Subclinical hypothyroidism (SCH), defined as elevated serum thyroid-stimulating hormone (TSH) in the presence of normal circulating free thyroxine (FT4) and triiodothyronine (T3), is a relatively common condition. Replacement treatment with levothyroxine is justified only for individuals with TSH levels >10 mIU/l. Serum lipid levels are influenced by thyroid status and there is evidence pointing to a link between SCH and an unfavorable lipid profile. Despite some conflicting data, most studies suggest that levothyroxine treatment may exert a beneficial effect on the lipid profile in SCH regarding mainly total cholesterol and low-density lipoprotein-cholesterol. Moreover, it appears that treatment may also improve some other markers associated with cardiovascular (CV) disease such as carotid intima media thickness (cIMT) indices of endothelial function and other predictors of vascular risk. The complex interaction between SCH and predictors of vascular disease may explain the variability of the results obtained from studies that assessed vascular events or even changes in some biochemical, functional or structural variables associated with an increased risk of vascular events. Further investigation is warranted by means of intervention studies to assess the clinical significance of levothyroxine treatment in SCH regarding CV risk.

BACKGROUND

Little is known of the association between thyroid hormones in the central nervous system and Alzheimer's disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population.

METHODS

Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=31), patients with stable MCI (SMCI, n=13), patients with other dementias (n=15), and healthy controls (n=19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE).

RESULTS

Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P=0.01) and healthy controls (both P=0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total T4 level correlated positively with MMSE score (r=0.26, P<0.05) and negatively with CSF total-tau (T-Tau) level (r=-0.23, P<0.05).

CONCLUSIONS

Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values.

OBJECTIVE

In previous serum thyroid studies, we reported an unusual thyroid profile, including elevated levels of total and free triiodothyronine (T3), total thyroxine (T4), and thyroxine-binding globulin (TBG) with no elevations in free T4 and thyrotropin (TSH) in Vietnam veterans with combat-related posttraumatic stress disorder (PTSD) compared to control subjects. In a subsample of Vietnam veterans, we found a significant positive correlation between total T3, free T3, and PTSD symptoms, specifically hyperarousal symptoms. In the present study, we explored the generalizability of our findings to World War II (WWII) veterans with PTSD.

METHODS

Clinical symptoms were assessed in and serum thyroid measures were obtained from 12 WWII veterans with PTSD and 18 WWII veterans without PTSD.

RESULTS

WWII veterans with combat-related PTSD showed elevations of serum total and free T3 with no elevations of free T4 and TSH compared to control subjects, replicating the results of our previous studies. A significant positive relationship between total and free T3 and PTSD symptoms, specifically hyperarousal symptoms, was also replicated in the total WWII group. Elevations of total T4 and TBG were not replicated in the WWII group with PTSD, which may indicate a shift with age in the free/bound dynamics of the thyroid alterations observed.

CONCLUSIONS

This study supports the observation that the thyroid system is altered in chronic combat-related PTSD. The observed alterations of thyroid function along with PTSD symptoms appear to be chronic, detectable 50 years after the war.

BACKGROUND

Research on thyroid activity among male combat veterans with posttraumatic stress disorder (PTSD) has consistently shown elevations in total triiodothyronine (TT3) and inconsistent elevations of other thyroid variables. This study is the first large scale investigation of thyroid function in women with PTSD.

METHODS

Thyroid function was measured in 63 women with PTSD due to childhood sexual abuse (PTSD-CSA) in comparison with a community sample of 42 women without current PTSD-CSA. Clinical measures included the Clinician Administered PTSD Scale (CAPS), the Evaluation of Lifetime Stressors, the Trauma Assessment for Adults and the Beck Depression Inventory.

RESULTS

Women with PTSD-CSA showed significant elevations in Total T3 and the TT3/free thyroxine (TT3/FT4) ratio, the FT3/TT3 ratio, and modest reductions in thyroid stimulating hormone relative to our community sample. These findings could not be explained by the influence of prior trauma, lifetime PTSD or depressive symptoms.

