Normal Thyroid-stimulating Hormone Levels Research Articles

Relation of Low T3 to One-Year Mortality in Non-ST-Elevation Acute Coronary Syndrome Patients.

Low T3 which is defined as decreased triiodothyronine (T3) and normal thyroid-stimulating hormone (TSH) and thyroxin (T4) levels is present in many acute diseases and is related to increased mortality. We studied low T3 level's relation to long-term mortality in non-ST-elevation acute coronary syndrome (NSTE-ACS) patients. T3, T4, and TSH levels of consecutive NSTE-ACS patients were measured. Patients with normal T4 and TSH levels, but low T3 level were defined as low T3 group. Patients with normal T3, T4, and TSH levels were defined as normal group. Clinical and laboratory findings in these two groups were compared. In addition, we examined low T3 level's relation to early and long-term mortality. Mean patient age was 61 ± 13 (67% male) and 31 (11%) patients had low T3 level. Free T3 values were negatively correlated with age, serum creatinine, and brain type natriuretic peptide values at the time of admission (r = -0.452, P < 0.0001; r = -0.255, P < 0.0001; r = -0.544, P < 0.0001, respectively). Mortality at 1 month and 1 year was higher in low T3 group (3% vs. 16%, P = 0.002; 6.4% vs. 23%, P = 0.003, respectively). In multivariate analysis, low T3 was found to be related to mortality at 1 year (OR: 2.6, 95% CI: 1.1-6.5, P = 0.02). In ROC analysis, free T3 had a good area under the curve (AUC) value for mortality at 1 year [AUC: 0.709 (95% CI: 0.619-0.799, SE: 0.0459)]. Low T3 is related to increased early and late mortality in NSTE-ACS patients. Free T3 levels may be used to identify NSTE-ACS patients with high mortality risk.

Thyroid Hormone Resistance and Its Management

The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as In the case presented herein.

Correlation of FOXE1 rs925489 gene polymorphism and high normal TSH level in Chinese Han population

Objective To explore the correlation of the gene polymorphism of the two single nucleotide polymorphisms(SNPs)rs1443434 and rs925489 on forkhead box El(FOXE1)with the high normal thyroid stimulating hormone(TSH)level in Chinese Han population. Methods 1 400 subjects with normal serum TSH and thyroid peroxidase antibody(TPOAb)levels were included. According to TSH or TPOAb levels, the subjects were divided into high normal TSH group(H-TSH group, n=195)and normal TSH control group(TSH control group, n=1 205)or high normal TPOAb group(H-TPOAb group, n=711)and low normal TPOAb group(L-TPOAb group, n=689), respectively. The genotypes on the two SNPs of all the subjects were performed by whole-genome genotyping chips. Results There were significant differences in rs925489 genotypic distributions and allele frequencies between H-TSH group and TSH control group(both P<0.05). The genotype TT and allele T in H-TSH group were significantly higher than those in TSH control group(89.75% vs 83.15%, 94.62% vs 91.29%). The normal TSH levels were positively associated with rs925489 genotypic distributions after adjustment for sex, age, and high density lipoprotein cholesterol(P<0.01). There were no significant differences in rs1443434 genotypic distributions and allele frequencies between two TSH groups or two TPOAb groups. Conclusion FOXE1 rs925489 gene polymorphism may be correlated with the high normal TSH level in Chinese Han population. Key words: Forkhead box El; rs925489; Polymorphism, single nucleotide; TSH

Thyroxine binding globulin excess detected by neonatal screening.

Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9–16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8–2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5–6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0–245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0–36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0–36.0 mg/L) and 50.20 mg/L (normal range, 14.0–28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration.

Low Normal TSH levels are Associated with Impaired BMD and Hip Geometry in the Elderly.

