I went hot, then cold, then started cursing my doctor. Not that it was his fault. Just another case of the blind leading the desperate.
In the podcast I was listening to, Dr. Jorge Flechas was explaining new research that showed the ovaries contain two enzymes responsible for the creation of thyroid hormone, thyroid peroxidase (TPO) and thyroglobulin (Tg) (also here).
These enzymes were expressed in granulosa cells in the ovaries and endometrial cells in the uterus.
Why this is important, to anybody with a thyroid condition and anyone taking thyroid hormone medication is this implies:
- The ovaries are capable of creating thyroid hormone.
- If you have an autoimmune thyroid condition with high antibodies for either TPO or Tg, your immune system is likely attacking your ovaries and endometrial tissue along with your thyroid.
Compensating for Autoimmune Thyroid: Hashimoto’s Thyroiditis
Being at a point in the Hashimoto’s disease stage where my body does not have enough healthy thyroid tissue to meet demands for thyroid hormone, I was struggling to get my thyroid hormone dosage right.
It had taken years (6 to be exact) from diagnosis to finding a thyroid literate doctor. In that 6 years, I was grossly undertreated, prescribed a mere 25 micrograms of levothyroxine (T4) to compensate for the gap between where I was and where I should be for levels of triiodothyronine (T3) and T4, the two thyroid hormones typically replaced in a treatment plan for people in my stage of the disease.
When I found that doctor, I was self-dosing with bovine desiccated thyroid because it was the only thing I could get over-the-counter without a prescription and because I knew I was under-medicated.
The problem with bovine desiccated thyroid is that the ratio of thyroid hormones do not mimic those found in man. When T4 is converted by deiodinase enzymes in the body, there are two possible pathways. Conversion by Type 3 deiodinase to rT3 and conversion by Type 1 deiodinase to T3. rT3 (reverse T3) binds to thyroid hormone receptors on cell membranes blocking the uptake of T3 and T4 by the cell, which slows metabolism.
Cows are known to produce more rT3 in the euthyroid state than people and even though I knew this, I was doing what I could with what was available to me, which meant by the time I found a thyroid literate doctor, my rT3 levels were so high he considered that most of the thyroid hormone receptors in my body (receptors on every cell of the body) were blocked.
A result like that would prompt most thyroid literate doctors to start T3 only therapy.
Normal ratio of T3 to T4 and why TSH doesn’t indicate thyroid function
The thyroid gland produces about 85 to 100 micrograms of T4 daily and only about 5 to 6.5 micrograms of the ~30 to 40 micrograms of T3 made by the body daily. The remaining T3 is made locally by cells within each tissue when T4 is converted into T3 by deiodinase enzymes. Three of these enzymes are known and expressed at different rates in different cell types.
- Deiodinase Type 1: converts T4 to T3
- Deiodinase Type 2: converts T4 to T3
- Deiodinase Type 3: converts T4 to reverse T3 (rT3)
Reverse T3 (rT3) is considered an anti-metabolic hormone because it binds to thyroid hormone receptors making them unavailable for either T3 or T4 to bind and enter the cell.
NOTE: This is why it’s impossible to diagnose thyroid dysfunction using TSH alone. The pituitary, which secretes TSH, maintains a different ratio of T4 to T3 than the rest of the body because of its unique ratio of deiodinase enzymes compared with the rest of the body. The pituitary secretes TSH based on the local levels of T3 in the pituitary, so it’s possible to be grossly hypothyroid before TSH values ever suggest there’s a problem.
Fat cells have different ratios of deiodinase enzymes compared to muscle cells. Liver cells have different ratios compared to cells in the reproductive tract and each cell type of the body expresses different ratios of deiodinase enzymes.
It’s known that people in various disease states (and on calorie restricted diets) have altered expression of deiodinase enzymes and can express more Type 3 deiodinase, the enzyme that preferentially makes rT3 from T4. In patients with high rT3, thyroid literate doctors frequently prescribe T3 only therapy.
Impact of Too Much Thyroid Replacement Hormone
I was up to 45 micrograms T3 per day and not only was I still struggling with symptoms, I started seeing cycles consistent with PCOS (polycystic ovarian syndrome). PCOS cycles showed up for me once before when I was actively struggling with chronic UTI symptoms. In the years since I had broken free of those symptoms, I had also seen a return to healthy cycling.
