In my previous article, I put into perspective the phenomenon of hypothyroidism and listed a number of factors that could lead to the development of this condition. In the article's conclusion, I noted that I would address subclinical - also known as tissue or cell – hypothyroidism, as well as goitrogens, in an upcoming issue of the journal. This is what we will do in this article. 

However, before addressing these topics, I would like to mention a hormone that is almost always overlooked when it comes to hypothyroidism, T2 or 3,5- diiodothyronine.

3,5-diiodothyronine

Despite the fact that our focus is almost exclusively on the two thyroid hormones T3 and T4, it should not be forgotten that the thyroid also produces T1 and T2. ¹ I would like to focus on the first part of this article on the latter, 3,5-diiodothyronine, especially its effect on fat loss.

Many individuals who are being medically treated for thyroid problems continue to show symptoms associated with hypothyroidism. This may happen even when they are taking medication to correct the problem and blood tests suggest that any hormonal problems have been resolved. These individuals continue to have symptoms such as fatigue and overweight, despite the fact that they are taking a medication that produces normal laboratory results.

Thyroid hormone T2

The thyroid hormone T2 often goes unnoticed by doctors - for two reasons. First, since this hormone has little affinity for thyroid hormone receptors, it was considered an inactive metabolite of the hormone T4. ² Second, where T2 was active, researchers felt it was acting in the same way as the T3 hormone. Therefore, it seemed unnecessary to study this hormone any further. 

Only recently have new studies demonstrated that T2 has metabolic effects independent from thyroid hormone receptors and that its effects are very different from those of T3 and T4. ³

One of the great challenges facing some individuals suffering from hypothyroidism is that, despite the normalization of markers after they start taking medication, they still cannot lose weight. 

Well, studies on animal models show that T2 directly affects fat metabolism. T2 helps burn fat, especially by increasing energy production from brown adipose tissue. ⁴ Studies have confirmed that taking T2 helps to reduce body weight and the percentage  of body fat. ⁵ This hormone also improves oxygen use in the mitochondria, the energy production sites in our cells, and also increases oxygenation of the liver. ⁶

If I wanted to give some background about the T2 hormone it is for information purposes only. Indeed, the role of the hormone and its exclusion from standard hormonal protocols may explain, at least in part, why a significant number of people do not benefit as much as they could from thyroid hormone treatment. However, since doctors do not prescribe this hormone, it is not possible to add it to the usual protocol for thyroid hormone. 

There is one option available from our American colleagues - thyroid glandular extract or desiccated thyroid. Thyroid glandular extract, which comes from either bovine or porcine sources, contains T3, T4 and T2. 

Nevertheless, use great caution with thyroid glandular extracts because they rarely provide standardized hormone levels and may contain contaminants such as mercury. The use of thyroid glandular extract requires more attention to detail than the use of conventional thyroid hormones. Therefore, it is essential - if you want to go that route - that you consult a health care professional who can prescribe these products.

Goitrogens

Some foods can prevent the thyroid from using iodine and thereby stop it from producing its hormones. These are called "goitrogens" and excessive consumption of these foods ⁷ is associated with the development of a goiter, or enlargement of the thyroid. The majority of these substances have a goitrogenic activity similar to that of propylthiouracil, a drug used to reduce thyroid activity in cases of hyperthyroidism. ⁸ Note that goitrogens are involved in cases where hypothyroidism is caused by iodine deficiency.

Goitrogenic foods include peanuts, foods from the cabbage family (cabbage, Brussels sprouts, broccoli, cauliflower, kale), soybeans, millet, turnips, pine nuts and rutabagas ⁹. Note that these foods are goitrogenic only if eaten raw. Indeed, cooking them causes the goitrogens to become inactive. 

Adding iodine to these foods (iodized salt or algae) reduces their effect on the thyroid. Thus, in cases of hypothyroidism associated with iodine deficiency, goitrogens may be a problem only when consumed raw and in excess.

Subclinical or tissue hypothyroidism

Indian researchers noted that "a large number of hypothyroid patients, receiving adequate doses of thyroxine supplementation, continue to complain of dissatisfaction and varied symptoms."¹⁰ These researchers have identified an issue that is often ignored, that of tissue hypothyroidism. 

