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Thyroid replacement


Date: Sat, 1 Apr 1995 13:33:03 -0800 (PST)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Thyroid replacement

It has been my experience that people on thyroid replacement therapy because of a previously diagnosed hypothyroidism must be given enough thyroid to keep the TSH in the lowest quartile of the normal range. Endocrinologists seem to be satisfied to give just enough thyroid replacement to get the TSH into the highest quartile of the normal range, but many patients will not respond to their antidepressants unless the TSH is reduced considerably below that. I am not suggesting hypermetabolic doses such as are used in the treatment of rapidly cycling bipolar patients -- just doses that will correct the hypothyroid state.


Date: Wed, 22 Nov 1995 02:12:38 -0500
From: "Paul Luisada, M.D." <pvl2@cornell.edu>
Subject: Thyroid replacement

My experience has been exactly that of Dr. Goldberg. In the good old days (before managed care) I'd do TRH stimulation tests on these patients to "prove" their hypothyroidism to endocrinologists or internists who often objected to increases in their Synthroid on the grounds that they were "clinically euthyroid." The TRH tests nearly always showed that they were on inadequate replacement therapy.

Our medical colleagues often fail to appreciate the notion that depression secondary to inadequate thyroid replacement is prima facie evidence that the patient is not "clinically euthyroid." Combined with the current fashion for therapeutic minimalism, this means that a patient often has their Synthroid lowered every few months, sometimes until they are off it completely. ("See, I told you that Old Family Doctor shouldn't have put you on this hormone--you didn't need it, and you've taken it for all these years for no good reason.") Three to twelve months later, the depressive symptoms begin to appear. Six months after that, the patient is started on an antidepressant by the internist and may go through more than one unsuccessful antidepressant trial before the psychiatric referral is made. By that time, the thyroid reduction has become a distant memory and appears to bear no relation to the depression because of the delay in the onset of the symptoms.


Date: Fri, 1 Dec 1995 11:13:01 -0500
From: Stephen Sokolov <sokolovs@fhs.csu.mcmaster.ca>
Subject: Thyroid replacement

On Thu, 30 Nov 1995, Peter Lucas wrote:

I've recently had 2 female patients develop slightly elevated TSH levels with free T4 in lowest quartile while on lithium for bipolar disorder. They are both doing well.
In general, our practice is to observe such patients for development of symptoms (either a worsening of their mood state or symptoms of hypothyroidism) prior to instituting thyroid replacement therapy. This approach may be particularly relevant given that thyroid replacement therapy for hypothyroidism may be associated with an increased risk of osteoporosis.


Date: Wed, 6 Dec 1995 09:05:15 -0500 (EST)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Osteoporosis from thyroid replacement

I would appreciate a reference to exogenous thyroid causing clinically significant osteoporosis. I searched the literature and found references to changes in femoral shaft cortical thinning by densitometry but little else. My concern is that I have been frequently warned off thyroid augmentation in low but euthyroid patients on these grounds but I suspect that this may be turf rather than clinical reality.


Date: Wed, 6 Dec 1995 10:16:38 -0500
From: Stephen Sokolov <sokolovs@fhs.csu.mcmaster.ca>
Subject: Osteoporosis from thyroid replacement

My understanding of the issue is that while it is well recognized that hyperthyroidism is associated with increased risk of osteoporosis, there is some controversy whether excessive thyroid replacement is also associated with a greater degree of decreased bone density.

Based on my conversations with a number of endocrinologists, including Enrique Silva, there still may be some concern with "optimal" thyroid replacement therapy. The rationale for this is that since exogenous T4 is relatively inefficient at suppressing TSH, higher than normal serum levels of T4 are required.