CONCLUSIONS

Altered thyroid activity, especially elevated Total T3 levels, was found in women with PTSD associated with childhood sexual abuse.

In a prospective, randomized study we examined the influence of prophylactic short-term thyrostatic therapy on thyroid iodine metabolism in patients with euthyroid autonomy undergoing elective coronary angiography. From a total of 1177 patients, 51 fulfilled the criteria of euthyroid autonomy before coronary angiography (negative thyrotropin-releasing hormone test, 10-min uptake of at least 1.2%, 99mTc and no elevation of free thyroxine and free triiodothyronine indices) and were randomized into three groups: group 1 (N = 17) received 20mg/day of thiamazole and group 2 (N = 17) received 900 mg/day of sodium perchlorate; thyrostatic therapy was begun on the day before angiography and continued for 14 days; group 3 (N = 17) served as controls without treatment. Parameters of thyroid function-free thyroxine (FT4) index and free triiodothyronine (FT3) index, thyrotropin (TSH) and delta-TSH urine iodine excretion and 99mTc uptake were determined before and 30 days after coronary angiography. At the end of the study the mean FT4 index and FT3 index were elevated significantly in the control group compared with baseline values, but were still within the normal range. In contrast, the mean FT4 index and FT3 index remained unchanged in the treated groups. Four mild cases of hyperthyroidism were observed at the end of the study: two cases in the control group and one case in each of the treated groups. Thyrotropin suppression, urine iodine excretion and 99mTc uptake differed significantly between the treated groups and the control group. In the treated groups TSH suppression, urine iodine excretion and 99mTC uptake remained unchanged 30 days after coronary angiography compared with baseline values. In the control group the degree of TSH suppression and the level of urine iodine excretion increased (about twofold) significantly after coronary angiography, whereas 99mTc uptake decreased significantly (ca. 50%). In conclusion, short-term prophylactic thyrostatic therapy seems to have a protective effect against iodine excess in patients with euthyroid autonomy. However, mild hyperthyroidism could not be prevented in some cases. Probably a combination therapy of thiamazole and perchlorate would be more effective.

Body mass, resting metabolic rates (RMRs), and serum thyroid hormones concentrations of six captive gray seals (Halichoerus grypus) were measured at regular intervals before, during, and after the annual molt. Changes in body mass suggested that the animals had increased energy expenditures during the last stage of the molt. These were associated with significantly elevated RMRs during the molt, the increase being more pronounced in juveniles ( < or = 53%) than in adults ( < or = 17%). The increase in RMR probably reflects the cost of generating a new pelt or to sustain a high skin temperature. Serum total and free thyroxine concentrations were elevated for all animals during the molt, but only juveniles had elevated serum triiodothyronine concentration. The increase in thyroid hormones occurred only during the last stage of the molt, suggesting that the role of thyroid hormones during the molt may be to sustain rapid hair growth in the last stage of molt or to maintain elevated heat production, rather than to initiate hair growth.

Triclosan (TCS) is a synthetic antibacterial chemical widely used in personal care products. TCS exposure has been associated with decreased thyroid hormone levels in animals, but human studies are scarce and controversial.

We evaluated the association between maternal TCS exposure and thyroid hormone levels of mothers and newborns.

TCS was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in urine samples collected during gestational weeks 38.8±1.1 from 398 pregnant women in a prospective birth cohort enrolled in 2012-2013 in Shanghai, China. Maternal serum levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were obtained from medical records. Cord blood levels of free triiodothyronine (FT3), FT4, TSH, and TPOAb were measured. Multiple linear and logistic regression models were used to examine the relationship between maternal urinary TCS and thyroid hormone levels.

TCS was detectable (≥0.1 ng/mL) in 98.24% of maternal urine samples with tertile of urinary TCS levels: low (>0.1-2.75 μg/g.Cr), medium (2.75–9.78 μg/g.Cr), and high (9.78–427.38 μg/g.Cr). With adjustment for potential confounders, cord blood log(FT3)pmol/L concentration was 0.11 lower in newborns of mothers with medium and high urinary TCS levels compared with those with low levels. At third trimester, the high TCS concentration was associated with 0.03 [95% confidence interval (CI) −0.08, −0.02] lower maternal serum log(FT4)pmol/L, whereas the medium TCS concentration was associated with 0.15 (95% CI: −0.28, −0.03) lower serum log(TSH)mIU/L with adjustment for covariates.

