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MKSAP Quiz: 3-month history of increasing fatigue and weight gain

A 38-year-old woman reports a 3-month history of increasing fatigue and weight gain. She underwent transsphenoidal surgery 4 years ago to remove a nonfunctioning pituitary macroadenoma, followed 4 months later by radiation therapy because of residual tumor. Following a review of medications, physical exam and lab tests, what is the most appropriate next diagnostic test?


A 38-year-old woman reports a 3-month history of increasing fatigue and weight gain. She underwent transsphenoidal surgery 4 years ago to remove a nonfunctioning pituitary macroadenoma, followed 4 months later by radiation therapy because of residual tumor. She started taking hydrocortisone 14 months ago after adrenal insufficiency was diagnosed. The patient developed amenorrhea 1 year ago and began taking an oral contraceptive. Medications are hydrocortisone, norethindrone with ethinyl estradiol, and a multivitamin.

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On physical examination, blood pressure is 102/68 mm Hg, pulse rate is 64/min, and respiration rate is 12/min. Mild periorbital edema is noted. The skin is pale.

Laboratory studies:

Which of the following is the most appropriate next diagnostic test?

A. Morning serum cortisol measurement
B. Serum free thyroxine (T4) measurement
C. Serum growth hormone measurement
D. Serum luteinizing hormone measurement

Reveal the Answer

MKSAP Answer and Critique

The correct answer is B: Serum free thyroxine (T4) measurement. This item is available to MKSAP 16 subscribers as item 57 in the Endocrinology & Metabolism section. More information is available online.

This patient most likely has central hypothyroidism and should have her serum free thyroxine (T4) level measured. Her hypopituitarism is a result of the radiation therapy she received as part of her treatment of a pituitary adenoma. Her symptoms are typical of hypothyroidism, and the signs and symptoms of central hypothyroidism are similar to those of primary hypothyroidism. However, the biochemical diagnosis of central hypothyroidism is established differently because patients may have either a low-normal to overtly low serum thyroid-stimulating hormone (TSH) level. Therefore, the diagnosis is made based on measurement of a low free T4 level in association with both a low to low-normal TSH level and clinical symptoms suggestive of hypothyroidism. This patient's mild hyponatremia may be caused by her hypothyroidism and should improve with T4 replacement. In a patient with central hypothyroidism who takes levothyroxine replacement therapy, the goal should be achievement of a normal free T4 level because monitoring the TSH value is not useful.

Measuring this patient's morning serum cortisol level is inappropriate management because she is receiving glucocorticoid replacement therapy for adrenal insufficiency, which guarantees that the cortisol level will be low.

A random measurement of the serum growth hormone (GH) level is not useful in the assessment of GH deficiency. A serum insulin-like growth factor 1 level would be useful for assessing GH production.

Measurement of this patient's serum luteinizing hormone level will not be useful because the oral contraceptive agent she is taking will have lowered her gonadotropin levels.

Key Point

  • The diagnosis of central hypothyroidism is made on the basis of the serum free thyroxine (T4) level.