Learn to answer troublesome questions about thyroid tests

Medical Laboratory Observer, Oct, 1996 by Diana Trundle

Does your medical staff repeatedly ask about discordant thyroid test results? This primer will help you respond.

One hectic Monday morning, you are up to your elbows in work when you receive a call from a family practitioner who recently joined the hospital's medical staff.

"Good morning, Dr. Leonard. How can I help you?"

"I'm in the CCU with Mrs. Rodriguez. She was admitted with a mild heart attack. She's better now, and we're about to move her out of the unit, but I can't explain her lab test results. Her TSH is 0.09, which is low, but her free [T.sub.4] is 1.5, which is normal. What's wrong with your TSH test? This woman doesn't look hyperthyroid - she shouldn't have a low TSH. And her EKG is fine."

You take a deep breath and ask what medication she's taking.

"Heparin, digoxin, prednisone, Lasix, Premarin ...."

"Okay, the problem is the prednisone. Since it suppresses TSH, it makes TSH assays unreliable. But free [T.sub.4] works for those patients, and it agrees with your clinical impression. Just ignore the TSH and use the F[T.sub.4]."

You make a note to write a memo for the medical staff about medications that affect thyroid tests. Using one test instead of two would reduce costs for some patients. The hospital administration would like that. Before writing anything, though, you'll check with the pathologists about whether to write that memo and what to include.

Meanwhile, you wish you knew more about those assays. And you wonder why Dr. Leonard ordered free [T.sub.4] (F[T.sub.4]) and thyrotropin (thyroid-stimulating hormone, or TSH) tests for a patient who was admitted with a heart attack.

AN APPARENT DISCREPANCY

In many hospital laboratories, this scenario is repeated several times a week. The calls may come to the pathologist, section supervisor, clinical chemist, laboratory manager, or anyone else who answers the phone. Doctors complain about thyroid test results that don't seem to agree, thyroid test results that don't support their clinical impression, and a TSH that's too high in patients taking the usual dosage of levothyroxine (Levothroid, Levoxine, Synthroid). A patient with severe dehydration may show abnormal thyroid test results, such as free [T.sub.4] greater than 6.0 ng/dL and TSH less than 0.01 mU/L. Often the doctor wants the test repeated at no charge. The repeat analysis provides the same answer.

In fact, third-generation TSH assays may present more problems than the old [T.sub.4] and [T.sub.3] tests ([T.sub.4] and [T.sub.3] uptake). Lab directors are expanding their test menus by adding the new F[T.sub.4] and TSH tests. Reference intervals are quickly confirmed with specimens from lab staff volunteers. When results fall within the recommended ranges, the normal ranges are accepted.

The apparent simplicity of setting up these new thyroid tests is misleading because test interpretation is not so easy. Thyroid test data must be interpreted carefully in the context of myriad complex factors that affect results.

Let's review the reasons doctors order thyroid function tests and the factors that affect test results. The concepts are simple and the facts will update your skills beyond what you still remember from training.

NORMAL THYROID PHYSIOLOGY

[T.sub.4] is a storage form of thyroid hormone, a stable structure for transport in the blood. The thyroid gland secretes [T.sub.4] and [T.sub.3] in a ratio of 10:1 with 80% of [T.sub.3] arising later from peripheral deiodination of circulating [T.sub.4]. The two hormones travel in the blood bound to proteins with a very small fraction free to enter cells. Only the free fraction is metabolically active.

At peripheral tissues, free [T.sub.4] and free [T.sub.3] enter cells. At the cell surface and within the cell, [T.sub.4] is converted to [T.sub.3], the active hormone that migrates into the cell nucleus to bind DNA.

In a normal individual, thyroid gland function and the level of free [T.sub.4] and free [T.sub.3] in the blood are carefully regulated by hormones from two other endocrine glands: the pituitary and the hypothalamus. When circulating levels of [T.sub.4] and [T.sub.3] fall, the hypothalamus releases thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary thyrotrope cells to release TSH, causing synthesis and release of new [T.sub.4] and [T.sub.3] by the thyroid to maintain homeostasis.

Rising blood levels of [T.sub.4] and [T.sub.3] exert negative feedback on the pituitary and hypothalamus, reducing further output of TSH and TRH. This exquisite control mechanism maintains most people in a euthyroid, eumetabolic condition. A dynamic equilibrium is maintained; TSH and TRH are secreted in a pulsatile fashion throughout the day. TSH shows a circadian variance, with the highest levels late at night and the lowest levels around noon.[1]

THYROID DISEASE

The normal physiology of thyroid hormones changes vastly when disease is present. For example, in the most common thyroid disorder, primary hypothyroidism, the thyroid gland fails to respond to rising TSH. The first physical changes are so subtle that they are barely noticeable to the patient or the physician.