Our results suggest significant inverse associations between maternal urinary TCS and cord blood FT3 as well as maternal blood FT4 concentrations at third trimester. https://doi.org/10.1289/EHP500.

Confluent fetal rat brown adipocytes in primary culture showed an almost undetectable level of uncoupling protein (UCP) mRNA and a low mitochondrial content of functional UCP. Treatment of confluent cells with 10 nM triiodothyronine in a serum-free medium, in the absence of noradrenergic stimulation, increased the amount of UCP mRNA in a time-dependent manner. This effect was due to an increased UCP gene transcription rate and UCP mRNA stabilization, resulting in a higher content of immunoreactive mitochondrial UCP and functional UCP (detected by its ability to bind GDP). Thus, triiodothyronine might play a significant physiological role in the UCP expression throughout fetal development, when brown adipose tissue starts to differentiate and UCP is primarily expressed.

We studied the incidence and potential prognostic value of thyroid abnormalities after allogeneic bone marrow transplantation (BMT) without total body irradiation (TBI) conditioning. 77 consecutive patients who received a chemotherapy-alone-based conditioning regimen pretransplant were included. Free serum thyroxine (FT4), free serum triiodothyronine (FT3) and serum thyrotropin (TSH) levels were assayed before and 3 and 14 months after BMT. Patients were classified in three categories: normal thyroid profile if FT3 and FT4 were within the normal range and TSH was normal or low, peripheral thyroid insufficiency (PTI) if TSH was >4 mIU/l, or an 'euthyroid sick syndrome' (ETS) if FT3 and/or FT4 were low and TSH was normal or low. The incidence of thyroid dysfunction at 3 months was 57%, and 29% at 14 months. This was mostly due to the occurrence of ETS which was more frequent at 3 months (48%, 29/61) than at 14 months (19%, 9/48). Furthermore, at 3 months, survival was significantly lower in the ETS group (34.5%) than in the euthyroid group (96.2%), or in the PTI group (83.3%) (P < 0.0001). PTI was observed even in the absence of TBI in 11 patients (14%) and was equally distributed at 3 months (n = 6) and 14 months (n = 5). In conclusion, thyroid dysfunction is not a rare complication even without pretransplant TBI conditioning regimen. Hypothyroidism prevalence was 10%, and ETS, which was more frequently observed, displayed a dismal predictive value at 3 months.

An increased free thyroxine (T4) index was observed in 73% of 33 consecutive pregnancies complicated by severe hyperemesis gravidarum. The free triiodothyronine (T3) index was increased in only four of 11 hyperthyroxinemic patients. In five hyperthyroxinemic patients tested, no increase in serum thyrotropin was observed after the injection of thyrotropin-releasing hormone (THR). Goiter, exophthalmos, or previous history of hyperthyroidism was absent in all patients. The thyroxinemia returned to normal in one to several weeks, whether or not it was treated with antithyroid drugs. The thyroid function during the period of hyperemesis had no influence on the subsequent rate of abortion or duration of pregnancy. A lower birth weight, however, was observed in children born to hyperthyroxinemic mothers. Hyperemesis gravidarum should be included in the differential diagnosis of elevations in free T4 index during pregnancy and included in the differential diagnosis of hyperthyroidism.

OBJECTIVE

Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects.

METHODS

The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant.

RESULTS

FLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29-1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70-0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39-1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P<0.0001).

CONCLUSIONS

Euthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.

