Thyroid hormones are key to everyday health.
Abnormal thyroid levels can have serious consequences on metabolism, growth, and development.
Overt hypothyroidism and hyperthyroidism are common thyroid disorders that occur due to abnormal levels of TSH (also called thyroid-stimulating hormone or thyrotropin).
The risk of these disorders during lifetime are quite high, especially in senior population.
In one study from Denmark, the overall risk of overt hypothyroidism or hyperthyroidism diagnosis–over the lifetime–was 9.2% (Carle’ 2006).
The risk among women was much higher at 14.6% in comparison to the risk in men at 3.7%. The risk for US, Europe, and countries with no iodine deficiency in the population should be similar.
Source: Epidemiology of sub-types of hypothyroidism in Denmark by Allan Carlé and others in European Journal of Endocrinology, vol. 154 (1), 2006.
What are normal TSH levels?
Ranges of normal TSH levels and other key thyroid hormones including TPO antibodies:
The TSH distribution in healthy population is an almost bell curve (but non-Gaussian distribution—not symmetric). It skews towards the higher TSH levels. Data for 1,671 healthy Danish women are
plotted in the figure below.
Healthy values fall between 0.1 mIU/L and 4.5 mIU/L. These are between 2.5th and 97.5th percentile (±3 standard deviation). Which means 95% of the population has thyroid levels in this range. However, variations occur due to age, gender, race, and iodine
Source: Lower prevalence of mild hyperthyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme by Vejbjerg & others, in Clinical Endocrinology, Vol 71 (3) 2009.
What are the reasons for high TSH levels?
Several factors affect TSH levels. Problems with the hypothalamus, pituitary, or thyroid gland can cause abnormal TSH levels.
Here are few other common factors that can also affect TSH levels:
How sleep affects TSH levels?
- Plot below shows TSH levels vary in two different cyclical patterns (Weeke and Gundersen 1978). T3—and even T4 to a less extent—follows similar trend.
- TSH increases by almost 150% in the night during sleep, compared to day time. The levels slowly decrease after waking up. However, results can vary significantly depending on the time of sample collection. This relatively stable 24 hour period is called diurnal (daily) rhythm.
- The pituitary gland releases TSH in short pulses. Levels rise by about 10-15% every 30 minutes. The peaks of these pulses are higher during sleep in comparison to day time.
- Insufficient sleep may disrupt this natural rhythm resulting in above normal TSH levels in the morning.
- This is one reason why night shift workers and those with abnormal circadian rhythm may observe unexpected TSH results from their tests.
Source: Circadian and 30 Minutes Variations in Serum TSH and Thyroid Hormones in Normal Subjects by Weeke and Gundersen inActa Endocrinol (Copenh), 1978, Vol. 89(4), pages 659‐672.
How pregnancy affects TSH levels?
- Pregnancy hormone, hCG (human chorio-gonadotropin) weakly stimulates the thyroid (as hCG is structurally similar to TSH).
- As hCG levels rise, TSH levels drop, especially in very early stage of pregnancy.
- Therefore, trimester specific ranges of TSH (and T3, T4) should be used by labs to test pregnant women (Laurberg 2011).
- Adequate TSH is important for fetal development and normal pregnancy.
Trend of mother’s hormone levels during pregnancy (plotted by week)
Sources: Thyroid disease in pregnancy: new insights in diagnosis and clinical management by Korevaar and others in Nature Reviews Endocrinology, 2017, Vol. 13, pages 610–622.
How illness and medication affect TSH levels?
- Illness may affect functions of hypothalamus, pituitary and thyroid glands. This may result in lower TSH in body.
- Medication to illness might also affect TSH levels.
- During recovery from illness, levels might temporarily spike as thyroid stabilizes.
- Obesity and overfeeding increases pituitary and thyroid function. This may result in higher TSH (Laurberg 2011).
- Always ask the lab for healthy range of your test. This is the range you should monitor since values vary as part of the normal sample processing.
How age affects TSH levels?
- TSH rises with age. The correlation between age and TSH is almost linear (Hollowell 2002).
- The risk of thyroid problems among 80+ year old is almost 5-times those below 50. This holds despite gender, race, and geography affecting TSH levels.
- In almost every age group, women tend to have higher TSH values than men.
- The risk of abnormal TSH is highest in older women and lowest among most men.
TSH levels continuously increase with age.
Source: National Health and Nutrition Examination Survey (NHANES III): Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994) by Hollowell and others in The Journal of Clinical Endocrinology & Metabolism, Vol. 87(2) 1 February 2002, Pages 489–499.
What happens if your TSH levels are high?
- High TSH is likely sign of an under-active thyroid gland. It is forcing the pituitary gland to release more TSH, a condition known as hypothyroidism.
- TSH values over 10 mIU/L is overt or clinical hypothyroidism. Studies show it results in higher levels of cholesterol—both total and low-density cholesterol (Mason 1930).
- Mildly elevated TSH (above 4.5 mIU/L) is a known risk factor for future overt hypothyroidism.
There is a general belief that the slow increase in TSH with age is not harmful and might help in longevity despite somecardiovascular risk (Atzmon 2009,
Rozing 2010, Gussekloo 2004).
What happens if TSH levels are low?
- Low TSH is an indication of hyperthyroidism. It is likely sign of an overactive thyroid gland that is producing high levels of thyroid hormones, T4 and T3 (Pantalone and Nasr 2010).
- Abnormally low (less than 0.1 mIU/L) TSH levels are almost always an indication of overt (or clinical) hyperthyroidism (Helfand 2004).
