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MKSAP Quiz: Sleeplessness in patient with panhypopituitarism

A 28-year-old woman is evaluated for a 2-month history of sleeplessness. She has had panhypopituitarism since surgery for a craniopharyngioma at age 15 years. Medical history includes hypoadrenalism, hypogonadism, and hypothyroidism. Following a physical exam, what is the most appropriate management?


A 28-year-old woman is evaluated for a 2-month history of sleeplessness. She has had panhypopituitarism since surgery for a craniopharyngioma at age 15 years. Medical history includes hypoadrenalism, hypogonadism, and hypothyroidism. She is taking estrogen, progesterone, hydrocortisone, and levothyroxine.

On physical examination, vital signs are normal. A small atrophic thyroid is noted; her hands are warm and dry, and no lower extremity edema or tremor is evident.

A thyroid-stimulating hormone level mistakenly obtained at her last office appointment was less than 0.01 μU/mL (0.01 mU/L).

Which of the following is the most appropriate management?

A. Free thyroxine measurement
B. Levothyroxine discontinuation
C. Thyroid scintigraphy with radioactive iodine uptake
D. Thyroid-stimulating immunoglobulin measurement

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A. Free thyroxine measurement. This content is available to MKSAP subscribers as Question 45 in the Endocrinology and Metabolism section. More information about MKSAP is available online.

The most appropriate management is free thyroxine (T4) measurement (Option A). Measuring serum thyroid-stimulating hormone (TSH) alone is sufficient to monitor thyroid replacement therapy in most patients, but not in patients with central hypothyroidism, for whom free T4 measurement is the laboratory test of choice. In patients with panhypopituitarism, deficiency of TSH results in the inability of the thyroid gland to produce T4. The result is insufficient T4 production with low or inappropriately normal TSH. Because TSH cannot be used to monitor therapy, it should not be measured. In patients with central hypothyroidism, dosing based on TSH level can lead to underdosing. Free T4 should be used to monitor dose adequacy and should be maintained in the mid to upper half of the normal range. In primary hypothyroidism, the time range is 6 to 8 weeks for TSH to accurately reflect thyroid hormone status, whereas in secondary hypothyroidism, free T4 levels can be checked 2 to 3 weeks after a dose change to assess for adequacy.

In patients with normal pituitary function, an undetectable TSH in a patient taking levothyroxine suggests overtreatment and the need for levothyroxine discontinuation (Option B). However, this patient has panhypopituitarism with central hypothyroidism, and thus TSH is an unreliable measure of thyroid function. T4 measurement should guide levothyroxine replacement in patients with central hypothyroidism.

Thyroid scintigraphy with radioactive iodine uptake (RAIU) (Option C) would be helpful to assess thyrotoxicosis unless contraindicated, such as during pregnancy or lactation. Although this patient has no apparent contraindication to thyroid scintigraphy, she is taking levothyroxine, which decreases RAIU uptake; therefore, scintigraphy with RAIU will have limited usefulness in the event that thyrotoxicosis is diagnosed in this patient.

Thyroid-stimulating immunoglobulin (TSI) measurement (Option D) is useful to assess thyrotoxicosis when RAIU is unavailable or unreliable or when thyroid scintigraphy is contraindicated. However, because thyrotoxicosis has not been established in this patient, there is no indication for TSI measurement.

Key Points

  • Measuring serum thyroid-stimulating hormone alone is sufficient to monitor thyroid replacement therapy except in central hypothyroidism, for which free thyroxine measurement is the laboratory test of choice.
  • In patients with central hypothyroidism, free thyroxine levels can be checked 2 to 3 weeks after a dose change to assess for adequacy.