Hypothyroidism II: Pathophysiology

Hypothyroidism is a disorder characterized by insufficient production of thyroid hormones, which regulate metabolism, energy balance, and multiple organ systems.

Types

Hypothyroidism is classified based on the level of dysfunction. Primary hypothyroidism results from intrinsic thyroid gland dysfunction, causing reduced hormone production despite normal or increased stimulation. Secondary hypothyroidism arises from inadequate thyroid-stimulating hormone (TSH) secretion by the pituitary. Tertiary hypothyroidism is due to deficient thyrotropin-releasing hormone (TRH) from the hypothalamus. Secondary and tertiary forms are collectively referred to as central hypothyroidism.

Pathophysiology of Hypothyroidism

Primary hypothyroidism is the most common form, where reduced thyroid hormone (T4 and T3) levels stimulate increased TSH and TRH release from the pituitary and hypothalamus, respectively. Causes include Hashimoto thyroiditis, thyroidectomy, radioactive iodine therapy, medications (lithium, amiodarone, propylthiouracil), and iodine deficiency. It is characterized by high TSH and low T4.

Secondary hypothyroidism occurs when the pituitary fails to secrete adequate TSH, leading to reduced thyroid stimulation and low levels of both TSH and thyroid hormones. Causes include pituitary tumors, trauma, surgery, radiation, and genetic defects affecting TSH production. TSH may appear normal, but is inappropriately low relative to reduced thyroid hormone levels, making diagnosis challenging.

Tertiary hypothyroidism (Hypothalamic dysfunction) results from insufficient TRH production by the hypothalamus, reducing pituitary TSH release and thyroid hormone synthesis. Causes include hypothalamic tumors, trauma, infiltrative diseases, and congenital TRH deficiency. TSH may be normal or slightly elevated but biologically inactive, and a delayed response to TRH stimulation testing may help confirm the diagnosis.