Dose‐dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function: comparison of 0·1, 0·3 and 0·9 mg of rhTSH

Context Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side‐effects are dose dependent. Objective To determine the effects on thyroid size and function of various doses of rhTSH. Design In nine healthy male volunteers, the effect of placebo, 0·1, 0·3 and 0·9 mg of rhTSH was examined in a paired design including four consecutive study rounds. Main outcome measures Main outcome measures were evaluated at baseline, 24 h, 48 h, 96 h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, free T3, free T4 and Tg levels. Results Following placebo or 0·1 mg rhTSH, the TV did not change significantly from baseline at any time. At 24 and 48 h after administration of 0·3 mg rhTSH, the TV increased by 37·4 ± 12·3% (SEM) (P = 0·03) and 45·3 ± 16·1% (P = 0·05) respectively. After 0·9 mg rhTSH, the TV increased by 23·3 ± 5·8% (P = 0·008) and 35·5 ± 18·4% (P = 0·02) respectively. The increase in serum FT3, FT4 and thyroglobulin (Tg) was greater when administering 0·3 mg compared with 0·1 mg (P = 0·02) and when administering 0·9 mg compared with 0·3 mg (P = 0·02). After 0·1 mg rhTSH, the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (P = 0·02 compared with placebo). Conclusions In healthy individuals, rhTSH‐induced thyroid swelling and hyperthyroidism is rapid and dose dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0·1 mg or less.     

Performance of a third‐generation TSH‐receptor antibody in a UK clinic

Background UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third‐generation TRAb autoantibody M22‐biotin ELISA assay was introduced in May 2008 in our centre. Objective To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre. Design A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH). Patients and Measurements Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought. Results In the retrospective cohort, the manufacturer’s cut‐off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves’ disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut‐off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves’ disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut‐off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut‐off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves’ disease for a particular patient by 25–35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing. Conclusions The assay studied specifically identifies patients with Graves’ disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost‐savings.     

Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice

Objective The suitability of TSH reference limits derived from national databases to outpatient practices has not been established. We aimed to determine whether race and age influence the distribution of TSH and free T4 (fT4). Design A cross‐sectional study of an urban outpatient medical practice. Participants Patients (n = 22 116) without clinical evidence of thyroid disease or use of thyroid‐specific medications. Measurements Comparison of TSH and fT4 distributions in specific racial and age groups including blacks, whites and Hispanics. Results TSH was distributed at higher concentrations, without skew, in whites compared to blacks (median, 1·54 mIU/l vs. 1·18 mIU/l, P < 0·001) and in old (>80 years old) compared to young (20–29 years old) (median, 1·61 mIU/l vs. 1·13 mIU/l, P < 0·001). In all patients, blacks and whites, 3%, 8% and 5%, respectively, of those aged > 80 years were misclassified as having high TSH compared to those aged 20–29 years (P < 0·001). Using TSH limits from national databases resulted in significant misclassification of patients with raised or lowered TSH. Mean fT4 was significantly lower in blacks than whites (17·5 ± 4·38 pmol/l vs. 18·3 ± 3·99 pmol/l, P < 0·001), did not differ between young and old, but decreased progressively (average 7%) as TSH increased to > 4·5 mIU/l. Conclusions Reference limits for TSH differ between races and with age. Use of race‐ and age‐specific reference limits decreases misclassification of patients with lowered or raised TSH in an urban practice. The unique fT4:TSH relationships of blacks and whites may be genetically determined. The implications of the small decrement in fT4 as TSH increases remain to be explored.     

Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle‐aged and older subjects: results from a 5‐year follow‐up

Background Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross‐sectional and case‐control studies. The aim was to assess whether SCH independently impacts development of LVH over time. Methods Of 3300 participants of the population‐based Study of Health in Pomerania those with overt hyperthyroidism, hypothyroidism, possible thyroid disease or missing echocardiographic baseline data or follow‐up were excluded, resulting in a study population of 1112 individuals (556 women) aged 45–81 years. Echocardiographic left ventricular mass divided by height^2·7 (LVMI_ht), and LVH_ht (LVMI_ht >44 g/m^2·7 in women and >48 g/m^2·7 in men) was measured at baseline and after 5‐year follow‐up (median 5·00; range 4·92; 5·08). Comparison of subjects with (n = 107) and without (n = 1005) SCH were made by linear and logistic regression models adjusted for age, gender, smoking status, hypertension, and waist circumference. Results At follow‐up, LVMI_ht did not differ between subjects with and without SCH (50·2 g/m^2·7, interquartile range (IQR) 41·2; 59·5 vs 47·8 g/m^2·7, IQR 39·3; 56·9; P = 0·29). LVH_ht was present in 66 (61·7%) subjects with and 543 (54·0%) persons without SCH (P = 0·13). Analyses revealed no association between SCH and progression of LVMI_ht (β = ?0·18; 95%‐confidence interval (CI) ?2·34; ?1·99; P = 0·873), and development of LVH_ht (relative risk 0·86, 95%‐CI 0·60; 1·26; P = 0·462), respectively. Conclusions In this population‐based sample, SCH had no impact on progression of LVMI and development of LVH during 5‐year follow‐up in subjects aged 45 years or older.     

Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome

Objective Metformin is widely used for the treatment of type 2 diabetes. Growing evidence supports the beneficial effects of metformin also in patients with polycystic ovary syndrome (PCOS). It was recently reported that metformin has a TSH‐lowering effect in hypothyroid patients with diabetes being treated with metformin. Design Aim of this study was to evaluate the effect of metformin treatment on the thyroid hormone profile in patients with PCOS. Patients and measurements Thirty‐three patients with PCOS were specifically selected for being either treated with levothyroxine for a previous diagnosis of hypothyroidism (n = 7), untreated subclinically hypothyroid (n = 2) or euthyroid without levothyroxine treatment (n = 24) before the starting of metformin. The serum levels of TSH and FT₄ were measured before and after a 4‐month period of metformin therapy. Results Thyroid function parameters did not change after starting metformin therapy in euthyroid patients with PCOS. In the 9 hypothyroid patients with PCOS, the basal median serum levels of TSH (3·2 mIU/l, range = 0·4–7·1 mIU/l) significantly (P < 0·05) decreased after a 4‐month course of metformin treatment (1·7 mIU/l, range = 0·5–5·2 mIU/l). No significant change in the serum levels of FT4 was observed in these patients. The TSH‐lowering effect of metformin was not related to the administered dose of the drug, which was similar in euthyroid as compared with hypothyroid patients with PCOS (1406 ± 589 vs 1322 ± 402 mg/day, respectively; NS). Conclusions These results indicate that metformin treatment has a TSH‐lowering effect in hypothyroid patients with PCOS, both treated with l ‐thyroxine and untreated.     

Reference range of thyroid hormones in normal Indian school-age children

Objective There is an ongoing debate on narrowing the TSH reference range in adults. In view of the scarce data on normal values of thyroid function tests in children from India, we planned to establish a reference range for thyroid hormones in school‐age children. Design and subjects All children (N = 9527; 6–19 years) from six schools representing various zones of Delhi were evaluated for clinical evidence of goitre, thyroid ultrasound, serum free T3 (FT3), free T4 (FT4) and TSH and anti‐thyroid peroxidase (anti‐TPO) antibodies. From this sample, a reference population (N = 5122) was obtained by excluding those with a personal or family history of thyroid disease, use of thyroid medications, goitre, hypoechogenicity/nodularity on ultrasound or serum anti‐TPO antibodies. Measurements Thyroid hormone (FT3, FT4 and TSH) reference ranges were established for each year of life for the total and reference populations. Results In the reference population, mean serum FT3 was in the range 4·19–4·84 pm /l for boys and 4·03–4·47 pm /l for girls, mean serum FT4 14·69–17·36 pm /l for boys and 14·32–15·88 pm /l for girls, and mean serum TSH 2·57–3·6 mIU/l for boys and 1·83–3·58 mIU/l for girls. For TSH, the 97th percentile was in the range 6·01–8·4 mIU/l for boys and 5·28–8·04 mIU/l for girls, suggesting that at least in children there may not be a need to reduce the upper limit of normal for serum TSH. Conclusions This study provides mean reference intervals for FT3, FT4 and TSH for each year of life for both the sexes separately using strict exclusion criteria.     

