Dr. Ron’s Research Review – November 6, 2019

©

This week’s research review focuses on recognizing iodine deficiency.

Thyroid enlargement (goitre) is the classic sign of iodine deficiency, and can take place at any age, even in newborn babies. It is a physiological adaptation to chronic iodine deficiency. As the iodine intake falls, secretion of thyroid-stimulating hormone (TSH) increases in an effort to maximise uptake of available iodine, and TSH stimulates thyroid hypertrophy and hyperplasia. (Zimmermann et al., 2008)

Several diseases may be associated with iodine deficiency. (Verheesen and Schweitzer, 2008)
Obesity has been associated with TSH increase within normal range
Recently, the association between iodine deficiency in pregnancy and ADHD of the child was shown
A relationship between (subclinical) hypothyroidism and anxiety disorders, memory disturbances, neurotic and attention disorders have been described. Brain hypothyroidism may be a crucial factor in the pathogenesis. Iodine deficiency and/or selenium deficiency can be the underlying causes, eventually leading to low brain T3 levels.
A complex of symptoms that resemble hypothyroidism characterizes Fibromyalgia. It is known that the more symptoms of hypothyroidism are present, the more likely the presence of this disorder becomes. In fibromyalgia patients several symptoms are frequently present, however, without the marked TSH increase as seen in full-blown hypothyroidism
Many studies have pointed out the relationship between cancer and thyroid disturbances. Iodine and selenium have been described as two independent factors playing a crucial role in the prevention of breast and prostate cancer, respectively.

Low iodine may be a risk factor for cardiovascular disease in Americans without thyroid dysfunction. (Tran et al., 2017)
Low urinary iodine concentrations associated with dyslipidemia in US adults. (Lee et al., 2016)
Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2. Routine annual urinary iodine determination is recommended and should target T2DM patients at risk of thyroid dysfunction. (Al-Attas et al., 2012)
Iodine is associated to semen quality in men who undergo consultations for infertility. (Partal-Lorente et al., 2017)
The urinary iodine level was significantly lower in women with postmenopausal osteoporosis, and iodine replacement may be important in preventing osteoporosis in areas where iodine deficiency is endemic. (Arslanca et al., 2018)
Body iodine status during postmenopausal period is associated with the menopausal symptoms and lipid profile including Lp(a). Urine spot iodine level was significantly correlated with Lp(a) (r = -0.287, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = -0.187, p = 0.006), cholesterol level (r = -0.573, p < 0.001), TG level (r = -0.211, p = 0.02), frequency of hot flashes per a day (r = -0.467, p < 0.001), durations of hot flashes (r = -0.424, p < 0.001), fasting glucose level (r = 0.331, p < 0.001), and fT3 level (r = 0.475, p < 0.001). In multivariate analysis, Lp(a) levels were significantly associated with the urine iodine level (beta coefficient = -0.342, p < 0.001) after adjustment for LDL-C (beta coefficient = 0.225, p < 0.001), glucose (beta coefficient = 0.303, p < 0.001), and age (beta coefficient = 0.146, p < 0.017). (Korkmaz et al., 2015)
Iodide and thyroglobulin play a role for in modulating the function of human immune cells. (Bilal et al., 2017)

 

Dr. Ron

 


Articles

 

Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2.
            (Al-Attas et al., 2012) Download
BACKGROUND:  Diabetes Mellitus (DM) is a major health problem worldwide and its prevalence in Saudi Arabia has reached 31.6%. 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. METHODS:  A total of 266 adult Saudis aged 18-55 years (109 T2DM patients and 157 healthy controls) were randomly selected from the Riyadh Cohort Study. Subjects were assessed for anthropometry, morning blood chemistries including fasting glucose, and lipid profile; serum concentrations of leptin, adiponectin, resistin, insulin, aPAI, hsCRP, Ang II, TNF-α, TSH, T3, T4, urine creatinine, urine iodine were measured using specific assays. RESULTS:  The concentration of urine iodine was significantly lower in T2DM than in healthy control subjects (84.6±2.3 vs. 119.4±3.4, p<0.001), which remained significant after creatinine correction and controlling for age (p=0.01). 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. CONCLUSIONS:  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.

Body iodine status in women with postmenopausal osteoporosis.
            (Arslanca et al., 2018) Download
OBJECTIVE:  Postmenopausal osteoporosis is a frequent cause of morbidity and can negatively impact life expectancy; iodine is an essential element for bone mineralization, and iodine deficiency is frequently observed. The aim of the present study was to understand the connection between postmenopausal osteoporosis and the level of iodine in the body. METHODS:  A total of 132 participants were divided into three groups: group 1 consisted of healthy postmenopausal women (n = 34), group 2 comprised osteopenic women (n = 38), and group 3 included women with postmenopausal osteoporosis (n = 60). The three groups were compared according to demographic, clinical, and laboratory findings. RESULTS:  The urinary iodine levels were recorded as 216.1 ± 125.2 in the control group, 154.6 ± 76.6 in the osteopenic group, and 137.5 ± 64.9 in the postmenopausal osteoporosis group (P < 0.001). These differences were maintained after adjustment for body mass index (P < 0.001). The urinary iodine level accurately correlated with the total T-score for the lumbar spine (r = 0.236, P = 0.008). Multiple regression analysis showed that corrected for body mass index, alkaline phosphatase isoenzyme, and urinary deoxypyridinoline, the urinary iodine level was significantly associated with total T-score (beta coefficient = 0.270, P = 0.006). CONCLUSIONS:  The urinary iodine level was significantly lower in women with postmenopausal osteoporosis, and iodine replacement may be important in preventing osteoporosis in areas where iodine deficiency is endemic.

