Clinical Thyroidology® for the Public

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The association between TSH and depression may not be what you expect

Clinical Thyroidology for the Public

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Common symptoms in patients with hypothyroidism often include fatigue, anxiety, depression and foggy brain. These symptoms are often attributed to thyroid disease if the TSH is even mildly abnormal, especially if it is high (mild hypothyroidism). On the other hand, depression symptoms are less likely to be attributed to low TSH levels (hyperthyroidism). It is clear that thyroid abnormalities with abnormal TSH and abnormal free hormone levels frequently have symptoms such as fatigue, problems with sleep, concentration or memory and weight changes. On the other hand, we do not really have consistent information whether mild thyroid abnormalities with abnormal TSH but normal free hormone levels can cause similar symptoms.

In the past, some studies showed higher risk of depression with low TSH levels and lower risk with high TSH and some did not show any association. The authors designed this study to look for an association between TSH levels and risk of developing depression going forward in a large group of Brazilian adults.

Varella AC et al Thyroid-stimulating hormone levels and incident depression: Results from the ELSA-Brasil study. Clin Endocrinol (Oxf ). Epub 2021 Jan 1. PMID: 33386609.

The study is called the Brazilian Longitudinal Study of Adult Health (Elsa-Brasil). A total of 15,105 civil servants between ages 35 to 74 were enrolled in the study between 2008 and 2010. At baseline, participants completed questionnaires including a well-studied survey called Clinical Interview Schedule-Revised (CIS-R) that was designed to assess mental health disorders across cultures. TSH and free T4 levels were measured at baseline. Participants were classified into categories based on TSH and free T4 levels: overt hyperthyroidism (low TSH, high FT4 or use of thyroid medication), subclinical hyperthyroidism (low TSH, normal FT4 and no use of thyroid medication), euthyroidism (normal TSH and FT4 and use of no thyroid medication), overt hypothyroidism (high TSH, low FT4, or use of levothyroxine) and subclinical hypothyroidism (high TSH, normal FT4 and no use of thyroid medication). The blood tests and surveys were repeated 4 years later at a follow-up visit. Participants who were taking medications that could affect the thyroid function, were undergoing treatment for cancer, or had depression at baseline were excluded.

At baseline, 169 participants (1.4%) had subclinical hyperthyroidism, 677 (5.7%) had subclinical hypothyroidism and 11,050 (92.9%) were euthyroid. At 4 year follow-up visit new onset depression was diagnosed by the CIS-R survey in 445 participants (3.7%). Depression rates were calculated in 5 different TSH ranges, third range (TSH 1.35-1.78 mU/L) was used as the reference range and had 3.4% depression rate. The lowest range (0-0.96 mU/L) had 4.5%, and highest range (2.59-35.5 mU/L) had 3.1%. The participants in the lowest TSH range had significantly higher rate of depression. When the ranges were compared separately in women and men, women in the lower two ranges had significantly higher rate of depression while there was no significant difference in men. Then the researchers analyzed participants with normal thyroid function only and found that even in the normal range lower TSH was significantly associated with new onset depression in women. There was no association with depression by category of thyroid function. There was also no association with clearly high TSH levels above 10 mU/L, and new onset depression, however, there weren’t many participants in this group (36).

The authors conclude that below normal and low-normal TSH levels are associated with risk of developing depression, especially in women. The findings from this study are important and should increase the awareness that mild hypothyroidism is not associated with depressive symptoms in all the studies and the opposite may be true. This knowledge may change the expectation that thyroid hormone therapy should improve the symptoms and the decision whether to use a medication should be made after a careful discussion between the physician and the patient.

— Ebru Sulanc, MD


Euthyroid: a condition where the thyroid gland as working normally and producing normal levels of thyroid hormone.

Overt Hypothyroidism: clear hypothyroidism an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with thyroid hormone pills.

Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not.

Hyperthyroidism: a condition where the thyroid gland is overactive and produces too much thyroid hormone. Hyperthyroidism may be treated with antithyroid meds (Methimazole, Propylthiouracil), radioactive iodine or surgery.

Subclinical Hyperthyroidism: a mild form of hyperthyroidism where the only abnormal hormone level is a decreased TSH.

Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tirosint™ and generic preparations

TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning