January is Thyroid Awareness Month, which calls attention to the various health problems connected to the thyroid. Most of us have heard about the thyroid gland, but may not realize its importance and associated symptoms. This month is dedicated to talking about thyroid illnesses– and why it’s often misdiagnosed!

By sharing information about thyroid diseases, we hope to educate our patients and encourage them to visit us for a simple blood test to determine if treatment is needed. Without further ado, here is Seaside’s founder, Dr. Yazdani with her thoughts on the mystery of the thyroid.


Sitting in a lecture hall at USC’s Thyroid Symposium shortly before the pandemic when lecture halls existed, I’ll never forget the glance shared between the doctor in the next chair over and I when we heard the speaker say, “You don’t need to treat TSH unless it’s above 8.” Then the following speaker presented data from a double-blind randomized controlled study, the gold standard in medical sciences, confirmed that TSH readings don’t correlate with a person’s clinical hypothyroid symptoms. Another mind-blowing fact we couldn’t wrap our heads around when all along we’ve been treating thyroid disorders based on clinical symptoms and TSH values. It was this moment that solidified for me, the ever-present enigma of the thyroid.

It should be way more simple, this walnut-weighted, butterfly-shaped endocrine organ that nestles low on the cricoid cartilage of the neck and only spews out 3 hormones, T3, T4, and calcitonin using a handful of elements such as iodine, selenium, and tyrosine. While the thyroid seems straightforward, its complexity likely stems from its reliance on tissues to decide the degree to which thyroid hormones are processed at the organ level, as well as thyroid’s intricate involvement with the hypothalamus-pituitary axis. More often than we’d like to believe, this mysterious organ evades the smartest clinician’s judgment leaving us perplexed, wondering like that instance in the lecture hall, “When will we ever figure you out?”

Here’s a brief synopsis of what we do know about the thyroid:

Thyroid hormones thyroxine (T4) and triiodothyronine (T3) are essentially a cluster of iodine molecules woven around the amino acid tyrosine. Almost all but a small percentage of circulating hormone is tightly bound by storage proteins. Only when they reach their sites of action do the hormones unbind and get to work on gene expression. Thyroid hormone receptors have a higher affinity to T3 than T4, and it’s the targeted organs and tissues that convert T4 with deiodinase family of enzymes, to the more potent activator T3 by deiodination (removing iodine particle). This allows the tissues to decide how much activation is needed in real-time. And it’s also the site of regulation by many factors such as other hormones, caloric intake, inflammation, drugs/toxins, etc. The liver and kidney are the major converters of T4 to T3, therefore kidney and liver dysfunction also play a critical role in thyroid homeostasis. Organs turn off thyroid activity by converting T3 to its inactive form, reverse T3.

Thyroid hormones affect on metabolism:

  • In the heart, thyroid hormones increase heart rate and cardiac output. In the lung, it increases oxygenation. In various tissues, thyroid hormones increase gene expression of Na+/K+ ATPase to increase oxygen consumption, respiration rate and body temperature all leading to increased basal metabolic rate.
  • Thyroid hormones melt fat, burn carbohydrates, and break down proteins. In children, thyroid hormones work with growth hormones to stimulate bone growth and stimulate brain maturation.
  • Calcitonin, helps regulate calcium metabolism in the body.
  • Control of thyroid secretion:
  • The brain controls the thyroid gland by releasing thyrotropin-releasing hormone (TRH) which stimulates the release of thyroid-stimulating hormone (TSH) from the pituitary gland, that then triggers increased production of T4. This axis tightly controls itself by a negative feedback loop where T4/T3 suppress TRH and TSH.

The labs:

  • The laboratory tests that detect thyroid status are TSH, as well as T4 and T3 in an unbound form. There are also total T4, total T3, reverse T3, and a host of autoantibodies we use to diagnose dysfunction.
  • Factors that affect the conversion of thyroid hormone to active form or accelerate conversion to reverse T3:
  • Stress, age, smoking, inflammation, trauma, fasting, vitamin D deficiency, iodine deficiency or excess, selenium deficiency, prolonged shift work, cirrhosis, kidney disease, drugs, and infection. Environmental toxins such as PCB’s in plastic or flame retardants containing bromide may also negatively impact thyroid function.

