Hypothyroidism

RE: Hypothyroidism

Mark Hedberg — Wed, 08 Nov 2017 10:53:43 GMT

Neat, I learned something new! (now to do that 'claim cpd button!)

RE: Hypothyroidism

Neil Wheadon — Wed, 08 Nov 2017 09:50:43 GMT

Interesting stuff please carry on

Neil

RE: Hypothyroidism

Richard Allport — Tue, 07 Nov 2017 22:13:53 GMT

Thank you - most illuminating - and thanks for the really interesting answer! Next question - has anyone seen a hypothyroid dog that didn't seem to be responding well to T4 and if so have they given (or thought of giving) T3?

RE: Hypothyroidism

Beats — Tue, 07 Nov 2017 20:11:16 GMT

I don't know any endocrinologists, but thankfully some have written helpful books :-) Here's my understanding from skim-reading what Catharine Scott-Moncrieff has to say in Feldman and Nelson's 'Canine and Feline Endocrinology, 4th ed' pages 77-135 from 2015:

[Edit - I've highlighted the bits of this post to skim read!]

The hormones of interest are:

Thyroxine (T4) and 3,5,3'-triiodothyronine (T3)

T4, and to a much lesser degree, T3 are released from the thyroid gland into the blood stream.

(a small quantity of thyroglobulin, containing unreleased T4 and T3, also escapes into blood stream; this amount is increased in lymphocytic thyroiditis)

TSH, produced in the pituitary causes the synthesis and release of both T3 and T4 in the thyroid. The negative feedback is technically primarily from T3 at the level of the pituitary, but this is synthesised locally at the level of the pituitary from T4.

TRH from the hypothalamus controls TSH production. However factors surrounding TRH production and release is not well understood. Nerves from the higher brain centres are implicated.

i.e. to answer the feedback question from an accepted physiology perspective:

T4 and T3 are accepted to provide negative feedback of TSH production. It is intuitive to hypothesize, but not yet clearly understood or accepted, that T4, T3 and TSH may indiviudally or collectively provide negative feedback on TRH. It is accepted that both positive and negative signals regarding TRH production and secretion are received from higher brain centres.

TSH is also produced in response to prostaglandins and alpha-adrenergic agonists, while its production is reduced in response to dopamine, serotonin, somatostatin and glucocorticoids.

There are regulatory mechanisms within the thyroid gland also which can affect its sensitivity to TSH amongst other mechanisms.

Most of the excreted T4 (andT3) from the thyroid into the blood is bound to proteins, the most important of which being imaginatively named thyroxine-binding globulin (TGB) in the dog. Differences between humans and dogs in TGB structure, as well as dogs having a lower amount, have been suggested as explanations for the much faster T4 metabolism in the dog.

T3 is 4 times as potent as T4 and goes into cells quicker and takes a quicker effect.

Half the T3 reaching cells is a result of T4 losing an iodine. The enzymes that catalyse this change can vary in different tissues and can also change T4 to the inactive reverse-T3 (rT3) instead. These enzymes found peripherally and having a local effect on effective thyroid hormone dose to the tissues they are in are critical to thyroid hormone effect.

As an acquired condition in adult dogs, primary hypothyroidism (due to idiopathic atrophy or lymphocytic thyroiditis, which may or may not be separate pathological causes), due to failure of the thyroid gland itself, is the common condition we recognise in dogs. Technically, acquired failures elsewhere (TSH production, TRH production, acquired defects with enzymes changing T4 to T3 in peripheral tissues) could also cause symptoms of hypothyroidism.

T3 assays may be of some use in greyhounds, but generally are not going to give any additional useful information compared to T4 in most dogs and are not routinely done. T3 autoantibodies (which can also be assayed, as indeed can rT3) are more common than T4 ones and can result in falsely elevated lab results for T3.

levothroxine (L-T4) is the recommended initial treatment both for confirmed cases and therapeutic trials. The patient can make T3 at the tissue level itself from this and regulate it and there is a lower risk of causing thyrotoxicosis. Giving L-T4 at sufficient doses normalises both T4 and T3, while giving only T3 does not normalise T4 levels. There is clear logic in not giving JUST T3, but that is not what we're discussing!

