Liothyronine Improves Biochemical Control of Congenital Hypothyroidism in Patients with Central Resistance to Thyroid Hormone

[helvella]

Rather than "Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.", shouldn't we be asking: Where is the evidence of the effect of T4 monotherapy on neurodevelopmental outcomes?

Shouldn't that evidence have been watertight, 100% proved, dating from BEFORE the start of T4 monotherapy in congenital hypothyroidism of all sorts? Indeed, how do you even define central resistance to thyroid hormone when ONLY levothyroxine is supplied?

Or was it the old, old story - seemed like a reasonable thought to try it.

J Pediatr. 2016 May 10. pii: S0022-3476(16)30070-1. doi: 10.1016/j.jpeds.2016.04.022. [Epub ahead of print]

Liothyronine Improves Biochemical Control of Congenital Hypothyroidism in Patients with Central Resistance to Thyroid Hormone.

Paone L1, Fleisch AF2, Feldman HA3, Brown RS2, Wassner AJ4.

Author information

1Endocrinology and Diabetic Unit, Bambino Gesù Children's Hospital, Rome, Italy.

2Division of Endocrinology, Boston Children's Hospital, Boston, MA.

3Clinical Research Center, Boston Children's Hospital, Boston, MA.

4Division of Endocrinology, Boston Children's Hospital, Boston, MA. Electronic address: [e-mail].

Abstract

OBJECTIVE:

To assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone.

STUDY DESIGN:

We retrospectively studied 12 patients with congenital hypothyroidism and central resistance to thyroid hormone (6 treated with LT3+LT4 combined therapy and 6 treated with LT4 monotherapy). In patients receiving combined therapy, we compared serum concentrations of TSH, T4, and triiodothyronine before and after addition of LT3. We used repeated measures analysis to compare thyroid function in participants receiving combined therapy vs monotherapy, while accounting for age and intrasubject correlation.

RESULTS:

In patients receiving combined therapy, the addition of LT3 was associated with normalization of mean TSH (9.2 vs 4.5 mIU/L, P = .002), a lower proportion of TSH values greater than 10 mIU/L (35% vs 8%, P = .03), and a decrease in mean serum T4 by 23 ± 9% (P < .001). Compared with patients receiving LT4 monotherapy, patients receiving combined therapy had lower mean TSH (8.5 ± 0.9 vs 4.3 ± 0.4, P < .001), lower odds of TSH elevation greater than 10 mIU/L (OR 0.20, 95% CI 0.10-0.41, P < .001), and lower odds of T4 elevation (OR 0.21, 95% CI 0.04-1.09, P = .06). LT3 treatment did not increase serum T3 levels significantly.

CONCLUSION:

The addition of LT3 to LT4 monotherapy facilitates normalization of both serum TSH and T4 in patients with congenital hypothyroidism and central resistance to thyroid hormone. Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS:

combined therapy; thyroid hormone resistance

PMID: 27178621 [PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/271...

As so often, access not possible due to paywall, link:

jpeds.com/article/S0022-347...

[Glynisrose]

And why do the BTA and GMC not recognise such studies as propose the use of T3?

[shaws Administrator]

If you had a child with congenital hypothyroidism you'd want the very best treatment for them. Not just a tiny study. Considering children don't have to convert levo (T4) into T3, it might be much better for them.

Can children really explain how they are feeling/symptoms/etc.

[humanbean in reply to shaws]

Why do you think children don't have to convert T4 into T3? That doesn't make any sense to me I'm afraid.

[helvella Administrator Thyroid UK in reply to humanbean]

I read that as:

Considering children who are given T3 don't have to convert levo (T4) into T3 in order to have a better T3 level, it might be much better for them.

[shaws Administrator in reply to humanbean]

Helvella explained it much more clearly than I did

[SilverAvocado]

Am I reading this correctly that the average TSH was around 9? And that even with the T3 they were getting down to around 4. Is this the kind of TSH children expect to have, and do they feel well on it?

[helvella Administrator Thyroid UK in reply to SilverAvocado]

Paediatric thyroid hormone and TSH ranges are different to those for adults and depend on age.

This, though, is specifically "congenital hypothyroidism and central resistance to thyroid hormone". That may have its own part to play in seeing higher TSH results than would otherwise be the case?

[helvella Administrator Thyroid UK]

One of the problems is that the number of paediatric patients diagnosed with "congenital hypothyroidism and central resistance to thyroid hormone" is going to be small. The number accessible to the authors of this paper, even smaller.

Of course a much larger cohort is highly desirable.

It strikes me as better to have reported 12 patients than to have not published anything. Would you rather they had left the information gathering dust, inaccessible and forgotten forever more?

[helvella Administrator Thyroid UK]

I agree. Just a tiny bit better than being totally ignored and nothing looked at - for this tiny handful.