Health Office of Dietary Supplements:

“Iodine status is typically assessed using urinary iodine measurements. Urinary iodine reflects dietary iodine intake directly because people excrete more than 90% of dietary iodine in the urine. Spot urine iodine measurements are a useful indicator of iodine status within populations. However, 24-hour urinary iodine or multiple spot urine measurements are more accurate for individuals.”

Journal of Nutrition 141 (9)Both 10 spot collections and one 24-hour collection are acceptable even though a study published in The Journal of Nutrition found a bit less intra-individual variation (CV) with the 24-hour collection:

“In a prospective, longitudinal, 15-mo study, healthy Swiss women (n = 22) aged 52–77 y collected repeated 24-h urine samples (total n = 341) and corresponding fasting, second-void, morning spot urine samples (n = 177). From the UIC in spot samples, 24-h urinary iodine excretion (UIE) was extrapolated based on the age- and sex-adjusted iodine:creatinine ratio. Measured UIE in 24-h samples, estimated 24-h UIE, and UIC in spot samples were (geometric mean ± SD) 103 ± 28 μg/24 h, 86 ± 33 μg/24 h, and 68 ± 28 μg/L, respectively, with no seasonal differences. Intra-individual variation (mean CV) was comparable for measured UIE (32%) and estimated UIE (33%). The CV tended to be higher for the spot UIC (38%) than for the estimated 24-h UIE (33%).”

American Journal of Clinical NutritionThe issue of how to test for iodine deficiency was examined in a study published in the American Journal of Clinical Nutrition in which the authors showed that the spot check ofurinary iodine concentration (UIC) could be confounded by hydration status, but that a 24-hour collection was not. They investigated how well each tracked the effect of iodine supplementation:

“Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6–12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples.”

It was only the 24-hour collection which matched the ‘real world’ changes:

“During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 μg I/d, whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased, whereas 24-h Uvol and 24-h UI increased. The final median 24-h UI reached 120 μg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period.”

Their conclusion highlights the 24-hour collection as a more dependable metric for iodine sufficiency (IS):

“Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status–independent tool to examine trends in IS and the contribution of relevant foods to IS.”

Clinical EndocrinologyClinical caution: There are a number of studies linking iodine supplementation to increases in autoimmune thyroiditis (Hashimoto’s thyroiditis). This is understandable considering that up-regulating thyroid peroxidase, thyroglobulin and other iodine driven activity could ‘wave a red flag in front of the bull’ in individuals who have lost tolerance and are in the stage of silent autoimmunity. Even iodine introduced cautiously can trigger this problem as described in a paper published in Clinical Endocrinology. The authors state:

“Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common can often be demonstrated in serum.”

They used these to measure the incidence of thyroid autoimmunity in the Danish population before and after their mandatory iodization of salt:

“Two identical cross-sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO-Ab and Tg-Ab using sensitive assays.”

There was a definite increase in thyroid autoimmunity:

Antibodies were more frequent in C2 than in C1: TPO-Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg-Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO-Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg-Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies.”

Clinicians considering iodine supplementation must take care to assess patients for the potential for loss of immune tolerance to thyroid, even when supplementation is undertaken with cautious amounts. The authors conclude:

The prevalence of both TPO-Ab and Tg-Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long-term effects of increased iodine intake on thyroid autoimmunity in the population.”

JAMA Vol 308 No. 23How much iodine should be supplemented during pregnancy and breast feeding? The authors of a paper published in JAMA last December first state:

Dietary iodine requirements are increased during pregnancy due to increased thyroid hormone production, increased renal iodine losses, and fetal iodine requirements. Dietary requirements remain increased in lactation due to the concentration of iodine in breast milk…Adverse effects of iodine deficiency in pregnancy, when the deficiency leads to severe decreases in maternal thyroxine (T4), include include…increased pregnancy loss and infant mortality. Decreases in maternal T4 associated with even mild iodine deficiency may have adverse effects on the cognitive function of offspring, and iodine deficiency remains the leading cause of preventable intellectual disability worldwide.”

This begs the question how much postpartum depression might be contributed to by suboptimal iodine. Regarding supplementation…

“…all US women who are pregnant, lactating, or planning a pregnancy should ingest dietary supplements containing 150 µg of potassium iodide per day. The Endocrine Society has recently advocated that all daily prenatal multivitamins should contain 150 to 200 µg. The addition of 150 µg does not pose a risk, even for women who are iodine replete, because a total iodine intake of as much as 500 too 1100 µg per day is considered safe in pregnancy.”

