Thyroxine induces pancreatic beta cell apoptosis

[August]

Jorns A, Tiedge M, Lenzen S.

Thyroxine induces pancreatic beta cell apoptosis in rats.

Diabetologia. 2002 Jun;45(6):851-5. Epub 2002 May 17.


Thyroxine induces pancreatic beta cell apoptosis in rats.
Jorns A, Tiedge M, Lenzen S.
Centre of Anatomy, Hannover Medical School, Hannover, Germany.

AIMS/HYPOTHESIS: Thyroid hormones reduce glucose tolerance in animals and humans. This effect is accompanied by a reduction in the beta-cell volume of the pancreas. METHODS: We studied the underlying mechanism using terminal UTP nick end labelling (TUNEL) and caspase-3 to analyse apoptosis and BrdU labelling of beta-cell proliferation. RESULTS: The reason for the reduction of the beta-cell volume of the pancreas after thyroxine treatment is apparently an increased rate of beta-cell apoptosis by an increase of TUNEL and caspase-3 positive rat beta cells. In parallel, thyroxine treatment increased the rate of apoptosis in rat pancreatic ductal cells which are considered to contribute to the pool of stem cells from which insulin-producing beta cells originate. The effects of thyroid hormone treatment are reversible through an increase of the beta-cell replication rate when thyroxine is withdrawn as documented by an increase of the BrdU labelling index.

CONCLUSION/INTERPRETATION: An increased rate of beta-cell death due to apoptosis causes a decrease of insulin content and glucose-induced insulin secretion from the pancreas in hyperthyroidism. The resulting reduction of beta cells in the pancreas can provide an explanation for the decrease of glucose tolerance in hyperthyroidism.
PMID: 12107729 [PubMed - indexed for MEDLINE]

[Tattoo azz]

Could you please explain in ENGLISH what this means to someone who takes 200 microgramms a day

[slipperyelm]

It means that thyroxin causes select lines of cells that give rise to beta cells as well as select lines of beta cells themselves to be killed off. The beta cells are those which secrete most of your insulin. (Type 1s presumably have no functional beta cells anyway.) However, when thyroxin is stopped, beta cells reproduce themselves at a greater rate and insulin insufficiency may reverse.

Personal opinion: If you have more than one endocrine problem, it is best to have an endocrinologist who would know about these interactions.

[duck]

Interesting...especially for those of us who had hypothyroid BEFORE coming down with diabetes...

[jen_slc]

duck, how much time passed between your hypothyroid diagnosis and your diabetes diagnosis? or how much time passed between the start of your hypothyroid treatment and your diabetes diagnosis?

It's an interesting thought, but thyroxine is a naturally-occurring hormone, so that's almost like saying that the normal, necessary levels of thyroxine may have an effect on your beta cells before your thyroid goes wacko? Or is the thought that it's the "fake" thyroxine replacement that's doing it? Or the "large" doses? But wouldn't your replacement dose be similar to what your normal biological levels would have been sans thyroid disease? I dunno, I don't know how thyroid hormone replacement works... do you take a pill every day, multiple times a day, is it difficult to match your "normal" pre-disease levels? do you get a pretty even dose of it?

[August]

HYPER-thyroidism and HYPO-thyroidism both cause hyperglycemia but via different pathways.

HYPO-thyroidism, causes hyperglycemia, by slowing down the RATE at which your mitochondria process glucose and fats. Thus leaving excess glucose in circulation.

Dr Broda Barnes, MD, the pioneer thyroid researcher/specialist, believed that hypothyroidism was a precursor to type2 diabetes. He said he gave all his diabetic patients thyroid Extract (not the synthetic stuff), and none of his diabetic patients ever developed diabetic complications(!). Food for thought there. (see:"Hypothyroidism The Undiagnosed Illness", Broda O. Barnes, MD ISBN 0-690-01029-X)

HYPER-thyroidism, causes hyperglycemia because:

1. Above normal levels of thyroxine cause Insulin to be cleared from the body prematurely.

2. Above normal levels of thyroxine cause the premature apoptosis of beta cells, which leaves fewer producing beta cells (which have to work harder) to produce Insulin, which results in lower insulin, and thus higher BG.

HYPER-thyroidism and HYPO-thyroidism both cause hyperglycemia but via different pathways.

Researchers following a cohort of slim physically fit people and rigourously testing them suggest that the optimal TSH, is around 1.0

This is also a level of thyroid activity that does not cause hyperglycemia.

--August

[duck]

duck, how much time passed between your hypothyroid diagnosis and your diabetes diagnosis? or how much time passed between the start of your hypothyroid treatment and your diabetes diagnosis?

It's an interesting thought, but thyroxine is a naturally-occurring hormone, so that's almost like saying that the normal, necessary levels of thyroxine may have an effect on your beta cells before your thyroid goes wacko? Or is the thought that it's the "fake" thyroxine replacement that's doing it? Or the "large" doses? But wouldn't your replacement dose be similar to what your normal biological levels would have been sans thyroid disease? I dunno, I don't know how thyroid hormone replacement works... do you take a pill every day, multiple times a day, is it difficult to match your "normal" pre-disease levels? do you get a pretty even dose of it?

A little more than four years...unless I consciously think about it, it felt like decades, though.

All the question you ask, I don't know. I am skeptical about the effects of thyroid-replacement therapy, actually. If you interviewed every hypothyroid sufferer in the world, I bet almost every single one of them would say taking Synthroid/Levothyroxine helps, but they don't feel "well". Without any solid evidence to back me up, I would say the replacement hormone is a shadow of the naturally produced hormone, so yeah, my paranoia would tell me that it is within the realm of possibility that taking replacement Thyroxine may have contributed to me becoming a Type 1.

Of course, there are many T-1's who don't have hypothyroid, so...

[dgrilli]

I have long suspected I have had Thyroid problems. I think there is something to this.

[JasonJayhawk]

I think I had untreated hyperthyroidism for several years before coming down with Type 1 diabetes. Whenever I'd get my blood pressure checked in the free machines placed throughout shopping centers, I'd notice that my pulse would be 110+ bpm.

Whenever I went to the doctor (about once or twice a year, at most) for whatever was causing me problems at the time, the nurses would take my vitals and point out my high pulse rate. It would always, always, always be "explained away" as dehydration. I can understand this, and I would never disagree because when a person is sick, there's always a good chance for beind dehydrated, too.

Later on, I started wondering if I should see a doctor about my high pulse rate. As a college student, I enjoyed being able to sleep 4 to 6 hours a day, though when I was awake, I didn't feel like I had as much focus as I did earlier in my education.

It wasn't until one month after my Type 1 dx that we tested TSH and found undetectable levels.

I've since read abstracts suggesting that untreated hyperthyroidism leads to type 1 diabetes. Sometimes when I can't sleep, I wonder if I had discovered hyperthyroidism earlier, if it would have preempted Type 1 from ever happening.

(I had a high dose of Tapazole for several months, and then I was able to stop it -- almost cold turkey -- and had about 18 months of normal levels; my latest two thyroid tests show hyperthyroidism creeping back up, so I'm trying a small, 5 mg maintenance dose to try to keep it from taking off.