From: "Watsky, Eric J." <WATSKYE@dirpc.nimh.nih.gov>
Subject: Osteoporosis from thyroid replacement
Date: Wed, 06 Dec 95 11:19:00 est

There is an excellent review of thyroxine replacement therapy by Toft in the NEJM 1994; 331 (3): 174. He sites a number of references regarding bone resorption and excessive thyroxine replacement that are based on markers such as serum calcium, serum parathyroid hormone, serum osteocalcin and urinary pyridinium cross-links. Eleven studies of thyroxine replacement in women are cited with some but not all finding significantly decreased bone mineral density. Two studies note no evidence of an increased rate of fracture. The author notes that "although overtreatment with thyroxine is likely to be a minor factor in the development of osteoporosis, if it is a factor at all, it is an argument against overtreatment of patients with primary hypothyroidism."


Date: Sun, 17 Dec 1995 12:51:01 -0500 (EST)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Thyroid replacement

Endocrinologists often treat thyroid deficiency by the lab test. There is a study indicating that once receiving exogenous thyroid the tests become unreliable. I would consider an empirical trial of increasing T4 + T3 to high normal levels. You should know in 4-6 weeks.


Date: Mon, 18 Dec 1995 17:19:36 -0500 (EST)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Thyroid replacement

I have the belief that a mix of T4 and T3 works best. The de-iodinase system is very open to pharmacological inhibition (Whybrow P).


Date: 18 Dec 95 00:09:15 EST
From: Troy Caldwell <75112.1676@compuserve.com>
Subject: Thyroid replacement

I have also replaced T4 until free T4 is high-normal, which has worked well to get more mood effect from thyroid replacement. Another tool some generalists use is measuring axillary basal body temp (before arising in AM) and replacing until it reaches about 98 degrees F (assuming they are not hyperthyroid). The take home message here is the usual lab tests cannot always be trusted to do the job of replacement optimally.


Date: 20 Dec 95 00:16:01 EST
From: Troy Caldwell <75112.1676@compuserve.com>
Subject: Thyroid replacement

The protocol, which I got from a letter to the editor in the Am. J. Psychiatry a couple of years ago, which I like is to measure free T3 and free T4 as the key tests. The author considered these much more accurate and clinically helpful than the routine T7. Then replace T4 (Synthroid) until free T4 is in the high-normal range. If the symptoms are still problematic, recheck the free T3 and then start adding T3 (Cytomel) until free T3 is high-normal also. If T4-to-T3 conversion is adequate, you may not even have to use Cytomel because T3 will increase along with Synthroid addition.


Date: 8 Feb 1996 11:06:54 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: T3 + T4 for thyroid replacement

I have very often found occult thyroid problems as a source of treatment resistance. The usual thyroid screen -- T3RU, T4, FTI, TSH -- is not adequate. I have noticed that many treatment resistant patients have a "normal" thyroid screen but will have low levels of T3 (T3RU is unrelated to level of T3). This abnormality is likely to be detectable with a TRH stimulation test as well. For these patients I have found it necessary to add Cytomel and Synthroid (interestingly, if you add only Cytomel, you can drive down the TSH and the net result can be a decrease in both T3 and T4).


Date: 9 Feb 1996 13:21:05 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: T3 + T4 for thyroid replacement

In some of these patients, trials of Synthroid did not change their clinical status although I did not at that time monitor the changes in their T3.

Recently we have been doing a lot of T3 augmentation in these patients and have consistently found that this suppresses TSH and T4. Ironically, it has on several occasions also caused a drop in T3. As a result, my current technique is to add both Cytomel and Synthroid. I suspect that the source of the low T3 in these patients is a deficit in the peripheral conversion of T4 to T3 which might explain why, for some patients, T4 augmentation would not be effective.


Date: Thu, 8 Feb 1996 19:43:04 -0800
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: T3 + T4 for thyroid replacement

While most endocrinologists to whom I have spoken believe that T3 and T4 do an equally good job of correcting hypothyroidism, it has been my experience that people with depressions and hypothyroidism who take T3 + T4 do better than those who take only one of these thyroid replacements.


Date: Fri, 9 Feb 1996 23:42:58 -0800
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: T3 + T4 for thyroid replacement

I often start people on 25 mcg of each and try to increase the dose to 50 mcg of each. I end up paying much more attention to the clinical response than to anyhting else, but monitor T3, T4, and TSH periodically.


