Let’s Talk About Goiters
28/06/10 07:56
Now, someone here (I think Francesco) has brought up the subject of isothiocyanates and goiters.
What are goiters and why do they come into existence? A goiter is a swelling of the thyroid gland, in the neck. Sometimes, a goiter is also caused by nodules on the thyroid gland. (These are usually not cancerous.) Either way, you got a lump in your neck and that ain’t good.
Let’s talk about the thyroid hormone and the pathway by which it is regulated: It is a self-regulating process, involving a feedback loop.
What is the result of this? The result is that you don’t have enough T-4, and of course, that you don’t have enough T-3, either.
What happens when you don’t have enough T-4? Well, the pituitary gland is secreting, probably, more TSH. And, in fact, this has been borne out by the research, specifically in terms of CF patients. [Eur. J. Pediatr. (1982) 138: 327-330] The same workers also showed that T-4 is lower in CF patients, which is exactly, again, what we would expect.
Now, hopefully, by now, you’re asking: Melanie, why are you centered on the lack of iodine causing these changes in the thyroid-hormone balance in CF patients? Well, because, as Philippe pointed out, the CFTR TRANSORTS IODIDE. And that’s exactly where the system breaks down in CF patients.
But, suppose you replace the CFTR with another protein that can transport the same things that the CFTR is supposed to transport? Such as iodine?
Now, remember why we are on this topic in the first place: Thiocyanates inhibit iodine uptake by the thyroid, leading to reduced iodination of amino acids, which results in the decreased production of T4.
So, with isothiocyanate, you’d end up with more iodine output into the extracellular space, where the blood cells can pick it up, but you also don’t have as much uptake by the thyroid, of the iodine. Do they balance each other out? I don’t know.
You’ve got two different mechanisms here, causing the same thing:
1. Not enough iodine causes not enough T4, which causes less T-4, which results in an increase in TSH.
2. Downregulation of uptake of iodine by the thyroid, caused by isothiocyanates, which causes less T-4, which results in an increase of TSH.
You end up with more iodine circulating, but less taken up. Are they a wash? I doubt it (most things aren’t).
Which one wins? Zinc wins, boys and girls. Zinc wins. You didn’t expect that answer, did you?
And, that will be the subject of one of my later blog posts. Here's a hint: BOTH of the two above RESULTS in less thyroxine (T-4). But what if the amount of thyroxine that you have is dependent on something else, too? Something else that is replaced (normal homeostasis is restored, in the case of CF) by having a functional ABC transporter protein, such as the MRP, in the place of the missing CFTR? Hmmm?
I want to apologize to you guys for having a dry spell here, and having to wait so long for another post. Sometimes I get real busy in my day job and it takes me away from CF for a little while.
In the meantime, peruse this VERY interesting article (WOW! That's a hell of a lot of goiters in CF patients treated with iodide, do you SUPPOSE that it's not the problem here? Duh :)
Volume 79, Issue 4, Pages 684-687 (October 1971)
William L. Nyhan (Editor), Harry C. Shirkey (Consultant), M.D. Thomas F. Dolan Jr., M.D. Lewis E. Gibson
Forty-seven of 55 patients receiving long-term daily iodile therapy as part of the therapeutic regimen for cystic fibrosis of the pancreas developed goiters. Goiters usually appeared 2 to 3 years after onset of therapy, with a range of 3 months to 12 years. Fourteen patients receiving iodides had laboratory or clinical evidence of hypothyroidism; 2 of these 14 did not have a goiter. No goiters were observed among 55 patients with cystic fibrosis not receiving iodides. Fourteen of 55 children receiving iodide therapy developed nasal polyposis whereas no polyps were seen in 40 patients not receiving iodide. This may be due to the age distribution of patients studied, since most children in the 5 to 15 year age range received iodide therapy.
What are goiters and why do they come into existence? A goiter is a swelling of the thyroid gland, in the neck. Sometimes, a goiter is also caused by nodules on the thyroid gland. (These are usually not cancerous.) Either way, you got a lump in your neck and that ain’t good.
