Central hypothyroidism related to antipsychotic and antidepressant medications: an observational study and literature review

Abstract

Objective: To investigate the final diagnosis and clinical outcome of patients referred to endocrinology in our district general hospital with biochemical isolated central hypothyroidism, and whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications. Methods: We performed a retrospective observational study of patients referred to endocrinology with unexplained biochemical isolated central hypothyroidism over a 5 year period. Results: Of the 29 patients included in the study, 4 were found to have a partially empty or empty sella, and 1 to have a bulky pituitary gland which was deemed to be an incidental radiological finding. No patients had any clinically significant pathology. On reviewing their medications, 18/29 (62%) were found to be on psychotropic medications. Conclusions: Our study suggests a relationship between patients on psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature prior to this. The mechanism behind this may be suppression of TSH secretion via antagonism of the dopamine-serotoninergic pathway. Determining a correlation between psychotropic medications and isolated central hypothyroidism could lead to the avoidance of further radiological investigations and unnecessary anxiety for patients. However, a larger observational study is needed to provide further evidence to support/refute our finding.

Isolated central hypothyroidism: Underlying pathophysiology and relation to antidepressant and antipsychotic medications—A multi‐centre South Wales study

“…Our initial research took place as a single-centre retrospective study. 5 and supported our suspicion that isolated CeH, in the absence of any other pituitary hormone dysfunction, did not appear to be associated with any significant pituitary pathology. Our study also demonstrated a convincing relationship between antidepressant and antipsychotic medications and biochemical CeH.…”

“…Our initial research took place as a single‐centre retrospective study 5 . and supported our suspicion that isolated CeH, in the absence of any other pituitary hormone dysfunction, did not appear to be associated with any significant pituitary pathology.…”

“…Note: List of medications taken from those implicated in our previous single-centre published study. 5 Abbreviations: NASSA, noradrenaline and specific serotonergic antidepressants; SNRI, serotonin-noradrenaline reuptake inhibitors; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressants. The inclusion criteria for identifying patients with biochemical evidence of CeH are as follows:…”

“… Note : List of medications taken from those implicated in our previous single‐centre published study 5 …”

Isolated anterior pituitary dysfunction in adulthood

“…Indeed, many drugs, such as bexarotene ( 97 ), mitotane ( 98 ) and immune checkpoint inhibitors ( 99 ) may alter the thyrotropic cell activity of TSH production or release determining, in general, permanent CH ( 96 ). Other drugs, like glucocorticoids, dopamine/dopamine-agonists, somatostatin analogues, metformin ( 100 ) as well as some antipsychotic and antidepressant medications ( 101 ), may exert a mild suppressive effect on TSH release without appreciably affecting circulating fT4 levels and hence without a real clinical significance ( 96 ). Finally, certain antiepileptic medications, including carbamazepine, oxcarbamazepine, valproic acid and phenytoin along with salsalate may determine falsely low levels of fT4 (secondary to pre-analytical variability due to sample dilution) and normal TSH levels in clinically euthyroid patients, mimicking the biochemical picture of ICH ( 96 , 102 , 103 ).…”