"The findings conform with previous studies indicating that the sympathetic nervous system can exert a direct, stimulatory effect on the secretion of thyroid hormone, by NE released from intrathyroidal adrenergic nerve terminals. In addition, the sympathetic nervous system seems to influence the peripheral metabolism of thyroid hormone."
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Has this research from the 1970s been disproven, or just overlooked? Thoughts..?
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ThyroidLadyLondon
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The repercussions for this are really really important., as I have written about in my previous post.
I appreciate this is a study on mice, but overall this line of enquiry seems to have been actively researched at the start of last century. Where has it gone? Why has the autonomic nervous system stopped featuring in the understanding of thyroid pathologies? I genuinely want to understand if this is oversight, or has this view been disproven.
Here is another article from the 1930s which talks about both human and canine physiology: (pubs.rsna.org/doi/abs/10.11...
"In man, the sympathetic nerves to the thyroid gland arise mainly from the middle cervical ganglion or, in the absence of this ganglion, directly from the cervical sympathetic trunks. These nerves probably include fibers arising in all the cervical sympathetic ganglia. Nonidez (9) recently described a definite bundle of fibers arising in the superior cervical ganglion and entering the corresponding lobe of the thyroid gland of the dog. He expressed the opinion that the superior cervical sympathetic ganglia are the sources of most of the sympathetic fibers which enter the thyroid gland.
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Of the later investigators, some have advanced experimental data which seem to indicate that thyroid activity is subject to direct nervous influences; ....."
Thank you for your further response. Much has been done with mice studies...
The cervical aspect is, for me, most interesting and I shall look further - double thanks!
Once afflicted with endocrinologists, I checked out much of the relatively long history of hypothyroidism - long in comparison to other disciplines - and was fascinated by the innovative, 'great works done by good men'... striving for all of the 'right' reasons, corrigible reasons, which have not been invalidated by the 1960's+ lot.
I got this later paper, whose conclusions I quote:
It is concluded that norepinephrine stimulates basal thyroid hormone secretion in vivo, and that its failure to alter plasma T4 levels is due to the low sensitivity of the technique. In contrast, it was found that norepinephrine inhibits the thyroid stimulatory effect of TSH in vivo. Under in vitro conditions, norepinephrine was found to increase the release of radioiodine that was bound to thyroid hormones from thyroid glands of mice that had been pretreated with 125I. In conclusion, the present study demonstrates that norepinephrine exerts a dual effect on thyroid hormone secretion in the mouse; it stimulates basal but inhibits TSH-induced thyroid hormone secretion
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Endocrinology. 1986 Sep;119(3):1058-62.
Effects of norepinephrine on basal and thyrotropin-stimulated thyroid hormone secretion in the mouse.
Ahrén B, Bengtsson HI, Hedner P.
The basal stimulation is not under TSH control. So it looks as if the unaltered plasma T4 comes from a cancelling out of the basal stimulation and the TSH-stimulated one, working in opposite directions. Another paper on burn patients shows higher norepinephrine in the low FT3 NTI syndrome. I think it plays a part, but it couldn't be used in therapy because the norepinephrine has widespread effects not just on thyroid tissue.
Diogenes, thanks for the response. I tried to get the paper via my sister at Cambdridge, but they didn't have a subscription to Radiology!
Your point at the end in respect of therapy is not where I was coming at this from, and I agree that giving patients norepinephrine is not a good idea! The point here is that the thyroid is stimulated not only via TSH but also through the nerves of the autonomic nervous system. This means that when we evaluate the state of the thyroid, we are currently missing this component completely. If you have, say a patient with symptoms of hyperthyroidism, with the low TSH reading that go with that, the treatment implications do not take into account the stimulation of the thyroid by the nervous system, but rather focus on the chemical supression of thyroid hormone formation. What if therapy could include the reduction of stimulation by the sympathetic nervous response instead? This is surely a less toxic and potentially much easier treatment to perform.
This is just a case from the literature, and there are several factors that may have contributed to this Grave's patients recovery, but overall a lifestyle change with relaxation techniques, that will reduce the sympathetic response, like yoga, seem to make sense to make an improvement on Graves, if the nerve stimulation of the thyroid is a significant factor in disease pathology.
The trouble with all this is that the supply of catecholamines fluctuates considerably from moment to moment in the normal body and the net effect over time on the thyroid might be negligible on the average, only changing momentarily one way and then the other. This could well get out of kilter in hyperthyroidism and exacerbate thyroid activity especially T3 production direct..
Sure, I see that argument. But just as "the net effect over time on the thyroid might be negligible on the average" it may equally be the very opposite. Take somebody who suffers from chronic anxiety, or works in chronically stressful conditions, or new mothers after a traumatic birth who also has irregular and insufficient sleep for months or years, or someone who has gone through some significant trauma, where the sympathetic system and the accompanying hormones are activated more frequently and for longer. That "average" is going to be higher, and perhaps not insignificantly so.
What I'd love to understand is what has happened to this line of research. If since the start of the 20th century , and right through to the 1980s the role of the nervous system was at least being investigated in thryoid pathology, where has this gone? If we know that sympathetic system activation generates thyroid production independently of TSH, why don't doctors mention this to patients and assess the possible impact of this in treatment plans?
Because in the mid 80's supersensitive TSH tests came along and in concert with the finding that there is a logTSH- FT4 linear relationship, the era of TSH only diagnostic testing was born. The total answer. Cheap, easy and totally misleading. Only now are we finding how misleading it is.
Also consider Graves disease. If you have TSH in the blood approaching zero, and TSH receptor antibodies blocking thyrotropin signalling, what is actually driving the overproduction of T3 in the thyroid?
You are asking questions the field cannot fully answer. See this in Wikipedia:
Scientists do not know the exact cause of Graves' disease. We know that, somehow, the body's immune system is tricked into targeting receptors on the thyroid gland, causing hyperthyroidism. Research suggests that Graves' disease may be caused by a combination of genetic and environmental factors.5 Apr 2019
So catecholamines may very well have a role by stress and thyroid stimulation
Yes, I came across this same explanation in papers I was reading yesterday. What I am puzzled by, is why would the blocking of TSH receptors by the immune system cause a proliferation of a process that is stimulated BY the TSH. Surely it would be the other way around if that was the only factor at play.
It may be something to do with the process of ubiquitinisation. The Deiodinase-2 that coverts T4 into T3 in the body is moderated in its activity by proteins called ubiquitin. For example if you give T4 in therapy this in excess can inhibit the deiodinases by ubiquitin interference. It's very complicated and I'm sure there's lots to find out. If these proteins are also affected by the antibodies, then this could boost conversion into T3 considerably into the hyper range. I can't see the thyroid being affected direct in this way because the T3 shunt there needsTSH to work.
The one doctor I have come across that is actually reversing Graves in patients, is doing this through the sedation of the nervous system alone. It seems to have a very significant effect on hyperthyroidsm in partuclar. In Hashimotos too, but it takes longer to work, because of the tissue damage the recovery process is longer.
I'm trying to understand why this works, and also why he is the only one doing this and no one else is.
The best summary I've seen of current info on Graves is:
Etiology is unknown, but there is a genetic predisposition to the disease. Both autosomal dominant and autosomal recessive inheritance have been suggested. May be multifactorial.
Production of thyroid-stimulating IgG immunoglobulins (TSI), which are antibodies to the thyroid stimulating hormone (TSH)-receptors of the thyroid follicular cell. TSI activate TSH receptors, which induces the intracellular production of cyclic AMP via adenylate cyclase, leading to excessive thyroid hormone secretion.
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