Dr Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for Psychiatric Times. Click here for Part 1.
Thyroid dysfunction, like many medical disorders, is a matter of degree, and the standard range cutoffs are guidelines.1 Thyroid stimulating hormone (TSH) over 2.5 mIU/L is not normal, a new review in the American Journal of Psychiatry (AJP) asserts. (For simplicity, all of the following TSH values are shown without the cumbersome unit).
As discussed by Bruce Cohen and colleagues (of Harvard, Stanford, and McLean),1 the range of TSH in the general population is not a bell-shaped curve. It is skewed, as shown schematically in the Figure. In people with no thyroid problems, > 90% have a TSH reading of less than 2.5. The middle of the laboratory “normal” range is not the middle of the range! A reading of 2.5 is more like the end of normal than the middle.
What does this mean for our clinical practice?
1. Target median for age
When prescribing thyroid hormone for mood, target a TSH at least around median for age, as shown in the Box (from a review in Medscape Endocrinology 2012).2 To remember on the fly: target around 1.5 to age 50, around 1.6 to age 60, around 1.7 to age 70, and around 1.8 to age 80.
Why “median for age”? It’s a nice euphemism for “Go Low!” Many practitioners will pull up short, pushing TSH into the laboratory normal range, leaving patients’ TSH at 2.5 to 3.0. But in major depression, TSH levels between 2.5 and 4.0 have been associated with more severe symptoms, and some data suggest poorer response to treatment.1 In a study of bipolar depression, “outcomes were relatively poor unless patients had TSH values below the median.”3
Per the AJP review,1 one should use doses adequate to get below 2.0 as an initial goal. In follow-up, if target symptoms remain that might respond to thyroid hormone, “a full trial of supplementation may require a target TSH near 1…”, say the authors (all emphases mine).
2. Initial dosing is not 25 mcg of levothyroxine
If your goal is to land the patient’s TSH between 1.0 and median for age, how much levothyroxine should you use? Per Cohen and colleagues,1 “initial doses or increases in dosages can be low, 50 mcg/day for T4.” But watching my colleagues’ prescribing, including primary care providers, it seems that they think 50 mcg is not “low;” it’s more like medium-aggressive.
Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books on bipolar disorder.
1. Cohen BM, Sommer BR, Vuckovic A. Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels. Am J Psychiatry. 2018;175:598-604.
2. Kahapola-Arachchige KM, Hadlow N, Wardrop R, et al. Age-specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction. Clin Endocrinol (Oxf). 2012;77:773-779.
3. Cole DP, Thase ME, Mallinger AG, et al. Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function. Am J Psychiatry. 2002;159:116-121.
4. Ojomo KA, Schneider DF, Reiher AE, et al. Using body mass index to predict optimal thyroid dosing after thyroidectomy. J Am Coll Surg. 2013;216:454-460.
5. Elfenbein DM, Schaefer S, Shumway C, et al. Prospective Intervention of a Novel Levothyroxine Dosing Protocol Based on Body Mass Index after Thyroidectomy. J Am Coll Surg. 2016;222:83-88.