The Symptoms:

  • When the TSH is high and free T4 is low, this suggests a low thyroid state, or hypothyroidism (common form Hashimoto’s).
  • Think slow and cold – cold hands and feet
  • Slow gut transit – constipation
  • Slow metabolic rate – weight gain
  • Slow brain function – depression and fatigue
  • Slow clearance of complex molecules from skin – edema and hair loss.
  • When TSH is low and free T4 is high, this indicates hyperthyroidism (common form is Grave’s Disease)
  • Think fast and warm – sweaty palms and jitteriness
  • Rapid heart rate
  • Rapid metabolism – weight loss
  • Rapid gut transit – diarrhea

Above is a very basic view of pathology arising from the thyroid. Rarely, is it ever this straightforward. For example, in the case of hypothyroidism, we’ve held fast to the notion of a one size fits all approach with supplementation of T4 alone. We’re learning now about polymorphisms in expression of deiodinase enzyme activity that prevent affected individuals from converting T4 to its active form T3, and that these patients would benefit from a T4/T3 combination regimen. We have learned that TSH has a diurnal secretion, challenging interpretation in patients with severe sleep disorders or night shift workers.

We have seen from elaborate trials on thousands of patients, that symptoms of hypothyroidism have little correlation with actual TSH lab values. Even TSH lab itself has come under scrutiny for its unreliability, not to mention how endocrinologists can’t seem to agree on a standardized approach to lab monitoring of patients on thyroid hormone. Some use TSH without T4 or T3, some use TSH with free T4 but not T3, and some look at total T3 but not free.

To add to the confusion, we have the Almighty search engines that offer patients an array of misinformation that attribute their fatigue, weight gain, or mental fog to low thyroid hormone, and encourage them to demand thyroid supplementation from their provider even when labs are within normal range. The fringes of medicine specialties have catapulted this phenomenon with coining terms such as relative TSH abnormalities, and prescribing thyroid hormones and excess iodine to many of their followers. I once came across a self-claimed health guru who developed a habit of prescribing massive amounts of active T3 hormone, having patients take it every 6 hours to prevent the crash that naturally would ensue from high intake. And more recently, I encountered a patient who was thrown into a transient state of menopause by excessive administration of iodine on the advice of her health coach. With all its feedback loops and layers of protection against chaos, the thyroid gland is extremely vulnerable to changes in the environment and stressors within the body. Not knowing how to interpret test results in the context of a patient’s clinical status can lead to disastrous outcomes.

Meanwhile, the commanding organizations such as American Thyroid Association and European Thyroid Association advise against treatment of hypothyroidism until TSH levels are above 10 mIU/L, unless there are overt clinical symptoms. In complete opposition to their guidelines, primary care providers by in large are initiating hormone replacement when TSH levels fall outside of normal reference range which is closer to 4-4.5 mIU/L, because we rarely see patients without corresponding symptoms when TSH approaches 4 mIU/L, let alone 10. The disconnect is profound placing the burden of proof among the societies to defend their guidelines and challenge the medical and non-medical communities will to treat.

In my opinion, thyroid hormone in small doses generally does make us feel better, at least temporarily but long term may not be beneficial when true disease doesn’t exist. We offer micro-dosing in weight loss medicine to drive metabolism in our favor. I also treat elevated TSH bordering abnormal in a symptomatic patient with iodine, selenium, and zinc, and at times with thyroid medication. In pregnant patients or pre-pregnancy planning, we treat subclinical hypothyroidism, because low thyroid state in early fetal development leads to detrimental outcomes.

The important step in managing a thyroid patient is close monitoring of symptoms and labs after supplementation and taking into consideration lifestyle, diet and interaction with other drugs.

A humble disposition to thyroid’s curveballs is really the only steadfast approach I’ve held on to over the years in the management of my patients with thyroid illness. I look forward to the bountiful research and expanding science in the field of thyroid illness, to further our limited understanding of this simply complex and marvelous organ.

In good health and well-being,

Yazdani, MD