Monthly Miracles

by Michael Gerber, MD, HMD

The Massive Underutilization of Thyroid Hormone Replacement Therapy

Part 1

Epidemic Hypothyroidism

Hypothyroidism its causes, diagnosis and treatment is an extremely multifactorial business. Misleading and misunderstood thyroid laboratory measures (TSH, T4) overshadow many important signs and symptoms of the physical examination. Environmental and genetic inhibitory factors are legion at every level of central and tissue thyroid receptors. Untreated thyroid dysfunction is responsible for untold misery such as unnecessary hysterectomies from menorrhagia, needless antidepressant drug administration and pain medication. Quality of life issues such as chronic fatigue, obesity, infertility and up to 300 different health issues could be solved with proper thyroid support and lifestyle changes.

Although none of this information is particularly new, there are many recent citations I will review which, I hope, will embolden doctors and patients who may not have heard them to resist the standard, allopathic only line that unless thyroid blood test parameters are grossly abnormal they don’t need exogenous thyroid support. In my 41 years of medical practice, we have had not just monthly but daily and weekly miracles related to sensitive thyroid replacement therapy. All of medical prescribing is an art as well as science and particularly so for thyroid. Balancing adrenal support is critical to avoid overstimulation during gentle titration of the thyroid hormone. I do like to repeat my “cup of coffee” rule of thumb. Patients who can drink a pot of coffee and go right to bed and sleep well can usually replace thyroid at a more vigorous rate than the patient who smells some coffee and is up for two days. Those who can’t stand any stimulation need to be started from 1/16 grain or less of my favorite thyroid, NatureThyroid (Westhroid) and the new even cleaner (fewer additives and excipients) NatureThyroid P especially for the more allergically sensitive patient.

Many good books and treatises have been written on hypothyroidism. The first that I read was Hypothyroidism The Unsuspected Illness, by Broda Barnes, MD. Stephen Langer, MD, wrote Solved the Riddle of Illness. More Lately Mark Starr, MD, wrote Hypothyroidism Type 2: The Epidemic. Also Stop The Thyroid Madness by Janie A Bowthorpe, MEd. Older endocrinology texts such as Wilson’s Endocrinology remind us that a high cholesterol level was the poor man’s measure of hypothyroidism. Extraordinarily complex biochemical evaluation of thyroid status will also be presented for informational contrast.

What About TSH Testing?

A good article gleaned from the National Academy of Hypothyroidism documents some convincing opinions and data about the unreliability of TSH as a reflection of thyroid status.

“The TSH is thought to be the most sensitive marker of peripheral tissue levels of thyroid, and it is erroneously assumed by most endocrinologists and other physicians that, except for unique situations, a normal TSH is a clear indication that the person’s tissue thyroid levels are adequate. A more thorough understanding of the physiology of hypothalamic-pituitary-thyroid axis and tissue regulation of thyroid hormones demonstrates that the widely held belief that the TSH is an accurate marker of the body’s overall thyroid status is clearly erroneous.

The TSH is inversely correlated with pituitary T3 levels but with physiologic stress, depression, insulin resistance and diabetes, aging, calorie deprivation (dieting), inflammation, PMS, chronic fatigue syndrome and fibromyalgia, obesity, and numerous other conditions, increasing pituitary T3 levels are often associated with diminished cellular and tissue T3 levels and increase reverse T3 levels in the rest of the body.^{1–62,108–114,116,117} The pituitary is both anatomically and physiologically unique, reacting differently to inflammation and physiologic stress than every other tissue in the body.^{1–20,50–52,62,63} The conditions above stimulate local mechanisms to increase pituitary T3 levels (reducing TSH levels), while reducing T3 levels in the rest of the body.^1–63 Thus, with physiologic or emotional stress, depression, or inflammation, the pituitary T3 levels do not correlate with T3 levels in the rest of the body, and thus, the TSH is not a reliable or sensitive marker of an individual’s true thyroid status.

