QUESTION-Dear,--Thank you very much for the free expert information you provide for practioners everywhere. I have a case I would like to run past an expert.

A 19 y.o. female patient was sent to our endocrinology offices from her primary care provider/gynecologist due to abnormal thyroid function tests. She has complaint of significant fatigue issues (no palpitations, tremors, heat intolerance, weight loss). Her mother has thyroid hormone "abnormalities" as well and is being treated with LT4.

Intial outside facility labs: (11/30/11) TSH 2.42 with FT4 1.57; TPO Ab: 44.7 (Ref < 9.0) TG Ab: 371 (Ref. <116)

Our labs: 3/20/12 TSH: 4.04 (Ref 0.27 -4.67) FT4: 1.5 (Ref 0.7 - 1.85) FT3: 3.7 (Ref: 2.0 -3.5)

These labs prompted evaluation into etiology of high normal to high thyroid hormones with TSH outside level expected for a young healthy female patient.

4/3/12: HAMA evaluation of TSH 3.9 (unlikely interference)/ FT3: 3.5 FT4: 1.54

Alpha Subunit 0.1 ng/mL (Ref <1.2)

It seemed that resistance to thyroid hormone was definite possibility. The duration of thyroid hormone abnormality from November 2011 to April 2012 seemed to speak against thyroiditis.

The test to address sensitivity to thyroid hormone was performed using liothyronine 50 mcg X 3 day, 100 mcg X 3 day, 200 mcg X 3 days. The baseline labs were as follows:

SHBG 84 (Ref 18-144), CK 73 (Ref 7-132), Ferritin 53 (Ref 14-186), TSH 3.01, FT4 1.48,

FT3 3.5

After the 9 day course of medication--SHBG 170, CK 79, Ferritin 126, TSH 0.044, FT4 0.94

FT3 9.9

The SHBG increased by 100% as expected for normal response to T3; CK was expected to decrese by 50% (did not); Ferritin expected to increse by 200% (increased by 100%). TSH responded appropriately, but should it have been undetectable by the end of this test?

I asked her mother to get her levels checked and her results are as follows on 50 mcg a day of LT4 (expected weight based total daily dose 150 mcg):TSH: 12.49, FT4: 1.39, FT3: 2.7

with same reference ranges. The mother was not taking medication in the appropriate fashion (alone and waiting before any other oral intake).

The patient appears to have responded to the supraphysiologic T3, however, is it possible she has a partial resistance? If so, what do we have to do to ensure safety/optimal hormone during future pregnancies? Is her fatigue due to this thyroid issue and if so, do we treat to a TSH goal instead of FT4/FT3? Is there a university center which will analyze a blood sample for mutations at no cost to the patient? Thank you for your time and assistance in this matter. Phenu Zachariah, DO

Cape Girardeau, MO 63701

RESPONSE-As you correctly state, the L-T3 results did not provide clear cut results relative to the average observed in normal individuals. However, her responses were within the broad range of normal. Furthermore, the complete suppression of TSH with the high dose of TSH comes from data carried oit with the second generation of TSH RIA when the level of minimal detection was 0.1 mU/L.

Although the presence of TG and TPO antibodies do not exclude resistance to thyroid hormone (RTH),the high TSH in the mother despite normal FT4 and FT3 are suggestive of dominant inheritance.

As for treatment, I am against treating a laboratory test. I would first put my effort in securing a diagnosis.

Again as you suggest, the next step would be to sequence the thyroid hormone receptor beta gene. This can be done by a commercial laboratory at a cost lesser that that spent to do the L-T3 suppression tests. As for free testing in an academic center, my lab has such capability. However, as we use taxpayer's money (NIH), our mission is research, not free diagnosis.

For the patient to qualify, we will need to obtain blood samples from the patient, both parents and all her siblings. Also all will have to sign a consent form. Samuel Refetoff, MD

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