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Low T4 and T3 but Normal TSH

Last Updated: · Doctors


I would appreciate your comments on this case.

This is a 24-year-old man who was referred for low normal values of T4 and T3 with normal TSH. He noted easy fatigability and a bit of weight gain during the last year. Otherwise he is a healthy young man who is studying medicine. His past medical history was irrelevant and he takes no medications. Laboratory examinations showed: TSH: 0.96 mU/ml (RV 0.27-4.2) T4: 5.19 mcg/dl (RV 5.1-13.5) T3: 73 ng/dl (RV 80-200) Repeated: TSH: 1.35 T4: 3.9 FT4: 0.74 ng/dl (RV 0.93-1.6) Antiperoxidase antibodies <5.0 UI/ml (RV 0-34).

He was clinically euthyroid and had no goiter.

Considering the possibility of a secondary hypothyroidism, pituitary function was evaluated: FSH: 5.3 mUI/ml LH: 2.5 mUI/ml total testoterone: 4.39 ng/ml (RV 2.8-8) PRL: 21.4 ng/ml (RV 1.6-18.8 ) cortisol: 20.97 mcg/dl (RV 5-25) TSH: 2.89 T4: 4 T3: 86 FT4: 0.71 Normal MRI scan except for a very small intrasellar aracnoidocele.

Although FT4 was also low, we considered TBG defficiency as a differetial diagnosis: TBG was in the low limit of the normal range: 15.2 mcg/dl (RV 15-30 Scatchard Delfia method).Is he really hypothyroid? Does he need treatment? Is it an isolated secondary hypothyroidism? Or is it a TBG deficiency?

Thank you in advance.

Ver'nica Ilera MD, Buenos Aires

Additional information:

The thyroid glands seems normal by palpation, I don't have an ultrasound. It's clearly not enlarged and consistency is also normal.Free T4 was measured by a direct method, I tried to measure it by dialysis but no lab can do this determination in Buenos Aires. For the same reason I couldn't measure reverse T3. I'm afraid I don't have a kidney function test. He isn't body builder nor he lifts weights. The last test I ordered was a TRH test and these are the results: basal TSH: 1.82, 20' : 15.8, 30': 13.46, 60': 8.32


The lowish T4 and T3 concentrations in your patient are not due a pituitary defect but a partial hypothalamic insufficiency cannot be excluded as you did not obtain TSH measurement 120 and 180 minutes after TRH to exclude the typical "hung up" (prolonged) response of tertiary hypothyroidism..

The thyroid fiction tests are also compatible with renal insufficiency and this is the reason I asked for creatinine and/or BUN values. The borderline low T4 and T3 with normal TSH, slightly low TBG and slightly high PRL are typical.

TBG abnormality is also a possibility, although free T4 should be normal. However if the defect is inherited and results in a mutant TBG with lower affinity for T4 and T3, rather than low amount of TBG, measurement of free T4 by direct method my give a spurious value.

Finally, use of a wide range of drugs can produce such results. Anabolic steroids are excluded as FSH and LH are not suppressed. However, other drugs could produce the laboratory pattern you obtained.

My suggestion is to obtain a general chemistry screen including kidney and liver function tests and blood count. Urinalysis. A complete history of medication and other substances use. Finally, obtaining thyroid function tests on family members (parents and sibling) could be very enlightening.

Hope this helps. I would love to receive a follow up.


Samuel Refetoff, MD