Value of Serum T4

The suppression of TSH with physiologic and emotional stress and illness suppresses the production of T4, which would tend to lower serum T4 levels.^{1,2,9,64–68} In the presence of such conditions, there are, however, competing effects that result in an increase in serum T4 while further reducing tissue levels of T3, making serum T4 (or free T4 a poor marker of tissue thyroid level, as is the case with the TSH. Such effects include a suppression of tissue T3 conversion (misleadingly increasing serum T4 levels)with an increased conversion of T4 to reverse T3 and an induced thyroid resistance with reduced uptake of T4 in the cells (misleadingly increasing serum T4 levels) in all tissues except for the pituitary.^1–74,76,85 Although all such effects reduced intracellular T3 in all tissues except for the pituitary, the serum T4 level can be increased, decreased or unchanged. Consequently, serum T4 levels oftentimes do not correlate with tissue T3 levels and, as with the TSH, the serum T4 level is often misleading and an unreliable marker of the body’s overall thyroid status. Many symptomatic patients with low tissue levels of active thyroid hormone but normal TSH and T4 levels significantly benefit from thyroid replacement, often with significant improvement in fatigue, depression, diabetes, weight gain, PMS, fibromyalgia and numerous other chronic conditions.^86–99

With an understanding of thyroid physiology, it becomes clear why a large percentage of patients treated with T4 only preparations continue to be symptomatic. Thyroxin (T4) only preparations should not be considered the treatment of choice and are often not effective in conditions associated with reduced T4 to T3 conversion, reduced uptake of T4, or increased T4 to reverse T3 conversion. With any physiologic stress, (emotional or physical), inflammation, depression, aging or dieting, T4 to T3 is reduced and T4 will be preferentially converted to reverse T3, which acts as a competitive inhibitor of T3 (blocks T3 at the receptor), reduces metabolism, suppresses T4 to T3 and blocks T4 and T3 uptake into the cell.^{12,14,18,35,41,53,69–74,85,100–114}

While a normal TSH cannot be used as a reliable indicator of global tissue thyroid effect, even a minimally elevated TSH (above 2) demonstrates that there is diminished intra pituitary T3 level and is a clear indication that the rest of the body is suffering from inadequate thyroid activity, because the pituitary T3 level is always significantly higher than the rest of the body and the most rigorously screened individuals for absence of thyroid disease have a TSH below 2 to 2.5.¹⁰⁶ Thus, treatment should likely be initiated in many symptomatic people with a TSH greater than 2. Additionally, many individuals will secrete a less bioactive TSH so for the same TSH level, a large percentage of individuals will have reduced stimulation of thyroid activity, further limiting the accuracy of TSH as a measure of overall thyroid status. Reduced bioactivity of TSH is not detected by current TSH assays used in clinical practice.

Due to the lack of correlation of TSH and tissue thyroid levels, as discussed, a normal TSH should not be used as the sole reason to withhold treatment in a symptomatic patient. A symptomatic patient with an above-average reverse T3 level and a below-average free T3 (a general guideline being a free T3/reverse T3 ratio less than 2) should also be considered a candidate for thyroid supplementation.^{13,18,69–75,85–106} A relatively low sex hormone binding globulin (SHBG) and slow Achilles reflex time can also be useful markers for low tissue thyroid and levels and can aid in the diagnosis of tissue hypothyroidism.^93,107,115

A study published in the Journal of Clinical Endocrinology and Metabolism assessed the level of hypothyroidism in 332 female patients based on a clinical score of 14 common signs and symptoms of hypothyroidism and assessments of peripheral thyroid action (tissue thyroid effect). The study found the clinical score and ankle reflex time correlated well with tissue thyroid effect but the TSH has no correlation with the tissue effect of thyroid hormones. ¹¹⁸ The ankle reflex itself had a specificity of 93% (93% of those with slow relaxation phase of the reflexes had tissue hypothyroidism) and a sensitivity of 77% (77% of those with tissue hypothyroidism had a slow relaxation phase of the reflexes), making both the measurement of the reflex speed and clinical assessment a more accurate measurement of tissue thyroid effect than the TSH.

A combination of the serum levels of TSH, free T3, free T4, reverse T3, anti-TPO antibody, antithyroglobulin antibody, and SHBG should be used in combination with the clinical assessment and measurement of reflex speed and basal metabolic rate to most accurately determine the overall thyroid status in a patient. Forgoing treatment based on a normal TSH without further assessment will result in the misdiagnosis and mismanagement of a large number of hypothyroid patients that may greatly benefit with treatment. Simply relying on TSH to determine the thyroid status of a patient demonstrates a lack of understanding of thyroid physiology and is not evidence-based medicine. In patients with elevated or high normal reverse T3 levels, T4 only preparations should not be considered adequate and T3 containing preparations, in particular timed released T3 should be considered the treatment of choice.”

