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Possible Resistance to Thyroid Hormone

Last Updated: · Doctors
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Question

Dear Doctors:

A 3 9/12 year old boy was referred to us because of elevated T3, T4 and positive microsomal antibodies. He has a history of developmental delay and hyperactive behavior. On 9/2/04:

  • T4 = 14.3 (5-12.5)
  • free T4 = 1.79 (.77-2.02)
  • T3 = 353 (75-250)
  • TSH = 1.26 (.4-8.1)
  • antithyroglobulin ab (<20)
  • antimicrosomal AB = 131

After phone consultation, the following labs were obtained on 11/23/04:

  • T4 = 9.3 (5.5-12.8)
  • free T4(dialysis) = 1.1 (.8-2.2)
  • T3=286 (75-250)
  • TSI = 92% (adult N<125%)

He was seen at our clinic on 11/30. Behavior was remarkably hyperactive but parents felt that this was typical and did not represent a recent change. He had no history of change in his appetite, weight loss, polydipsia, polyuria or diarrhea. He typically has had some difficulties sleeping through the night. On exam, wt. was at the 90-95th %ile and ht. was at the 50-75th%ile. BP could not be obtained but heart rate was normal after having the child sit for a few minutes. He had no exophthalmos or goiter and the remainder of his exam was unremarkable. PTU 45mg tid was started (7.5 mg/kg). Inderal 5 mg tid was also recommended. On 1/7/05, labs were repeated:

  • free T4 = 1.6
  • T4 = 11.8
  • TSH = .68
  • T3 = 305

Mother reported no improvement in behavior at home or in school. On 2/3/05, PTU was discontinues when the child developed a pruritic rash. Tapazole 3 mg tid (.47mg/kg/day) was started a few days later but he developed an urticarial rash and this was discontinued after a few days. The child was retested a few weeks later:

  • free T4 = 2.42. (.77-2.02)
  • T3 = 441 (75-250)
  • TSH = 1.53 (.4-8.1)

I am not sure why his TSH has increased as T3 has increased. Do you think that thyroid hormone resistance is a possibility even though he was positive for microsomal antibodies? I have increased his inderal to 10 mg tid but I have not restarted antithyroid meds? What do you suggest? Thanks.

Lou Ann Gartner, M.D. Buffalo, NY

Response

Dear Dr. Gartner:

This is certainly a puzzling case. I do not think that your patient is hyperthyroid both because of the normal TSH, the absence of goiter and the fact that he is at the 90th-95th %ile for weight. Also, in my experience, commercial TSI assays are insensitive and unreliable. To R/O Graves’ disease, I would thereforecheck TSH receptor Abs by binding assay (called either “TBII” or “TRAbs”, depending on the lab). Both Quest and Exotrix have reliable assays but any other commerciallab using the Kronus assay should also be able to do the assay. I suppose that the child could also have a TSH-secreting tumor (highly unlikely, to the extent that it is probably reportable at this age) so you could add a beta subunit.

We certainly see mild thyrotoxicosis associated with Hashimoto’s not infrequently in children, but Hashimoto’s is sufficiently common that he may have the disease but it is asymptomatic and not related to the symptomatology. Alternately, he couldbemaking Abs to T4 and T3, accounting for the high levels of these hormones in his serum. If you’re stuck, and need to assess whether or not he is hyperthyroid, you could always do an 123-I uptake.

That leaves you with TBG excess or thyroid hormone resistance. Again, the absence of goiter, and the absence of failure to thrive make the latter dx less likely but not impossible. To R/O the former I would check TBG.I would hold off on treatment for the moment. I hope this is helpful to you. I would be most interested in learning what you find.

NB- The T3 suppression test for DDX of GRTH is described in Thyroidmanager, Chapter 16D. LDeG

Rosalind S. Brown, M.D.