Dr Phelps is Medical Director at PsychEducation.org and Bipolar Disorder Section Editor for Psychiatric Times.
“What is the risk of driving thyroid stimulating hormone (TSH) below the lower limit of the normal lab range when using levothyroxine as an adjunct treatment for depression?” Here are new data and associated conclusions on that question posed at the end of Part 2 of this series.
Endogenous hyperthyroidism increases the risk of atrial fibrillation and decreased bone density. Population studies also note an increased risk of congestive heart failure and death.1 But TSH suppressed by exogenous levothyroxine (“high-dose thyroid,” or HDT) may not carry the same risks as endogenous hyperthyroidism (eg, Grave disease)
HDT is used by endocrinologists as an adjunct treatment for high-risk differentiated thyroid cancer.2 Dr Tam Kelly scrutinized this literature in two previous reviews;3,4 his monograph provides even more detail.5
Two different groups have followed patients with bipolar disorder for nearly 6 years and shown no greater decline in women on HDT than controls matched for age and gender (see pages 54-55 of Kelly’s monograph5 for the details). Together these studies followed 43 patients. Yes, that’s a small sample.
Meta-analyses from the much larger cancer literature were interpreted by a surgical team (they, too, need to know the risks and benefits of HDT).6 Thus, “detrimental effects on bone metabolism were very small or not significant in both premenopausal women and men; the results for postmenopausal women were less convincing.”6
At minimum, potentially accelerated osteoporosis—if it is a risk at all—is associated with years of exposure, like tardive dyskinesia (which does not seem to dissuade us from aggressive use of dopaminergic agents). By comparison, the more immediate and potentially catastrophic risks of atrial fibrillation and cerebral infarction (from atrial clot fragments) may be more likely to drive decision-making by practitioners and patients.
Kelly’s book5 reiterates and expands his previous review.3 Trying to follow his analysis is like being back in residency learning how to critique study design, methodology, and statistical methods. I was still hesitant to adopt his conclusions afterwards. (Dr Kelly wisely invited me to “be skeptical of your skepticism”). But an examination of his reviews by other specialists familiar with this literature has just arrived, with additional data on HDT’s cardiac risk.
Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but he receives royalties for his books.
1. Selmer C, Olesen JB, Hansen ML, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab. 2014;99:2372-2382.
2. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-133.
3. Kelly T. An examination of myth: a favorable cardiovascular risk-benefit analysis of high-dose thyroid for affective disorders. J Affect Disord. 2015;177:49-58.
4. Kelly T. A favorable risk-benefit analysis of high dose thyroid for treatment of bipolar disorders with regard to osteoporosis. J Affect Disord. 2014;166:353-358.
5. Kelly T. The Art and Science of Thyroid Supplementation for the Treatment of Bipolar Depression. CreateSpace, 2018. .
6. Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: a prospective controlled study. Surgery. 2011;150:1250-1257.
6. Pilhatsch M, Berghöfer A, Mayer-Pelinski R, et al. Long-term treatment with supraphysiologic doses of levothyroxine in treatment-refractory mood disorders - A prospective study of cardiovascular tolerability. J Affect Disord. 2018;238:213-217.