Leptin Resistance and Abnormal Thyroid Lab Markers

Leptin resistance causes a diminished TSH secretion, a suppressed T4 to T3 conversion, an increase in reverse T3, an increase in appetite, an increase in insulin resistance, and an inhibition of lipolysis. These effects of leptin resistance on thyroid hormones contribute to the drop in
TSH and T3 levels that occur with dieting and results in decreased tissue thyroid action and a depressed metabolic rate that inhibits weight loss and promotes weight gain.

Leptin is secreted by fat cells and the levels increase with the accumulation of fat. Unfortunately, with the suppression of TSH that occurs with leptin resistance, the usual feedback mechanism is interrupted and a normal TSH level cannot be used to rule out a significant thyroid deficiency. Low intracellular leptin levels are inversely correlated with reverse T3, which may currently be the best marker, along with the T3/T4 ratio, for diminished T4 to T3 conversion and cellular hypothyroidism in chronic illness. Reverse T3 has been shown to be a more potent inhibitor of T4 to T3 conversion than PTU (propylthiouracil), a medication used to decrease thyroid hormone levels in hyperthyroidism.¹¹⁸

Remember that there are no T4 receptors in the human body, only T3 receptors.

Tune in next month for surprising environmental, chemical, genetic, and food blockers of thyroid function. There are up to 2500 of them.

Notes

1. Peeters RP, Geyten SV, Wouters PJ, et al. Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab. 2005;12:6498–6507.

2. Docter R, Krenning EP, de Jong M, et al. The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism. Clin Endocrinol (Oxf). 1993;39:499–518.

3. Fliers E, Alkemade A, Wiersinga WM. Thy hypothalamic-pituitary—thyroid axis in critical illness. Best Pract Res Clin Endocrino Metab. 2011;15(4):453–464.

4. Chopra IJ. Euthyroid sick syndrome: Is it a misnomer? J Clin Endocrinol Metab. 1997;82(2):329–334.

5. Van der Poll T, Romijn JA, Wiersigna WM, et al. Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J Clin Endocrinol Metab. 1994;79(5):1567–1572.

6. Stouthard JM, van der Poll T, Ender E, et al. Effects of acute and chronic interleukin-6 administration of thyroid hormone metabolism in humans. J Clin Endocrinol Metab. 1994;79(5):1342–1346.

7. Corssmit EP, Heylingenberg R, Endert E, et al. Acute effects of interferon-alpha administration on thyroid hormone metabolism in healthy men. Clin Endocrinol Metab. 1995;80(11):3140–3144.

8. Nagaya T, Fujieda M, Otsuka G, et al. A potential role of activated NF-Kappa B in the pathogenesis of euthyroid sick syndrome. J Clin Invest. 2000;106(3): 393–402.

9. Bianco AC, Salvatore D, Gereben B, et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodieidinases. Endocr Rev. 2002;23:38–89.

10. Chopra IJ, Huang TS, Beredo A, et al. Evidence for an inhibitor of extrathyroidal conversion of thyroxine to 3,5,3’-triidothyronine in sera of patients with nonthyroidal illnesses. J Clin Endocrinol Metab. 1985;60:666–772.

11. Peeters RP, Wouters PJ, Kaptein E, et al. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab. 2003;88:3202–3211.

12. Chopra IJ, Chopra U, Smith SR, et al. Reciprocal changes in serum concentrations of 3,3’,5–triiodothyronine (T3) in systemic illnesses. J Clin Endocrinol Metab. 1975;41:1043–1049.

13. Iervasi G, Pinitore A, Landi P, et al. Low-T3 syndrome a strong prognostic predictor of death in patients with heart disease. Circulation. 2003;107(5):708–713.

14. Peeters RP, Wouters PJ, van Toor H, et al. Serum 3,3’,5’-Triiodothyronine (rT3) and 3,5,3’-triodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J Clin Endocrinol Metab. 2005;90(8):4559–4565.

15. Wartofsky L, Burman K. Alterations in thyroid function in patients with systemic illness;the “euthyroid sick syndrome.” Endocr Rev. 1982;3(2):164–217.

16. Hennemann G, Everts ME, de Jong, et al. The significance of plasma membrane transport in the bioavailability of thyroid hormone. Clin Endocrinol. 1998;48:1–8.

