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Exceptions to the “TSH Rule:” How Certain Physiologic and Emotional Conditions Thwart the Ability to Detect Cellular Hypothyroidism

According to the American Thyroid Association, “the TSH blood test is the best way to monitor thyroid hormone … [because] TSH is made in the pituitary, and the blood levels reflect how [the] body is responding to the amount of thyroxine.”1 Further, “levothyroxine is recommended as the preparation of choice for the treatment of hypothyroidism due to its efficacy in resolving the symptoms of hypothyroidism.” 2 Yet, countless patients still suffer the effects of this condition, even in the presence of normal or low-normal serum thyroid-stimulating hormone (TSH) levels. Further, many of these patients do not respond well to traditional levothyroxine (T4) therapy.

Why? This is the question addressed in a comprehensive review conducted by AARM conference presenter Kent Holtorf, M.D. In this review titled “Peripheral Thyroid Hormone Conversion and its Impact on TSH and Metabolic Activity,” [Journal of Restorative Medicine, Vol. 3, No. 1] Holtorf examines the role of cellular deiodinase activity in relation to its activity in the pituitary and peripheral tissues.3

Based on the results of this inquiry, he makes a compelling case against relying on serum TSH levels as the gold standard for indicating thyroid function. Serum TSH, produced by the pituitary, doesn’t necessarily reflect thyroid status in peripheral tissues — especially in patients suffering from a range of specific conditions listed below. He also argues that sustained-release triiodothyronine (T3) therapy is a superior choice for treating hypothyroid symptoms in these patients.

Deiodinase, the pituitary and local control

The mechanisms by which deiodinase enzymes control thyroid hormone expression in the pituitary versus peripheral tissues is key to understanding Holtorf’s conclusions.

Both type I deiodinase (D1) and type II deiodinase (D2) convert inactive thyroxine (T4) to active triiodothyronine (T3), thereby increasing cellular thyroid activity. Conversely, type III deiodinase (D3) reduces cellular thyroid activity by converting T4 to reverse T3, an anti-thyroid agent. Deiodinases may act completely different on the pituitary as compared to peripheral tissues, therefore signaling a normal TSH level only as it relates to T3 levels in the pituitary, even if the rest of the body suffers from T3 deficiency.

 

In the New England Journal of Medicine, Larsen et al. confirm with this comment: “Recognition that the intracellular T3 concentration in each tissue may be subject to local regulation and an understanding of the importance of this process to the regulation of TSH production should permit a better appreciation of the limitations of the measurements of serum thyroid hormone and TSH levels.”4

This pituitary versus peripheral tissue dichotomy especially occurs in the presence of specific, yet broad-ranging conditions — including diabetes, depression, dieting, inflammation, stress, obesity, premenstrual syndrome (PMS), leptin resistance, autoimmune disease, fibromyalgia, chronic fatigue syndrome, and insulin resistance. Clearly, there are many common, chronic conditions related to peripheral tissue hypothyroidism in patients that are shown to have “normal” TSH tests.

Noting that both of these phenomena have been thoroughly investigated and confirmed by independent studies conducted by leading thyroid researchers, Holtorf asserts that “[w]ith an improved understanding of thyroid physiology that includes the local control of intracellular activation and deactivation of thyroid hormones by deiodinases, it becomes clear that standard thyroid tests often do not reflect the thyroid status in the tissues of the body, other than in the pituitary …
[c]onsequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator [of thyroid function].”

Cellular hypothyroidism and T4 versus T3 therapy

Citing several prominent studies of patients suffering from one or more of the above conditions, Holtorf affirms that T4-only therapies often fail to resolve symptoms of cellular hypothyroidism. This is because in many — though not all — of these cases, the physical or emotional insult triggers upregulation of reverse T3. This suppresses T4 to T3 conversion, blocks the T3 receptor, and ultimately worsens symptoms. Introducing T4 perpetuates, not resolves, the cycle — as it will encourage the production of even more reverse T3.  On the other hand, T3 therapies can significantly benefit patients by stabilizing thyroid activity.

To learn more about the relevance of TSH testing and other methods to diagnose and treat hypothyroidism, be sure to attend Dr. Holtorf’s courses at the upcoming 14th Annual International Restorative Medicine conference, held in Hilton Head Island, South Carolina, from Sept. 15th – 18th, 2016.  He will present a research review and will provide protocols for treating hypothyroid cases.  Dr. Holtorf, along with Dr. Denis Wilson, will be offering a full day of courses on the preconference day, September 15, and the opportunity to become certified in T3 protocols, which many doctors have found to be life-changing for them personally, their patients, and their practices. For more information about the conference, see the website www.RestorativeMedicine.org/2016.

References:

1          Q and A: TSH (thyroid stimulating hormone). American Thyroid Association Web site. http://www.thyroid.org/patient-thyroid-information/what-are-thyroid-problems/q-and-a-tsh-thyroid-stimulating-hormone/. Publication date unknown. Accessed June 2, 2016.

2          Jonklaas Jacqueline, Bianco Antonio C., Bauer Andrew J., Burman Kenneth D., Cappola Anne R., Celi Francesco S., Cooper David S., Kim Brian W., Peeters Robin P., Rosenthal M. Sara, and Sawka Anna M. Thyroid. December 2014, 24(12): 1670-1751. doi:10.1089/thy.2014.0028.

3          Holtorf, K. Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity. Journal of Restorative Medicine, Volume 3, Issue 1, pages 30-52

4          (Larsen PR. Thyroid-pituitary interaction: feedback regulation of thyrotropin secretion by thyroid hormones., 1982)