The term “subclinical hypothyroidism” has two medical meanings. Initially, in its classical definition, it describes hypothyroidism where TSH levels are high, while T3 and T4 are normal. ¹¹

The second definition, which I will address here, is used mainly by holistic doctors, chiropractors and naturopaths. It refers to a situation where blood tests are normal, but symptoms of hypothyroidism persist. It is battling a disease that goes under the radar, so to speak.

Many people show symptoms associated with hypothyroidism, yet blood tests show no abnormality whatsoever. They are told they are "healthy" or "there is nothing wrong with them" all the while knowing that there is. 

Other individuals have analyses which show a thyroid imbalance. They take the proper medication for a period of time, redo the blood work and are told that the situation has normalized. However, although the blood tests show their hormone levels are normal, some symptoms persist. In both cases, it could be due to subclinical or cellular hypothyroidism. ¹²

To put this in perspective, let me use the analogy of a lock and key. The hormone (the key) can trigger reactions if it can interact with the receptors (locks) in our cells. So, you can have the proper key for your lock, but if it is rusty or is covered with chewing gum, the key will not unlock it. 

It is the same with respect to cell or subclinical hypothyroidism. Blood tests will show that the blood parameters for hormone production by the pituitary (TSH) and thyroid (T3 and T4) are normal, but there are still symptoms that may be due to hypothyroidism. This occurs also in individuals receiving hormone replacement, eg. Synthroid, but who continue to have symptoms of hypothyroidism.

Some researchers have shown that individuals with normal levels of T3 and T4 still had symptoms of hypothyroidism because the two hormones were not being properly transported into the cells. ¹³ A number of disorders are associated with cellular transport problems. These include: obesity, depression, chronic fatigue, joint pain, high cholesterol and high triglycerides. ¹⁴

Some studies suggest that people who follow restrictive diets or have undergone significant stress are more likely to develop this problem. ¹⁵ This may explain, in part at least, why people following low-calorie diets to lose weight have more and more difficulty losing weight afterwards. 

Other studies have confirmed that chronic physical or emotional stress can also reduce the transport of T4 hormone into cells. ¹⁶ Some studies have measured a reduction of 25 to 50% in the cellular uptake of T4 following restrictive diets. ¹⁷ This confirms the idea that when people follow severe calorie restricted diets they have more trouble losing weight. There is also an important implication for anorexics who can, because of their caloric restriction, reduce the cellular use of thyroid hormones.

This is just a brief overview of the phenomenon of cellular hypothyroidism, but it helps us to understand the dilemma of many individuals. Yes, it is possible to have symptoms associated with thyroid dysfunction without having abnormal blood work.

What to do ?

What can we do to determine if cellular hypothyroidism is a factor in the symptoms experienced by some individuals when blood tests show that everything is “normal”?

1. The individual must have some symptoms associated with hypothyroidism. See the table published in the previous article.
2. Make sure symptoms are not explained by other disorders. Indeed, other disorders such as food intolerances, "adrenal fatigue", certain nutritional deficiencies and candida can manifest similar symptoms.
3. Make sure that clinical hypothyroidism is not present as diagnosed by standard blood tests.
4. Taking a basal temperature reading can help determine if metabolism is low. The temperature of the body at rest is largely determined by the metabolism which is controlled by the thyroid. The basal body temperature may therefore be useful as a tool for measuring hypothyroidism. ¹⁸ Caution! Basal temperature is not an absolute indicator, because it can be affected by other factors. ¹⁹ Nevertheless, it remains a useful tool when its results are confirmed by other data. See below for instructions on how to take the basal temperature.
5. The sex hormone binding globulin, SHBG, is produced in the liver in response to estrogen levels or thyroid hormones. ²⁰ Therefore, if a patient has a normal level of estrogen, either naturally or through hormone replacement, SHBG can be used to determine the T3 levels in the tissues. In cases of cellular hypothyroidism, SHBG will be low compared to normal. ²¹ A physician or naturopath (where permitted by law) may request the blood test for SHBG.
6. The analysis of reverse triiodothyronine (rT3) can also help detect cellular hypothyroidism. High rT3 levels in the blood suggest an inadequate transport of T4 hormone. Again, a physician or naturopath (where permitted by law) may request the blood test for rT3.

What can we do ?