Subclinical hyperthyroidism is known to be associated with the risk of fractures in elderly people. However, there are few studies assessing whether low normal thyroid-stimulating hormone (TSH) levels affect bone density and geometry. Here, we aimed to assess the influence of the TSH level on bone mineral density (BMD) and geometry in elderly euthyroid subjects. This was a cross-sectional cohort study. A total of 343 men and 674 women with euthyroidism were included and analyzed separately. The subjects were divided into tertiles based on the serum TSH level. The BMD and geometry were measured using dual-energy X-ray absorptiometry and a hip structural analysis program. Multiple regression analysis was used to compute the odds ratios of osteoporosis in the lower TSH tertile group and the association between geometry parameters and the TSH level. We found that the femoral neck and total hip BMDs were lower in the lower TSH tertile group. In women, the cross-sectional area and cortical thickness of the femur were negatively associated with the TSH level in all three regions (the narrow neck, intertrochanter, and femoral shaft); however, in men, these geometry parameters were significantly associated with the TSH level only in the intertrochanter region. The buckling ratio, a bone geometry parameter representing cortical instability, was significantly higher in the lower TSH tertile group in all three regions in women, but not in men. Our results indicated that lower TSH levels in the euthyroid range are related to lower BMD and weaker femoral structure in elderly women.

Risk of Thyroid Cancer in Euthyroid Asymptomatic Patients with Thyroid Nodules with an Emphasis on Family History of Thyroid Cancer.

ObjectiveTo determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules.Materials and MethodsThis retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors–such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels–were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics.ResultsAlthough all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041–0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values.ConclusionUltrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.

Relationship between gestational transient thyrotoxicosis and vitamin D.

Gestational transient thyrotoxicosis (GTT) is a transient, mild hyperthyroidism that occurs early in pregnancy and is due to human chorionic gonadotropin. There is no clear information about why only some pregnant women develop GTT. Previous papers stated that vitamin D plays a role in thyroid functions. We aimed to evaluate the relationship between vitamin D and GTT. Fifty-three patients diagnosed with GTT at the 6th to 10th weeks of gestation were included in the study (GTT group). Thirty-five pregnant women with normal thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) levels served as a control group. Vitamin D, TSH, fT3, and fT4 levels were followed during entire the pregnancy. TSH levels had been normalized at the 20th week of gestation in all patients with GTT (mean TSH: 0.56 ± 0.2 μIU/mL). Vitamin D levels were significantly lower in the GTT group than the controls (11.1 ± 7.7 and 16.5 ± 0.5 ng/mL, respectively; P = 0.008). Pregnant women who are diagnosed with GTT should be evaluated for possible vitamin D deficiency.

Should Free Thyroxine Go Back into the Routine Thyroid Profile?

Many clinical chemistry laboratories offer thyroid-stimulating hormone (TSH) alone as a first-line test of thyroid function, and only reflex a free thyroxine (fT4) test if the TSH result is abnormal (i. e., outside of the laboratory reference range). In secondary hypothyroidism, a low fT4 may be accompanied by a low or a normal TSH level. A testing strategy that measures baseline TSH only risks missing cases of secondary hypothyroidism in which the TSH level is normal. The current authors examined 26,106 consecutive thyroid function test (TFT) results in our initial analysis. If the TFT results were compatible with hypopituitarism, with fT4 below the reference range (9-20 pmol/L) and a TSH result ≤5 mU/L (reference range: 0.5-5 mU/L), the laboratory performed further tests of pituitary function. The cost of identifying pituitary insufficiency by measuring both fT4 and TSH was estimated for our population (in 2004 and 2013) and compared with 2 other relevant studies. A total of 121 patients had a normal TSH with a low fT4. 8 new cases of secondary hypopituitarism were identified when fT4 was combined with TSH as the front-line TFT profile. Of these, 5 were found to have pituitary adenomas, 2 of which were macroprolactinomas. The reagent cost of identifying each case by inclusion of fT4 in the TFT profile decreased from £11,568 (€16,089) in 1998 to £1451 (€2018) in 2013. 8 cases of pituitary insufficiency would not have been identified with a strategy of TSH testing alone, which calls for the addition of fT4 to the routine TFT profile. The cost per case of identifying those with pituitary insufficiency by additional measurement of fT4 has become cheaper with time.

Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study.