For selected food sources of iodine and other information see the National Institute of Health Office of Dietary Supplements.

Study associates iodine deficiency with type 2 diabetes

Experimental and Clinical Endocrinology & DiabetesAstute clinicians are cautious with iodine supplementation due to the risk for triggering latent thyroid autoimmunity, but a study just published in the journal Experimental and Clinical Endocrinology & Diabetes is a reminder to remain vigilant about the potential need for iodine when managing type 2 diabetes. The authors note:

Patients with diabetes mellitus are at an increased risk of thyroid disease. The purpose of this study was to examine the urinary excretion of iodine in type 2 DM (T2DM) patients, and to assess the clinical implication of iodine status on T2DM.”

They examined data for 266 adult subjects aged 18-55 years, 109 of whom were T2DM patients along with 157 healthy controls, and correlated urinary iodine with anthropometry, fasting glucose, lipid profile; serum concentrations of leptin, adiponectin, resistin, insulin, aPAI, hsCRP, Ang II, TNF-α, TSH, T3, T4, and urine creatinine. There was a marked association of urinary iodine and type 2 diabetes:

The concentration of urine iodine was significantly lower in T2DM than in healthy control subjects (84.6±2.3 vs. 119.4±3.4), which remained significant after creatinine correction and controlling for age. Furthermore, urinary iodine is negatively correlated with waist, hips, SAD, glucose, insulin, HOMA-IR triglyceride, resistin, angiotensin II (Ang II), and CRP, while it was positively associated with TSH.”

Although care must be taken to avoid potentiating autoimmune thyroiditis by iodine supplementation, physiological deficiencies may contribute to T2DM and other disorders (fibrocystic breast disease among them). These results beg for follow-up studies to determine if repleting iodine improves the T2DM biomarkers while supporting, or at least not harming, thyroid function. Meanwhile, this is something that clinicians can monitor carefully with individual patients. The authors conclude:

“The decreased levels of iodine concentration in T2DM patients and its likely deleterious effects on metabolic functions calls for a systematic approach to thyroid disease screening in diabetic patients. Routine annual urinary iodine determination is recommended and should target T2DM patients at risk of thyroid dysfunction.”

Radiation protection and iodine supplementation

Ionizing radiation damages DNA and other proteins directly, but does most of its dirty work through oxidative damage when a storm of free radicals are generated by the effect of radiation on water molecules inside the cells. That makes the best protection from ionizing radiation a comprehensive approach that optimizes intrinsic resources for ameliorating oxidative and mutagenic damage. Additionally, it is well known that iodine (potassium iodide) can help to protect the thyroid gland by displacing radioactive forms of the element, but should it be taken preventively? In fact, there is a substantial amount of scientific evidence that great care must be taken when recommending iodine for any health concern. Most clinicians that practice according the functional model are aware that the widespread surge in autoimmune disease presents a specific risk because iodine supplementation can trigger latent or aggravate pre-existing autoimmune thyroiditis (Hashimoto’s disease), as illustrated by a paper published recently in the journal Hormones. The authors state:

“Epidemiological studies have linked increased iodide intake from dietary or other sources to the development of hypothyroidism, and it appears that in several—though not all—cases, this phenomenon has an autoimmune basis.”

They further note:

“Within an immunological context, iodine may mediate thyroiditis induction via at least two mechanisms: a) by increased post-translational modification of thyroglobulin (Tg), an event which may enhance the immunopathogenicity of this molecule as detailed further in this review; and b) via apoptotic/necrotic effects of thyrocytes, a step that could initiate presentation of thyroid antigens at immunostimulatory levels.”

All clinicians who manage conditions for which supplemental iodine therapy is contemplated should bear in mind the authors’ conclusion:

High dietary iodide intake may lead to the development of thyroid autoimmunity via at least two pathways. First, iodide may epigenetically modify the Tg molecule and create iodinated neoantigenic determinants to which immune tolerance has not been established or alter the processing of Tg to facilitate generation of pathogenic but cryptic Tg determinants that may not contain iodine. Second, iodine may precipitate apoptotic/necrotic effects on thyrocytes, thus releasing increased amounts of thyroid antigens that can activate autoreactive T cells in situ or in thyroid-draining lymph nodes. The genetic background of the host may be permissive to one or both of these pathways that may act in synergy or independently of each other.”

The authors of a study published in the Journal of Clinical Endocrinology & Metabolism also weigh in on the subject of hypothyroid due to thyroiditis from high iodine intake:

“Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid [normal thyroid] after restriction of iodine intake for 3 weeks (reversible type).”

