A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences

Objective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy.

Method: In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD).

Result: A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24-55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10^-20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10^-7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018).

Conclusion: During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management.