High serum circulating telopeptide type I in multinodular goiter.

Recently, concentrations of serum carboxy-terminal-1-telopeptide (ICTP), a marker of bone collagen resorption, were found to be more sensitive than sex hormone-binding globulin (SHBG) in identifying peripheral overexposure to thyroid hormones in exogenous subclinical hyperthyroidism. The aim of the present study was to assess serum ICTP and SHBG in multinodular goiter with (pretoxic goiter) or without biochemical evidence of endogenous subclinical hyperthyroidism. Forty-five women affected by multinodular goiter were enrolled in this study. They were subdivided into two groups: group 1, consisting of 27 patients affected by pretoxic goiter; group 2, consisting of 18 patients affected by non toxic goiter; group 3, consisting of thirty-six euthyroid women matched with the other groups for age and lifestyle. In group 1, serum ICTP (mean +/- SD: 5.8 +/- 2.9 microg/l) concentrations were significantly higher when compared either to group 2 (3.6 +/- 1.2 microg/l; p < 0.02) or controls (2.7 +/- 0.7 microg/l; p < 0.0001); serum ICTP concentrations were also slightly but significantly higher in patients of group 2 compared to controls (p < 0.003). In contrast, mean serum SHBG concentrations did not show any difference among the three groups. No significant correlation was found between serum TSH and ICTP concentrations, while a weak positive correlation (p < 0.05) was only found between serum FT 3 and ICTP concentrations when data from the two patient groups were analyzed together. Moreover, when we subdivided patients into pre- and postmenopausal patients, we observed that SHBG but not ICTP serum concentrations were influenced by estrogenic status. In summary, the measurement of serum ICTP seems to be more suitable than SHBG for identifying those with a higher degree of peripheral thyroid hormone exposure in women affected by endogenous subclinical hyperthyroidism.     

Changes of serum angiotensin-I-converting enzyme in patients with thyroid disorders

In 149 subjects (63 euthyroid, 21 hyperthyroid, 26 with autonomous nodules, subdivided into 20 euthyroid and 6 hyperthyroid, 17 hypothyroid subjects and 22 women taking estrogens) the serum angiotensin-I-converting enzyme (SACE) was spectrophotometrically measured and correlated with age, systolic and diastolic blood pressure, free thyroid hormones (FT4, FT3) and delta TSH level. In patients with diffuse hyperthyroidism and with regional autonomy, systolic blood pressure was elevated. The highest values for FT4 and FT3 were found in patients with hyperthyroidism and hyperthyroid autonomous nodules. SACE correlated with age for the euthyroid control group (p less than 0.05). In this group, SACE levels were higher in men than in women (p less than 0.02). Regarding all 149 subjects together, significant linear correlations between SACE and systolic blood pressure as well as with FT4 and FT3 concentrations could be demonstrated (p less than 0.01-0.001). Among the individual groups the mean SACE activities were significantly elevated in hyperthyroid patients (p less than 0.01). No significant differences could be observed between controls and euthyroid subjects with autonomous nodules as well as in hypothyroid cases. In comparison to euthyroid patients the mean SACE levels of hyperthyroid patients with autonomy were significantly (p less than 0.05) elevated. The SACE activities of women taking estrogens for contraception did not differ significantly from SACE in age-matched female controls.     

Prolonged ventricular repolarization measured by corrected QT interval (QTc) in subclinical hyperthyroidism.

Overt hyperthyroidism and hypothyroidism exert a major effect on cardiac function and on ECG. The influence of subclinical hyperthyroidism on the circulatory system is still under debate. Few studies examined the effect of thyroid hormones on ventricular repolarization measured by corrected QT interval (QTc). Longer QTc is associated with increased risk of arrhythmia and cardiac mortality. The aim of this study was to examine the influence of subclinical hyperthyroidism on ventricular repolarization measured by corrected QTc in a standard 12-lead electrocardiogram. The examined group consisted of thirty-two patients with subclinical hyperthyroidism; the controls were thirty-nine healthy individuals. In the group with subclinical hyperthyroidism, we observed a significant increase in heart rate (80.3 +/- 10.59 vs. 73.7 +/- 11.37 bpm, p < 0.05). The mean corrected QTc was 0.434 +/- 0.0207 seconds and 0.414 +/- 0.0208 in the examined groups and in controls, respectively (p < 0.001). QTc did not correlate with free thyroxin concentrations (p = 0.5084). Conclusion: Corrected QT intervals were significantly longer in patients with subclinical hyperthyroidism.     