Of particular interest is the finding that:

“Seven patients with the reversible type were given 25 mg iodine daily for 2–4 weeks; all became hypothyroid again...The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland.”

Their conclusion is consonant with those of the previously mentioned study, and implies that milder forms of thyroiditis may recover if iodine is discontinued:

“These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.”

Another study published in the journal Biological Trace Element Research finds more evidence for the role of iodine in promoting hypothyroidism. The authors first state:

Excessive iodine intake is known to induce hypothyroidism in people who have underlying thyroid disorders. However, few studies have been performed on subjects with normal thyroid function without a history of autoimmune thyroid disease. We hypothesized that high iodine intake may cause a subtle change in thyroid function even in subjects with normal thyroid function.

They examined 337 subjects with normal levels of thyroid antibodies for urinary iodine excretion, free T4 (FT4), and thyroid-stimulating hormone (TSH).

“The results showed urinary iodine excretion had negative correlation with FT4 and showed a positive trend with TSH. We found that 61.7% of subjects had circulating TPO-Ab within normal reference range. In all subjects, TPO-Ab levels were negatively correlated with FT4 and positively with TSH.”

In other words, as iodine went up the thyroid hormone free T4 went down and TSH (thyroid stimulating hormone)—bother markers for hypothyroid disease. Additionally, while 38.3% had high levels of thyroid peroxidase antibody (proof of autoimmune thyroiditis), for everyone higher levels of TPO-Ab correlated with lower free T4 and higher TSH. (Personally, I have observed that the standard reference ranges for thyroid antibodies are too ‘generous’.) They authors summarize the implications of their data:

“In conclusion, high iodine intake can negatively affect thyroid hormone levels in subjects with normal thyroid function.”

I have heard the Japanese consumption of seaweed cited as evidence for allowing higher levels of iodine intake, but a study published in the Endocrine Journal (of the Japanese Endocrine Society) contradicts this assumption.

“The effect of ingesting seaweed “Kombu” (Laminaria japonica) on thyroid function was studied in normal Japanese adults. Ingesting 15 and 30 g of Kombu (iodine contents: 35 and 70 mg) daily for a short term (7-10 days) significantly increased serum thyrotropin (TSH) concentrations, exceeding the normal limits in some subjectsDuring long term daily ingestion of 15 g of Kombu (55-87 days), the TSH levels were elevated and sustained while the FT4 and FT3 levels were almost unchanged. Urinary excretion of iodine significantly increased during ingestion of Kombu. These abnormal values returned to the initial levels 7 to 40 days after discontinuing the ingestion of Kombu.”

In other words, a diet  heavy on the seaweed Kombu can introduce enough iodine to suppress thyroid function. The authors conclude by recommending:

Based on these findings that thyroid function was suppressed during ingestion of Kombu, though the effect was reversible, we recommend Japanese people avoid ingesting excessive amounts of seaweed.”

Their findings are echoed in a paper published recently in The Medical Journal of Australia which reports…

“…a series of cases of thyroid dysfunction in adults associated with ingestion of a brand of soy milk manufactured with kombu (seaweed), and a case of hypothyroidism in a neonate whose mother had been drinking this milk. We also report two cases of neonatal hypothyroidism linked to maternal ingestion of seaweed made into soup. These products were found to contain high levels of iodine.”

Happily, in both cases the TSH returned and the patients recovered after discontinuing the seaweed enriched soy milk. The conclude with this alert:

Despite increasing awareness of iodine deficiency, the potential for iodine toxicity, particularly from sources such as seaweed, is less well recognised.

Another paper just published in the Journal of Paediatrics and Child Health reports a similar phenomenon and offers a balanced conclusion:

“Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable.

Caution should be used even when applying topical iodine as an antiseptic as reported in a paper published in the journal Anales española de pediatría. They note that iodine-containing antiseptics are still common in obstetrics and neonatology, and that…

“Topical iodine given both to the mother before delivery and to the neonate causes iodine overload. The absorption of maternal iodine through the skin is so fast that iodine in the blood of the umbilical cord increases by 50% a few minutes before delivery. Iodine overload also occurs in the mother. Urinary and breast-milk iodine are increased more than 10-fold in the days after delivery if providone-iodine is used in episiotomy. The overload in the neonate is even higher if breast-fed….this overload can produce thyroid blockade…”

The effects of thyroid blockade in the infant are potentially very serious, especially considering the importance of thyroid function for brain development. The authors conclude with a warning:

Attention should be drawn to the undesirable effects of iodine antiseptics and their use in the perinatal period should be avoided.

