Almost every physician remembers seeing a patient in a medical intensive care unit and/or surgical intensive care unit who appeared edematous, obtunded, with periorbital edema, and a swollen tongue. Such patients are often seen to have fluid compartment abnormalities and metabolic disturbances (almost to the point of metabolic collapse). In the context of Wilson's Temperature Syndrome are these abnormalities very difficult to understand? In November of 1988 Dr. Howard Silverman and his associates at the University of Southern California and the Los Angeles County - USC Medical Center reported a study in which the thyroid function tests were observed in 73 patients within 48 hours of admission to an intensive care unit. When the thyroid indices were stratified to see which tests, if any, were predictive in terms of outcome, the mortality rate was found to be significantly increased among those patients having low T4 or T3; or high T3 uptake or RT3 values exceeding 100 nanograms per deciliter. It is significant to me in these findings that low T3 and elevated RT3 were more likely to be found in patients who subsequently died.

Another study in the Japanese medical journal titled Nippon Geka Gaika Zashi, Dec. 1988, showed that dogs in cardiogenic shock were more likely to survive than the controls when administered T3 therapy and were less likely to survive than the controls when administered RT3. These studies suggest that peripheral thyroid hormone system function can sometimes mean the difference between life and death.

Is it any wonder that the critically ill trauma patient or a patient recovering from major surgery might experience a clinically significant T4 to T3 conversion impairment? Such an impairment might not be inappropriate but it may very well be maladaptive. Some might consider T3 therapy to be a less than natural influence in such a circumstance, but it is no less natural than IV fluids, gastric suctioning, respirators, electrolyte replacement, antibiotics, cardiac medications, blood transfusions, and most every other "unnatural" modality used in the care and treatment of the critically ill. I look forward to the time that body temperature abnormalities are among the first things considered in the care and treatment of illness rather than the last.

There will come a time in the near future (the technology is already available) when a specially programmed pump will infuse just the right amount of T3, 24 hours a day in order to provide for optimal body temperature patterns for optimal clinical functioning and healing (especially in the critically ill). Body temperature patterns can be monitored via probe 24 hours a day and stored in a data base. The specially programmed pump can then use this information to calculate the proper infusion rate (almost like an artificial thermostat). And when this modality is implemented I imagine that it will make all the difference in the world in the survival and recovery and quality of life of many patients who are critically ill and severely injured and perhaps even those battling cancer and AIDS.
 

Patient Education Aids
The book, Wilson's Temperature Syndrome - A Reversible Thyroid Problem, has proven to be an excellent patient education aid. It has made a vast difference in how well the patients understand and recognize the manifestations, the pathophysiological mechanism, and rationale for treatment of Wilson's Temperature Syndrome. And therefore, there is much better patient compliance and far less time needed for patient orientation. I, personally, was quite surprised at what a difference it makes. I always try to make a point of making sure that the patient understands very well all the issues pertinent to his/her treatment. I feel as if I do pretty well at explaining everything, and I'm sure to answer as well as I can any questions the patient might have. So imagine my surprise when my patients read the book when it came out, and many exclaimed, "Oh-h-h, now I understand what's going on, and reading that book was like reading the story of my life, and I'm sure now more than ever that we're on the right track." The amazing thing was that these patients were ones that I had thought I had thoroughly educated. These were patients with whom I had personally spent a lot of time training over about 6 months during about 8 or more visits. If patients read the book, it saves everyone a lot of time, and many take great comfort in reading it. Having read the book, patients are much less likely to use the medicine inappropriately because of faulty assumptions. The book answers for the patients most of the questions that come up during treatment. Understanding better the management and the expected clinical course helps patients with longer-standing cases that require more management to experience less frustration and discouragement. So that patients can conveniently obtain a copy of the book from their doctor, the publisher will wholesale copies to physicians (1-800-621-7006).

Also, the Wilson's Temperature Syndrome Patient Instruction Sheet (see page 211-214) (or click here to see online version) is printed on one sheet of paper and is designed to quickly convey all the information patients need to know to get started on the treatment. It is available in quantities of 20, 50, and 100. It explains certain important principles, and contains specific instructions about the treatment. It explains how to take, average, and log temperatures; how to take the medicine; what side effects may occur and why, and what to do about them; what one might expect from the treatment. In short, it removes much of the burdens and difficulties on patients and doctors of implementing this approach.