To evaluate the relationship between idiopathic recurrent pregnancy loss (RPL) and oxidative stress (OS) by means of thiol/disulfide homeostasis via a novel technique. Thirty-nine pregnant women diagnosed with idiopathic RPL were compared with 50 healthy pregnant women without a history of abortion. Idiopathic RPL was defined as experiencing two or more consecutive miscarriages prior to 20 weeks of gestation with the presence of normal karyotypes of couple and/or abortus materials, negative maternal screening for anticardiolipin, anti β 2 glycoprotein antibodies and lupus anticoagulant, normal thyroid stimulating hormone, prolactin and hemoglobin A1C levels and normal pelvic sonography and/or hysterosalpingography. A new and fully automated method was used to measure plasma native thiol, total thiol and disulfide levels, based on the reduction of dynamic disulfide bonds to functional thiol groups by sodium borohydrate. Women with idiopathic RPL had significantly lower plasma levels of native thiol (341.89 ± 50.0 μmol/L vs. 390.84 ± 38.5 μmol/L, P < 0.001) and total thiol (386.18 ± 51.7 μmol/L vs. 435.78 ± 42.3 μmol/L, P < 0.001). Disulfide/thiol and disulfide/total thiol ratios were significantly higher in the study group. The native thiol/total thiol ratio was significantly lower in patients with idiopathic RPL. No difference was measured in disulfide, albumin and total protein plasma levels. The main outcome of our study indicates a relation between idiopathic RPL and OS. More importantly, the new method used in our study proposes a promising, practical and daily applicable test for evaluating patients with idiopathic RPL.

Rapid Levothyroxine Absorption Testing: A Case Series of Nonadherent Patients.

Background:Nonadherence to levothyroxine therapy is one cause of persistent hypothyroidism. To distinguish nonadherence from malabsorption, a levothyroxine absorption test is required. Typically, this test measures the serum free thyroxine (FT4) response to 1000 mcg of oral levothyroxine over 4 to 24 hours. Published data indicate that serum levels of FT4 are at or near their peak 2 hours after levothyroxine ingestion.Objectives:We present the successful completion of 2-hour levothyroxine absorption testing in 3 patients as a retrospective case series.Patients and Methods:Serum levels of thyroid stimulating hormone (TSH), FT4, and free triiodothyronine (FT3) were drawn at 0, 60, and 120 minutes after 1000 mcg of oral levothyroxine.Results:In all 3 cases, baseline thyroid function indicated the patients had taken their prescribed doses of levothyroxine prior to the absorption test. Despite high baseline levels both FT3 and FT4 increased during each absorption test, providing more evidence of adequate levothyroxine absorption. Subsequently, patients achieved normal TSH levels on lower doses of levothyroxine.Conclusions:Levothyroxine absorption testing over 2 hours may offer a more rapid alternative to the commonly used longer protocols to rule out malabsorption. Scheduling a levothyroxine absorption test may induce some patients to start adhering to levothyroxine therapy.

Lower-normal TSH is associated with better metabolic risk factors: A cross-sectional study on Spanish men

Background and aimsSubclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. Methods and resultsWe studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. ConclusionsTSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters.

Goiter, an enlargement of the thyroid gland, is a common problem in clinical practice associated with iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, and lack of selenium and iron. Evidence suggests that heredity also has an important role in the etiology of goiter. The current classification divides goiter into diffuse and nodular, which may be further subdivided into toxic (associated with symptoms of hyperthyroidism, suppressed TSH or both), or nontoxic (associated with a normal TSH level). Nodular thyroid disease with the presence of single or multiple nodules requires evaluation due to the risk of malignancy, toxicity, and local compressive symptoms. Measurement of TSH, accurate imaging with high-resolution ultrasonography or computed tomography, and fine-needle aspiration biopsy are the appropriate methods for evaluation and management of goiter. This review discusses the clinical presentation, diagnostic evaluation, and treatment considerations of nontoxic diffuse and nodular goiters.

Left Atrial Appendage Aneurysm

A 57-year-old woman presented to our emergency department with intermittent episodes of palpitations, which began abruptly without significant precipitants and resolved spontaneously. Physical examinations showed a rapid heart rate of 130 beats per minute approximately, with irregular pattern; the remainder was unremarkable. She was otherwise healthy, without history of panic disorders or cardiovascular diseases. No remarkable family history was reported. She did not take medicine and did not use illicit drugs, alcohol or tobacco. No emotional stress was noted recently. An electrocardiogram showed atrial fibrillation with rapid ventricular responses. The patient received transthoracic echocardiography initially in our emergency department, and the preliminary findings showed no significant structural abnormalities. Surprisingly, the chest x-ray revealed a bulky mass, obliterating the left cardiac border (Figure 1A, arrow). Under the impression of possible structural heart disease, advanced computed tomography of the chest confirmed a large aneurysm (Figure 1B, arrow), arising from the left aspect of atrium (Figure 1B, asterisk). Blood testing showed normal serum thyroid-stimulating hormone and electrolyte levels. The patient underwent an aneurysmectomy. After surgery, the patient recovered and was discharged uneventfully, with a regular sinus rhythm and resolution of symptoms.