Of course there is a place for iodine supplementation in cases of deficiency conditions (which can manifest in a variety of ways) along with prophylaxis for disastrous exposure to ionizing radiation, but generally speaking, how much is enough? A very nice study on a chronically iodine-deficient population was recently published in the journal Endokrynologia Polska (Polish Journal of Endocrinology):

“Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ± 10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 μg KI/100 mL and voluntary supplementation of pregnant and breast-feeding women with additional 100-150 μg of iodine. Our aim in this study was to evaluate the iodine status of pregnant women ten years after iodine prophylaxis was introduced.

They examined 100 healthy pregnant women between the fifth and the 38th week of pregnancy for serum TSH, fT(4), fT(3), thyroglobulin (TG), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (TGAb), urinary iodine concentration (UIC) and thyroid volume and structure by ultrasonography. This really was an iodine-deficient population—28% of the subjects had a goiter. What did their data show?

“Median UIC was significantly higher in the group receiving iodine supplements than in the group without iodine supplements…Serum TSH, fT(3) and fT(3)/fT(4) molar ratio increased significantly during pregnancy while fT(4) declined. Median serum TG was normal: 18.3 ng/mL (range 0.4-300.0 ng/mL) and did not differ between trimesters. Neonatal TSH performed on the third day of life as a neonatal screening test for hypothyroidism was normal.”

Thus the authors concluded:

Iodine supplements with 150 μg of iodine should be prescribed for each healthy pregnant [Polish] woman according to the assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply.”

Here is a point worth noting for those who are aware of a recent trend for prescribing extremely high doses of supplemental iodine, as high as 50 mg per day and sometimes more: 50 mg = 50,000 μg (micrograms). That’s 333 times the amount recommended by the Polish study. This is not to say that there are never cases where megadoses of iodine may be indicated, but clinicians should maintain a biological perspective and exercise caution.

Regarding tools to support the practitioner’s thoughtful efforts to structure a careful approach to thyroid case management and iodine supplementation, can we rely on urinary iodine concentration (UIC) as a metric? A study published in Clinical Endocrinology suggests that we can’t. The authors set out to…

“…measure breast milk iodine (MI) and urinary iodine (UI) concentrations in healthy newborns and their nursing mothers from an iodine-sufficient region to determine adequacy and to relate these parameters to thyroid function tests in mothers and infants.”

Their study cohort included 48 healthy neonates of 37 to 42 weeks’ gestation and their mothers. Serum thyroid function tests and urinary iodine excretion were measured for infants and mothers, and maternal milk iodine concentration were measured. What did their data show?

Neonatal and maternal UI did not correlate with serum thyroid function tests…Among euthyroid neonates, UI was adequate despite low median maternal UI and MI concentrations. There were no significant correlations between UI or MI and thyroid function tests in the mothers and infants.

What about in cases where there is documented thyroid dysfunction? Is urinary iodine a correlative marker in this patient population. An interesting study published in the journal Endocrine implies that it is not. The authors state:

“The prevalence of thyroid dysfunction varies in different populations. The aim of this cross-sectional study was to analyze the prevalence of undiagnosed thyroid dysfunction and thyroid antibodies and their relationship with urine iodine excretion in a representative sample of 1,124 (55.5% women; mean age: 44.8 ± 15.2 years) non-hospitalized Mediterranean adults, in Catalonia (Spain).”

They measured free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroperoxidase and thyroglobulin antibodies, and urine iodine. Interestingly, they found thyroid dysfunction in 8.9% of their subjects with 5.3% previously undiagnosed (13.61% and 9.8% in those over age 60). Rough indicators of autoimmune thyroiditis were present: thyroperoxidase antibodies in 2.4% of men and 9.4% of women and thyroglobulin antibodies in 1.3% of men and 3.8% of women. What about the correlation with urine iodine?

No differences were observed in urine iodine between groups with thyroid dysfunction and euthyroidism, or between subjects with positive or negative antibodies.

In other words, urine iodine completely failed to discriminate between those with normal and abnormal thyroid function.

Here’s what the evidence boils down to: iodine supplementation has its place when used with sound clinical judgment and a biological perspective in the hands of a practitioner with the knowledge and experience to assess the need and tolerance of each individual patient with care. As for protection from harmful doses of ionizing radiation, clinicians who employ a functional medicine perspective are well equipped to evaluate your resources for ameliorating oxidative and mutagenic stresses.