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes

Objective The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline. Design The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80·0%) participated in the 5‐year follow‐up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B‐mode ultrasonography of the thyroid was performed. Results In the reference population, there was a urinary iodine‐related increment of serum TSH levels (r = 0·21, P = 0·000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1·15, 1·28 and 1·93 mIU/l, respectively (P = 0·000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0·3–4·8 mIU/l. TSH concentrations obtained in the follow‐up study correlated well with those at baseline (r = 0·58, P = 0·000). A baseline serum TSH > 1·9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1·0 mIU/l was associated with an increased incidence of subnormal TSH development. Conclusions Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1·0–1·9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.     

Maternal thyroid function during gestation is related to breech presentation at term

Objective To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. Design Prospective follow‐up study during three trimesters of gestation. Patients A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (≥37 weeks) delivery. Measurements Maternal thyroid parameters [TSH, free T4 (FT4) and auto‐antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. Results At term, 58 women (5·5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0·007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH ≥ 2·5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4·8% in the women with TSH < 2·50 mIU/l (P = 0·006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (≥2·5 mIU/l) at 36 weeks gestation (O.R.: 2·23, 95% CI: 1·14–4·39), but not at 12 and 24 weeks gestation. Conclusions Women with TSH levels above 2·5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.     

The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized,double blind,cross‐over study in thyroidectomized patients

Context The substitution of liothyronine (L‐T3) for levothyroxine (L‐T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L‐T3 for L‐T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of L‐T3 and L‐T4. Design Randomized, double‐blind, cross‐over intervention study. Setting NIH clinical center. Patients Ten thyroidectomized patients. Interventions Study participants were treated with L‐T3 or L‐T4 with a target TSH ≥ 0·5 ≤ 1·5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed‐over according to the same scheme. Main outcome measures Area under the serum concentration–time curve of TSH from 0 to 60 min (AUC_0–60) and peak TSH serum concentration (C_max) following thyrotropin‐releasing hormone (TRH) stimulation test, total L‐T4 and L‐T3 dose (mcg/kg), and L‐T4/L‐T3 ratio. Results No difference was observed for time 0 TSH values between L‐T3 and L‐T4 replacement phases (1·48 ± 0·77 vs. 1·21 ± 0·62 mU/l, P = 0·293) at average daily doses of 40·3 ± 11·3 mcg L‐T3 and 115·2 ± 38·5 mcg L‐T4, L‐T3: L‐T4 ratio 0·36 ± 0·06. TRH stimulation test resulted in similar L‐T3 vs. L‐T4 TSH responses with AUC_0–60 of 326·1 (95% CI 232·6–457·1) and 247·1 (95% CI 153·8–397·1) mU* min/l (P = 0·285); and C_max of 6·83 (95% CI 4·88–9·55) and 5·23 (95% CI 3·31–8·3) mU/l (P = 0·383). Conclusions This is the first study addressing the equivalency between L‐T3 and L‐T4 therapy measured by baseline and TRH‐stimulated TSH. The therapeutic substitution of L‐T3 for L‐T4 was achieved at approximately 1:3 ratio.     

