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‘Sluggishness’ unacceptable when working up thyroid disease
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A 58-year-old man presents for an initial evaluation of “sluggishness.” He denies palpitations, nervousness, sweats, multiple daily bowel movements or goiter. He reports weight gain of 10 lb during the past 6 months, constipation, dry skin and hair loss. There have been no recent hospitalizations.
Past medical history is remarkable for hypertension, well-controlled type 2 diabetes, lower urinary tract symptoms and mycosis fungoides, which has responded to treatment during the past 6 months.
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Medications include quinapril, diltiazem, hydrochlorothiazide, metoprolol, silodosin (Rapaflo, Watson Pharmaceuticals), tolterodine (Detrol, Pfizer), methoxsalen (Oxsoralen, Valeant Pharmaceuticals) and bexarotene (Targretin, Eisai).
Family history is remarkable for diabetes in both parents. The patient denies the use of tobacco and recreational drugs. He drinks five alcoholic drinks per week.
Pertinent physical exam: black man in no acute distress with truncal obesity; blood pressure 152 mm Hg/86 mm Hg; heart rate 88; height 5’6”; weight 228 lb (103.42 kg).
The thyroid gland has no bruit, thyroid enlargement, palpable nodule or tenderness. The cardiovascular, abdominal and respiratory exams are also unremarkable. The patient has no tremor or lid lag. He has unremarkable deep tendon reflexes. Skin is warm and very dry. No foot ulcers, but there are multiple round dark lesions about the size of a quarter, particularly on the extremities, representing healing mycosis fungoides, and acanthosis nigricans around neck, and many skin tags.
His thyroid-stimulating hormone is a bit low at 0.27 uIU/mL (normal, 0.45-5.0).
In addition to starting a workup for secondary hypertension in a man taking four antihypertensive agents, what is the best course of action to investigate the source of his sluggishness?
A. Nothing for now; repeat TSH in a few months because his TSH is close to normal, and the patient is probably recovering from nonthyroidal illness.
B. Send the patient for a nuclear radioactive iodine uptake and scan of the thyroid to evaluate for hyperthyroidism.
C. Send the patient for surgery to treat hyperthyroidism.
D. Get a free thyroxine (T4) or a thyroxine/thyroxine-binding globulin index.
E. Start daily oral methimazole 10 mg(Tapazole, King Pharmaceuticals).
CASE DISCUSSION:
Answer: D
This patient has a low TSH, which is generally accepted as an indicator of overactive thyroid function. Exceptions to that rule are nonthyroidal illness and the rare condition of secondary (central) hypothyroidism. Given the fact that the patient’s signs and symptoms are more consistent with hypothyroidism, it appears unwise to rush to medical (E) or surgical treatment (C) of hyperthyroidism.
In this case, it helps to know that the rexinoid and vitamin A-derivative bexarotene not just interacts with its intended target — retinoid X receptor — but also with the thyroid hormone receptor. The drug has been reported to cause central hypothyroidism. The patient’s free T4 was low at 0.5 ng/dL (normal 0.7-1.4). A nuclear uptake and scan may show a decreased uptake and may be confused for thyroiditis (B).
Finally, this patient is not acutely sick. Waiting for the TSH to normalize, as it would be expected in nonthyroidal illness, would merely delay necessary treatment. The patient is currently taking levothyroxine 75 mcg daily and is clinically euthyroid. Monitoring is performed by measuring free T4 levels.
Ronald Tamler, MD, PhD, MBA, is assistant professor in the division of endocrinology at Mount Sinai School of Medicine, N.Y.