Course Of Subclinical Hypothyroidism Research Articles

Features of the natural course of subclinical hypothyroidism in young athletes

Objective: to assess the natural course of subclinical hypothyroidism in young athletes.Methods: In the prospective single-center uncontrolled study, data from 3,062 outpatient records of young athletes (members of the Russian national team) of both sexes (middle age — 15 [14; 16] years) and underwent medical examination in the period from January 2021 to September 2022 were studied. All athletes were divided into 2 groups according to the presence of subclinical hypothyroidism (an increase in the level of thyroid-stimulating hormone from 5 to 10 mUn/l with a normal level of T4 free). During a dynamic follow-up (1 year), athletes with subclinical hypothyroidism underwent a repeated study of the concentration of thyroid-stimulating hormone, free thyroxine and antibodies to thyroperoxidase.Results: Signs of subclinical hyperthyroidism were found in 58 young athletes (30 boys (51.7 %) and 28 (48.3 %) girls). During dynamic observation with continued habitual physical activity, spontaneous normalization of the level of thyroid-stimulating hormone was observed in 74 % of young athletes. At the same time, normalization of thyroid-stimulating hormone in girls was observed less often compared to boys (p = 0,272). In no case did clinically pronounced hypothyroidism develop.Conclusion: The majority of young male and female athletes with subclinical hypothyroidism have spontaneous normalization of hormonal profile against the background of persistent physical and psycho-emotional stress. The data obtained make it possible, subject to the possibility of dynamic observation, to recommend doctors working with young elite athletes not to prescribe hormonal replacement therapy and not to modify the usual lifestyle.

Subclinical hypothyroidism in children and adolescents as mild dysfunction ofthe thyroid gland: asingle-center study.

Subclinical hypothyroidism (SH) is a biochemical diagnosis made when a serum thyroid-stimulating hormone (TSH) is ele-vated with circulating thyroid hormone levels within their reference ranges. Aim of our prospective non-randomized study was to evaluate the course of SH. All patients with suspicion of SH referred to the Endocrinology Outpatient Clinic between 2014 and 2018 were recruited to prospective study. A total of 130 patients with SH were recruited for this study. Thirty-five (26.9%) patients were followed up without levothy-roxine (L-T4) (SH-T0 group) and therapy with L-T4 was randomly introduced in 95/130 (73.1%) SH children (SH-T1 group). We did not find statistical differences in hSDS and BMI Z-score between the SH-T0 and SH-T1 groups (p = 0.761 and p = 0.843, respectively). Introducing L-T4 in patients with short stature did not affect the linear growth at the end of FU ex-pressed as hSDS. OH developed in six children (6.3%) in the SH-T1 group. After conducting a multivariate logistic regres-sion, we found that the baseline TSH concentration and BMI Z-score are possible predictors of OH. Our study confirmed a low risk of progression of SH to overt hypothyroidism. The majority of patients remains SH or resolved for nor-mal thyroid function. The L-T4 therapy did not effect on linear growth and body weight. The main predictor of worsening to hypothyroidism were a higher TSH level and Z-score BMI.

Risk of progression to overt hypothyroidism in Indian patients with subclinical hypothyroidism: a prospective observational study

Background: Subclinical hypothyroidism (SCH) is a common endocrine disorder but spontaneous course of SCH in India is lacking. The aim of the study is to determine the spontaneous course of SCH and to identify the risk factors, which enhances the occurrence of overt hypothyroidism (OH).Method: This is a real world prospective observational study. 58 SCH were followed up six monthly for one year to determine the course of SCH.Results: After one year of follow up 11 (18.97%) patients progressed to OH. 37 (63.79%) remained in subclinical hypothyroid category. In 10 (17.29%) patients TSH (thyrotropin) normalized. Rate of progression (odds ratio: 4.58; 95% CI: 1.14, 18.28) was significantly more in anti-thyroid peroxidase (TPO) positive group as compared to anti-TPO negative group.Conclusions: This first data from India clearly shows that SCH has a variable course. Rate of progression to OH is high (18.97%) in Indian SCH patients. In a cohort of 58 patients followed for one year only the presence of anti-TPO antibody was predictive of OH. The initial risk stratification can identify patients with SCH at greatest risk for progression to OH in which treatment is mandatory.

Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down's Syndrome.

IntroductionThyroid dysfunctions are one of the most common abnormalities coexisting in children with Down’s syndrome (DS) and have been reported in up to 54% of cases.Aim of the StudyThe purposes of this retrospective study were to investigate the course of subclinical hypothyroidism in children with DS, to evaluate the thyroid function of these subjects in relation to the risk of developing overt thyroid disease and autoimmunity, and to identify clinical and biochemical characteristics of patients prescribed L-T4 therapy in children and adolescents with DS and SH.Material and MethodsThe records of DS patients referred to the Endocrinology Outpatient Clinic between 2010 and 2015 for screening of thyroid function were observed till the end of 2019 June and analyzed retrospectively. The children diagnosed with congenital hypothyroidism, acute lymphoblastic leukemia, and seizures and treated with drugs that may have interfered with thyroid function like lithium, antiepileptic, or iodinated drugs and glucocorticoids were excluded from the study.ResultsThe data of 77 DS patients were collected, evaluated, and analyzed. The study group consisted of 73 patients (32 girls and 41 boys with the mean age at baseline of 3.0 ± 4.5 years). A total of 63/73 (87%) children were diagnosed with SH. The 16/63 (25.4%) patients were followed-up without the treatment (group SH-T0), and therapy with levothyroxine (L-T4) was introduced in 47/63 (74.6%) SH children with a mean dosage of 1.8 ± 1.0 μg/kg/day (group SH-T1). Thyroxine supplementation did not improve growth expressed as ΔhSDS (0.1 ± 1.3, ranged −2.1 to 3.8 in SH-T0 vs. 0.0 ± 0.7, ranged −1.7 to 1.4 in SH-T1, p = 0.96) and ΔBMI Z-score (0.3 ± 0.9, ranged −0.9 to 2.6 in SH-T0 vs. 0.3 ± 1.1, ranged −2.1 to 2.9 in SH-T1, p = 0.65). Positive anti-TPO and anti-TG antibodies were detected in 7/63 (11.1%) DS cases.ConclusionsSH is the most frequent presentation of thyroid gland dysfunction in DS children. A small percentage of patients develop an overt hypothyroidism, particularly in females with mostly positive titer of antithyroid autoantibodies.

Subclinical hypothyroidism in women at the stage of natural pregnancy planning and with the use of assisted reproductive technologies in the iodine deficiency region

The problem of infertility does not lose its relevance and is global in nature. According to state statistics, in 2016, 38,998 cases of female infertility were registered in Ukraine. During 2006—2015, the number of started treatment cycles by methods of assisted reproductive technologies increased by 3.5 times. Despite the rapid development of reproductive medicine in Ukraine and all around the world, many questions about the mechanisms that ensure the onset of pregnancy in assisted reproductive technology programs remain relevant. In Ukraine, almost 25 % of women of reproductive age have pathology of the thyroid gland, which affects the state of the neuroendocrine and immune systems, which play a significant role in the pathogenesis of infertility and the effectiveness of assisted reproductive technologies. There is a close interaction between thyroid hormones and the normal action and secretion of steroids, which is necessary for normal ovarian function and, consequently, fertility. Thus, the multilateral mechanism of influence of thyroid pathology on menstrual and reproductive functions of the woman is accurately defined. The prevalence and incidence of thyroid disease vary in different regions of the country depending on the influence of environmental factors and their combination, one of which is iodine deficiency. Iodine deficiency is an important medical and social problem in many countries around the world. The most common consequences of iodine deficiency in pregnancy planning are subclinical hypothyroidism. Therefore, the study of the pecu­­liarities of the course of subclinical hypothyroidism at the stage of pregnancy planning and with the use of assisted reproductive technologies in the iodine-deficient region today remains an urgent problem. The article presents an analysis of publications of PubMed and Medline databases for the last decades.

