Thyroid Function and Autoimmunity: Impact on Health and Management of Hypothyroidism

Thyroid hormones are pivotal in fetal development and maintaining normal organ functions later in life. Thyroid hormones are key components in regulating vital processes within the cells, such as energy expenditure and oxidative metabolism. A deficit of thyroid hormones may, therefore, have serious consequences. The most common cause of hypothyroidism is autoimmune thyroiditis, which is characterized by thyroid peroxidase antibodies (TPOAb) in the blood. Previous reports suggest that thyroid autoimmunity per se may impact health and fetal neurodevelopment, even in the absence of thyroid hormone aberrations.

Previous studies, with different designs, evaluated the effect of maternal thyroid autoimmunity and thyroid hormones on fetal neurodevelopment, with conflicting results. In Paper 1, we investigated whether maternal thyroid autoimmunity and thyroid function in the first trimester in euthyroid pregnant women were associated with early language development in the offspring. We included 735 mother-child pairs from the Odense Child Cohort. Language acquisition was assessed with MacArthur Bates Communicative Development Inventories (MBCDI) every third month when the child was 12 to 36 months. The study showed that offspring from TPOAb-positive mothers had a lower productive vocabulary than offspring from TPOAb-negative mothers. The thyroid function did not mediate these results, as low-normal free thyroxine tended to be associated with a better productive vocabulary.

Oxidative stress is an imbalance between prooxidants and antioxidants, with a preponderance of prooxidants leading to a disturbance of redox control and signaling, which causes molecular damage. Previous studies suggest that oxidative stress may be increased in hypothyroid patients. Paper 2 investigated the whole-body oxidative stress burden in hypothyroid patients. The urinary excretion of 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8- dihydro-2’-deoxyguanosine, representing whole-body RNA and DNA oxidation, was measured in forty-five women with autoimmune thyroiditis before and after treatment with levothyroxine, and in eighteen matched and healthy control women. The excretion rates of the oxidative stress biomarkers did not differ significantly before and after treatment with levothyroxine. Interestingly, the levels of both biomarkers were significantly higher in the levothyroxine-treated euthyroid patients compared to controls.

Standard therapy for hypothyroidism is levothyroxine, but regimens with levothyroxine/liothyronine combination or desiccated thyroid extract are also available. In Paper 3, we conducted a questionnaire survey among Danish endocrinologists on their use of thyroid hormone substitutions available for treatment of euthyroid and hypothyroid patients. Approximately 31% of the members of the Danish Endocrine Society (DES) responded to the questionnaire. The vast majority used levothyroxine as the first-choice treatment for hypothyroid patients. Combination therapy with levothyroxine/liothyronine was mainly considered for patients with persistent symptoms on levothyroxine. Only a few respondents would consider desiccated thyroid extract for hypothyroid patients, but never as the first choice. More than half of the participants indicated that thyroid hormone substitutions should not be used in euthyroid patients, while 42% would consider thyroid hormones for euthyroid infertile women with thyroid autoimmunity.

In Paper 4, we conducted a review of the potential risks and benefits of treatment with desiccated thyroid extract. The limited use of desiccated thyroid extract among Danish endocrinologists is justified by previous studies showing no superiority of desiccated thyroid extract - in terms of quality of life, memory assessment, symptoms of hypothyroidism or depression - as compared to either levothyroxine or levothyroxine/liothyronine combination treatment. The available literature on desiccated thyroid extract could not elucidate the long-term consequences of desiccated thyroid extract use. Still, previous reports suggest a negative impact on the cardiovascular system.