Changes within the thyroid axis after long-term TSH-suppressive levothyroxine therapy

Objective The effects of long‐term TSH‐suppressive levothyroxine (LT4) therapy on thyroid hormone metabolism in patients with differentiated thyroid carcinoma (DTC) are unknown. The aim of the study was to investigate the changes in thyroid hormone metabolism after long‐term TSH‐suppressive LT4 therapy in patients with DTC. Patients and Methods Sixty one patients with DTC were followed. For each patient, frozen remnant sera from two time points were selected: time1 (drawn within 1 year of I‐131 ablation; TSH on file <0·3 mIU/l; recruitment period 1999–2002) and time2 (last available sample with TSH on file <0·3 mIU/l; minimum of 3 years of continuous TSH‐suppressive LT4‐therapy on record). TSH, reverse triiodothyronine (rT3), total triiodothyronine (TT3) and total thyroxine (TT4) levels were measured at both time1 and time2, and relationships between these parameters were analysed. Results Total triiodothyronine, TT4 and TSH levels were significantly reduced at time2 (P < 0·001), whereas LT4 dose, bodyweight and rT3 levels remained constant between time1 and time2. There were no significant changes in the relationship between the dose of LT4/kg bodyweight and TT4 levels (P = 0·14). TT4/TT3 was increased at time2 (P < 0·001), whereas TT4/rT3 and TT3/rT3 were significantly decreased at time2. There appeared to be no relationship of the effects found and advancing age. Conclusion After long‐term TSH‐suppressive LT4 therapy for DTC, there are significant changes in thyroid hormone metabolism, which are best explained by a combined downregulation of deiodinases subtypes 1 and 2 and an upregulation of deiodinase subtype 3.     

Effects of 18 months of l-T4 replacement in women with subclinical hypothyroidism

Context Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short‐term l ‐T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima‐media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of l ‐T4 replacement in SCH are poorly understood. Objectives To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of l ‐T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. Design Fifty‐six women with SCH before and after l ‐T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin‐C] in women with SCH before and after 18 months of l ‐T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after l‐ T4 in a subgroup of women with SCH. Results Systolic and diastolic BP, total cholesterol, triglyceride, LDL‐cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0·05), and following l‐ T4 replacement decreased (P < 0·05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin‐C increased (P < 0·05) in SCH. These variables also normalized following l ‐T4. Following l ‐T4 replacement the carotid artery baseline diameter increased by 7·1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12·5% and following endothelium‐dependent vasodilatation by 17·5% (P < 0·05). However, the increment following reactive hyperaemia did not differ before or following l‐ T4 replacement. Conclusion Normalization of cardiovascular risk factors following l‐ T4 replacement in SCH potentially explains reduced CIMT. Increased carotid and brachial artery diameters and normalized eGFR indicates a haemodynamic effect of l‐ T4 replacement, the importance of which requires further investigation.     

How should we treat patients with low serum thyrotropin concentrations?

Subclinical hyperthyroidism (SH) is defined by a low serum thyrotropin (TSH) concentration in the presence of normal levels of free thyroxine (FT4) and free triiodothyronine (FT3). However, it is helpful to distinguish between those with a detectable but low TSH value (in the 0·1–0·4 mU/l range) and those with a fully suppressed TSH (<0·1 mU/l), and we suggest the designation of grade I and grade II SH, respectively. Together, these patterns of thyroid function tests are found in 1–3% of the elderly population, and are associated with significant morbidity and mortality in longitudinal epidemiological surveys. There are a number of causes for this picture, which include endogenous thyroid disease, drug effects and concomitant nonthyroidal illness. Treatments commonly employed in the management of thyrotoxicosis are effective at correcting the biochemical abnormalities of SH but have not been shown to improve clinical outcome or symptoms. There is little good quality evidence available to guide the assessment or management of these patients. This review summarizes the clinical significance of SH and aims to provide guidance about whether we should treat patients with low serum TSH concentrations.     

Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study

Objective Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. Design Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community‐dwelling US adults. Participants Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. Measurements TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. Results At baseline, 684 participants met criteria for metabolic syndrome. At 6‐year follow‐up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1·03; 95% CI, 1·01–1·06; P = 0·02), and the association was stronger for TSH within the normal range (OR, 1·16; 95% CI, 1·03–1·30; P = 0·02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2·3; 95% CI, 1·0–5·0; P = 0·04); the odds of incident MetS was similar (OR 2·2), but the confidence interval was wide (0·6–7·5). Conclusions Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.     

Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5·25‐year follow‐up study

Objective To investigate the long‐term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45–54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy. Design This was an observational follow‐up study of 5·25 years (median; range 1·7–10·4). Patients and measurements Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1–3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI. Results Tumour growth control was 100%. At the end of follow‐up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4·2 (range, 2·3–6·5) to 1·1 (range, 0·5–1·5) μg/l (P < 0·001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT‐related deaths. Conclusion According to this long‐term follow‐up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.     

Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease - a community-based study

OBJECTIVES: The aim of this study was to evaluate whether subclinical thyroid disease is associated with impaired health-related quality of life and a more adverse cardiovascular disease risk profile. DESIGN: A community-based cross-sectional study. SETTING AND PARTICIPANTS: A total of 1423 non-healthcare-seeking women, aged 18-75 years were randomly recruited from the community via the electoral roll from April 2002 to August 2003. MAIN OUTCOME MEASURES: These were the scores for the Short-Form 36 (SF-36), the Psychological General Well-being Index (PGWI), thyroid hormone levels, serum lipids and high sensitivity C-reactive protein (hsCRP). Subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper) were defined as serum TSH > 4.0 mIU/l and < 0.5 mIU/l, respectively, with a normal free thyroxine (free T4) level. RESULTS: Evaluable data were available for all participants. 10.7% of all women had an abnormal TSH value. The prevalence of a low TSH level by age group ranged from 1.2% to 6.4%, whereas the prevalence of an elevated TSH level ranged from 2.8% to 9.2% and increased with age (P = 0.002). There were no significant differences between women with SCH or SCHyper and age-matched controls for the total PGWI score or the Mental and Physical Component Scores of the SF-36. Women with SCH were no different from controls for serum lipids or hsCRP. Using linear regression, SCH vs. euthyroidism did not make an independent contribution to variation in either total cholesterol or triglycerides, with or without adjustment for age +/- age(2) +/- BMI. CONCLUSIONS: Our data indicate that subclinical thyroid disease in women in the community is not associated with lower well-being or impaired health-related quality of life and SCH is not associated with increased serum markers of CVD risk.     

Subclinical hypothyroidism and cardiovascular risk: recommendations for treatment

The definition of subclinical hypothyroidism (SCH) is solely biochemical: a serum free T4 level within the reference range in the presence of an elevated serum thyroid-stimulating hormone (TSH) level. While overt hypothyroidism is associated with an increased cardiovascular disease risk, SCH, the mildest form of hypothyroidism, may also be associated with an increased cardiovascular disease risk, but to a lesser degree. Recent evidence points to a significant trend toward an increase in cardiovascular risk at higher TSH levels, with TSH levels ≥10 mIU/L associated with increased cardiovascular morbidity and mortality. It is generally recommended to treat with thyroid hormone those individuals with SCH and TSH values ≥10 mIU/L. Treatment of patients with SCH and TSH values <10 is controversial but may be considered in selected patients.     