The aim of this study was to evaluate the association between persistent organic pollutants (POPs) and thyroid hormones in an aging population. Forty-eight women and 66 men, aged 55-74 years and living in upper Hudson River communities completed a questionnaire and provided blood specimens. Serum was analyzed for thyrotropin (thyroid stimulating hormone, TSH), free (fT4) and total thyroxine (T4), total triiodothyronine (T3), and for POPs. POPs included 39 polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) determined by gas chromatography with electron capture detection (GC-ECD), and nine polybrominated diphenyl ethers (PBDEs) determined by high-resolution gas chromatography with high-resolution mass spectrometry detection (HRGC-HRMS). Multivariable linear regression analysis was used to evaluate associations between thyroid hormones and sums of POPs, adjusted for covariates and stratified by sex. Effects were expressed as differences in thyroid hormone levels associated with a doubling in the level of exposure. Among women, DDT+DDE increased T4 by 0.34μg/dL (P=0.04) and T3 by 2.78ng/dL (P=0.05). Also in women, sums of PCBs in conjunction with PBDEs elicited increases of 24.39-80.85ng/dL T3 (P<0.05), and sums of PCBs in conjunction with DDT+DDE elicited increases of 0.18-0.31μg/dL T4 (P<0.05). For men estrogenic PCBs were associated with a 19.82ng/dL T3 decrease (P=0.003), and the sum of estrogenic PCBs in conjunction with DDT+DDE elicited an 18.02ng/dL T3 decrease (P=0.04). Given age-related declines in physiologic reserve, the influence of POPs on thyroid hormones in aging populations may have clinical implications and merits further investigation.

BACKGROUND

Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland.

OBJECTIVE

To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice.

METHODS

Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model.

RESULTS

We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range.

CONCLUSIONS

Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

Elevated concentrations of C-reactive protein (CRP) and decreased concentrations of triiodothyronine (T3) were shown to predict poor outcomes in patients with stroke. However, the prognostic value of CRP and T3 has not been studied simultaneously in relation to stroke functional and cognitive outcomes despite of close interaction between inflammatory markers and thyroid function. We evaluated the association of thyroid hormone and CRP concentrations with immediate outcomes after ischemic stroke. Eighty-eight ischemic stroke patients on admission to the stroke unit were evaluated for clinical stroke severity (Scandinavian stroke scale or SSS) and concentrations of thyroid-stimulating hormone, free thyroxin, free T3, and CRP. Functional outcome (modified Rankin scale) and cognitive outcome (Mini mental state examination) were evaluated at discharge. Greater ln CRP concentrations (r = -0.35, p = 0.001), but not thyroid hormone concentrations, correlated with score on the SSS. In univariate analyses lower free T3 concentrations and higher CRP concentrations were associated with poor functional and poor cognitive outcomes. After adjustment for clinical stroke severity, higher CRP concentrations (β = 0.18, p = 0.04) remained associated with worse functional outcome and lower free T3 concentrations with worse cognitive outcome (β = 0.23, p = 0.03). In sum, clinical stroke severity is associated with elevated CRP concentration. Higher CRP concentration is independently associated with worse functional outcomes and lower free T3 concentration with worse cognitive outcomes at discharge. T3 and CRP can be important biomarkers in patients with acute ischemic stroke.

BACKGROUND

Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition.

METHODS

This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry.

RESULTS

REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group (p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups (p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition.

CONCLUSIONS

LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

The present study was undertaken to evaluate the change of circulating visfatin, C-reactive protein (CRP) concentrations, and insulin sensitivity in patients with hyperthyroidism. We studied 19 adult patients (14 women and 5 men aged 32.6 +/- 1.8 years) with hyperthyroidism due to Graves disease and 19 age- and sex-matched euthyroid controls (17 women and 2 men aged 36.7 +/- 2.7 years). All hyperthyroid patients were treated with 1 of 2 antithyroid drugs and were reevaluated after thyroid function normalized. Before antithyroid treatment, the hyperthyroid group had significantly higher visfatin plasma concentration (mean +/- standard error of the mean, 20.7 +/- 1.8 ng/mL) than the control group (16.2 +/- 1.3 ng/mL, P = .044); but the visfatin level dropped significantly after treatment (12.0 +/- 1.4 ng/mL, P < .001). The reciprocal index of homeostasis model assessment of insulin resistance (HOMA-IR) in the hyperthyroid group was higher before treatment (2.06 +/- 0.26 mmol mU/L*L) than after treatment (1.21 +/- 0.16 mmol mU/L*L, P = .027). There was no significant difference in serum glucose, high-sensitivity CRP, and insulin levels between hyperthyroid and control groups and in the hyperthyroid group before and after treatment. Body mass index-adjusted visfatin levels were significantly elevated in the hyperthyroid group. Pearson correlation revealed that visfatin, glucose, insulin, and HOMA-IR values positively correlated with triiodothyronine and free thyroxine levels. However, visfatin did not correlate with insulin and HOMA-IR levels. The results indicated that plasma visfatin concentration was elevated in hyperthyroidism due to Graves disease, but serum CRP levels were not. Plasma visfatin levels were not associated with indicators of insulin resistance in hyperthyroid patients.

