HYPOTHYROIDISM
Background
The thyroid gland is a butterfly-shaped endocrine organ that is located in the lower front of the neck. The thyroid’s job is to make thyroid hormones, which are secreted into the blood and then carried to every tissue in the body. Thyroid hormones help the body use energy, stay warm and keep the brain, heart, muscles and other organs working properly.
A hormone released by the hypothalamus (thyrotropin-releasing hormone) leads to the secretion of thyroid‑stimulating hormone (TSH) from the anterior pituitary gland. TSH stimulates the synthesis of thyroglobulin, the precursor to thyroid hormones, liothyronine (T3) and levothyroxine (T4), in the thyroid gland. T3 and T4 are secreted by the thyroid gland into the blood. T4 is converted in tissues to T3 by a class of enzymes (deiodinases). Although the thyroid gland produces both T3 and T4, T3 is the more pharmacologically active hormone.
Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Diagnosis of hypothyroidism is based on a combination of symptoms (e.g., fatigue and weight gain) and the results of blood tests that measure the level of TSH and sometimes the levels of the thyroid hormones T3 and/or T4. Since the pituitary gland produces more TSH in response to deficient thyroid hormone levels, a high level of TSH indicates hypothyroidism.
Common causes of hypothyroidism are autoimmune disease, such as Hashimoto’s thyroiditis (approximately 2 out of 3 cases [Carle 2006, Diez 2002, Tariq 2018]), surgical removal of the thyroid and radiation treatment. Other causes include congenital (from birth) hypothyroidism, thyroiditis, certain medicines (e.g., lithium, amiodarone, interferon alpha and interleukin-2), too little or too much iodine and damage to the pituitary gland.
Hypothyroidism is associated with a wide range of signs and symptoms (see image below):
Nearly 1 out of 20 individuals 12 years and older in the US suffer from hypothyroidism (National Institutes of Health 2021). Women are 5 to 8 times more likely than men to have thyroid problems (American Thyroid Association 2021).
Current Treatments
Currently, there are 3 types of prescription medications available in the US for the treatment of hypothyroidism:
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Levothyroxine (brand name Synthroid), or synthetic T4, is the standard, FDA-approved, first-line treatment for hypothyroidism
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Liothyronine (brand name Cytomel), or synthetic T3, is an FDA-approved treatment that is sometimes used as an adjunct to levothyroxine
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Desiccated thyroid extract, or DTE (brand names Armour Thyroid and NP Thyroid) is a natural source of thyroglobulin, T3 and T4 derived from porcine thyroid glands
For many patients, the level of satisfaction with the standard, first-line treatment for hypothyroidism is low, which underscores the need for novel therapies. According to a recently published survey of 11,166 patients conducted by program committee members of the Satellite Symposium on Hypothyroidism organized by the American Thyroid Association (ATA) (Peterson 2018):
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Patients taking levothyroxine monotherapy rated their satisfaction with treatment a median of 5 on a 10-point scale
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Patients taking levothyroxine plus liothyronine rated their satisfaction with treatment a median of 5 on a 10-point scale
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Patients taking DTE rated their satisfaction with treatment a median of 7 on a 10-point scale
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The majority of patients indicated that there was a strong need for new treatments for hypothyroidism