My suspicion was I was getting too much T3 and not enough T4, a suspicion that bloodwork confirmed by low free T4 values. Even though my doctor assured me this was fine (T3 is the active form of thyroid hormone after all), I asked if we could test combo therapy with both T3 and T4. He agreed. Once the doses of each were titrated, I was still taking about 45 micrograms T3 each day and about 100 micrograms of T4 and my hypothyroid symptoms had gotten worse (weight gain, swollen lymph nodes, frequent headache).
While it’s common to prescribe super physiological doses of thyroid hormone to hypothyroid patients, I wasn’t sold on my dosage. My estrogen levels were tanked and I was barely ovulating. And, I knew I was too young to be menopausal regardless of what my doctor said.
Dogs, Radiation, and Iodine
A chance conversation that week with a co-worker who was treating her dog with radiation therapy for cancer brought up the topic of iodine. Back when I was first diagnosed with Hashimoto’s, the endocrinologist I was referred to recommended I stop all iodine intake to try to reduce the anti-TPO antibody level and thereby the autoimmune attack on my thyroid.
Within 1 month of following her advice, I’d developed a breast cyst. This was abnormal for me, so I started researching the connection between iodine and fibrocystic breast disease, reincorporated iodine into my diet, and voila, that breast cyst went away. Iodine has continued to pop up on my radar more than once since then and here we were in the middle of another conversation that turned to iodine (because of its effectiveness in improving the outcomes of cancer treatment among many cancers… and I don’t mean radioactive iodine, we’re talking naturally occurring iodine).
I bring this up because this seemingly unrelated lunch chat catapulted me right back into the iodine research rabbit hole, which led me to the discovery of several papers discussing the presence of thyroid peroxidase, the enzyme that converts T4 to T3, in the ovaries. This suggests that the ovaries don’t just create T3 with deiodinase enzymes, they’re far more involved in thyroid hormone synthesis than that and if the ovaries contain the very same enzyme that’s attacked in about 80% of Hashimoto’s patients, well… it’s no wonder that PCOS and infertility struggles are so prevalent among women with Hashimoto’s. The body isn’t just attacking the thyroid. It’s attacking the ovaries too.
Is This Worth Altering Treatment for Hypothyroidism?
Why would this information make me piping mad? Well, I have long believed that the body makes T4 for a reason (even if doctors will argue T4 is a storage hormone), that reason being to provide the cells of the body with iodine when one atom of iodine is cleaved from T4 by deiodinase enzymes to make either T3 or reverse T3. Iodine is profoundly important for many essential processes in various tissues and organs of the body and again is closely linked with positive outcomes for a number of cancers (which in my mind makes this theory even more likely).
This was my main reason for requesting my doctor add T4 therapy back into my treatment plan. And, while I am glad to have a doctor who is agreeable enough to concede to my request on that point, shouldn’t it be expected for a thyroid literate doctor to be up on his research and know that the ovaries also appear to be equipped to make thyroid hormone on their own by the same mechanism used in the thyroid?
It would have saved some bitter debates over ovarian function. And, it would have been a great metric for adjusting my replacement hormone levels on the fly. Had I known the ovaries might also be making part of the body’s daily T3 and T4 rations, as soon as I started experiencing PCOS cycles while titrating up on T3 therapy, I would have backed off because that was an indication I was overdosing T3.
In the moment I started pulling up research papers showing this finding about the presence of thyroglobulin (Tg) and thyroid peroxidase (TPO) in the ovaries, observations I’d been flummoxed by suddenly made sense. It now made sense why women with hyperthyroidism also struggle with cycle disturbances. It made sense why my estrogen levels were through the floor recently. It made sense why my FSH levels were higher than they “should” be and still I wasn’t in menopause.
I backed off on my T3 dosage immediately. And, within a week’s time my estrogen levels were finally climbing consistent with follicular recruitment in preparation for ovulation. I felt better, less inflamed, less responsive to some of my known dietary triggers. I was struggling less with headaches. Is this everything I need to know about hypothyroidism? Probably not. But in the words of Bono, I’m one step closer to knowing.
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