Thyroid autoimmunity affects cognitive and emotional function

Thyroid autoimmunity (autoimmune thyroiditis, Hashimoto's disease) in overt and subclinical hypothyroid manifestations is rampantly common. A paper just published in the journal Brain, Behavior, and Immunity reports that thyroid autoantibodies can cause cognitive and affective function even when the thyroid hormone levels are still normal. The authors state:

"Hashimoto’s thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state."

In other words, the studies mentioned have pointed out the association between the presence of thyroid antibodies (loss of immune tolerance for thyroid tissue) with cognitive and affective disorders even when the thyroid hormone levels have not yet become abnormal.Moreover...

"Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto’s encephalopathy (HE)."

This is, of course, an expression of autoimmunity:

"The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system."

Clinical note: Rarely is there only one tissue target in autoimmunity. Anti-brain antibodies seem to be appearing more frequently and should be screened in suspicious cases.

"In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits."

Bottom line: Autoimmune thyroiditis is "associated with cognitive and affective disorders also in the euthyroid [normal thyroid hormone level] state. Thereby thyroid antibodies might play a direct role or indicate an autoimmune process." And this just in...a study hot of the presses of The Journal of Clincial Endocrinology & Metabolism that also documents the association of depression with the so-called 'normal thyroid' state:

"Overt hypo- and hyperthyroidism are associated with an increased risk of depression. Little is known about the effects of variation in thyroid function within the normal range on the risk of depression...The objective of the study was to examine the association between normal-range thyroid function and the risk of depression."

The authors examined serum TSH, thyroperoxidase antibody levels, and symptoms of depression in 1503 Dutch men and women around the age of 70 over eight years and found a significant association:

"Cross-sectionally, persons in the lowest TSH tertile (0.3–1.0 mU/L) had more depressive symptoms as well as an increased risk of a CES-D [Center for Epidemiologic Studies Depression Scale] of 16 or greater compared with persons in the highest normal range TSH tertile (1.6–4.0 mU/L). In the prospective analyses, persons in the lowest TSH tertile who were depression free at baseline had a higher risk of incident depressive syndromes."

Clinical note: This study reports an association of depression with low TSH—the implication is 'subclinical primary/central hypothyroid' in which chronic low grade inflammation or other factors result in reduced pituitary stimulation of thyroid function (lower TSH). I am seeing this with disconcerting frequency on lab tests in clinically relevant situations. These levels of TSH should not be ignored in practice.