Get a bunch of doctors together and ask about thyroid testing, and you’re likely to get a range of responses. One might say that TSH (thyroid stimulating hormone) is the best and, oftentimes, only test needed, and another might say that TSH is not the answer. When experts disagree about the utility of evaluating thyroid function beyond just TSH, how is a patient supposed to make sense of things? If a patient is experiencing classic signs of hypothyroidism, yet their TSH is normal, are they to be patted on the head, brushed aside and told “it’s all in your head,” or is it prudent for physicians to dig a little deeper into other ways to assess thyroid gland function and hormone levels?
Patient reports as well as a solid body of research suggest it’s entirely possible to have a normal TSH level while still manifesting hypothyroidism. There are numerous situations in which TSH may be normal, but total and/or free T4 or total and/or free T3 are low. One such situation is during or after weight loss achieved via drastic caloric restriction, especially if combined with a lot of exercise. This has been called “famine response hypothyroidism,” and has been documented among obese or overweight patients who have experienced weight loss, but then reach a plateau where further weight loss is not achieved despite continuing to follow the formerly effective diet and exercise recommendations. This well-recognized metabolic slowdown that occurs in many weight loss patients was written about with reference to contestants from the TV show “The Biggest Loser,” most of whom regained the weight they lost and had slower metabolisms as well. So much for all that calorie burning.
A patient experiencing a similar situation in the real world and not in front of TV cameras, might be dealing with hair loss, constipation, depression, high cholesterol, brain fog, feeling cold, and be struggling to lose weight despite adhering to a diet and exercise program that was previously working. Telling this to their doctor, they might be dismissed and told to eat even less and exercise even more. And if TSH is normal, they’ll be told there’s nothing wrong with their thyroid, despite the obvious symptoms. It might be assumed that their self-reporting of food intake and physical activity is untruthful. This can be extremely demoralizing to someone working hard to lose additional weight, whose own body appears to be sabotaging them.
Two thyroid experts wrote: “We would agree that there is nothing ‘wrong’ with the patient’s thyroid function. The hypothalamic-pituitary-thyroid (HPT) axis is performing in a highly evolved manner to help the patient live through the current caloric limitations.”
Indeed, a slowdown in thyroid function, or alterations in hormone levels, may be expected in such a situation: as a survival mechanism to keep the body from burning out while over-exercising and undereating, production of T3 is decreased and that of reverse T3 (rT3) is upregulated. Reverse T3 binds to the thyroid hormone receptor, but does not have the same metabolic effects. Reverse T3 is typically elevated during acute illness or severe physical stress—the kind the body experiences while being tasked with performing a lot of exercise with reduced energy intake, particularly over an extended period of time. TSH, however, often remains normal, as does T4, with the T4 being converted into the metabolically inactive rT3 rather than the active T3.
This well-documented effect led researchers to admit, “…it is our job as clinicians to educate our patients that their challenges with weight are not lack of will power but a highly evolved system which can be treated. To continue to view our patients’ failures as a weakness of will power is to ignore the reality of this condition and do a major disservice to our patients and society at large.”
Hypocaloric-induced hypothyroidism cannot be detected by testing TSH alone. And even testing total or free T4 may miss the hormonal shift responsible for the metabolic slowdown associated with weight loss or caloric restriction. Measuring levels of free T3 and rT3 is critical, because other hormones often remain normal, but the increased ratio of rT3 to free T3 is the “smoking gun” of this form of hypothyroidism. These measurements can also guide treatment, because if T4-only medication is given, this may be converted to rT3, which will not ameliorate the patient’s symptoms. It may be best to provide only T3 in this situation, to ensure the patient receives the intended beneficial effects.
With the growing popularity of ketogenic diets (KDs) for weight loss, it would be prudent to address the affect of ketogenic diets on thyroid function. It has been documented that after some length of time on a KD, T3 levels decrease in some people. This is not solely an artifact of weight loss, though, as many people adopt ketogenic diets for reasons unrelated to body weight. It appears to be something some people—but not all—experience on a KD even if there’s no caloric restriction. This doesn’t necessarily mean KDs are harmful for thyroid health or hormone regulation. World renowned KD researcher Stephen Phinney, MD, PhD, has speculated that it’s possible the state of ketosis makes the body more sensitive to thyroid hormone, such that a lower level of T3 is needed to induce the same metabolic effects. To be clear, this is speculation; we don’t know for sure what the implications of decreased T3 on a KD are, but as long as the individual is asymptomatic and feels well, that’s the critical issue. If there are no signs or symptoms of hypothyroidism, then decreased T3 could be, at least for some people, a natural feature of being in nutritional ketosis.
The numerous different thyroid-related tests, pitfalls in how to interpret these, and uncertainty regarding what should be considered the “normal” reference ranges all point toward assessing each patient individually, and considering the clinical context and especially symptomology when interpreting results.