A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells.
            (Bilal et al., 2017) Download
Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes. Treatment of leukocytes with sodium iodide (NaI) resulted in significant changes in immunity-related transcriptome with an emphasis on increased chemokine expression as probed with targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol's iodine induced increased protein production of both pro- and anti-inflammatory cytokines. These alterations were not attributed to iodide-induced

Relationship between the body iodine status and menopausal symptoms during postmenopausal period.
            (Korkmaz et al., 2015) Download
AIM:  The aim of this study was to assess the effect of body iodine status on hot flashes and cardiovascular disease risk in postmenopausal women. METHODS:  Two hundred and ten consecutive postmenopausal women without known any risk factor for cardiovascular disease risk or systemic disorder were recruited for the study. All participants underwent serum screening consisted of lipid profile including lipoprotein-a (Lp(a)) and urinary iodine excretion. Participants were also asked for the frequency and the duration of hot flashes. All parameters were assessed for the association between urine iodine excretion and other parameters. RESULTS:  Urine spot iodine level was significantly correlated with Lp(a) (r = -0.287, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = -0.187, p = 0.006), cholesterol level (r = -0.573, p < 0.001), TG level (r = -0.211, p = 0.02), frequency of hot flashes per a day (r = -0.467, p < 0.001), durations of hot flashes (r = -0.424, p < 0.001), fasting glucose level (r = 0.331, p < 0.001), and fT3 level (r = 0.475, p < 0.001). In multivariate analysis, Lp(a) levels were significantly associated with the urine iodine level (beta coefficient = -0.342, p < 0.001) after adjustment for LDL-C (beta coefficient = 0.225, p < 0.001), glucose (beta coefficient = 0.303, p < 0.001), and age (beta coefficient = 0.146, p < 0.017). CONCLUSION:  Body iodine status during postmenopausal period is associated with the menopausal symptoms and lipid profile including Lp(a).

Low Urinary Iodine Concentrations Associated with Dyslipidemia in US Adults.
            (Lee et al., 2016) Download
Iodine is an essential component of the thyroid hormone which plays crucial roles in healthy thyroid function and lipid metabolism. However, the association between iodine status and dyslipidemia has not been well established at a population level. We aimed to test the hypothesis that the odds of dyslipidemia including elevated total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and apolipoprotein B, and lowered high-density lipoprotein (HDL) cholesterol and HDL/LDL ratio are associated with urinary iodine concentration (UIC) in a population perspective. Data of 2495 US adults (≥20 years) in the National Health and Nutrition Examination Survey 2007-2012 were used in this study. Two subgroups (i.e., UIC below vs. above the 10th percentile) were compared of dyslipidemia as defined based on NCEP ATP III guidelines. The differences between the groups were tested statistically by chi-square test, simple linear regressions, and multiple logistic regressions. Serum lipid concentrations differed significantly between two iodine status groups when sociodemographic and lifestyle covariates were controlled (all, p < 0.05). Those with the lowest decile of UIC were more likely to be at risk for elevated total cholesterol (>200 mg/dL) (adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI): 1.03-2.23) and elevated LDL cholesterol (>130 mg/dL) (AOR = 1.58, 95% CI: 1.11-2.23) and lowered HDL/LDL ratio (<0.4) (AOR = 1.66, 95% CI: 1.18-2.33), compared to those with UIC above the 10th percentile. In US adults, low UIC was associated with increased odds for dyslipidemia. Findings of the present cross-sectional study with spot urine samples highlight the significant association between UIC and serum lipids at population level, but do not substantiate a causal relationship. Further investigations are warranted to elucidate the causal relationship among iodine intakes, iodine status, and serum lipid profiles.

Iodine is associated to semen quality in men who undergo consultations for infertility.
            (Partal-Lorente et al., 2017) Download
The role that adequate iodine intake could have on the male reproductive function is not entirely known. The aim of this study is to determine whether there is a relation between male infertility and urinary and semen iodine levels in 96 couples who underwent consultation for infertility. The median of semen iodine was higher in men who consumed iodized salt than in those who consumed non-iodized salt (p=0.019). Men with a higher semen iodine level had more morphological alterations in spermatozoa (p=0.032). Men with a higher urinary iodine level had a lower motile sperm count according to the "direct swim-up" technique (p=0.044). Men >3years without successfully achieving pregnancy had a higher urinary iodine level than those with ≤ 3years (p=0.035). In conclusion, iodine may play a role in the quality of semen: an increase in semen iodine levels is associated with different variables related to male infertility.