17. Vos RA, de Jong M, Bernard HF, et al. Impaired thyroxine and 3,5,3’-triidothyronine handling by rat hepatocytes in the presence of serum of patients with nonthyoidal illness. J Clin Endocrinology Metab. 1995;80:2364–2370.

18. Chopra IJ, Solomon DH, Hepner GW, et al. Misleadingly low free thyroxine index and usefulness of reverse triiodothyronine measurement in nonthyroidal illnesses. Ann Intern Med. 1973;90(6):905–912. Usefulness of rT3 in NTI.

19. De Jong N, Docter R, Van Der Doek HJ, et al. Transport of 3,5,3’-triiodothyronine into the perfused rat liver and subsequent metabolism are inhibited by fasting. Endocrinology. 1992;131:463–470.

20. Mooradian AD, Reed RL, Osterweil D, et al. Decreased serum triiodothyronine is associated with increased concentrations of tumor necrosis factor. J Clin Endocrinol Metab. 1990;71(5):1239–1242.

21. Carrero JJ, Qureshi Arm Axelsson J, et al. Clinical and biochemical implications of low thyroid hormone levels (total and free form) in euthyroid patients with chronic kidney disease. J Intern Med. 2007;262:690–701.

22. 234. Zoccali C, Tripepi G, Cutrupi S, et al. Low triiodothyronine: a new facet of inflammation in end-stage renal disease. J Am Soc Nephrol. 2005;16:2789–2795.

23. Zoccali C, Mallamaci F, Tripepi G, et al. Low triiodothyronine and survival in endstage renal disease. Kidney Int. 2006;70:523–528.

24. Pingitore A, Landi P, Taddei MC, at al. Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am J Med. 2005;118(2):132.6.

25. Kozdag G, Ural D, Vural A, et al. Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur J Heart Fail. 2005;7(1):113–118.

26. Karadag F, Ozcan H, Karul AB, et al. Correlates of non-thyroidal illness syndrome in chronic obstructive pulmonary disease. Respir Med. 2007;101:1439–1446.

27. Kok P, Roelfsema FM, Langendonk JG, et al. High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction. J Clin Endocrinol Metab. 2005;90:4659–4663.

28. Parr JG. The effect of long-term metabolic control on free thyroid hormone levels in diabetics during insulin treatment. Ann Clin Biochem. 1987;24(5):466–469.

29. Dimopoulou I, Ilias I, Mastroakos G, et al. Effects of severity of chronic obstructive pulmonary disease on thyroid function. Metabolism. 2001;50 (12):1397–401.

30. Mariotti S, Barbesino G, Cauregli P, et al. Complex alterations of thyroid function in healthy centenarians. J Clin Endocrinol Met. 1993;77(5):1130–1134.

31. Nomura S, Pittman CS, Chambers JB, et al. Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis. J Clin InvestI. 1975;56:643–648.

32. Pingitore A, Galli EM, Barison A, et al. Acute effects of triiodothyronine replacement therapy in patients with chronic heart failure and low T3 syndrome: a randomized placebo-controlled study. J Clin Endocrinol Met. 2008;93:1351–1358.

33. 268. Premachandra BN, Kabir MA, Williams IK, Low T3 syndrome in psychiatric depression. J Endocrinol Invest. 2006;29:568–572.

34. Jackson I. The thyroid axis and depression. Thyroid. 1998;8(10):952–956.

35. Linnoila M, Lamberg BA, Potter WZ, Gold PW, Goodwin FK. High reverse T3 levels in manic and unipolar depressed woman. Psychiatry Research. 1985;6:271–276.

36. Kjellman BF, Ljunggren JG, Beck-Friis J, Wetterberg L. Revers T3 levels in affective disorders. Psychiatry Research. 1983;10:1–9.

37. 272. Stipcevic T, Pivax N, Kozaric-Kovacic D, Muck-Seler D. Thyroid activity in patients with major depression. Coll Antroplol. 2008;32(3):973–976.

38. Gold MS, Pottach LC, Extein I. Hypothyroidism and depression. JAMA. 1981;245(19):1919–1922.

39. Islam S, Yesmine S, Khan SA, Alam NH, Islam S. A comparative study of thyroid hormone levels in diabetic and non-diabetic patients. SE Asain J Trop Med Public Health. 2008;39(5):913–916. 50% reduction in free t3 in diabetics.