Insurance
Claims can be submitted for: 783.9 Wilson's Temperature Syndrome (persistently impaired conversion of T4 to T3 brought on by a major stress and characterized by a consistently low body temperature). The preceding code, diagnosis, and definition should be included on superbill and claim form. Treatment for Wilson's Temperature Syndrome is usually covered by insurance companies but letters of explanation are sometimes requested. They can include presenting complaints, clinical presentation and reason for suspected diagnosis. Patient's response to therapeutic trial may also be included, if available. Wilson's Temperature Syndrome can be considered a subset of Hypometabolism but may be given a separate code by ICD-9 if a separate code is decided to be advantageous.

Informed Consent
Proper informed consent is an important tool that provides both physician and patient the necessary opportunity to make informed decisions. Informed consent has become a familiar part of the practice of medicine, and seems to be appreciated by the patients. An extremely frank consent form that errs on the side of overstating the risks, while referring to alternative approaches and risk of nontreatment has a couple of advantages. One, it reinforces to the patients that they are anything but being "talked into" taking treatment. Two, patients are more likely to take their treatment seriously with better compliance (which is quite important especially in terms of obtaining optimum benefit from treatment). Three, patients are reminded of the inexact nature of the practice of medicine which helps allay any unrealistic expectations and misunderstandings that might create problems down the road. Finally, since the potential benefit from successful treatment of Wilson's Temperature Syndrome can be so great (almost too good to be true), strongly worded consent forms that err on the side of overstating the risk help balance the input so the patients can hopefully make a more reasonable, conscious decision about whether they really want to pursue treatment. It is easy, and well worth the time to get unusually good informed consent.
 

The following is an informal review article with references to medical journals. There are numerous articles in the medical literature of which the cited references are representative.

Wilson's Temperature Syndrome: The cluster of often debilitating symptoms especially brought on by significant physical, or emotional stress that can persist even after the stress has passed, which responds characteristically to the special thyroid hormone treatment method recently developed (see this manual). It is characterized by a body temperature that runs on average below normal, and routine thyroid blood tests are often in the "normal range."

There is a very large body of information available in the medical literature about the thyroid hormone system. It has become expedient for some of this information to be organized under separate headings, for ease of reference, with respect to problems, their characteristics, and their management. A portion of the information comes to mind when one refers to "primary hypothyroidism," for example. Similarly, "secondary hypothyroidism," and "tertiary hypothyroidism," are terms that can apply to slightly different portions. In science, when information is added or emphasis is changed it is sometimes convenient to apply different terms to apply to the different portions of information. For example, the terms "secondary" and "tertiary" hypothyroidism were coined to distinguish them from "primary" hypothyroidism, and to therefore facilitate communication and more appropriate and effective diagnosis and management of thyroid system problems. Unfortunately, information that obviously has important clinical implications has been available for years yet has continued to be overlooked, and has not been satisfactorily collected or applied under any term.

"Recent data on thyroid hormone production and metabolism have altered concepts of normal thyroid physiology and have many clinical implications as well... These new data have forced a reassessment of long held views of thyroid hormone production and have important clinical implications as well."1

It would be cumbersome to refer to, discuss, or order a pizza if there was no term for it. The collection of the medical information above I have given the term Wilson's Temperature Syndrome. It is a cluster of seemingly unrelated symptoms because at "various stages of illness hypothyroid patients often have subtle symptoms or complaints and may be diagnosed erroneously as having an unrelated problem..."2 "The key to accurate diagnosis of thyroid disease is clinical suspicion of subtle signs...A high index of suspicion is needed to identify 'symptoms of living' as potential symptoms of thyroid disease."3

It has been well documented that the conversion of T4 to T3 decreases under periods of physical injury, and chronic or acute illness.1,4 Conversion of T4 to T3 can also be impaired by glucocorticoids,1 levels of which are known to increase under periods of mental, and emotional stress. In addition, T4 to T3 conversion has been shown to decrease under fasting conditions.5 Fasting conditions have also been shown to produce a slowing of the metabolism (as measured by energy expenditure).6,7 And sometimes fasting can result in a persistent slowing of the metabolism even after the starvation is over.6,8,9 Other findings have also demonstrated a peripheral autoregulatory mechanism of thyroid hormones. 10,11