Let’s talk about the thyroid hormone and the pathway by which it is regulated: It is a self-regulating process, involving a feedback loop.
- Not enough iodine, which causes less T-4, which results in an increase in TSH.
- IN RESPONSE to more TRH, the pituitary gland releases a hormone called thyroid stimulating hormone (TSH).
- TSH causes the thyroid gland to trap iodine from the blood and this iodine is an essential component of thyroxine (T-4)
- Thyroxine (T-4) can be converted into the biologically active form of hormone, called tri-iodothyronine (T-3).
- This is the feedback loop: If you have enough T-4, the pituitary gland becomes less sensitive to TRH, and secretes less TSH, slowing down the cycle.
What is the result of this? The result is that you don’t have enough T-4, and of course, that you don’t have enough T-3, either.
What happens when you don’t have enough T-4? Well, the pituitary gland is secreting, probably, more TSH. And, in fact, this has been borne out by the research, specifically in terms of CF patients. [Eur. J. Pediatr. (1982) 138: 327-330] The same workers also showed that T-4 is lower in CF patients, which is exactly, again, what we would expect.
Now, hopefully, by now, you’re asking: Melanie, why are you centered on the lack of iodine causing these changes in the thyroid-hormone balance in CF patients? Well, because, as Philippe pointed out, the CFTR TRANSORTS IODIDE. And that’s exactly where the system breaks down in CF patients.
But, suppose you replace the CFTR with another protein that can transport the same things that the CFTR is supposed to transport? Such as iodine?
Now, remember why we are on this topic in the first place: Thiocyanates inhibit iodine uptake by the thyroid, leading to reduced iodination of amino acids, which results in the decreased production of T4.
So, with isothiocyanate, you’d end up with more iodine output into the extracellular space, where the blood cells can pick it up, but you also don’t have as much uptake by the thyroid, of the iodine. Do they balance each other out? I don’t know.
You’ve got two different mechanisms here, causing the same thing:
1. Not enough iodine causes not enough T4, which causes less T-4, which results in an increase in TSH.
2. Downregulation of uptake of iodine by the thyroid, caused by isothiocyanates, which causes less T-4, which results in an increase of TSH.
You end up with more iodine circulating, but less taken up. Are they a wash? I doubt it (most things aren’t).
Which one wins? Zinc wins, boys and girls. Zinc wins. You didn’t expect that answer, did you?
And, that will be the subject of one of my later blog posts. Here's a hint: BOTH of the two above RESULTS in less thyroxine (T-4). But what if the amount of thyroxine that you have is dependent on something else, too? Something else that is replaced (normal homeostasis is restored, in the case of CF) by having a functional ABC transporter protein, such as the MRP, in the place of the missing CFTR? Hmmm?
I want to apologize to you guys for having a dry spell here, and having to wait so long for another post. Sometimes I get real busy in my day job and it takes me away from CF for a little while.
In the meantime, peruse this VERY interesting article (WOW! That's a hell of a lot of goiters in CF patients treated with iodide, do you SUPPOSE that it's not the problem here? Duh :)
Volume 79, Issue 4, Pages 684-687 (October 1971)
Complications of iodide therapy in patients with cystic fibrosis*
*William L. Nyhan (Editor), Harry C. Shirkey (Consultant), M.D. Thomas F. Dolan Jr., M.D. Lewis E. Gibson
Forty-seven of 55 patients receiving long-term daily iodile therapy as part of the therapeutic regimen for cystic fibrosis of the pancreas developed goiters. Goiters usually appeared 2 to 3 years after onset of therapy, with a range of 3 months to 12 years. Fourteen patients receiving iodides had laboratory or clinical evidence of hypothyroidism; 2 of these 14 did not have a goiter. No goiters were observed among 55 patients with cystic fibrosis not receiving iodides. Fourteen of 55 children receiving iodide therapy developed nasal polyposis whereas no polyps were seen in 40 patients not receiving iodide. This may be due to the age distribution of patients studied, since most children in the 5 to 15 year age range received iodide therapy.