Is low iodine a risk factor for cardiovascular disease in Americans without thyroid dysfunction? Findings from NHANES.
            (Tran et al., 2017) Download
BACKGROUND AND AIMS:  Low body iodine levels are associated with cardiovascular disease, in part through alterations in thyroid function. While this association suggested from animal studies, it lacks supportive evidence in humans. This study examined the association between urine iodine levels and presence of coronary artery disease (CAD) and stroke in adults without thyroid dysfunction. METHODS AND RESULTS:  This cross-sectional study included 2440 adults (representing a weighted n = 91,713,183) aged ≥40 years without thyroid dysfunction in the nationally-representative 2007-2012 National Health and Nutrition Examination Survey. The age and sex-adjusted urine iodine/creatinine ratio (aICR) was categorized into low (aICR<116 μg/day), medium (116 μg/day ≤ aICR < 370μg/day), and high (aICR ≥ 370μg/day) based on lowest/highest quintiles. Stroke and CAD were from self-reported physician diagnoses. We examined the association between low urine aICR and CAD or stroke using multivariable logistic regression modeling. The mean age of this population was 56.0 years, 47% were women, and three quarters were non-Hispanic whites. Compared with high urine iodine levels, multivariable adjusted odds ratios aOR (95% confidence intervals) for CAD were statistically significant for low, aOR = 1.97 (1.08-3.59), but not medium, aOR = 1.26 (0.75-2.13) urine iodine levels. There was no association between stroke and low, aOR = 1.12 (0.52-2.44) or medium, aOR = 1.48 (0.88-2.48) urine iodine levels. CONCLUSION:  The association between low urine iodine levels and CAD should be confirmed in a prospective study with serial measures of urine iodine. If low iodine levels precede CAD, then this potential and modifiable new CAD risk factor might have therapeutic implications.

Iodine deficiency, more than cretinism and goiter
            (Verheesen and Schweitzer 2008) Download
Recent reports of the World Health Organization show iodine deficiency to be a worldwide occurring health problem. As iodine status is based on median urinary iodine excretion, even in countries regarded as iodine sufficient, a considerable part of the population may be iodine deficient. Iodine is a key element in the synthesis of thyroid hormones and as a consequence, severe iodine deficiency results in hypothyroidism, goiter, and cretinism with the well known biochemical alterations. However, it is also known that iodine deficiency may give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. This led us to the hypothesis that iodine deficiency may give rise to subtle impairment of thyroid function leading to clinical syndromes resembling hypothyroidism or diseases that have been associated with the occurrence of hypothyroidism. We describe several clinical conditions possibly linked to iodine deficiency, a connection that has not been made thus far. In this paper we will focus on the relationship between iodine deficiency and obesity, attention deficit hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.

Iodine-deficiency disorders
            (Zimmermann, Jooste et al. 2008) Download
2 billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficiency disorders. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Assessment methods include urinary iodine concentration, goitre, newborn thyroid-stimulating hormone, and blood thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is iodisation of salt, which is one of the most cost-effective ways to contribute to economic and social development. When iodisation of salt is not possible, iodine supplements can be given to susceptible groups. Introduction of iodised salt to regions of chronic iodine-deficiency disorders might transiently increase the proportion of thyroid disorders, but overall the small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. International efforts to control iodine-deficiency disorders are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges.

 

References

Al-Attas, OS, et al. (2012), ‘Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2.’, Exp Clin Endocrinol Diabetes, 120 (10), 618-22. PubMed: 23203253
Arslanca, T, et al. (2018), ‘Body iodine status in women with postmenopausal osteoporosis.’, Menopause, 25 (3), 320-23. PubMed: 28953213
Bilal, MY, et al. (2017), ‘A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells.’, Front Immunol, 8 1573. PubMed: 29187856
Korkmaz, V, et al. (2015), ‘Relationship between the body iodine status and menopausal symptoms during postmenopausal period.’, Gynecol Endocrinol, 31 (1), 61-64. PubMed: 25211538
Lee, KW, D Shin, and WO Song (2016), ‘Low Urinary Iodine Concentrations Associated with Dyslipidemia in US Adults.’, Nutrients, 8 (3), 171. PubMed: 26999198
Partal-Lorente, AB, et al. (2017), ‘Iodine is associated to semen quality in men who undergo consultations for infertility.’, Reprod Toxicol, 73 1-7. PubMed: 28755858
Tran, HV, et al. (2017), ‘Is low iodine a risk factor for cardiovascular disease in Americans without thyroid dysfunction? Findings from NHANES.’, Nutr Metab Cardiovasc Dis, 27 (7), 651-56. PubMed: 28689680
Verheesen, R. H. and C. M. Schweitzer (2008), ‘Iodine deficiency, more than cretinism and goiter’, Med Hypotheses, 71 (5), 645-48. PubMed: 18703293
Zimmermann, M. B., P. L. Jooste, and C. S. Pandav (2008), ‘Iodine-deficiency disorders’, Lancet, 372 (9645), 1251-62. PubMed: 18676011