A 30-year-old woman comes to the office due to excessive weight gain without any changes in her diet or physical activity. She has also been feeling more tired lately and has had frequent constipation. The patient has no prior medical problems and takes no medications. She has been pregnant once and gave birth to a healthy infant 3 years ago. Family history is significant for a thyroid disorder in her mother. Blood pressure is 116/90 mm Hg and pulse is 58/min. BMI is 28.5 kg/m2. Physical examination reveals a diffusely enlarged and nontender thyroid with no nodules. There is delayed relaxation of deep tendon reflexes. Her hair is thin and the skin appears dry. Which of the following sets of laboratory findings is most likely to be seen in this patient?
Show Explanatory Sources
Regulation of thyroid hormone secretion involves feedback inhibition along the hypothalamic-pituitary-thyroid axis. The hypothalamus releases thyrotropin-releasing hormone (TRH), which triggers release of TSH from the pituitary. TSH stimulates secretion of thyroid hormone from the thyroid, which in turn inhibits release of both TRH and TSH. Thyroid hormone exists in 2 primary forms: T4 (thyroxine), the predominant form secreted by the thyroid, and T3 (triiodothyronine), the more active form produced mainly by deiodination of T4 in peripheral tissues.
This patient has a very typical presentation of primary hypothyroidism with weight gain, fatigue, and a delayed relaxation phase of deep tendon reflexes. Her diffuse goiter suggests chronic autoimmune (Hashimoto) thyroiditis, which is the most common cause of hypothyroidism in developed countries. As autoimmune destruction of the gland progresses, thyroid hormone production declines, leading to loss of feedback inhibition of TSH secretion; therefore, patients have low T4 and elevated TSH levels. However, because T3 is produced mainly in peripheral tissues and has a short half-life, serum T3 levels fluctuate widely and correlate poorly with clinical status; T3 is often normal in primary hypothyroidism.
(Choice B) TSH secretion is very sensitive to changes in thyroid status and rises in response to even small declines in thyroid hormone production. Subclinical hypothyroidism is a common biochemical state in which an elevated TSH is necessary to maintain normal thyroid hormone levels. However, most patients are asymptomatic.
(Choices C, E, and F) Primary hyperthyroidism (eg, Graves disease) is characterized by elevated thyroid hormone levels and suppressed TSH. Subclinical hyperthyroidism is characterized by suppressed TSH with normal thyroid hormone levels. Central (secondary) hyperthyroidism (eg, TSH-secreting pituitary adenoma) shows elevated levels of both TSH and thyroid hormone. Common clinical features of hyperthyroidism (primary or secondary) include weight loss, heat intolerance, and tachycardia; patients with subclinical hyperthyroidism may be asymptomatic or have mild symptoms. T3 levels correlate with clinical status in hyperthyroidism more closely than in hypothyroidism and are often elevated.
(Choice D) Euthyroid sick syndrome is a constellation of abnormal thyroid tests seen in patients with severe systemic illness (eg, sepsis). Excess cortisol, inflammatory cytokines, starvation, and certain medications (eg, amiodarone) can cause reduced conversion of T4 to T3, leading to low serum T3; reverse T3 (the inactive metabolite of T4) is typically elevated but TSH and T4 are usually normal.
Educational objective:
Primary hypothyroidism is characterized by decreased T4 levels and increased TSH. T3 is primarily produced by conversion from T4 in peripheral tissues; serum levels widely fluctuate due to its short half life, and can often be within the normal range in patients with hypothyroidism.