Review Article

Wilson's Temperature Syndrome - A Reversible Thyroid Problem.

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 the Doctor's 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.

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.

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 was based on clinical information in the first place! Obviously, clinical evaluation needs to be the gold standard for the evaluation of patients, since it is the gold standard for the evaluation of the thyroid blood tests.

Bibliography

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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. (Current Head of the American Board of Endocrinology and Metabolism):Thyroid Function Tests. Postgraduate Medicine Vol. 85, No. 5:333 - 352, 1989