TSH Reference Range Research Articles

Qu'est ce qu'un taux de TSH élevé ?

Measurement of TSH is the most sensitive test of thyroid function. The diagnostic of mild forms of dysthyroidism depends of the definition of the normal limits of serum TSH. The upper limit of TSH remains controversial. The conventional cut off of 4 to 4,5 mU/l is now under debate. Recent laboratories guidelines indicate that more than 95% of normal individuals have TSH levels below 2,5 mU/l. However this statistical value is not clinically receivable when summarizing the data available in several populations. The application of such an upper value of TSH would dramatically increase the diagnosis of subclinical hypothyroidism and might increase the use of thyroxin therapy in patients for whom there is no demonstrated therapeutic benefit. In conclusion, the conventional reference range of TSH from 0,4 to 4 mU/l remains applicable in a care practice setting.

Prevalence of Elevated Thyroid Stimulating Hormone (TSH) Levels Using the Conventional Cut-Off of 4.0 uIU/mL Versus 3.0 uIU/mL

Background: Although controversial, the guidelines from the American Association of Clinical Endocrinologists (AACE) have suggested lowering the upper reference range of TSH to 3.0 uIU/mL for the diagnosis of hypothyroidism. In reproductive-age women, hypothyroidism has a prevalence that ranges between 7.5–8.5 percent. Hypothyroidism has many sequelae, including infertility and asymptomatic hypothyroidism, that can have adverse effects on the offspring of pregnant women, such as diminished cognitive function.

The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study

The association between TSH and serum lipids in people with no apparent thyroid disease is insufficiently understood. We have studied the association between normal thyroid function, defined as TSH within the reference range of a general population, and concentrations of serum lipids. Cross-sectional, population-based study with 30,656 individuals without known thyroid disease. Using general linear models, we calculated mean concentrations of total serum cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, HDL cholesterol and triglycerides across categories of TSH. Within the reference range of TSH, there was a linear and significant (P for trend <0.001) increase in total serum cholesterol, LDL cholesterol, non-HDL cholesterol and triglycerides, and a linear decrease (P for trend <0.001) in HDL cholesterol with increasing TSH. Subgroup analyses showed statistically significant associations for all lipids in men above 50 years of age, and for triglycerides in all age groups. For women, associations were statistically significant in all age groups except for HDL cholesterol in women below 50 years of age. The associations with triglycerides and HDL cholesterol were stronger among overweight than normal weight individuals. Within the range of TSH that is considered clinically normal, we found that increasing level of TSH was associated with less favourable lipid concentrations. The association with serum lipids was linear across the entire reference range of TSH.

Association between Blood Pressure and Serum Thyroid-Stimulating Hormone Concentration within the Reference Range: A Population-Based Study

The association between thyroid function and blood pressure is insufficiently studied. The objective of the investigation was to study the association between TSH within the reference range and blood pressure. This was a cross-sectional, population-based study. A total of 30,728 individuals without previously known thyroid disease were studied. The main outcome measures were mean systolic and diastolic blood pressure and pulse pressure and odds ratio for hypertension (>140/90 mm Hg or current or previous use of antihypertensive medication), according to categories of TSH. Within the reference range of TSH (0.50-3.5 mU/liter), there was a linear increase in blood pressure with increasing TSH. The average increase in systolic blood pressure was 2.0 mm Hg [95% confidence interval (CI) 1.4-2.6 mm Hg] per milliunit per liter increase in TSH among men, and 1.8 mm Hg (95% CI 1.4-2.3 mm Hg) in women. The corresponding increase in diastolic blood pressure was 1.6 mm Hg (95% CI 1.2-2.0 mm Hg) in men and 1.1 mm Hg (95% CI 0.8-1.3 mm Hg) in women. Comparing TSH of 3.0-3.5 mU/liter (upper part of the reference) with TSH of 0.50-0.99 mU/liter (lower part of the reference), the odds ratio for hypertension was 1.98 (95% CI 1.56-2.53) in men and 1.23 (95% CI 1.04-1.46) in women. Within the reference range of TSH, we found a linear positive association between TSH and systolic and diastolic blood pressure that may have long-term implications for cardiovascular health.

The Evidence for a Narrower Thyrotropin Reference Range Is Compelling

Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. It has become clear that previously accepted reference ranges are no longer valid as a result of both the development of more highly sensitive TSH assays and the appreciation that reference populations previously considered normal were contaminated with individuals with various degrees of thyroid dysfunction that served to increase mean TSH levels for the group. Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter. The remainder with higher values are outliers, most of whom are likely to have underlying Hashimoto thyroiditis or other causes of elevated TSH. Importantly, data indicating that African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.

The Thyrotropin Reference Range Should Remain Unchanged

Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis. The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease. The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months. About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine. Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr.

Where does subclinical hypothyroidism start?

SummaryThe upper limit of the TSH reference range is currently under discussion. In its recent guidelines, the National Academy of Clinical Biochemistry (NACB) recommended the use of ~2.5 mIU/L, rather than ~4 mIU/L, due to the fact that reference populations, on which the definition of the reference range is based, contain persons undergoing an initial phase of autoimmune thyroid disease. This will skew the upper reference limit of TSH. Ultrasonography, in addition to measurement of thyroid autoantibodies, should be used to exclude these persons. Objective: The present study investigates whether the NACB recommendation also applies for a region of mild iodine deficiency. Methods: According to NACB criteria, a reference population (713 persons) was defined out of a total study population of 1442. The TSH reference range was calculated in this reference group and in further subgroups by percentiles. The results were compared with the total study population and the NACB recommendation. All assays used were provided by BRAHMS Diagnostica AG, Hennigsdorf, Germany. Results: As expected, all median TSH values, excluding the median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The 97.5th percentile in the reference population was 3.35 mIU/L. However, there was no difference compared to the total study population. Conclusion: The upper reference limit for TSH based on a reference population according to NACB criteria came down to 3.35 mIU/L, but not to ~2.5 mIU/L. Interestingly, there is no difference compared to the total study population.

INSULIN RESISTANCE AND BODY MASS INDEX WITH REGARD TO VARIOUS THYROID STIMULATING HORMONE REFERENCE INTERVALS

Objective:Previous studies have shown an association between thyroid function and insulin resistance and obesity. We compared insulin resistance and body mass index (BMI) in patients with normal TSH levels (2.5–4.2 µIU/mL), patients diagnosed with subclinical hypothyroidism, and healthy control subjects.Methods:The study included 104 subjects and was conducted at the Taksim Education and Research Hospital. The subjects were divided into three groups according to TSH levels: Group 1 (high-normal), TSH levels were 2.5–4.2 µIU/mL (n=33); Group 2 (subclinical hypothyroidism), TSH levels were 4.2–10 µIU/mL (n=42); and Group 3 (healthy control), TSH levels were 0.27–2.5 µIU/mL (n=29). The fT3 and fT4 levels were within normal limits in all groups. Insulin resistance and BMI were compared among groups. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin resistance.Results:HOMA-IR and BMI were not significantly different among groups (p>0.05). A significant positive correlation was found between BMI and HOMA-IR in the high-normal TSH (p>0.059) and subclinical hypothyroidism (p>0.05) groups.Conclusions:HOMA-IR and BMI are important for the assessment of diabetes and cardiovascular diseases. We found no significant difference in HOMA-IR and BMI values among the three TSH reference range groups.