Subclinical thyroid disease (SCTD) is defined as serum free T4 and free T3 levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine t...

The clinical significance of subclinical thyroid dysfunction.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60276-6.pdf

Subclinical thyroid disease

Iodine-deficiency disorders

Background The prevalence of thyroid nodules in a healthy population is high: in the German Papillon study, nationwide ultrasound screening of more than 90 000 people using 7·5 MHz scanners revealed the presence of thyroid nodules in 33% of the normal population. A study employing more sensitive 13 MHz scanners has not been conducted so far.



Materials and methods  Six hundred and thirty-five consecutive patients (33% female, 67% male, mean 56·7 years) presenting for a preventive health check up underwent ultrasound screening of the thyroid gland (Siemens Acuson Antares, 13 MHz-linear scanner, B-mode and Power mode) and measurement of the basal TSH (thyroid stimulating hormone) value. Size and degree of vascularization of the thyroid gland and of nodules were determined and analysed retrospectively.



Results  In 432 of 635 patients, thyroid nodules could be detected with an increasing incidence with age, in 338 without goiter. Mean thyroid size was 12·3 mL for women and 20·5 mL for men correlating strongly with body weight. Fifty-three percentage of the nodules were smaller than 5 mm. Incidence of thyroid dysfunction was only 4%. No cancerous lesions could be found.



Conclusions  Using the 13 MHz technology, we found a substantially higher prevalence of thyroid nodules (68%) than the Papillon study (33%). Even if our population is older than in Papillon, the difference remains in comparable age groups. This is due to the higher sensitivity of 13 MHz scanning. Our study underlines the clinical significance of iodine deficiency and should renew the discussion on routine iodine supplementation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2362.2009.02162.x

Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination.

Background Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 μg per liter), more than adequate (median, 243 μg per liter), and excessive (median, 651 μg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease. Methods Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up. Results Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function. Conclusions More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis.

/pdf/effect-of-iodine-intake-on-thyroid-diseases-in-china-1yccfw50ic.pdf

Effect of iodine intake on thyroid diseases in China.

Objective: An increasing incidence of hyperthyroidism has been observed when iodine supplementation has been introduced to an iodine-deficient population. Moreover, the influence of chronic more than adequate or excessive iodine intake on the epidemiological features of hyperthyroidism has not been widely and thoroughly described. To investigate the influences of different iodine intake levels on the incidence of hyperthyroidism, we conducted a prospective community-based survey in three communities with mild-deficient, more than adequate (previously mild deficient iodine intake), and excessive iodine intake. Subjects and methods: In three rural Chinese communities, a total of 3761 unselected inhabitants aged above 13 years participated in the original investigation and 3018 of them received identical examinations after 5 years. Thyroid function, levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody and urinary iodine excretion were measured and thyroid ultrasound examination was also performed. Results: In three communities, median urinary iodine excretion was 88, 214, and 634 mg/l (P!0.05) respectively. The cumulative incidence of hyperthyroidism was 1.4, 0.9, and 0.8% (PO0.05) respectively. Autoimmune hyperthyroidism was predominant in thyroid hyperfunction in all the three cohorts. Either positive TPOAb (O50 U/ml) or goiter in original healthy participants was associated with the occurrence of unsuspected hyperthyroidism in 5 years (logistic regression, ORZ4.2 (95% CI 1.7‐8.8) for positive TPOAb, ORZ3.1 (95% CI 1.4‐6.8) for goiter). Conclusion: Iodine supplementation may not induce an increase in hyperthyroidism in a previously mildly iodine-deficient population. Chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.

/pdf/chronic-iodine-excess-does-not-increase-the-incidence-of-2hvg39uthm.pdf

Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China.

BACKGROUND
Subclinical hypothyroidism (SCH) is associated with an increased risk of metabolic disorders and cardiovascular events. There is a delicate interplay between thyroid hormones and thyrotropin (TSH) and metabolic homeostasis. However, the association between thyroid hormone sensitivity and metabolic indices has not been elucidated in SCH.


METHODS
We enrolled 11,109 participants with SCH. All participants had a TSH level>4.2 mIU/L and normal free thyroxine (FT4) (12.0-22.0 pmol/L). Metabolic indices (body mass index [BMI], blood pressure, serum lipid, serum uric acid [sUA], plasma glucose and glycosylated hemoglobin [HbA1C]) were measured. The thyroid hormone sensitivity indices which include feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI) and thyrotroph thyroxine resistance index (TT4RI) were calculated based on FT4 and TSH. Higher thyroid feedback quantile-based index (TFQI) quartiles indicated lower thyroid hormone sensitivity. The relationship between thyroid hormone sensitivity indices and metabolic indices and cardiovascular disease (CVD) risk were calculated.