Review of the natural course of subclinical hypothyroidism and study of its costs

IntroductionSubclinical hypothyroidism is defined as elevation of thyroid-stimulating hormone (TSH) levels, with normal thyroid hormone levels and negative autoimmunity, in asymptomatic patients with no findings on examination. Because of the unwarranted increase in thyroid function tests in asymptomatic children, the main objective of this review was to analyze the course of these patients. Analysis of associated costs was a secondary objective. Material and methodsA longitudinal, observational, retrospective study of patients referred to the endocrinology department of a tertiary hospital for high TSH levels (TSH 5–20mIU/l). Clinical and laboratory variables, number of visits until discharge, need for treatment, monitoring time, and economic variables were collected. ResultsThe study sample consisted of 155 patients with a mean age of 7.8years±3.6SD. Referrals to endocrinology accounted for 4% of first office visits. Baseline mean TSH level was 7.8mU/l (5.03–15.8mU/l). TSH levels normalized after the first repeated measurement during the subsequent month in 60% of cases. A total of 83.6% of patients were discharged within a maximum of 3years, with a mean follow-up of 8.14±6.8months and 2.4visits/patient. Average cost per patient was €251.27 (range €143.49–444.21). ConclusionIt is essential not to alarm the family when subclinical hypothyroidism is detected, because this is a biochemical situation which normalizes in most cases. This fact, together with the mean cost of specialized care, suggests that the first step should be repeated TSH measurements in primary care.

Follow-up in children with non-obese and non-autoimmune subclinical hypothyroidism.

Background The aim of our study was to evaluate clinical, laboratory and imaging findings and to have an idea about the clinical course of subclinical hypothyroidism in children. Methods Our study included 25 patients who were diagnosed with non-autoimmune subclinical hypothyroidism without goitre, between the ages of 3 and 18 and with body mass index (BMI) below the 85th percentile. Results The mean thyroid-stimulating hormone (TSH) level was 6.92±0.92 μIU/mL at diagnosis, 4.77±1.57 μIU/mL in the third month and 4.51±1.79 μIU/mL in the first year of follow-up. About 73.7% of subclinical hypothyroidism was recovered. There was no statistically significant difference between heart rate, diastolic blood pressure, lipid profile, fasting blood glucose (FBG), fasting insulin level, homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin, white blood cell, platelet, C-reactive protein (CRP) levels and thyroid volume at diagnosis and in the first year of follow-up. In the first year of follow-up, systolic blood pressure and high-sensitivity CRP value were significantly higher than at diagnosis. However, it was observed that these values were similar in the present group with subclinical hypothyroidism. Conclusions We concluded that there was no progression to overt hypothyroidism during 1-year follow-up and that subclinical hypothyroidism had no effect on height standard deviation score (SDS), BMI SDS, blood pressure, glucose and lipid metabolism during follow-up without treatment.

Hypothyroidism in Clinical Practice

Hypothyroidism in Clinical Practice

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto's Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia.

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto’s thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5−18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.

Response: The Biochemical Prognostic Factors of Subclinical Hypothyroidism (Endocrinol Metab2014;29:154-62, Myung Won Lee et al.)