40. Carle A, Laurberg P, Pedersen IB, et al. Thyrotropin secretion decreases with age in patients with hypothyroidism. Clin Thyroidol. 2007;17:139–44.

41. Anneweike W, van den Beld AW, Visser TJ, Feelders RA, et al. Thyroid hormone concentrations, disease, physical function and mortality in elderly men. J Clin Endocrinol Metab. 2005;90(12):6403–6409.

42. Van Coevorden A, Laurent E, Decoster C, et al. Decreased basal and stimulated thyrotropin secretion in healthy elderly men. J Clin Endocrinol Metab. 1989;69: 177–185.

43. Rubenstein HA, Butler VPJ, Werner SC. Progressive decrease in serum triidothyronine concentrations with human aging: radioimmunoassay following extraction of serum. J Clin Endocrinol Metab. 1973;37:247–253.

44. Chakraborti S, Chakraborti T, Mandal M, et al. Hypothalamic-pituitary-thyroid axis status of humans during development of ageing process. Clin Chim Acta. 1999;288(1–2):137–145.

45. Piers LS, Soars MJ, McCormack LM, et al. Is there evidence for an age-related reduction in metabolic rate? J Appl Phys. 1998;85:2196–2204.

46. Poehlman ET, Berk Em, Joseph JR, et al. Influence of aerobic capacity, body composition, and thyroid hormones on the age-related decline in resting metabolic rate. Metabolism. 1992;41:915–921.

47. Magri F, Fioravanti CM, Vignati G, et al. Thyroid function in old and very old healthy subjects. J Endocrinol Invest. 2002;25(1):60–63.

48. Goichot B, Schlienger JL, Grunenberger F, et al. Thyroid hormone status and nutrient intake in the free-living elderly. Interest of reverse triiodothyronine assessment. Eur J Endocrinol. 1994;130:244–252.

49. Cizza G, Bradly LS, Calogero AE, et al. Central hypothyroidsm is associated with advanced age in male Fischer 344/n rats: in vivo and in vitro studies. Endocribology. 1992;131:2672–2680.

50. Cheron RG, Kaplan MM, Larsen PR. Psychological and pharmacological influences on thyroxine to 3,5,3’-triiodothyronine conversion and nuclear 3,5,3’-triiodothyronine binding in rat anterior pituitary. J Clin Invest. 1979;64:1402–1414.

51. Kaplan MM, Utiger RD. Iodothyronine metabolism in rat liver homogenates. J Clin Invest. 1978;61:459–471.

52. Kaplan MM. Subcellular alterations causing reduced hepatic thyroxine 5’-monodeiodinase activity in fasted rats. Endocrinology. 1979;104:58–64.

53. Portnay GI, O’Brien JT, Bush J, et al. The effect of starvation on the concentration and binding of thyroxine and triiodothyronine in serum and on the response to TRH. J Clin Endocrinol Metab. 1974;39:191–194.

54. Croxson MS, Hall TD Kletzky OA, Jaramillo JE, et al. Decreased serum thyrotropin induced by fasting. J Clin Endocrinol Metab. 1977;45:460–568.

55. Carlson HE, DRenick EJ, Chopra IJ, Hershman JM. Alterations in basal and TRH-stimulated serum levels of thyrotropin, prolactin and thyroid hormones in staved obese men. J Clin Endocrinol Metab. 1977;45:45:707–713.

56. Vinik AI, Kalk W, McLaren JH, Paul M. Fasting blunts the TSH response to synthetic thyrotropinreleasing hormone (TRH). J Clin Endocrinol Metab. 1975;40:509–511.

57. Azizi F. Effect of dietary composition of fasting induced changes in serum thyroid hormones and thyrotropin. Metab Elin Exp. 1978;27:935–942.

58. Brayshaw ND, Brayshaw DD. Thyroid hypofunction in premenstrual syndrome. NEJM. 1986;315(23):1486–1487.

59. Girdler SS, Pedersen CA, Light CK. Thyroid axis function during the menstrual cycle in women with premenstrual syndrome. Psychoneuroendocrinology. 1995;20(4):395–403.

60. Neek G, Riedel W. Thyroid function in patients with fibromyalgia syndrome. J Rheum. 1992;19(7):1120–1122.

61. Wikland B, Lawhagen T, Sandberg PO. Fine needle aspiration cytology of the thyroid in chronic fatigue. Lancet. 2001;357:956–57.

