MKSAP Quiz: 2-month history of fatigue, cold intolerance
A 35-year-old woman is evaluated for a 2-month history of fatigue, cold intolerance, constipation, and menorrhagia. She has no recent history of iodinated contrast or iodine supplementation. Following a physical exam and lab studies, what is the most appropriate next diagnostic test?
A 35-year-old woman is evaluated for a 2-month history of fatigue, cold intolerance, constipation, and menorrhagia. She has no recent history of iodinated contrast or iodine supplementation. She takes no medications.
On physical examination, other than a pulse rate of 56/min, vital signs are normal. BMI is 22.
The thyroid is firm and diffusely enlarged two times the normal size. Also noted are dry cool skin and dry coarse hair. No thyroid nodules are palpated.
Laboratory studies show a thyroid-stimulating hormone level of 12 μU/mL (12 mU/L).
Which of the following is the most appropriate next diagnostic test?
A. Free thyroxine measurement
B. Free triiodothyronine measurement
C. Thyroid peroxidase antibody titer
D. Thyroid ultrasonography
MKSAP Answer and Critique
The correct answer is A. Free thyroxine measurement. This item is Question 59 in MKSAP 19's Endocrinology and Metabolism section. More information about MKSAP is available online.
The most appropriate diagnostic test to perform next is free thyroxine (T4) measurement (Option A). This patient presented with classic symptoms of hypothyroidism: fatigue, cold intolerance, constipation, and dry skin and hair. Her physical examination is notable for bradycardia and a goiter. The thyroid-stimulating hormone (TSH) level is elevated, suggestive of primary hypothyroidism. The diagnosis of primary hypothyroidism is made by measuring serum TSH, and if elevated, measuring free T4. Serum TSH is elevated in both overt and subclinical hypothyroidism, but free T4 is normal in subclinical hypothyroidism and low in hypothyroidism. The free T4 result will confirm hypothyroidism and the need for thyroid hormone replacement.
Although triiodothyronine (T3) is the active hormone producing thyroid action in the body, free T3 measurement (Option B) is unnecessary for diagnosing hypothyroidism. Free T3 levels are variable and the product of deiodination of T4; their levels may be misleading because many drugs (e.g., amiodarone) and physiologic states (fasting and illness) may cause free T3 to be low in conditions of normal thyroid function. Measurement of T3 is recommended in three settings: (1) in the evaluation of thyrotoxicosis to identify isolated T3 toxicosis; (2) to assess the severity of hyperthyroidism and response to therapy; and (3) to potentially differentiate hyperthyroidism from destructive thyroiditis. In T3 toxicosis, the T3-to-T4 ratio is often greater than 20 because of preferential secretion of T3.
A thyroid peroxidase (TPO) antibody titer (Option C) is unnecessary unless the diagnosis of hypothyroidism is unclear. The most common cause of primary hypothyroidism is Hashimoto thyroiditis, which is an autoimmune thyroid disorder characterized by diffuse infiltration of the thyroid gland by lymphocytes and plasma cells with subsequent follicular atrophy and scarring. It is more common in patients with other autoimmune disorders or a family history of thyroid autoimmunity. Diffuse goiter is most common in younger patients. Most patients (90%) have TPO antibodies, and the risk for developing hypothyroidism is four times higher in euthyroid patients with TPO antibodies.
Thyroid ultrasonography (Option D) is useful in evaluating goiters associated with normal TSH levels. It is also recommended for patients with Graves disease or Hashimoto thyroiditis in cases of thyroid gland asymmetry or nodules on examination. Because this patient has neither thyroid gland asymmetry nor nodules, ultrasonography is not indicated.
Key Points
- The diagnosis of primary hypothyroidism is made by measuring serum thyroid-stimulating hormone and free thyroxine.
- A thyroid peroxidase antibody titer is unnecessary in the evaluation of hypothyroidism.