In discussing the reasons for treatment failures in the section on L-T4 use, the authors state " If poor gastrointestinal absorption is suspected, T₃ may be substituted for T₄." but do not have any figures for how often this may be required. The general thrust of the chapter is that treatment failures are rare and presumably therefore treatment failures that require T3 are very rare.

A further, detailed, section on use of L-T3 discusses both its use and abuse in canine patients further. In a nut shell it is indicated to give alongside L-T4 in cases with poor response to (appropriate) L-T4 treatment, while it is daft to give it as a sole therapy on the assumption that an adult dog has an acquired problem in converting T4 to T3.

Combo L-T4/L-T3 products are not recommended in dogs and reasons are given.

Every day's a school day!

Thanks for the interesting question, Richard

RE: Hypothyroidism

Rob Loxley — Tue, 07 Nov 2017 19:33:01 GMT

[quote user="Clive Ansell"]I believe T3 is measured in some of the more comprehensive canine profiles?[/quote]

It can be measured, but my understanding was T3 autoantibodies were quite common and intefer with measuring T3.

[quote user="Richard Allport"]t's known that 10% or so of humans with hypothyroidism do not convert T4 to T3 and therefore need medication with Liothyronine as well as or instead of Levothyroxine to achieve improvement in symptoms. Are there any comparable figures for hypothyroid canines?[/quote]

A quick google throws up https://www.vetmed.wsu.edu/outreach/Pet-Health-Topics/categories/diseases/hypothyroidism-in-dogs which says "Most hypothyroid dogs given T4 will convert it to T3 so almost all hypothyroid dogs receive T4 (levothyroxine or L-thyroxine). A few dogs are unable to make this conversion and require T3 medication" but no more detailed figures.

RE: Hypothyroidism

Thomas Johnson — Tue, 07 Nov 2017 18:30:48 GMT

[quote user="Clive Ansell"]

How many folk routinely measure TSH when diagnosing or monitoring therapy for hypothyroidism?

Presumably, in both humans and canines, if there were a problem in the T4 -> T3 conversion, T4 and TSH levels would be normal or raised, which could lead to a missed or misdiagnosis?

[/quote]

I wouldn't be confident to make a diagnosis of hypothyroidism without a TSH.

If T4 wasn't being converted to T3 would the dog present with clinical signs of hypothyroidism but elevated T4 and TSH? Does anyone know if it is low T3 or low T4, or a combination of both, that stimulates release of thyrotropin releasing hormone from the pituitary?

RE: Hypothyroidism

Martin Atkinson — Tue, 07 Nov 2017 17:33:40 GMT

[quote user="Clive Ansell"]My GP was telling me recently that they often only measure TSH levels, and not T4 or T3, although in a recent health screen my TT4 and TSH were both measured.[/quote]On mine they measured Free Thyroxine not TT4, possibly because I'd been taking aspirin which can effect TT4 apparently and TSH.

RE: Hypothyroidism

Clive Ansell — Tue, 07 Nov 2017 17:22:17 GMT

My GP was telling me recently that they often only measure TSH levels, and not T4 or T3, although in a recent health screen my TT4 and TSH were both measured.

I believe T3 is measured in some of the more comprehensive canine profiles?

How many folk routinely measure TSH when diagnosing or monitoring therapy for hypothyroidism?

Presumably, in both humans and canines, if there were a problem in the T4 -> T3 conversion, T4 and TSH levels would be normal or raised, which could lead to a missed or misdiagnosis?

What importance do T4 and T3 play on the feedback mechanism for TRH and TSH?

RE: Hypothyroidism

Richard Allport — Tue, 07 Nov 2017 16:44:38 GMT

But the treatment is still T4 isn't it, and if this isn't being converted to T3, there may be poor response to treatment. Or perhaps the pathway is different in dogs and T4 isn't converted to T3 to become active. Any endocrinologists out there?

Richard

RE: Hypothyroidism

Sarah Keir — Tue, 07 Nov 2017 13:22:05 GMT

I can't speak for what humans get but as dogs almost entirely get primary hypothyroidism due to autoimmune destruction of the thyroid gland, I don't think this would apply.

RE: Hypothyroidism

Beats — Tue, 07 Nov 2017 13:15:23 GMT

I've never heard of T3 supplementation being discussed in the dog (and wasn't aware there were products for this), so would be interested in hearing any answers from those more educated!

Good question - I always appreciate a head-scratcher