Endocrine Abstracts

Introduction: TRH, thyroid hormones, dopamine, somatostatin and glucocorticoids have a recognized influence on TSH secretion. On the other hand, serotoninergic, histaminergic, catecholaminergic, opioidergic and GABAergic systems establish connections with hypophysiotropic neurons involved in TSH regulation; their relative contribution to TSH secretion is unknown. Still, there are a few reports of H1 receptor antagonists impact on TSH levels.

Case report: Thirty-years-old woman with autoimmune hypothyroidism. She had been pregnant the previous year; two months after delivery she remained on euthyroidism on 112 mcg levothyroxine [TSH-1.07 μUI/ml; FT4-1.11 ng/dl]. Nine months after delivery she repeated laboratorial evaluation [TSH-16.3 μUI/ml); FT4-1.04 ng/dl] and her general practitioner increased levothyroxine dose to 137 mcg. However, two months later her TSH was still high [TSH-14.62 μUI/ml; FT4-0.91 ng/dl] and levothyroxine dose was further increased (retrospectively, she had been taking metoclopramide/betahistine on a regular basis for the previous 2 weeks). When she presented to endocrinology appointment, her pharmacologic habits included 150 mcg levothyroxine, COCP and dimenhydrinate (prescribed 3 weeks earlier for vertiginous syndrome). On that occasion, she disclaimed intermittent compliance with levothyroxine therapy. Her laboratorial re-evaluation revealed a TSH of 159.43 μUI/ml and FT4 of 1.04 ng/dl. She was summoned to repeat analysis and advised to withhold dimenhydrinate. She denied exposure to other medicines, St.John’s wort, iodine supplements, iodinated contrast or amphetamines, but admitted sporadic levothyroxine omission. The following blood sample was collected one week after the former and over 24 hours off dimenhydrinate: TSH-31.86 μUI/ml; FT4-1.38 ng/dl. The laboratory was requested to exclude macro-thyrotropin: serial dilutions revealed a linear recovery. The sample was also analysed by a different method/laboratory: TSH-38.46 μUI/ml; FT4-1.45 ng/dl; rheumatoid factor assay was negative. Five weeks after dimenhydrinate withdrawal and reinforcement of the importance of medication adherence, she presented a TSH of 3.84 μUI/ml and FT4 of 1.79 ng/dl.

Discussion: A normal FT4 with a very high TSH level on a patient with a personal history of hypothyroidism might be ascribable to intermittent compliance, iatrogenic or analytical interference factors. It is important to clarify pharmacologic habits, namely exposure to dopamine antagonists, amphetamines and drugs that impair levothyroxine absorption. Likewise, methodologic interference factors such as macro-thyrotropin, rheumatoid factor and heterophile antibodies should also be regarded. Considering dimenhydrinate actions and temporal coincidence between drug exposure/withdrawal and TSH levels increase/normalization, this H1 receptor antagonist might be an important interference cofactor in the reported case.