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PharmD Student Department of Pharmacy: Clinical and Administrative Sciences College of Pharmacy University of Oklahoma Oklahoma City, Oklahoma
Clinical Pharmacology Service Coordinator and Clinical Assistant Professor Department of Pharmacy: Clinical and Administrative Sciences College of Pharmacy University of Oklahoma 1110 North Stonewall Oklahoma City, Oklahoma 73117-1223 fax 405/271-2988 nancy-brahm{at}ouhsc.edu
Consultant Psychiatrist Enid, Oklahoma
State Medical Director Department of Developmental Disabilities Services Adjunct Clinical Associate Professor Department of Pharmacy: Clinical and Administrative Sciences College of Pharmacy University of Oklahoma
Published Online, July 13, 2004. www.theannals.com, DOI 10.1345/aph.1E054
Case Report. An 18-year-old African American man was diagnosed with conduct disorder, adolescent onset type, severe; schizoaffective disorder, bipolar type; moderate mental retardation; and features of borderline personality disorder. Patient records and laboratory reports were available from admission into a state intermediate care facility for the mentally retarded in February 2002 to the present. Thyroid function laboratory tests taken on March 22, 2002, were quetiapine-naïve and the results were within normal limits. At that time, the drug regimen included methylphenidate extended release 36 mg/day, ziprasidone 240 mg/day, paroxetine 40 mg/day, gabapentin 3200 mg/day, lithium carbonate 1200 mg/day, trazodone 200 mg/day, and desmopressin 0.2 mg/day, although lithium-induced or neurogenic diabetes insipidus is unresponsive to this agent.1
The patient changed facilities on May 8, 2002, and was readmitted to our treatment facility on July 9, 2002, with the following regimen: methylphenidate sustained release 54 mg/day, quetiapine 600 mg/day, fluoxetine 80 mg/day, gabapentin 2400 mg/day, trazodone 200 mg/day, and benztropine 2 mg/day for extrapyramidal symptoms (EPSs). No thyroid blood tests were taken upon readmission. Quetiapine was increased to 1200 mg/day on February 4, 2003, and a thyroid panel was performed at that time. Quetiapine was ultimately titrated to 1500 mg/day. Variances were noted in the thyroid laboratory values obtained on August 5, 2003 (Table 1). The quetiapine dose was maintained. Thyroid-stimulating hormone (TSH) was rechecked and found to be within normal range on October 8, 2003. No other medication changes were made.
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The possibility of quetiapine-mediated hypothyroidism was raised.2,3 Based on the reports, a review of quetiapine doses and laboratory results in our patient led us to conclude that quetiapine may have contributed to changes in thyroid function. An objective causality determination based on the Naranjo probability scale indicated the adverse effect was possible.4 We were able to compare the total daily dosage of quetiapine at a given point in time with the corresponding thyroid laboratory measurements. When a patient is treatment-naïve, all measured thyroid indices are within normal limits. With the initiation and upward titration of quetiapine, the total thyroxine (T4) level showed a steady decline.
Discussion. The basis for the effects of quetiapine on the thyroid axis remains unknown. Our case is of interest as it shows persistent and significant decreases in both total T4 and unbound thyroxine (fT4) levels, associated with increased triiodothyronine resin uptake (T3RU), in the absence of TSH excursions. Thus, quetiapine effects are seemingly more complex than inhibition of thyroid hormone formation/secretion. Similarly, such effects are not merely due to a euthroid sick syndrome/nonthyroidal illness type of state; the latter is typically associated with normal fT4, high-normal TT4, and low TT3 and fT3. Therefore, the mechanism of induction of thyroid hormone indices alterations in our case seems to be multifactorial and could include a combination of thyroid- and hypothalamo–pituitary system-based actions of quetiapine, as well as complex interactions with thyroid hormone plasma binding proteins, suggested by the increased T3RU and possibly changes in T4 and T3 deiodination. Further study of the mechanisms of quetiapine-induced changes on thyroid axis function is certainly warranted. At our institution, the decision was made to obtain baseline thyroid function and metabolic status prior to quetiapine initiation and periodically during the course of therapy. Additional clinical interventions will be based on medication response and significant changes in thyroid function indicators.
References
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