Hormone resistance syndromes are not so uncommon. For example, insulin resistance is the cause of type 2 diabetes. Thyroid resistance is much less common, but important to know about because it is effectively treatable.
Hormones work by traveling through the bloodstream a distance to enter a cell, bind to its receptor, and cause a change in the cell’s function. Having resistance to a hormone means the binding of it to its receptors does not work normally. Sometimes this is a genetic condition that people are born with. But, sometimes hormone resistance is acquired in life. One example is when HIV-positive patients become resistant to cortisol.
There are three known types of thyroid resistance, based on whether the cells of the pituitary gland are involved along with all the other cells in the different organ systems of our bodies.
Diffuse, or generalized, thyroid resistance has been studied the most. This is because mutations in the genes that create and regulate the thyroid hormone receptor in cells are the main cause. Many of these mutations have been discovered and reported on. Normally, pituitary TSH goes down when thyroid hormone levels from the thyroid gland in our necks, get too high. This is a classic negative feedback system. In generalized thyroid resistance thyroid hormone level are high, and TSH is also high. There is no negative feedback. TSH is “non-suppressed.” People with generalized thyroid resistance tend to be fine since they have so much thyroid hormone it makes up for their resistance. The best treatment is often no treatment.
If the pituitary TSH-making cells are the only group that is resistant, then there is no negative feedback again and TSH levels are again high, but the resulting high thyroid hormone levels function normally and the person is revved up and clinically hyperthyroid. They are anxious, tremulous and unable to get to sleep or gain or keep weight on, even with being hungry all the time, inappropriately hot, fatigued, sweaty, and with a fast resting heart rate. In such cases treatment is required by reducing thyroid hormone levels with medication.
The third form of thyroid resistance is under-diagnosed. It is partial peripheral resistance to thyroid hormone (PPRTH). In people with PPRTH all their cells in different organ systems are resistant but their pituitary TSH-making cells are normal. As such, they have normal TSH levels and normal amounts of thyroid hormone, but this thyroid hormone is not effective at normal levels and the person is very hypothyroid. They gain weight, are tired all the time, are inappropriately cold, dull-witted, with dry skin and constipation. Treatment of PPRTH requires very high dosing, and blood levels, of thyroid hormones to overcome the resistance.
Peripheral thyroid resistance is tricky to diagnosed. The person has all these hypothyroid symptoms, but, their blood tests show normal thyroid hormone levels and normal TSH levels. The doctor has to be aware of PPRTH in order recognize it and help these folks.