- Elevated T4 and T3 with abnormally low TSH may indicate nodular thyroid disease or an autoimmune Grave’s disease.
There is good evidence that undetectable low TSH levels (less than 0.1 mIU/L) increase the risk of atrial fibrillation later in life (Helfand 2004). These
are associated with higher probability of stroke. In one study of those older than 60 years, the risk of atrial fibrillation over 10 years was around 32% in comparison to 8% in people with healthy TSH (Sawin 1994).
Some studies suggest low TSH levels result in loss of bone mineral density and bone fracture. However, this seems true only for vertebral fracture. Data do not suggest any correlation to hip fracture (Helfand 2004).
The Cleveland Clinic Journal of Medicine recommends that low TSH levels (0.1 – 0.4 mIU/L) should always follow a measurement of T4 and T3. They should be re-checked within few weeks to
unambiguously confirm the results and to avoid potential variation due to one-off event.
What are the symptoms of high TSH levels?
Well known symptoms of high TSH levels include:
- Cold intolerance (compared to those around you)
- Weight gain
- Loss of appetite
- Low energy and weakness
- Coarse dry hair
- Dry rough skin
- Fatigue (which can happen with both low and high TSH values)
What are the symptoms of low TSH levels?
Common symptoms of low TSH levels include:
- Heat intolerance (compared to those around you)
- Difficult sleeping or insomnia
- Unusually high appetite and weight loss
- Fatigue (which can happen with both low and high TSH)
How TSH affects weight loss and BMI?
Measurement of TSH from samples collected by the famous Framingham Heart Study shows a linear correlation between weight gain and above normal TSH levels. Women show even larger weight gain with TSH.
Source Relations of Thyroid Function to Body Weight – Cross-sectional and Longitudinal Observations in a Community-Based Sample by Caroline Fox and others inArchives of Internal Medicine, Vol 168 (6), MAR 24, 2008.
Chart below shows an average weight gain after 6-months of testing. Weight increases almost linearly with higher TSH levels. Similar gains have been reported after 5 years, except for those with values above 3.6 mU/L—they gained over 10 lbs.
Source: Small Differences in Thyroid Function May Be Important for Body Mass Index and the Occurrence of Obesity in the Population by Nils Knudsen and others inThe Journal of Clinical Endocrinology & Metabolism, Volume 90 (7), July 2005, Pages 4019–4024.
Why a TSH test alone is not enough?
Thyroid health is determined by the hypothalamus-pituitary-thyroid (HPT) axis. One gland might compensate for abnormality of another gland, to maintain a balanced cycle.
For example, if thyroid gland cannot release enough T4, the pituitary gland will release more TSH to compensate and balance T4 levels. Therefore, knowing TSH values alone might not be sufficient for a full diagnosis.
There is well known age correlation to TSH, with levels increasing over age. But T4 values do not show age correlation. With advancing age, there is a lower pituitary response to thyroid function which TSH test alone might not capture.
If TSH values are abnormal, one should check T4 and T3 for thyroid dysfunction. Also, checking for TPO antibodies can help assess the presence of autoimmune thyroid disease (Glinoer and Spencer 2010).
Autoimmune diseases–and presence of TPO antibodies–in certain groups can be very high, e.g., elderly white women have a rate of almost 50% positivity (Laurberg 2011) and those aged 55+ year with TSH above 4.5 mIU/L have a rate of
36-76% (Boelaert 2013).
In certain cases, e.g., in pregnancy, a combination of thyroid dysfunction and TPO antibodies positivity may predict pregnancy complications and maternal morbidity in in later life (Männistö’ 2010).
What to know about repeat TSH testing?
If TSH levels are outside normal range, a repeat test is very useful. In one study, repeat of 400k patients after 5 years suggested only 2% developed abnormal levels, and 50% of those with abnormal levels tested within healthy levels (Meyerovitch 2007).
- How do you know the measured high TSH levels were not a random event? Analytical studies suggest a deviation of over 40% from your last measurement is not a random event (Karmisholt 2010).
- Mean values of healthy TSH in a person are mostly determined by their genetics. However, environmental factors can affect them considerably (e.g., iodine content in food).
- The TSH variation is much narrower for individual person in comparison to population variation (50% tighter variation compared to data for large population).
- TSH is the most sensitive indicator of thyroid gland function when pituitary-hypothalamus function is healthy. For example, a 30% reduction in T4 results in a 6-x increase in TSH (Eisenberg 2009).
- The TSH upper reference limit: where are we at? by P. Lauerber et al., Nature Reviews Endocrinology 7, p.232-239 (2011)
- Approach to a low TSH level: Patience is a virtue by K. Pantalone and C. Nasr, Cleveland Clinic Journal of Medicine, 77 (2010)
- Serum TSH determinations in pregnancy: how, when and why? by D. Glinoer and C. Spencer, Nature Reviews Endocrinology 6, p.526–529 (2010)
- Circadian and 30 minutes variations in serum TSH and thyroid hormones in normal subjects by J. Weeke and H. Gundersen, European Journal of Endocrinology 89(3), p.659-672 (1978)
- Serum Thyrotropin Measurements in the Community by Meyerovitch et al., Arch Intern Med. 167(14), p.1533-1538 (2007)
- Screening for Subclinical Thyroid Dysfunction in Nonpregnant Adults: A Summary of the Evidence for the U.S. Preventive Services Task Force by M. Helfand, Ann Intern Med. 140, p.128-141 (2004)