RESULTS
Participants with decreased central sensitivity to thyroid hormone had lower BMI and higher sUA levels. The odds ratio of the fourth vs. the first quartile of thyroid feedback quantile-based index (TFQI) was 0.85 (95% confidence interval [CI]: 0.73, 0.96) for obesity, 1.64 (95% CI: 1.37, 1.92) for hyperuricemia, and 12.22 (95% CI: 5.32, 28.07) for 10-year risk distribution for CVD >20%. Further adjustment for BMI when analyzing HbA1C, hyperuricemia, and CVD risk generated similar results. TSHI and TT4RI also yielded similar results.


CONCLUSIONS
Impaired sensitivity to thyroid hormone in SCH is associated with higher risk of hyperuricemia and CVD and lower risk of obesity. These findings are potentially useful for understanding the interaction between thyroid hormone sensitivity and metabolic diseases in SCH.

Impaired Sensitivity to thyroid hormones is associated with hyperuricemia, obesity, and cardiovascular disease risk in subclinical hypothyroidism subjects.

OBJECTIVE To investigate the prevalence of thyroid diseases in a community which did not use iodized salt. METHODS The survey was conducted in Panshan, Liaoning Province. 1 103 inhabitants aged 14 years or more attended the examinations, which included questionnaire, physical examination and serum analysis. Iodine in the urine and thyroid B ultrasound examination were also conducted. RESULTS The prevalence of overt hyperthyroidism and hypothyroidism was 16.3 per thousand and 2.7 per thousand, respectively. Subclinical hyperthyroidism and hypothyroidism were detected in 37.2 per thousand and 9.1 per thousand of the subjects, respectively. Serum autoantibodies to thyroid were detected in 10.9% of the entire population. The prevalence of goiter was 20.7% (diffuse goiter 16.8% and nodular goiter 3.9%). CONCLUSION In the iodine deficient areas, perhaps autoimmununization is not only related to the development of goiter but is also the main cause of subclinical hyperthyroidism and hypothyroidism.

The study of thyroid diseases in a community not using iodized salt.

BACKGROUND
Metabolic disorders (MDs) and the Metabolic Syndrome (MetS) may be associated with thyroid diseases. The aim of this study was to investigate the relationship between MDs and various types of thyroid nodules (TNs), according to gender.


METHODS
We analyzed cross-sectional data from the Thyroid Disorders, Iodine Status, and Diabetes Epidemiological (TIDE) survey in China. A total of 56,729 subjects aged ≥18 years were included. Thyroid gland morphology was assessed by thyroid standardized ultrasonography. A multivariate logistic regression model was used to explore the odds ratio (OR) and 95% confidence intervals (95%CI) for any associations between MDs and TNs. Subgroup analyses were conducted according to gender and TN type (solitary, S-TN; multiple, M-TNs)..


RESULTS
The prevalence of TNs was increased in several MDs, and was higher in women than men regardless of whether they suffered from MDs [22.0% 95%CI (21.6%, 22.5%) vs. 15.7% 95%CI (15.3%, 16.7%), p<0.001]. TNs were associated with the presence of MDs [OR=1.189, 95%CI (1.107, 1.278), p<0.001], hypercholesterolemia [OR=1.235, 95%CI (1.177, 1.296), p<0.001], high LDL-C [OR=1.249, 95%CI (1.186, 1.316), p<0.001], and hyperuricemia [OR=1.206, 95%CI (1.126, 1.293), p<0.001]. MDs and MetS were respectively significantly associated with TNs, S-TNs and M-TNs in men, while MDs were significantly associated with the three TN profiles in women. With respect to dyslipidemia, hypercholesterolemia and high LDL-C had the strongest association with TNs, while hypertriglyceridemia had no effect.


CONCLUSIONS
TNs (especially M-TNs) may be associated with MDs and their various components and there appear to be some gender-specific associations.

Di Teng

Papers

Effect of iodine intake on thyroid diseases in China.

Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China.

Impaired Sensitivity to thyroid hormones is associated with hyperuricemia, obesity, and cardiovascular disease risk in subclinical hypothyroidism subjects.

The study of thyroid diseases in a community not using iodized salt.

Gender-Specific Associations Between Metabolic Disorders and Thyroid Nodules: A Cross-Sectional Population-Based Study From China.