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MKSAP Quiz: fatigue, constipation, and cold intolerance

A 54-year-old man is evaluated because of fatigue. He also notes constipation and cold intolerance. Medical history is significant for tonsillar squamous cell carcinoma treated with radiation 3 years ago. There is no family history of thyroid disorders. Following a physical exam and lab studies, what is the most appropriate next step in management?


A 54-year-old man is evaluated because of fatigue. He also notes constipation and cold intolerance. Medical history is significant for tonsillar squamous cell carcinoma treated with radiation 3 years ago. There is no family history of thyroid disorders.

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On physical examination, the skin is dry. Mild periorbital edema is present. The thyroid is of normal size and without nodules. Reflexes are delayed.

Laboratory studies show a hemoglobin level of 11 g/dL (110 g/L), a serum sodium level of 129 mEq/L (129 mmol/L), and a serum thyroid-stimulating hormone (TSH) level of 1.4 µU/mL (1.4 mU/L).

Which of the following is the most appropriate next step in management?

A. Free thyroxine (T4) measurement
B. Repeat TSH measurement in 4 weeks
C. Thyroid scintigraphy
D. Thyroid ultrasound

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A: Free thyroxine (T4) measurement. This item is available to MKSAP 17 subscribers as item 36 in the Endocrinology & Metabolism section. More information is available online.

Measurement of the serum free thyroxine (T4) level is the most appropriate next step in management for this patient who has clinical evidence of hypothyroidism (fatigue, constipation, cold intolerance, dry skin, delayed reflexes, anemia, and mild hyponatremia) but has had radiation to the base of the skull, including the pituitary gland. Although measurement of thyroid-stimulating hormone (TSH) is the most accurate reflection of thyroid status in patients with an intact hypothalamic-pituitary-thyroid axis, it is not a reliable measure of thyroid function in patients in whom there is loss of hypothalamic-pituitary function, such as seen in this patient. His low-normal TSH in the context of clinical hypothyroidism suggests possible central hypothyroidism, and measurement of the circulating level of thyroid hormone, the free serum T4, would therefore be a more accurate indication of his thyroid status.

Repeating the TSH measurement would not be appropriate in this patient with signs and symptoms of hypothyroidism, as untreated hypothyroidism leads to increased cardiovascular morbidity and mortality. In addition, because of likely central hypothyroidism, the TSH level would remain an inaccurate indicator of thyroid function.

Thyroid scintigraphy is unlikely to distinguish the source of the hypothyroidism, as patients with primary or secondary hypothyroidism have decreased radioactive uptake. Thyroid scanning is most helpful in elucidating the cause of hyperthyroidism.

Ultrasound of the neck is normal in patients with central hypothyroidism and would be unlikely to provide any additional information about this patient's thyroid status.

Key Point

  • When central hypothyroidism is suspected, measurement of the serum free thyroxine (T4) level is essential.