The nutritional approaches suggested in my previous article about hypothyroidism help improve the the patient's general condition. Regarding specific cases, it is best to consult a health professional and establish a general profile followed by an appropriate action plan.

Unsuspected thyroid problems can be the root cause of a serious disease. Therefore, it is essential to find the cause, develop possible solutions and to make those who are suffering symptoms aware that the problem is not all in their heads.

Table 1: Symptoms associated with hypothyroidism 

How to take your basal body temperature

References

¹ Laycock, John and Karim Meeran Integrated Endocrinology, Wiley Publ. (2012)

² Goglia, F. Biological Effects of 3,5Diiodothyronine (T2)  Biochemistry Vol. 70, No. 2, 2005, pp. 164-172.

³ Ibid

⁴ Lombardi A, Senese R, De Matteis R, Busiello RA, Cioffi F, Goglia F, et al. (2015) 3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats. PLoS ONE10(2): e0116498

⁵ Antonia Lanni, Maria Moreno, Assunta Lombardi,  Pieter de Lange, Elena Silvestri,  Maurizio Ragni, Paola Farina, Gabriella Chieffi Baccari, Pupah Fallahi, Alessandro Antonelli, and Fernando Goglia  3,5-Diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats  The FASEB  Journal  express article  10.1096/fj.05-3977fje. July  12,  2005.

⁶ Goglia, F. Biological Effects of 3,5Diiodothyronine (T2)  Biochemistry Vol. 70, No. 2, 2005, pp. 164-172

⁷ Lesley Braun, Herbs & Natural Supplements: An evidence-based guide, Churchill Livingstone (2010)

⁸ Hechtman , Leah Clinical Naturopathic Medicine, Churchill Livingstone (2012)

⁹ Murray, M. and J. Pizzorno The Encyclopedia of Natural Medicine Simon & Schuster (2012)

¹⁰ Sanjay  Kalra  and  Sachin  Kumar  Khandelwal Why are  our  hypothyroid  patients  unhappy?  Is  tissue  hypothyroidism the  answer? Indian  J  Endocrinol  Metab.  2011  Jul;  15(Suppl2): S95–S98.

¹¹ Boucher, Andrée L’hypothyroïdie subclinique : traiter ou ne pas traiter? Le clinicien octobre 2004

¹² S.  Refentoff, R. E. Weiss, and S. J. Usala The Syndromes of Resistance to Thyroid Hormone Endocrine reviews Vol. 14, No. 3 July 01, 2013

¹³ Hennemann G, Docter R, Friesema EC,  et  al.  Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocrine Rev.  2001;22(4):451–76.

¹⁴ Holtorf, Kent Thyroid Hormone Transport into Cellular Tissue Journal of Restorative Medicine 2014; 3: page 53-68

¹⁵ Hennenmann G, Everts ME, de Jong M,  et  al.  The  significance of plasma membrane transport in the bioavailability of thyroid hormone.  Clin Endocrinol (Oxf).  1998;48:1–8.

¹⁶ Sarne DH, Refetoff S. Measurement of thyroxine uptake from serum by cultured human hepatocytes as an index of thyroid status: reduced thyroxine uptake from serum of patients with nonthyroidal illness.  J Clin Endocrinol Metab.  1985;61:1046–52.

¹⁷ Leibel RL, Jirsch J. Diminished energy requirements in reduced-obese patients.  Metabolism. 1984;33(2):164–70.

¹⁸ Murray, M. And J. Pizzorno Textbook of Natural Medicine, Churchill Livingstone (2006)

¹⁹ Lecomte P, Lecureuil N, Lecureuil M, Salazar CO,  Valat C.  Age modulates effects of thyroid dysfunction on sex hormone binding globulin (SHBG) levels.  Exp Clin Endocrinol. 1995;103:339–42.

²⁰ Sarne DH, Refetoff S, Rosenfield RL, Farriaux JP. Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the valued of changes after short term triiodothyronine administration. J Clin Endocrinol Metab. 1988;66(4):740–6.

²¹ Barnes B.  Temperature versus basal metabolism.  J Am Med Assoc.  1942;119(14):1072–4.

²² Holtorf, Kent Thyroid Hormone Transport into Cellular Tissue Journal of Restorative Medicine 2014; 3: page 53-68