Therefore, in considering thyroid hormone production and its regulation, it is necessary to consider not only the function of the hypothalamic-pituitary-thyroid axis, but also the activity of the pathways of extrathyroidal T4 metabolism. Since monodeiodination of T4 may yield T3 which is more active than T4, or RT3, which has little or no thyroid hormone biological activity, it is obvious that alterations in the pathways of extrathyroidal T4 deiodination may profoundly affect the availability of biologically active thyroid hormone.1

Too often physicians do consider only the hypothalamic-pituitary-thyroid axis. Physicians demonstrate this by concluding that just because the patient's blood tests are normal (indicating normal glandular function), that necessarily the thyroid hormone system is working appropriately.

The points we have discussed above have "important clinical implications.''1 Namely, a patient can have insufficient availability of the biologically active hormone (leading to classic hypothyroid symptoms) in the face of normal blood tests, especially under conditions of stress. "Is this alteration in T4 metabolism beneficial or deleterious in the adaptation to illness?''1 Are these symptoms adaptive or maladaptive? Apparently, these symptoms are easily recognized as being maladaptive and needing treatment by physicians judging from how such patients are often handled. A patient may develop classic symptoms of decreased thyroid system function (DTSF) after a major stress. And when while caring for such a patient the physician notices that the symptoms persist even after the stress has passed, he and the patient often make the determination that something is wrong (maladaptive), and that the symptoms are in need of treatment. Since many doctors consider only the hypothalamic-pituitary-thyroid axis, and since many are not aware that people can develop a sustained depression of the metabolic rate,8 an impairment in the thyroid hormone system (which regulates the metabolic rate) is often not considered. Instead, such patients are often far less appropriately and less effectively treated one symptom at a time with antidepressants, diuretics, headache medicines, acne medicines, etc. When one considers not only the hypothalamic-pituitary-thyroid axis but also peripheral metabolism and autoregulation of thyroid hormones, it is easy to understand how a patient can develop classic DTSF symptoms from a stress, how the depression of the metabolic rate could be sustained, and why the patient might respond so well to proper T3 therapy (another important clinical implication).

Any mechanism that can malfunction, will malfunction at one time or another. "The finding that serum T3 and RT3 concentrations may change in opposite directions in certain situations clearly suggests that deiodination is not a random process and is subject to some form(s) of regulation.''l It has been shown that RT3 can inhibit the conversion of T4 to T3.12,13 And, it has been speculated for years that a transient elevation in RT3 could then secondarily inhibit T4 to T3 conversion peripherally (resulting in a sustained or persistent impairment and the associated symptoms).1 14

This could explain the sustained or persistent depression of the metabolic rate/ metabolic state often observed in people who have undergone severe dieting or stress.8 It is interesting that increased RT3 levels and decreased T3 levels are so significant that they can also sometimes mean the difference between life and death.15,16

Low body temperature or hypothermia is a well known finding in decreased thyroid hormone system function.2 When the availability of biologically active hormone decreases, because of decreased production of thyroid hormone by the thyroid gland, then the body temperature characteristically drops. Likewise, since "it is obvious that alterations of extrathyroidal T4 deiodination may profoundly affect the availability of biologically active thyroid hormone,''1 it is also obvious that impaired T4 to T3 conversion can be characterized by a low body temperature. Since thyroid medicines are to be given and adjusted in every case based on "clinical response and laboratory findings,''17 then it is logical that the body temperature (a part of the clinical picture and, therefore, of the clinical response) could be used in helping to adjust a patient's thyroid medicine. "More information often can be brought to the physician with only the aid of an ordinary thermometer than can be obtained with all other thyroid function tests combined."18

Also, "regardless of the testing approach, authorities caution that biochemical evaluation is only one aspect of diagnosis. The key to accurate diagnosis of thyroid disease is clinical diagnosis of subtle signs."3 This caution underscores the fact that a patient may have normal blood tests, yet still be suffering from classic symptoms of decreased availability of biologically active thyroid hormone.

"Thyroid function tests have certain limitations that must be recognized before they can be used effectively. Most important is the physician's awareness that the tests do not replace good clinical judgment and should not be used alone to confirm a diagnostic impression or to dictate therapy.''19 They do not replace good clinical judgment and should not be used alone to dictate therapy, or the withholding of it because they can be wrong/misleading/inconclusive. Thyroid blood tests, like all tests, have false positives and negatives. Even expensive and sophisticated thyroid tests can have about 20% false negatives (when tests are normal even though the patient may benefit from thyroid treatment).19

Tests do not replace good clinical judgment because the clinical picture often has more predictive value than the tests. This should not be too surprising because up to 85% of all medical diagnoses are based on the patients' descriptions of their symptoms. So patients may have deficient availability of biologically active thyroid hormone that should be treated even when thyroid blood tests are normal. To further emphasize the relative value of clinical information vs. biochemical information in the evaluation of thyroid system status, it should be pointed out that third generation TSH assays are now regarded as the most accurate test for thyroid function. Yet, this determination has been made based on clinical information. So one can see how clinical information needs to be the gold standard for the evaluation of patients, since it is the gold standard for the evaluation of the blood tests.
 

1.	Schimmel M
	Thyroidal and Peripheral Production of Thyroid Hormones. Annals of Internal Medicine 87:760-768,1977
2.	Karkal S
	Overcoming Diagnostic and Therapeutic Obstacles in Hypothyroidism. Emergency Medicine Reports 11,23:219-227, 1990
3.	Hershman J
	Getting the Most from Thyroid Tests. Patient Care April 30, 1989
4.	Felicetta J
	Effects on Illness on Thyroid Function Tests. Postgraduate Medicine 85, 8:213-220, 1989
5.	Vagenakis AG
	Diversion of Peripheral Thyroxine Metabolism from Activating to Inactivating Pathways During Complete Fasting. J Clin Endocrine Metab 41:191-194, 1975
6.	DeBoer J
	Adaptation of Energy Metabolism of Over Weight Women to Low - Energy Intake Studied With Whole -body calorimeters. Am J Clin Nutr 44:585-95, 1986
7.	McCarter RJ
	Transient Reduction of Metabolic Rate by Food Restriction. Am J Clin Nutr 49(1):93-96, 1989
8.	Elliot DL
	Sustained Depression of the Resting Metabolic Rate After Massive Weight Loss. Am J Clin Nutr 49(1):93-6, 1989
9.	Leibel RL
	Diminished Energy Requirements in Reduced - Obese Patients. Metabolism 33(2):164-70, 1984
10.	Lum S
	Peripheral Tissue Mechanism for Maintenance of Serum Triiodothyronine Conversion in Man. Hormone Metabolism Research Suppl.14:74-79, 1984
11.	Nicoloff, JT
	Peripheral Autoregulation of Thyroxine to Triiodothyronine Conversion in Man. Hormone Metabolism Research Suppl. 14:74-79,1984
12.	Grussendorf M
	Pathways of Thyroxine Monodeiodination in Rat Liver Homogenate. Acta Endocr. 84, Suppl. 208:15-16, 1977
13.	Chopra IJ
	A Study of Extrathyroidal Conversion of Thyroxine(T4) to 3,5,3' - triiodothyronine(T3) In Vitro. Endocrinology 101:453-463, 1977
14.	Szabolcs I
	The Possible Reason for Serum 3,3'5' - (Reverse) Triiodothyronine Increase in Old People. Acta Medica Academia Scientaruim Hunaricae Tomes 39(1-2):11-17, 1982
15.	Dr. Silberman
	Thyroid Values Reflect Outcome of Intensive Care Units Patients. Family Practice News Magazine Nov.:36, 1988
16.	Shigenmatsu H
	The Effect of Triiodo-thyronine(T3) and Reverse Triiodothyronine (RT3) on Canine Hemorrhagic Shock. Nippon Geka Gakkai Zasshi 89(10):1587-93, 1988
17.	1986 Physicians Desk Reference
	Medical Economics Company
18.	Barnes Broda O
	Hypothyroidism: The Unsuspected Illness Harper & Row, 1976
19.	Mazzaferri Ernest L., M.D.
	Thyroid Function Tests. Postgraduate Medicine Vol. 85, No. 5:333 - 352, 1989