Thyroid nodules are less frequent in childhood than in adulthood, but are more often malignant. Recent estimates suggest that up to 25% of thyroid nodules in children are malignant, therefore, a more aggressive approach is recommended. In this review, we suggest an approach based on a first-step clinical, laboratory, and sonographic evaluation. A history of irradiation of the neck, cranium or upper thorax, previous thyroid diseases or thyroid neoplasms in the family should alert clinicians as being associated with a greater likelihood of malignant nodules. Signs or symptoms of hyperthyroidism and dysmorphic features should be carefully considered during the physical examination. Palpable firm lymph nodes, found in some 70% of cases, are the most significant clinical finding in children with malignant nodules. Although the routine determination of calcitonin levels is not uniformly practiced, it can help recognize sporadic or familial medullary thyroid neoplasms. Blood thyroid stimulating hormone, free thyroxine, and free triiodothyronine determinations (the latter in case of symptoms of hyperthyroidism) are aimed at identifying the few hyperthyroid patients, for whom the next step should be scintiscan. Hyperthyroid patients usually disclose an increased uptake, and a diagnosis of toxic adenoma is commonly made. Cases with normal thyroid function or hypothyroidism (which is usually subclinical) should be evaluated by fine-needle aspiration biopsy (FNAB). In eu/hypo-thyroid patients, scintiscan provides poor diagnostic information and should not be routinely employed. Thyroid ultrasonography is used to select cases for FNAB. Although ultrasound cannot reliably discriminate between benign and malignant lesions, it does provide an index of suspicion. Sonographic features that increase the likelihood of malignancy are microcalcifications, lymph node alterations, nodule growth under levothyroxine treatment, and increased intranodular vascularization demonstrated by color Doppler. There is growing evidence that elastography may provide further information on nodule characteristics. FNAB is indicated in all cases with a likelihood of malignancy. FNAB has a diagnostic accuracy of approximately 90% and is used in selection of patients which require surgery. Recently, histological markers and elastography have been introduced to increase the specificity of FNAB and ultrasound, respectively. The pitfall in FNAB cytology is the follicular cytology, in which it is not possible to distinguish between adenoma and carcinoma and therefore thyroidectomy is advised.

BACKGROUND

Thyroid abnormal function and and/or autoimmune thyroid disease (ATD) are observed in 6% to 33.8% patients with rheumatoid arthritis (RA).

OBJECTIVE

The aim of the study was to determine whether ATD is more prevalent in patients with RA compared to the control group involving age and sex-matched subjects without RA and whether these patients should be screened for thyroid disease.

METHODS

In 100 patients with RA and 55 patients without RA (control group) hormonal thyroid function and antithyroid antibodies were assessed.

RESULTS

ATD was more prevalent (16%) in patients with RA than in the control group (9%). The difference was no statistically significant. The RA patients with concomitant ATD had lower RA activity than non-ATD RA patients. Antithyreoglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies were present in similar percentage of patients with RA (12% and 15%, respectively) and in the control group (9% and 18%, respectively). The most common thyroid dysfunction observed in both groups was subclinical hypothyroidism. An association between thyroid dysfunction and clinical symptoms suggestive of thyroid disease in RA patients was not demonstrated. In patients with RA low free triiodothyronine concentrations were significantly more common.