We sincerely thank the editors and reviewers for giving us the opportunity to publish this article. Our response to Professors Ahn and Chung's letter are included below. Previous studies of subclinical hypothyroidism (SHT) mainly focused on the aggravation of SHT to overt hypothyroidism [1,2]. However, the clinical significance of long-term, persistent SHT and clinically reliable prognostic factors for predicting the disease course of SHT, including aggravation, maintenance, and improvement, have not been established. Given our present clinical environment, in which increasing numbers of patients with SHT are consistently increasing, as well as our corresponding need to manage them as clinicians, we aimed to identify factors that influence the natural course of SHT. In line with this purpose, our study primarily focused on initial clues and evidence that enable us to predict whether newly-diagnosed SHT will improve spontaneously to a euthyroid state. In this retrospective study, we compared two groups according to thyroid function at follow-up: an SHT maintenance group and a spontaneous improvement group. The mean follow-up period was 10.1 months for the SHT maintenance group and 9.6 months for the spontaneous improvement group. By comparing initial parameters in patients with newly-diagnosed SHT between the two groups using t tests, this study presents evidence that only initial thyroid stimulating hormone (TSH) level was a definite prognostic factor for SHT, and that thyroid peroxidase antibody (TPO-Ab) titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH levels. As mentioned in the letter from the reviewers, multivariate Cox regression analysis would be a more concrete method to prove the prognostic value of a specific factor because it can correct for the influence of other confounding variables on prognosis. However, our data were determined to be inappropriate for a Cox regression model by the test of goodness of fit during the analysis. There are several possible reasons for this relating to the characteristics of our patients. The range of TSH levels was too narrow: subjects with TSH levels of 5 to 7 µIU/mL accounted for 59.5% of all subjects. When we also consider the short follow-up period in this study (less than 12.0 months), it was difficult to detect a significant odds ratio for SHT prognosis according to TSH range. Also, with regard to TPO-Ab, a large majority of subjects (79.3%) had TPO-Ab titers of <60 U/mL, i.e., within the normal range. With data for TSH and TPO-Ab with wider ranges and a longer follow-up period, we think that TSH level and TPO-Ab titer might have been shown to be strong prognostic factors for SHT in more powerful and sophisticated analyses, such as multivariate Cox regression analysis and survival analysis. In spite of these limitations, this study is useful for daily practice in clinics. Faced with patients with newly-diagnosed SHT, TSH level and TPO-Ab titer at initial presentation could be considered as evidence to predict spontaneous improvement. Also, another notable finding of this study is that TSH level was a very strong prognostic factor in SHT. As Professors Ahn and Chung mention, a large-scale, prospective study is needed to definitively identify prognostic factors for SHT. Thank you again for your insightful and comprehensive review of our paper.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.

Natural history of subclinical hypothyroidism in children and adolescents

Diagnosis of subclinical hypothyroidism (SH) is based on interpretation of biochemical tests in the absence of the evident clinical symptoms. Mildly elevated TSH with normal fT4 are common in adults and the prevalence of this finding is reported to be 1-10% of general population, being higher in the elderly. In pediatric population its prevalence is lower than 2%. Moreover in about 60% of subjects the natural course of SH is a reversal of the elevated TSH to normal values. Only 3% of them progress to overt hypothyroidism with TSH values above 10 mUI/l. The risk of progression is higher in patients with elevated anti-thyroid antibodies and higher degree of hypoechogenicity at thyroid ultrasound. Increased prevalence of SH is described in obese and overweight subjects, children with Down’s syndrome, with diabetes type 1 and in girls with Turner’s syndrome. Studies regarding the natural history of SH and its consequences in children are scarce and their conclusions are controversial. Meta-analysis of 39 potentially relevant articles showed that SH in children seems to be a remitting process with a low risk of progression toward overt hypothyroidism regardless of the L-T 4 treatment. There was also no clear evidence of the beneficial effect of L-T4 treatment on psychological and physical development. Replacement therapy did not seem to be justified in children with SH and TSH values between 5 -10 mUI/l, no goiter and negative anti-thyroid antibodies. Therefore decision regarding the treatment of the young patient with elevated TSH but normal fT4 value continues to be controversial.

