Thyroid Health Blog: An Approach to the Patient with Thyroid Disease and High Symptom Burden

Benjamin Gigliotti, MD

An Approach to the Patient with Thyroid Disease and High Symptom Burden

Benjamin Gigliotti, MD
University of Rochester Medical Center, NY
January 15, 2021


A common clinical dilemma is the management of patients with treated hypothyroidism and/or Hashimoto’s thyroiditis who feel unwell despite normal thyroid function tests. Weight gain, fatigue, brain fog, depressed mood, cold intolerance, constipation, dry skin, joint/muscle aches, hair loss, and brittle nails may be reported. These symptoms are commonly referred to as “thyroid symptoms,” and an internet search will reveal innumerable sources that reinforce a link between these and inadequate treatment or thyroid autoimmunity itself. However, clinicians must be cautious not to reflexively infer causation from correlation since:


– Even the most classic symptoms of hypothyroidism are non-specific and are commonly found in other diseases and in the general population.
Anti-thyroid antibodies are often ordered in patients with unexplained symptoms, so autoimmune thyroid disease is disproportionately diagnosed in this setting; it remains unclear if this causes symptoms in and of itself.
– Most online resources emphasize the voices of people with thyroid disease who feel unwell since those who feel well do not tend to seek out or contribute to these resources.


In my experience, vague symptoms in this setting often have a multifactorial explanation, and thyroid disorders are rarely the dominant or only cause. Although the severity or number of symptoms can be daunting to evaluate, it is critical to meet the patient’s frustration with compassion, longitudinal relationship-building and thoughtful inquiry. Asking the following questions may prove helpful in determining the source(s) of symptoms:


-Is the normal TSH truly reflective of the patient’s thyroid axis?

  • Repeating the TSH over time can exclude spuriously or transiently normal results.
  • The upper limit of the TSH reference range (4-5mIU/L for most assays) is debated and may be lower in young patients or higher in older or obese patients. Regardless, I have never seen resolution of severe symptoms from treatment of a TSH that is within (or even slightly above or below) the reference range; several studies support this observation.(1)
  • Checking a free T4 level at least once can ensure concordance with the TSH and exclude assay interference (e.g. biotin or heterophile antibodies) or rare cases of central hypothyroidism).(2)
  • Total T3, free T3, and reverse T3 assays perform poorly in hypothyroidism and are rarely helpful, especially if the TSH and free T4 are normal


-Could there be an alternative explanation for each symptom that warrants workup, treatment, or counseling?

  • Weight gain and/or fatigue are particularly common, occurring in up to half of all adults. Inadequate or poor-quality sleep, excessive work, suboptimal diet, and inadequate exercise are common causes. Menopause can also contribute, especially if vasomotor symptoms disrupt sleep.
  • Hashimoto’s is associated with a higher rate of other clinically significant autoimmune diseases (e.g. lupus, rheumatoid arthritis, celiac disease) and numerous functional disorders (e.g. depression, migraines, irritable bowel syndrome, fibromyalgia).
  • Iron deficiency is common in menstruating women, a population enriched in autoimmune thyroid disease, and can cause a similar spectrum of symptoms, even without anemia or frankly low ferritin levels.


– Can thyroid hormone therapy be optimized?

  • Some patients on levothyroxine report improved symptoms after targeting a “low normal” TSH, although it is increasingly unclear if this approach is effective, and caution should be used in patients at risk for harm from iatrogenic hyperthyroidism.(3)
  • Many patients express interest in therapies other than standard-of-care levothyroxine (4); Dr. Shrestha recently wrote a thoughtful blog post on thyroid hormone formulations ( It is prudent to consult with an experienced endocrinologist familiar with the literature and pros/cons of using T3 and T4+T3 combination therapy to determine their appropriateness on a case-by-case basis.


While there is rarely a panacea, engaging in supportive listening, initiating an appropriately comprehensive evaluation, setting realistic expectations, and seeking consultation with endocrinology (especially when questions about assay reliability or optimal thyroid hormone replacement arise) can prove beneficial.

1. Biondi B 2013 The normal TSH reference range: what has changed in the last decade? J Clin Endocrinol Metab 98:3584-3587.
2. Burch HB 2019 Drug Effects on the Thyroid. N Engl J Med 381:749-761.
3. Samuels MH, Kolobova I, Niederhausen M, Janowsky JS, Schuff KG 2018 Effects of altering levothyroxine (L-T4) doses on quality of life, mood and cognition in L-T4 treated subjects. J Clin Endocrinol Metab. ePub 2018 Mar 2.
4. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, et al. 2014 Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 24:1670-1751.

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