老年亚临床甲状腺功能减退症临床研究进展

亚临床甲状腺功能减退症为一种常见的甲状腺疾病,临床症状隐蔽而不典型,好发于老年女性。亚临床甲状腺功能减退症可引起血脂的改变、心功能不全、冠心病等动脉粥样硬化性疾病,可行左旋甲状腺激素替代治疗,治疗需权衡利弊,大多数研究建议促甲状腺素〉10mlU／L的亚临床甲状腺功能减退症患者进行左旋甲状腺激素替代治疗,老年亚临床甲状腺功能减退症患者治疗有其自身特点。     

Impact of moderate vs stringent TSH suppression on survival in advanced differentiated thyroid carcinoma

Objectives To assess (i) the influence of Thyrotropin (TSH) suppression at a level of <0·1 mU/l and (ii) whether FT3 and FT4 levels have a prognostic significance independently of TSH values with regard to survival in patients with differentiated thyroid carcinoma (DTC) and distant metastases. Patients and methods In a retrospective patient chart study, we reviewed survival in 157 DTC patients with distant metastases treated between September 1985 and 1 July 2010. Patients with at least three available FT3 and FT4 values during TSH suppression were eligible. Results Fifty‐three of 157 patients died from DTC. DTC‐specific survival was significantly better in patients with a median TSH level ≤0·1 mU/l (median survival 15·8 years) than those with a non‐suppressed TSH level (median survival 7·1 years; P < 0·001). However, there was no further improvement in survival caused by TSH suppression to a level ≤0·03 mU/l (P = 0·24). FT3 and FT4 levels were also significantly associated with poorer survival; of these, only the prognostic value of FT3 was independent from that of TSH levels. Conclusion The care of patients with DTC and distant metastases is like walking an endocrinological tightrope: non‐suppressed TSH levels, that is, >0·1 mU/l, are associated with an impaired prognosis. There is, however, no prognostic benefit from suppressing TSH to levels lower than 0·1 mU/l. On the contrary, an improvement in prognosis might be achieved by keeping FT3 levels as low as possible.     

Diagnostic significance of low thyrotropin in internal medicine

In an attempt to determine the significance of low plasma thyrotropin (TSH) concentrations in internal medicine and the usefulness of systematic TSH assays in hospitals, 732 consecutive TSH measurements were performed in first-admission patients. TSH concentrations below 0.15 mU/l were found in 33 patients (4.5%) divided into 4 groups: a) in 5 patients a second assay made within 10 days of the first one showed no fall in TSH levels; b) 5 patients had known endocrine disease; c) in 8 patients hyperthyroidism could be asserted; the diagnosis had not been suspected in 3 elderly women and 1 pregnant women; d) 15 patients remained with low TSH concentrations but had normal free T3 and free T4 levels; in this group a goitre was detected in 7 patients and 8 had a severe chronic disease. These results showed that a TSH concentration below 0.15 mU/l corresponded to hyperthyroidism in less than one out of three patients in this population and that the 0.07 to 0.15 mU/l range is particularly misleading. A second TSH assay, free T3 and free T4 measurements ant thorough investigations in search of a goitre must be made. Severe organic diseases and several drugs may induce a fall in TSH. All considered, the 1% prevalence of hyperthyroidism in this population does not justify systematic TSH assays, but in subjects over 60 years of age, the clinical manifestations of hyperthyroidism may be misleading or unrecognized, and TSH assays should be widely performed.     

HYPERTHYROIDISM IN GESTATIONAL TROPHOBLASTIC NEOPLASIA

The thyroid status of twenty-seven African patients with gestational trophoblastic neoplasia (GTN) was studied. Fifteen patients were found to be biochemically hyperthyroid (eight patients with choriocarcinoma; seven with hydatidiform mole). Of these fifteen patients, nine were clinically thyrotoxic. The most serious complication of thyrotoxicosis was life-threatening acute pulmonary oedema with associated cardiac failure. It was found that when serum levels of the human chorionic gonadotrophin (hCG) reached a level of about 0·1 ± 10⁶ iu/l, thirteen of sixteen patients were biochemically hyper-thyroid; at serum levels of 0·3 ± 10⁶ iu/l of hCG most patients were clinically thyrotoxic. A feature of hyperthyroidism associated with GTN is that whereas T4 is invariably raised the T3:T4 ratio tends to be low (0·015 ± 005); rT3:T3 ratios were high in this group. TSH levels were not increased.