Subclinical hypothyroidism in children: natural history and when to treat

Subclinical hypothyroidism (SH) is a quite common disorder in the pediatric age group. The aim of this paper is to present a review of the studies investigating the natural course of SH and the effects of replacement therapy with levothyroxine in childhood. We systematically searched PubMed, Cochrane, and EMBASE (1990 to 2012) and identified 14 articles suitable to be included. SH is a benign process that does not influence anthropometric parameters or puberty onset, and in most cases, it is a remitting disease, with a low risk of development of overt hypothyroidism, more frequently evolving toward euthyroidism or steadily remaining in a condition of isolated hyperthyrotropinemia. Studies analyzing the effects of replacement therapy in SH have reported an increased growth velocity in children with short stature or chronic diseases, discordant effects on thyroid volume reduction, and no effects on neurocognitive function. SH in children and adolescent is often a self-remitting process and its treatment should be considered only when thyroid stimulating hormone values are higher than 10 mIU/L, when clinical signs or symptoms of impaired thyroid function or goiter are detected, or when SH is associated with other chronic diseases.Conflict of interest:None declared.

Subclinical Hypothyroidism in Children Can Normalize after Changes in Dietary Intake

Background: There is no effective treatment for children with subclinical hypothyroidism. The natural course of subclinical hypothyroidism shows a normalization rate of 41% for Thyroid Stimulating Hormone (TSH). Objective; The thyroid needs (among others) iron, iodine, and vitamin A for a proper thyroid hormone synthesis. We hypothesize that with a dietary change, more children can normalize their TSH. Design: In this case-control study, 54 children aged 1 - 14 years with subclinical hypothyroidism were divided into a diet group and a control group. The diet consisted of green vegetables, beef, full fat milk, and butter. The diet was followed for at least 3 months. A total of 27 patients comprised the diet group and 27 the control group. TSH, Free T4 (FT4), and Body Mass Index (BMI) were evaluated during the follow up. Results: By following this diet, TSH levels decreased significantly compared to when following the natural course. FT4 levels did not change during the follow up. The diet group realized a change of normalizing their TSH with a RR 2.8 (95% CI 1.45 - 5.61). There were no changes in BMI after following the diet. Conclusions: Even though our study population was small, we observed the association of a dietary change and normalization of TSH in children with subclinical hypothyroidism, without adverse effects.

At the end of a two-year follow-up elevated TSH levels normalize or remain unchanged in most the children with subclinical hypothyroidism

Data about the natural evolution of subclinical hypothyroidism (SH) in pediatric age are very scanty. Moreover all the available reports in both aged and young patients were based on unselected study populations including also patients with either thyroid disorders or other pathological causes that are well known to be able to affect SH development and evolution. Aim of the study by Wasniewska et al was to prospectively evaluate for the first time the natural course of SH in children and adolescents with no underlying diseases and no risk factors that might interfere with the progression of SH. On the basis of the 2-year follow-up results, the Authors concluded that: a) the natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; b) the majority of patients (88%) normalized or maintained unchanged their TSH; and c) TSH changes were not associated with changes of either FT4 values or clinical status or auxological parameters.Study design of this study is very accurate and the results are robust, thus supporting the Authors' conclusions.

Role of Ultrasonography in Outcome Prediction in Subclinical Hypothyroid Patients Treated with Levothyroxine