Color-Flow Doppler Sonography in Patients with Subclinical Thyroid Dysfunction

ObjectiveTo assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction.MethodsIn this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal serum free thyroxine (FT₄) and free triiodothyronine (FT₃) in the presence of high (subclinical hypothyroidism), or lowsuppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT₄, FT₃, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroidism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements.ResultsThe study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 ± 5.6 cm/s vs 15.7 ± 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 ± 10.7 cm/s vs 21.9 ± 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P <.001] and 53% vs 15%; [P <.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity.ConclusionWe have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.(Endocr Pract. 2010;16:376-381)     

A Stepwise Approach to the Evaluation and Treatment of Subclinicalhyperthyroidism

ObjectivesTo review a stepwise approach to the evaluation and treatment of subclinical hyperthyroidism.MethodsEnglish-language articles regarding clinical management of subclinical hyperthyroidism published between 2007 and 2012 were reviewed.ResultsSubclinical hyperthyroidism is encountered on a daily basis in clinical practice. When evaluating patients with a suppressed serum thyrotropin value, it is important to exclude other potential etiologies such as overt triiodothyronine toxicosis, drug effect, nonthyroidal illness, and central hypothyroidism. In younger patients with mild thyrotropin suppression, it is acceptable to perform testing again in 3 to 6 months to assess for persistence before performing further diagnostic testing. In older patients or patients with thyrotropin values less than 0.1 mIU/L, diagnostic testing should proceed without delay. Persistence of thyrotropin suppression is more typical of nodular thyroid autonomy, whereas thyroiditis and mild Graves disease frequently resolve spontaneously. The clinical consequences of subclinical hyperthyroidism, such as atrial dysrhythmia, accelerated bone loss, increased fracture rate, and higher rates of cardiovascular mortality, are dependent on age and severity. The decision to treat subclinical hyperthyroidism is directly tied to an assessment of the potential for clinical consequences in untreated disease. Definitive therapy is generally selected for patients with nodular autonomous function, whereas antithyroid drug therapy is more appropriate for mild, persistent Graves disease.ConclusionThe presented stepwise approach to the care of patients presenting with an isolated suppression of serum thyrotropin focuses on the differential diagnosis, a prediction of the likelihood of persistence, an assessment of potential risks posed to the patient, and, finally, a personalized choice of therapy. (Endocr Pract. 2012;18: 772-780)     

Atypical forms of hyperthyroidism

Except from well-known the most frequent reasons of the hyperthyroidism such as the Graves-Basedow disease, multinodular goitre and the autonomous adenoma we should also remember the other rarer illnesses leading to the excess of thyroid hormones in the serum. Authors presented the problem of atypical forms of thyrotoxicosis which run without the overproduction of thyroid hormones and are characterized by low 24 h 131 J uptake by the thyroid gland. So called masks of hyperthyroidism such as apathetic, neuromuscular, gastrointestinal and cardiovascular forms were also discussed in the article.     

The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study

ObjectiveMandatory universal salt iodization in China was implemented 20 years ago. However, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown.MethodsA nationally representative cross-sectional study with 26 166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urinary iodine concentration (UIC) were measured.ResultsThe median UIC was 178.7 μg/L, indicative of adequate iodine status. pHowever, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalence of thyroid disorders was as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for thyroid peroxidase antibodies, and 14.55% were positive for thyroglobulin antibodies. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for thyroid peroxidase antibodies and thyroglobulin antibodies.ConclusionIodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies remain prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.     