Early Discrimination between Transient and Permanent Congenital Hypothyroidism in Children with Eutopic Gland

Aim: To analyze the factors that might allow an early discrimination between permanent (P) and transient (T) congenital hypothyroidism (CH). Methods: Clinical, biochemical and imaging data of 64 children with eutopic gland, who were positively screened and treated for CH during the period 1998-2011, were retrospectively analyzed. Results: During a 3-year treatment period, the mean doses of <smlcap>L</smlcap>-thyroxine (L-T4) per kilogram of body weight at various times were significantly lower in the 46 children with T CH than in the remaining 18 with P CH. No patients with T CH had required any increment of the doses of L-T4 per kilogram of body weight to maintain normal thyroid-stimulating hormone levels over time, whereas 16/18 children with P CH during the same period had needed some dose increments (p < 0.0001). Conclusions: (a) L-T4 requirements >4.9 µg/kg/day at 12 months or >4.27 µg/kg/day at 24 months are highly suggestive of P CH, irrespective of gland ultrasonography; (b) L-T4 requirements <1.7 µg/kg/day at 12 months or <1.45 µg/kg/day at 24 months are highly suggestive of T CH, at least in the cases with eutopic gland, and (c) the analysis of L-T4 requirements during the first years of treatment might allow an early discrimination between T and P CH in the cases with eutopic gland.

SERUM T3 LEVEL AND ITS RELATION TO CHRONIC HAPATITIS C VIRUS IN DIABETIC VERSUS NON DIABITIC PATIENTS

Background: Thyroid gland disorders represent one of the commonest endocrine manifestations of chronic hepatitis C (HCV). Objective: This study was performed to evaluate thyroid hormones profile in patients with chronic hepatitis C and its relation to severity of liver damage in the presence or absence of diabetes mellitus. Patients and methods: This study was performed on sixty patients with liver cirrhosis due to hepatitis C virus with or without diabetes mellitus. The patients were divided into three equal groups according to Child-Pough score as following: Group A, group B and group C. All patients were subjected to medical history, clinical examination and laboratory investigations including liver functions tests, renal function tests, complete blood picture (CBC), viral markers for hepatitis, hepatitis C virus antibody (HCV-Ab) and hepatitis B virus antigen (HBs-Ag), polymerase chain reaction (PCR), fasting blood sugar (FBS), postprandial blood sugar(PPBS) hemoglobin A1 C (HbA1c), tetra-iodothyronin (T4), tri-iodothyronin( FT3), thyroid stimulating hormone (TSH) and abdominal ultrasound. Results: Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood platelet and FT3 were significantly lower in group C than group B and group A, while serum levels of bilirubin andprothrombin time(PT) were significantly higher in group C than B and A. Serum levels of FT3 was positively correlated with serum albumin and negatively correlated with serum bilirubin and PT. There were no significant changes in the serum levels of FT3, FT4 and TSH between diabetic and non-diabetic patients. On the other hand, serum levels of ALT, AST, and albumin significantly elevated in diabetic versus non-diabetic patients. Conclusions: A highly significant reduction of serum FT3 in liver cirrhosis with normal serum FT4 and TSH levels was attributive to decreased deiodination of T4 to T3. Decreased serum FT3 level correlated with the severity of liver disease, and may be helpful in assessing the course and diagnosis of liver cirrhosis. Also, serum FT3 hormone level could be used as a marker for grading and assessment of the severity of hepatic dysfunctions.

Relationship between thyroid-stimulating hormone levels and risk of depression among the general population with normal free T4 levels

This study assessed the relationship between thyroid-stimulating hormone (TSH) level and risk of depressive symptom in a population with no clinical or laboratory evidence of thyroid dysfunction. This retrospective cohort study included 13,017 subjects (7913 males and 5104 females), 17-84 years of age, who underwent health examinations at the hospital. Subjects had a Beck Depression Inventory (BDI) total score of ≤9 and fell within the normal range of free T4 levels at baseline. The association between gender-specific serum TSH tertile at baseline and the development of clinically significant depressive symptom (i.e., ≥19 BDI total score) on the follow-up visit was evaluated using the Cox proportional hazards model, with adjustment for demographic and life style factors. The risk of depressive symptom was increased among subjects with the highest tertile TSH level (adjusted hazard ratio [HR], 2.236; 95% confidence interval [CI], 1.443-3.466; p<0.001) as compared with subjects with the lowest tertile in females, but not in males. Even among patients with normal TSH levels, females in the lowest-normal TSH tertile had a higher risk of depressive symptoms (adjusted HR, 2.279; 95% CI, 1.456-3.567; p<0.001) than did those in the highest tertile. The TSH level as a continuous variable significantly predicted the depressive symptoms in females (adjusted HR, 1.402; 95% CI, 1.002-1.812; p=0.027). Our finding suggests that suboptimal thyroid function increases vulnerability to the occurrence of depressive symptom and represents a modifiable risk factor for depression in females.

Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny.

Maternal hypothyroxinemia can induce neurodevelopmental impairments in the developing fetus. We here review recent studies on the epidemiology and molecular mechanisms associated with this important public health issue. In 2011, the American Thyroid Association defined maternal hypothyroxinemia as low serum free thyroxine (FT4) levels (<5th or <10th percentile) existing in conjunction with normal serum free triiodothyronine (FT3) or thyroid stimulating hormone (TSH) levels during pregnancy. Compared to clinical or subclinical hypothyroidism, hypothyroxinemia is more commonly found in pregnant women. Hypothyroxinemia usually ensues in response to several factors, such as mild iodine deficiency, environmental endocrine disrupters, or certain thyroid diseases. Unequivocal evidence demonstrates that maternal hypothyroxinemia leads to negative effects on fetal brain development, increasing the risks for cognitive deficits and poor psychomotor development in resulting progeny. In support of this, rodent models provide direct evidence of neurodevelopmental damage induced by maternal hypothyroxinemia, including dendritic and axonal growth limitation, neural abnormal location, and synaptic function alteration. The neurodevelopmental impairments induced by hypothyroxinemia suggest an independent role of T4. Increasing evidence indicates that adequate thyroxine is required for the mothers in order to protect against the abnormal brain development in their progeny.

Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA)

BackgroundResistance to thyroid hormone is characterised by a lack of response of peripheral tissues to the active form of thyroid hormone (triiodothyronine, T3). In about 85% of cases, a mutation...

Thyrotropin and Alzheimer's Disease Risk in the Elderly: a Systematic Review and Meta-Analysis.

Although several epidemiological studies assessed the relationship between thyrotropin and risk of Alzheimer's disease in the elderly, the results were inconsistent. A systematic review and meta-analysis of cohort studies was conducted to assess the impact of serum thyrotropin levels on Alzheimer's disease risk. PubMed, Embase, and Web of Science were searched through September 20, 2014 to identify cohort studies on the relationship between serum thyrotropin levels and risk of Alzheimer's disease in the elderly. Pooled relative risks (RR) and 95% confidence intervals (95% CI) were calculated to assess the risk of Alzheimer's disease according to serum thyrotropin levels. Eight prospective cohort studies were included, with a total of 9456 participants and 640 cases of Alzheimer's disease. Low thyrotropin level was significantly associated with an increased risk of Alzheimer's disease (fixed RR = 1.69, 95% CI 1.31-2.19, P < 0.001; I(2) = 38.0%). High thyrotropin level was also significantly associated with an increased risk of Alzheimer's disease (fixed RR = 1.70, 95% CI 1.18-2.45, P = 0.005; I(2) = 42.2%) when compared with normal thyrotropin level. When using random effect model, low thyrotropin level was still significantly associated with risk of Alzheimer's disease (random RR = 1.65, 95% CI 1.14-2.37, P = 0.007), but high thyrotropin level was not (random RR = 1.54, 95% CI 0.88-2.68, P = 0.129). When investigating thyrotropin levels continuously, an inverse but not significant association between serum thyrotropin levels and Alzheimer's disease risk was observed (per standard deviation increment of thyrotropin: RR = 0.89, 95% CI 0.78-1.01, P = 0.06; I(2) = 31.3%). This meta-analysis supports that low thyrotropin level is significantly associated with an increased risk of Alzheimer's disease in the elderly.

Hypothyroidism.

In the general adult population (excluding pregnant women and older people), a normal thyroid-stimulating hormone (TSH) level is defined as the 95% laboratory-specific reference interval (about 0.45–4.50 mIU/L).[1][1]–[3][2] In adults (other than in pregnancy), TSH values greater than 10 mIU/L