CONCLUSIONS

A higher prevalence of ATD in female RA patients compared with controls indicates the need for screening not only of thyroid function, but also of the presence of anti-TPO antibodies as the ATD marker in RA patients. Their presence does not correlate with the occurrence of thyroid disorders in RA patients. Monitoring of thyroid function is of particular importance since as already shown the course of thyroid disease in RA patients is often asymptomatic.

Two orders of saturable binding sites for L-triiodothyronine were found on washed rat erythrocyte membranes. The high affinity, low capacity site showed values of Kd 0.19 X 10(-10) M. This value was in the range of concentration of free L-triiodothyronine found in the plasma and was several orders of magnitude higher than the Kd values previously reported for other L-triiodothyronine membrane-binding systems. The binding site also showed a high stereospecificity for L-triiodothyronine. D-3,5,3'-triiodothyronine and L-thyroxine were less potent (about 1000-fold) than L-triiodothyronine in competing for these sites. L-3,3,5'-triiodothyronine and triiodothyroacetic acid were inactive. The physiological relevance of this site is considered.

BACKGROUND

Thyroid disorders are prevalent in Western society, yet many subjects experience limited symptoms at diagnosis, especially in hypothyroidism. We hypothesize that health-related quality of life (HR-QOL) is more severely impaired in subjects with more abnormal thyroid hormone function tests.

METHODS

This is a cross-sectional study of Dutch adults participating in the LifeLines Cohort Study between December 2009 and August 2010. In 9491 Western European participants (median age 45 years; 3993 men and 5498 women), without current or former use of thyroid medication, we compared HR-QOL using the RAND 36-Item Health Survey between subjects with normal thyrotropin (TSH) values and subjects with disturbed thyroid hormone status (serum TSH, free thyroxine, and free triiodothyronine). The influence of possible confounders (age, smoking, co-morbidity) on HR-QOL was evaluated as well.

RESULTS

Suppressed TSH values (TSH < 0.5 mU/L) were found in 114 (1.2%), while 8334 (88.8%) had TSH within the normal range, 973 participants (10.3%) had TSH between 4 and 10 mU/L, and 70 (0.7%) had TSH>> 10 mU/L. Men had a higher HR-QOL than women (70-92 vs. 65-89; p < 0.001), except for the domain "general health" (72 vs. 72; p = 0.692). Men with suppressed or elevated TSH values did not score significantly lower than euthyroid men for any of nine domains of the RAND 36-Item Health Survey. Compared with euthyroid women, women with suppressed TSH scored significantly lower in the domains "physical functioning" (84 vs. 89, p = 0.013) and "general health" (67 vs. 72, p = 0.036). Women with markedly elevated TSH >> 10 mU/L) had a score in all HR-QOL domains that was similar to that of women with normal TSH values. There were no differences in the physical component score and the mental component score between any of the TSH groups. Physical component score and mental component score were mainly determined by smoking status, co-morbidity, and body mass index or waist circumference.

CONCLUSIONS

In this population-based study, HR-QOL scores of subjects with suppressed TSH values or markedly elevated TSH values were generally not significantly lower than those of subjects with normal or mildly elevated TSH values.

: Although pituitary thyrotropin (TSH) and thyroid hormones are physiologically interrelated, interpretation of measurements is conventionally done separately. Classification of subclinical thyroid dysfunction depends by definition solely on an abnormal TSH. This study examines a composite multivariate approach to disease classification.

METHODS

Bivariate and trivariate reference limits were derived from a thyroid-healthy control group (n=271) and applied to a clinically diverse sample (n=820) from a prospective study, comparing their diagnostic efficiency with the conventional method.

