A 55-year-old woman comes to the office due to increasing fatigability and a 4.54-kg (10-lb) weight gain over the last few months. The patient used to swim daily but now does so only once or twice a week due to fatigue. She takes a daily multivitamin and an over-the-counter medication for constipation. Blood pressure is 140/96 mm Hg and pulse is 55/min. Physical examination shows hair loss involving the lateral third of the eyebrows. There is delayed relaxation of the deep tendon reflexes of the knee and ankle. Which of the following laboratory tests is the most appropriate next step in evaluation of this patient's symptoms?
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This patient's symptoms (eg, fatigue, weight gain, constipation) and examination findings suggest hypothyroidism. Vital signs typically show bradycardia and hypertension (due to increased vascular resistance). Hypothyroidism can also cause slowed hair growth and alterations in hair growth cycles, leading to thinning of the scalp hair and lateral eyebrows. Slowed reuptake of calcium by the sarcoplasmic reticulum manifests as a delayed relaxation phase of deep tendon reflexes.
Most patients with hypothyroidism have primary hypothyroidism (ie, dysfunction within the thyroid gland). The thyroid releases thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) in response to TSH from the pituitary. In turn, TSH secretion is regulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. Thyroid hormone suppresses TSH and TRH via negative feedback, and small changes in thyroid hormone levels lead to large changes in TSH levels. As thyroid hormone production slows, TSH secretion increases rapidly to restore thyroid activity, often before T4 levels fall below standard laboratory reference ranges. Therefore, serum TSH is the most sensitive marker for primary hypothyroidism.
(Choices A and B) The 24-hour urinary cortisol assay and the dexamethasone suppression test are used to screen for Cushing syndrome. Although this patient is hypertensive, she does not have other Cushingoid features (eg, central obesity, skin striae, proximal muscle weakness).
(Choice C) Initial tests for diabetes mellitus include fasting glucose, hemoglobin A1c, and oral glucose tolerance tests. Diabetes can cause peripheral neuropathy (eg, paresthesias, loss of distal sensation, decreased ankle reflexes), but bradycardia, diastolic hypertension, and delayed relaxation of reflexes are more suggestive of hypothyroidism.
(Choice D) The initial evaluation of hereditary hemochromatosis includes serum iron studies (eg, serum iron, ferritin, transferrin saturation). Although pituitary dysfunction with secondary (central) hypothyroidism can occur, patients commonly also have arthritis, diabetes mellitus, abnormal skin pigmentation, and hepatomegaly.
(Choice E) TSH is more sensitive than either T3 or T4 for diagnosing primary hypothyroidism. TSH is not elevated in pituitary or hypothalamic disease (ie, secondary hypothyroidism), but this is a much less common cause of hypothyroidism (<5% of cases). In addition, patients with secondary hypothyroidism usually have other clinical features of hypothalamic or pituitary dysfunction.
Educational objective:
The thyroid releases thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) in response to TSH from the pituitary, which is regulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. Thyroid hormone suppresses the secretion of TSH and TRH via negative feedback, and small changes in thyroid hormone levels cause large changes in TSH. Serum TSH is the most sensitive test for primary hypothyroidism.