The Challenges and Complexities of Thyroid Hormone Replacement

Shayri M. Kansagra, BS; Christopher R. McCudden, PhD; Monte S. Willis, MD, PhD


Lab Med. 2010;41(6):229-348. 

In This Article

Diagnosis and Pathophysiology of Hypothyroidism

Hypothyroidism is defined as the deficient production of thyroid hormones from the thyroid gland. Hypothyroidism is broadly classified as a primary, secondary, or tertiary disease depending on the underlying cause. In primary disease there is impaired hormone release from the thyroid gland; in secondary disease, there is defective TSH signaling from the pituitary; in tertiary or central disease, the hypothalamus fails to stimulate thyroid hormone release.[20] Hypothyroidism ranges in severity from subclinical disease, where patients may be asymptomatic, to full blown clinical disease, where patients are severely affected in the presence of multiple laboratory abnormalities.[21]

Because of the range of symptom severity and the relatively common and non-specific nature of clinical findings, diagnosis of hypothyroidism is highly dependent on laboratory testing. The frontline laboratory test for hypothyroidism is thyroid-stimulating hormone (TSH). TSH is elevated in primary hypothyroidism as the pituitary responds to the relative lack of circulating T3 and T4; TSH is abnormal in all clinical and subclinical cases of primary hypothyroidism.[21] As the disease progresses toward clinical or overt hypothyroidism, T4 and T3 become measurably decreased.[21] In secondary and tertiary hypothyroidism, TSH, T4, and T3 levels are variably abnormal depending on the duration, cause, and severity of disease. As a result of the complexity of hypothyroid etiology, laboratory testing for hypothyroidism is complex and beyond the scope of this review.[22]

In the Western world, the most common cause of hypothyroidism is Hashimoto's thyroiditis,[23] where autoantibodies promote destruction of thyroid tissue. Several other common causes of primary hypothyroidism are the result of treatment for thyroid hormone excess (hyperthyroidism) including radioablation or surgical thyroidectomy.[24–26] Irrespective of the individual pathophysiology, treatment of hypothyroidism involves thyroid hormone replacement.