RESULTS

The following 95% reference limits were derived from the control group: (i) separate reference intervals for TSH, free thyroxine (FT4) and free triiodothyronine (FT3); (ii) bivariate composite reference limits for the logarithmically transformed TSH and FT4, and (iii) trivariate composite reference limits including all three parameters. A multivariate approach converts the "rectangular" or "cuboid" graphical representations of the independent parameters into an ellipse or ellipsoid. When applying these reference limits to the clinical sample, thyroid dysfunctions were classified differently, compared with the separate method, in 6.3 or 12% of all cases by the bivariate or trivariate method respectively. Of the established dysfunctions according to the separate intervals, 26% were reclassified to "euthyroid" by using the bivariate limit. Discrepancies from the laboratory-evaluated reference range were less pronounced.

CONCLUSIONS

Frequent divergencies between composite multivariate reference limits and a combination of separate univariate reference intervals suggest that statistical analytic techniques may heavily influence thyroid disease classification. This challenges the validity of the conjoined roles of TSH currently employed as both a sensitive screening test and a reliable classification tool for thyroid disease.

The presence of the Thr92Ala polymorphism of deiodinase-2 (D2) has been thought to have several effects. It may influence its enzymatic function, is associated with increased expression of genes involved in oxidative stress in brain tissue, and may predict favorable response to combination levothyroxine (LT4) plus triiodothyronine (T3) therapy. It was hypothesized that homozygous carriers of the D2-92Ala allele have different thyroid hormone parameters, and reduced health-related quality of life (HRQoL) and cognitive functioning.

In 12,625 participants from the LifeLines cohort study with genome-wide genetic data available, the effects of the Thr92Ala polymorphism (rs225014) were evaluated in the general population and in 364 people treated with thyroid hormone replacement therapy, the latter mainly because of primary hypothyroidism. In addition to evaluating anthropometric data, medication use, and existence of metabolic syndrome, HRQoL was assessed with the RAND 36-Item Health Survey, and the Ruff Figural Fluency Test was used as a sensitive test for executive functioning. Data on thyrotropin, free thyroxine (fT4), and free T3 (fT3) levels were available in a subset of 4479 participants.

The mean age (±standard deviation) was 53 ± 12 years and the body mass index was 27.0 ± 4.5 kg/m2 in the LT4 users compared with 48 ± 11 years and 26.2 ± 4.1 kg/m2 in participants from the general population. The Ala/Ala genotype of the D2-Thr92Ala polymorphism was present in 11.3% of LT4 users and in 10.7% of the general population. In total, 3742/4479 subjects with thyroid hormone data available had normal TSH (0.4-4.0 mIU/L), and 88% of LT4 users were females. LT4 users had higher fT4, lower fT3, and a lower fT3/fT4 ratio, and female patients had lower scores on the HRQoL domains of physical functioning, vitality, mental health, social functioning, bodily pain, and general health compared with those not using LT4 (p < 0.005). Executive functioning scores, as part of cognitive functioning, were comparable between female LT4 users and the general population. In both groups, the D2-Thr92Ala polymorphism was not associated with differences in TSH, fT4, fT3, the fT3/fT4 ratio, presence of metabolic syndrome or other comorbidities, use of medication, HRQoL, and cognitive functioning.

The Thr92Ala polymorphism of D2 was not associated with thyroid parameters, HRQoL, and cognitive functioning in the general population and in participants on thyroid hormone replacement therapy.

The endocrine profile of FK 33-824, 0.5 mg i.m., was determined in comparison with placebo or pretreatment with naloxone, 4 mg i.v., in 14 healthy men. Prolactin (PRL), growth hormone (GH), ACTH, cortisol, gonadotropins (LH, FSH), thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), insulin and glucagon were measured and free water clearance was calculated from urine volumes and osmolar clearances. FK 33-824 increased PRL and GH (p less than 0.001). ACTH was below assay sensitivity but cortisol was significantly lowered (p less than 0.001). Free water clearance was enhanced (p less than 0.01) and the remaining parameters were unchanged. Naloxone alone had no hormonal effect but abolished the increase in PRL and GH following injection of FK 33-824 without modifying the decrease in plasma cortisol or the increase in free water clearance following the same treatment. The results indicate that the effect of FK 33-824 on PRL and GH release is mediated by opiate receptors. Other mechanisms or naloxone nonsensitive receptors may be implicated in the effects recorded on cortisol and FWC.