62. Chopra IJ. A study of extrathyroidial conversion of thyroxine (T4) to 3, 3’, 5-triiodothyronine (T3) in vitro. Endocrinology. 1977;101:453–463. Blocks T4 to T3 conversion.

63. Kaplan MM. Thyroxine 5’-monodeiodination in rat anterior pituitary homogenates. Endocrinology. 1980;106(2):567–576.

64. Wartofsky and Burman. Op cit.

65. Rothwell PM, Lawler PG. 1995 Prediction of outcome in intensive care patients using endocrine parameters. Crit Care Med. 23:78–83.

66. De Groot LJ. Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of the current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22:57–86.

67. Schilling JU, Zimmermann T, Albrecht S, et al. Low T3 syndrome in multiple trauma patients– a phenomenon or important pathogentic factor? Medizinische Klinik. 1999;3:66–69.

68. Girvent M, Maestro S, Hernandez R, et al. Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation. Surgery. 1998;123:560–567.

69. Chopra IJ, Williams DR, Orgiazzi J, SolomonDH. Opposite effects of dexamethasone on serum concentrations of 3, 3’,5’-triiodothyronine (reverse T3­) and 3,3,5’-triiodothyronine (T3). JCEM. 1975;41:911–920. Increased rt3 decrease t3 with steroids.

70. Danforth EJ, Desilets EJ, Jorton ED, Sims EAH, et al. Reiprocal serum triiodothyronine (T3) and reverse (rT3) induced by altering the carbohydrate content of the diet. Clin Res. 1975;23:573. Increased reverse T3 with carbohydrate diet.

71. Palmbald J, Levi J, Burger AG, Melade H, et al. Effects of total energy withdrawal (fasting) on the levels of growth hormone, thyrotropin, cortisol, noradrenaline, T4, T3, and rT3 in healthy males. Acta Med Scand. 1977;201:150.

72. Islam S, Yesmine S, Khan SA, Alam NH, Islam S. A comparative study of thyroid hormone levels in diabetic and non-diabetic patients. SE Asian J Trop Med Public Health. 2008;39(5):913–916. 50% reduction in free t3 in diabetics.

73. De Jong F, den Heijer T, Visser TJ, et al. Thyroid hormones, dementia, and atrophy of the medial temporal lobe. J Clin Endocrinol Met. 2006;91()7):2569–2573. High reverse t3 with brain atrophy.

74. Goichot B, Schlienger JL, Grunenberger F, et al. Thyroid hormone status and nutrient intake in the free-living elderly. Interest of reverse triiodothyronine assessment. Eur J Endocrinol. 1994;130:244–252.

75. Peeters RP, Wouters PJ, van Toor H, Kaptein R, Visser TJ, Van den Berghe G. Serum 3, 3, 5- triiodothyronine (rT3) and 3,5,3-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J Clin Endocrinol Metab. 90(8):4559–4565.

76. Everts ME, De Jong M, Lin CF, Docter R, et al. Different regulation of thyroid hormone transport in liver and pituitary: It’s possible role in the maintenance of low T3 production during nonthyroidal illness and fasting in man. Thyroid. 1996;6(4):359–368. Increased T4­ with NTI.

77. Lim CF, Docter R, Visser, Drenning. Inhibition of thyroxine transport into cultured rat hepatocytes by serum of nonuremic critically ill patients: effects of bilirubin and nonesterified fatty. JCEM. 1993;76(5):1165–1172.

78. Hennemann G, Vos RA, de Jong M, Krenning EP, Docter R. Decreased peripheral 3,5,3’ –triiodothyronine (T3) production from thyroxine (T4): a syndrome of impaired thyroid hormone activation due to transport inhibition of T4- into T3-producing tissues. JCEM. 1993;77(5):1431–1435.

79. De Jong M, Docter R, Bernard BF, van der Heijden JT, van Toor H. T4 uptake into the perfused rat liver and liver T4 uptake in humans are inhibited by fructose. Am J Physiol Endocrinol Metab. 1994;266:E768–E775.

80. De Jong M, Docter R, Van Der Hoek HJ, et al. Transport of 3,5,3’-triiodothyronine into the perfused rat liver and subsequent metabolism are inhibited by fasting. Endocrinology. 1992;131:463–470.

81. Hennemann G, Krenning EP. The kinetics of thyroid hormone transporters and their role in non-thyroidal illness and starvation. Best Pract Res Clin Endocrinol Metab. 2007;21(2);323–338.