Date: Sun, 11 Feb 1996 00:52:29 -0500 (EST)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Thyroid replacement

The major medical red herring is osteoporosis which is a problem in postmenopausal wopmen correctable by estrogen.

For useful medical references try:

Wartofsky L. Levothyroxine therapy and osteoporosis. An end to the controversy? Archives of Internal Medicine. 155 (11): 1130-1, 1995 Jun 12

Florkowski CM, Brownlie BE, Elliot JR, Ayling EM, Turner JG. Bone mineral density in patients receiving suppressive doses of thyroxine for thyroid carcinoma. New Zealand Medical Journal. 106 (966): 443-4, 1993 Oct 27.

There is a turf battle here but i handle thyroid myself rather than depend on an unstable alliance.

I use T3 + T4 and aim for .1 mg T4 + 50 mcg T3. For uselessness of thyroid indices once exogenous thyroid given, see Fraser WD et al. Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? Brit Med J. 293:808-810, 27 Sept 1986.


Date: Sun, 11 Feb 1996 10:23:02 -0800
From: tgarton@ix.netcom.com (Theresa Garton )
Subject: T3 + T4 for thyroid replacement

I have been following free T3 and free T4 recently (after a suggestion on this list) and have found it enormously helpful with my patients. I have also found the drop in T4 with T3 supplementation, and that T4 very often does not correct low T3.

I have been using the T4 + T3 combo and am glad to see this matches others' practices. This combo seems to work well. It has made a difference in mood/energy improvement, though this is not always dramatic. The thyroid seems particularly helpful with stubborn sleep problems. Many of these pts have already had thyroid studies which have been deemed within normal limits by internists, but T3/T4 levels are in the lower 1/2 of the normal range, or more often, borderline low.


Date: Sun, 11 Feb 1996 23:42:28 -0800
From: jgmd@mindlink.bc.ca (Jane Garland)
Subject: T4 drop with T3

It is my understanding that T3 is produced from T4 and that T3 may be what the brain detects and uses to adjust TSH level. Therefore if you supplement with T3, the body produces less TSH and less T4, but T3 is high because you gave it.


Date: Sun, 28 Apr 1996 23:02:06 -0400 (EDT)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Thyroid replacement

On Sat, 27 Apr 1996 rbrand@MEM.po.com wrote:

Dear Dr. Klein, I am now more confused than ever. Would you explain or provide a reference for the relationship between these various thyroid moieties and how to use labs to follow progress and determine which, T3 or T4, should be increased or decreased and when?
I don't blame you for being confused. The facts as I see them are patients with hypothyroidism are both prone to depression and lose benefit or are not benefited by antidepressants. It is not clear if any given person has receptor resistance to T3, antibody blockade to TRH or TSH, deiodinase inhibition, iodide uptake failure, transthyretin deficiency in transferring T4 into CSF, or god knows what other defect we know zippo about. We also have both controlled and anecdotal data suggesting thyroid supplementation may help when all else fails. Also the initial calibrations of blood levels against clinical diosease showed substantial insensitivity. The downside to thyroid supplementation is not evident. Current thinking is osteoporosis is only a problem in postmenopausal women and is blocked by reasonable estrogen supplementation.

Therefore when in trouble try T4/T3, monitor pulse, blood pressure, and irritability and use labs skeptically.

The appropriate trials on treatment resistant depression are slim to non-existent. That's what we need but damned difficult to do. So we are stuck with clinical inference in a non-dangerous intervention.


Date: Mon, 5 May 1997 22:07:19 -0400 (EDT)
From: "Paul Luisada, M.D." <pvl2@cornell.edu>
Subject: Thyroid replacement

Hypothyroid patients -- especially those who have been so for some time -- sometimes develop an exquisite sensitivity to thyroid hormones, and can develop thyrotoxic-like symptoms even on minimal initial replacement doses. This happens, at first, when they are put on replacement therapy.


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