Decreased levels of ionized calcium one year after hemithyroidectomy: importance of reduced thyroid hormones

BACKGROUND: Previously we have found reduced levels of total serum calcium and 1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1 year after hemithyroidectomy. The present study was undertaken to elucidate the possible relationship between calcium homeostasis, thyroid hormones and bone resorption in a group of 45 consecutive patients subjected to hemithyroidectomy because of a solitary nodule. All patients had free T4 and T3 levels within normal range preoperatively. METHODS: Thyroid hormones, bone mineral and biochemical variables known to reflect calcium homeostasis were studied. Patients were divided into three separate groups depending on their pre- and postoperative thyroid hormone status. RESULTS: One year postoperatively, serum levels of free T4 were decreased and that of thyrotropin (TSH) increased in the entire group of patients. The concentration of ionized calcium was reduced from 1.25 +/- 0.05 to 1.22 +/- 0.04 (p < 0.001) despite an unaltered PTH value (2.8 +/- 1.0 vs. 3.1 +/- 1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05). Subgroup analysis showed that a reduction in ionized calcium was seen only among patients with a postoperative decrease in free T4. Patients with subclinical hyperthyroidism preoperatively presented the lowest postoperative levels of ionized calcium, significantly reduced levels of 1CTP and increased levels of phosphate and creatinine. Multiple linear regression analysis showed that age (p < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated with altered levels of ionized calcium. CONCLUSION: We conclude that the reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH deficiency. Instead our results suggest that the reduced effects of thyroid hormones on bone and kidney function is essential.     

Selected markers of endothelial dysfunction in patients with subclinical and overt hyperthyroidism

INTRODUCTION: There are many factors causing endothelial dysfunction. The aim was to observe chosen markers of endothelial function in patients with subclinical and overt hyperthyroidism. MATERIAL AND METHODS: We studied 97 patients with hyperthyroidism: 51 with subclinical (44 F/7 M; mean age 49.3 +/- 15.9 y) and 46 patients with overt (39 F/7 M, mean age 50.4 +/- 13.2 y). The control comprised of 39 healthy volunteers (26 F/13 M, mean age 47.5 +/- 11.8 y). Concentration of TSH, FT3, FT4 were measured by MEIA, TPO Ab, TG Ab, E-selectin, interleukin 6, VCAM-1, ICAM-1 by ELISA. RESULTS: The goiter was found in 71 persons 63F/8M, mean age 49.9 +/- 15.3 y, (42-subclinical, 29-overt). Morbus Graves-Basedow was diagnosed in 26 persons, 20 F/6 M, mean age 49.5 +/- 12.8 y (9-subclinical, 17-overt). There were no significant differences serum concentration of E-selectin, IL-6, ICAM-1 in patients with subclinical and overt hyperthyroidism compared to the control. Statistically significant differences were shown between concentration of IL-6 in patients with Graves-Basedow compared with the control (p < 0.05). Significance of VCAM-1 values were found in the patients with subclinical and overt hyperthyroidism compared to the control (p < 0.001; p < 0.001, respectively). CONCLUSIONS: Among persons with overt and subclinical hyperthyroidism occurs endothelial dysfunction which doesn't depends on exciting cause of thyrotoxicosis but on degree of hyperthyroidism. Elevated concentrations of endothelial markers may confirm that persons with thyroid disorders are extremely exposed to the occurrence of the cardiovascular diseases.     

南京社区人群甲状腺功能亢进症的患病率调查

目的：调查南京社区人群甲状腺功能亢进症（甲亢）的患病率。方法：随机抽取南京某社区的常驻居民1 540 例，分别测定该 人群的空腹血清三碘甲状腺游氨酸（FT3）、促甲状腺激素（TSH）和游离甲状腺素（FT4）的水平。结果：（1）南京社区人群临床甲亢 和亚临床甲亢的患病率分别为1.23%，1.62%。人群中临床甲亢知晓率15.8%。（2）临床甲亢、亚临床甲亢的患病率男女之间比较无 显著性差异（P>0.05）。（3）不论男女，临床甲亢和亚临床甲亢的患病率在不同年龄组间均无差异（P>0.05）。结论：南京社区人群甲 亢患病率较高，人群知晓率低，应注意早期诊治。     

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.     

Thyroid and bone

The hypothalamic-pituitary-thyroid axis plays a key role in skeletal development, acquisition of peak bone mass and regulation of adult bone turnover. Euthyroid status is essential for maintenance of optimal bone mineralization and strength. In population studies, hypothyroidism and hyperthyroidism have both been associated with an increased risk of fracture. Furthermore, recent studies in healthy euthyroid post-menopausal women indicate that thyroid status in the upper normal range is also associated with low bone mineral density and an increased risk of non-vertebral fracture. Studies in mutant mice have demonstrated that thyroid hormone receptor α is the major mediator of T3 action in bone and that thyroid hormones exert anabolic actions during growth but have catabolic effects on the adult skeleton. Nevertheless, TSH has also been proposed to be a direct negative regulator of bone turnover, although the relative importance of T3 and TSH actions in the skeleton has yet to be clarified.     

Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome?

In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymic involution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism.     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

Osteoporosis in thyroid diseases

Thyroid hormones play the essential role in the regulation of metabolism and bone remodeling in physiological conditions and in the course of thyroid dysfunction. Introduction of densitometry to the diagnostics of osteoporosis has made possible the evaluation of influence of both hyperthyroidism and hypothyroidism and their treatment on bone mineral density. Moreover it became possible to estimate the influence of treatment with exogenous thyroid hormones on the skeletal system. Authors presented mechanisms of the thyroid hormones action on bone tissue and analysed current state of knowledge concerning the influence of the thyroxine treatment with replacement and suppressive doses on the bone mineral density. The influence of thyroid hormones on the skeletal system with respect to premenopausal and postmenopausal period was also discussed. Great discrepancies in literature data and its reasons were underlined.     

Autoimmune thyroid diseases in women with breast cancer and colorectal cancer

The aim of the study was to compare the prevalence of autoimmune thyroid diseases in three groups of women (66 with breast cancer (CaB), 68 with colorectal cancer (CaC) and 49 without oncological diseases as a control group). Serum levels of thyroid-stimulating hormone (TSH), free thyroxin (fT4), antibodies to thyroglobulin (TGB-ab) and thyroperoxidase (TPO-ab) and tumor markers CEA, CA 15-3 and CA 19-9 were investigated in all subjects by using the chemiluminiscence method. In contrast to Graves' disease (no observed case), autoimmune thyroiditis was diagnosed in 24.2 % women with CaB (4.5 % euthyroid and 19.7 % with subclinical or overt hypothyroidism), compared to 16.7 % in women with CaC (2.0 % euthyroid and 14.7 % with subclinical or overt hypothyroidism) and 16.2 % controls (4.0 % euthyroid and 12.2 % with subclinical or overt hypothyroidism). Serum levels of TGB-ab were higher in the group with breast cancer as compared to those with colorectal cancer and the control group (medians: 35.80 vs. 31.75 vs. 27.70, p<0.001). Similarly, the percentage of positive TGB-ab and TPO-ab serum levels was higher in women with breast cancer as compared to those with colorectal cancer and the control group. The results of the study support the controversial theory that there is an increased prevalence of autoimmune thyroiditis in women with breast cancer.     

Clinical Aspects of Hyperthyroidism,Hypothyroidism, and Thyroid Screening in Pregnancy

ObjectiveTo evaluate the peer-reviewed literature on hypothyroidism, hyperthyroidism, and thyroid autoimmunity in pregnancy.MethodsWe review published studies on thyroid autoimmunity and dysfunction in pregnancy, the impact of thyroid disease on pregnancy, and discuss implications for screening.ResultsOvert hyperthyroidism and hypothyroidism are responsible for adverse obstetric and neonatal events. Several studies of association suggest that either subclinical hypothyroidism or thyroid autoimmunity increase the risk of complications. One randomized controlled trial showed that pregnant women with subclinical hypothyroidism benefit from treatment in terms of obstetric and neonatal complications, whereas another study demonstrated no benefit in the intelligence quotient of babies born to women with subclinical hypothyroidism. Thyroid autoimmunity has been associated with increased rate of pregnancy loss, recurrent miscarriage, and preterm delivery.ConclusionCurrent guidelines agree that overt hyperthyroidism and hypothyroidism need to be promptly treated and that as potential benefits outweigh potential harm, subclinical hypothyroidism also requires substitutive treatment. The chance that women with thyroid autoimmunity may benefit from levothyroxine treatment to improve obstetric outcome is intriguing, but adequately powered randomized controlled trials are needed. The issue of universal thyroid screening at the beginning of pregnancy is still a matter of debate, and aggressive case-finding is supported. (Endocr Pract. 2014;20:597-607)     

Serum fructosamine in assessment of diabetic control and relation to thyroid function