82. Krenning EP, Docter R, Bernard B, Visser T, Hennemann G. Decreased transport of thyroxine (T4), 3,3,5’-triiodothyronine (T3) and 3,3’,5’-triiodothyronine (rT3) into rat hepatocytes in primary culture due to a decrease of cellular ATP content and various drugs. FEBS Lett. 1982 Apr19;40(2):229–233.

83. Hennemann G, Krenning EP, Bernard B, et al. Regulation of influx and efflux of thyroid hormones in rat hepatocytes: possible physiologic significance of the plasma membrane in the regulate of thyroid hormone activity. Horm Metab Res Suppl. 1984;14:1–6.

84. FW Wassen, EP Moerings, H van Toor, G Hennemann, and ME Everts. Thyroid hormone uptake in cultures rat anterior pituitary cells: effects of energy status and bilirubin. J Endocrinology. 2000;1965:599–606. Pituitary different transport not suppressed with decrease energy.

85. Visser TJ, Lamberts WJ, Wilson JHP, Docter WR, Hennemann G. Serum thyroid hormone concentrations during prolonged reduction of dietary intake. Metabolism. 1978;27(4):406–409.

86. Lowe J, Garrison R, Reichman A, MD, Yellin J, Thompson BA, Kaufman D. Effectiveness and safety of T3 (triiodothyronine) therapy for euthyroid fibromyalgia: a double-blind placebo-controlled response-driven crossover study. Clin Bull Myofasc Ther. 1997;2(2/3):31–58.

87. Lowe JC, Reichman AJ, Yellin J. The process of change during T3 treatment for euthyroid fibromyalgia: a double-blind placebo-controlled crossover study: Clin Bull Myofasc Ther. , 1997;2(2/3):91–124.

88. Lowe JC, Reichman AJ, Garrison R, Yellin J. Triiodothyronine (T3) treatment of euthyroid fibromyalgia: a small-n replication of a double-blind placebo-controlled crossover study. Clin Bull Myofasc Ther. 1997;2(4):71–88.

89. Yellin BA, Reichman AJ, Lowe JC. The process of change during T3 treatment for euthyroid fibromyalgia: a double-blind placebo-controlled crossover study. In: Metabolic Treatment of Fibromyalgia. McDowell Publishing; 2000.

90. Wikland B, Lowhagen T, Sandberg PO. Fine needle aspiration cytology to the thyroid in chronic fatigue. Lancet. 2001:357:956–957.

91. Teitelbaum J, Bird B, Greenfield R, Weiss A, Muenz L, Gould L. Effective treatment of chronic fatigue syndrome (CFIDS) & fibromyalgia (FMS) – a randomized, double-blind, placebo-controlled, intent to treat study. J Chronic Fatigue Syndr. 2001;8(2).

92. Gitlin M, Altshuler LL, Frye MA, et al. Peripheral thyroid hormones and response to selective serotonin reuptake inhibitors. J Psychiatry Neurosci. 2004;29(5):383–386.

93. Krotkiewski M, Holm G, Shono N. Small doses of triiodothyronine can change some risk factors associated with abdominal obesity. International J Obesity. 1997;21:922–929.

94. Nierenberg AA, Fava M, Trivedi MH, Wisniewski SR. A comparison of lithium and T3 augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163:1519–1530.

95. Brayshaw ND, Brayshaw DD. Thyroid hypofunction in premenstrual syndrome. N Engl J Med. 1986;3185(23):1486–1487.

96. Abraham G, Milev R, Lawson JS, T3 augmentation of SSRI resistant depression. J Affect Disord. 2006;914:211–215.

97. Posternak M, Novak S, Stern R, Hennessey J, Joffe R, et al. a pilot effectiveness study: placeo-controlled trial of adjunctive “L-triiodythronine (T3) used to accelerate and potentiate the antidepressant response. Int J Neuropsychopharmacol. 2008;11:15–25.

98. Klein I, Danzi S. Thyroid hormone treatment to mend a broken heart. J Clin Endocrinol Metab. April 2008;93(4):1172–1174.

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Correction

In the May 2013 editon of this column (“Nevada Homeopathic and Integrative Medical Association (NHIMA) 2012 Fall Conference: Part 3”), Dr. Robert Rowen’s name was misspelled.