Progression to overt hypothyroidism and the associated adverse effects on lipid metabolism and the cardiovascular system are major concerns for patients diagnosed with subclinical hypothyroidism (SCH). No consensus regarding the clinical parameters associated with prognosis for this mild thyroid dysfunction has yet been established, although elevation of serum anti-thyroid peroxidase antibody (TPOAb) and decreased or heterogeneous echogenicity (diffuse thyroid disease, DT) on ultrasonography (US) are commonly observed. We investigated the value of ultrasonographic examination compared to the measurement of serum TPOAb and anti-thyroglobulin antibody (TgAb) for the evaluation of levothyroxine treatment on SCH. We analyzed 204 SCH patients who initially underwent thyroid ultrasonography and were given a low dose of levothyroxine for a mean of 6.94 months. Outcome was determined by the normalization or sustained elevation of serum TSH, and evaluated according to the presence of DT on subsequent US and serum TPOAb or TgAb. Sustained TSH elevation after levothyroxine replacement was more frequent in patients who initially showed DT on US, regardless of thyroid autoantibody level. Ultrasonographic morphology had a higher negative predictive value (81.8%) compared with the absence of TPOAb (73.9%) or TgAb (73.7%) and a similar positive predictive value (48.9%) to that of thyroid autoantibodies (46.8% for TPOAb and 50.0% for TgAb) in the outcome prediction of SCH. Thyroid US may provide valuable information on the course of SCH, and DT pattern can serve as a prognostic factor when combined with other known parameters.

Prospective evaluation of the natural course of idiopathic subclinical hypothyroidism in childhood and adolescence

To prospectively evaluate the course of subclinical hypothyroidism (SH) in children and adolescents with no underlying diseases and no risk factors, which might interfere with the progression of SH. Clinical status, thyroid function, and autoimmunity were prospectively evaluated at entry and after 6, 12, and 24 months in 92 young patients (mean age 8.1+/-3.0 years) with idiopathic SH. During the study, mean TSH levels showed a trend toward a progressive decrease while FT(4) levels remained unchanged. Overall, 38 patients normalized their TSH (group A): 16 patients between 6 and 12 months, and 22 patients between 12 and 24 months. Among the remaining 54 patients, the majority maintained TSH within the baseline values (group B), whereas 11 exhibited a further increase in TSH above 10 mU/l (group C). Baseline TSH and FT(4) levels were similar in the patients who normalized TSH, compared with those with persistent hyperthyrotropinemia. Even in the patients of group C, both TSH and FT(4) at entry were not different with respect to those of groups A and B. No patients showed any symptoms of hypothyroidism during follow-up and no changes in both height and body mass index were observed throughout the observation period. (a) The natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; (b) the majority of patients (88%) normalized or maintained unchanged their TSH; and (c) TSH changes were not associated with either FT(4) values or clinical status or auxological parameters.

Natural Course of Subclinical Hypothyroidism

Objectives of this retrospective study were to evaluate the natural course of subclinical hypothyroidism (SH) and to estimate possible predictable factors of overt hypothyroidism. Population of the study was selected from the patients with spontaneously elevated thyrotropin (TSH) and normal free thyroxin (fT4) levels. Overall 87 patients (12 male, 75 female) with SH without any therapy with thyroid hormones or iodide drugs or without previous thyroid surgery, thyrostatic therapy, or radioactive iodine therapy were included in the analysis. Results: the main risk factors of overt hypothyroidism in this population were positive thyroid antibodies (odds ratio = 3.99) and high initial level of TSH (&gt;8 mU/l) (odds ratio = 4.77). Patient’s age, gender or duration of SH did not affect significantly the risk of overt hypothyroidism. Conclusions: rational substitutive therapy with thyroid hormones was not discussed in this study, however the data suggest that positive thyroid antibodies and relatively high TSH level may be useful to decide upon such therapy in individuals with SH. Key words: hypothyroidism, Hashimotos, thyroiditis, thyrotropin.

Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure.

We aimed to analyze the natural course of subclinical hypothyroidism, quantify the incidence rate of overt hypothyroidism, and evaluate the risk factors for the development of definitive thyroid failure in elderly patients. One hundred seven patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and no previous history of thyroid disease were prospectively studied. Subjects were followed up for 6-72 months (mean, 31.7 months) with repeated determinations of TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism, and 40 (37.4%) showed normalization of their TSH values. The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter, respectively. Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline. A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration (P < 0.0001). In conclusion, TSH concentration is the most powerful predictor for the outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr. Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism. We recommend follow-up with clinical and biochemical monitoring in these patients.

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies.

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.