Measurement of serum fructosamine using a Roche kit is a simple and reliable method for the estimation of glycated serum proteins. The value of serum fructosamine can be affected by hyperglycemia in diabetics and an abnormal turnover rate of serum protein in patients with thyroid dysfunction. We measured the serum fructosamine level in 18 normal control subjects, 71 diabetics (8 IDDM, 63 NIDDM) and 46 non-diabetic untreated patients with thyroid dysfunction (28 hyperthyroidism, 18 hypothyroidism). The serum fructosamine level was significantly increased in the diabetics compared with the normal control subjects (3.84 +/- 0.15 mmol/l vs 2.58 +/- 0.08; mean +/- SE, P less than 0.01). The serum fructosamine level in the diabetics was positively correlated with the fasting plasma glucose and HbAlc level, showing the highest correlation with fasting plasma glucose at 2 weeks before and with the HbAlc level at 2 weeks after serum fructosamine measurement. In the patients with thyroid dysfunction, the serum fructosamine level in hyperthyroidism (2.08 +/- 0.03 mmol/l) and hypothyroidism (3.11 +/- 0.07 mmol/l) were significantly lower (P less than 0.001) and higher (P less than 0.001) than the normal control subjects (2.58 +/- 0.08 mmol/l), respectively. Furthermore, the serum fructosamine level in these patients was negatively correlated with the level of serum thyroid hormones such as T3 (P less than 0.001) and T4 (P less than 0.001). It is concluded that measurement of serum fructosamine is clinically useful for the evaluation of shorter-term glycemic control in diabetics, but its level for diabetic patients with thyroid dysfunction must be cautiously interpreted.     

Graves' ophthalmopathy and subclinical hypothyroidism: diagnostic value of the thyrotropin releasing hormone test.

Five patients with Graves'' ophthalmopathy and no previously documented clinical or laboratory evidence of hyperthyroidism were studied. Their serum levels of thyroxine and triiodothyronine (T3) and their T3 uptake were normal. Although the baseline serum level of thyrotropin (TSH) was normal in two patients, it was increased on the other three, and when TSH releasing hormone (TRH) was administered the T3 response was impaired in three patients and the TSH response was exaggerated in all five. These findings facilitated the diagnosis of subclinical hypothyroidism and distinguished the patients from those with Graves'' ophthalmopathy and normal thyroid function or subclinical hyperthyroidism. Thyroid antibodies were detected in the serum of four of the five patients, suggesting the coexistence of chronic autoimmune thyroiditis; this disorder could account in part for the subclinical hypothyroidism, which was even present in the two patients in whom thyroid-stimulating immunoglobulin was found in the serum. These observations indicate the value of a TRH stimulation test in detecting subclinical hypothyroidism in patients with Graves'' ophthalmopathy who appear from clinical and routine laboratory studies to have normal thyroid function but could have normal function or subclinical hyperthyroidism.     

Cardiovascular events in thyroid disease: a population based, prospective study

No consensus exists whether subclinical thyroid disease should be treated or just observed. Untreated overt thyroid disease is associated with increased risk of cardiovascular disease, and this study was conducted to assess the risk of cardiovascular events in subclinical thyroid disease. The population-based prospective study was conducted in Denmark. A total of 609 subjects from general practice aged 50 years or above with normal left ventricular function were examined. During a median of 5 years of follow-up, major cardiovascular events were documented. In subjects with abnormal TSH at baseline, information about potential thyroid treatment during follow-up was obtained from case reports and mailings. At baseline, 549 (90.7%) were euthyroid (TSH 0.40-4.00?mU/l), 31 (5.1%) were subclinical hypothyroid (TSH>4.00?mU/l), and 25 (4.1%) were subclinical hyperthyroid (TSH<0.40?mU/l). 1 overt hyperthyroid and 3 overt hypothyroid participants were excluded from the analyses. At baseline, the levels of NT-proBNP were inversely associated with the levels of TSH; the lower the levels of TSH, the higher the NT-proBNP concentration. During follow-up, 88 participants died, 81 had a major cardiovascular event, and 28 had a stroke. The incidence of stroke was increased among subjects with subclinical hyperthyroidism, HR 3.39 (95% CI 1.15-10.00, p=0.027) after adjusting for sex, age, and atrial fibrillation. Subclinical hypothyroidism was not related with any of the outcome measurements. Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function.