Levothyroxine Replacement Doses Are Affected by Gender and Weight, But Not Age

Abstract

Background: Body weight (BW) and age have been shown to affect the dose of levothyroxine (LT 4 ) that results in normalization of serum thyroid-stimulating hormone (TSH) in hypothyroid patients. Our objective was to determine whether gender, menstrual status, and ideal BW (IBW) also affect the LT 4 dose required to achieve a serum TSH within the normal range. Methods: We retrospectively reviewed the charts of patients being treated for primary hypothyroidism who had TSH values within a normal range. We selected patients aged 18-85 years who were taking LT 4 without any confounding medications, and who had no serious chronic conditions. Their LT 4 doses, referred to here as LT 4 dose requirements, based on both BW and IBW were documented. The relationship between gender, menstrual status, age, serum TSH concentrations, and the degree of overweight on LT 4 dose requirements were determined using multivariate analyses. Results: Women were significantly more overweight than men (ratio of BW/IBW was 1.35 for women vs. 1.17 for men, p < 0.0001). LT 4 requirements based on BW did not differ by gender when age was included in the model. However, when degree of overweight was also included, men required lower LT 4 doses than both premenopausal women (1.34 mg/kg vs. 1.51 mg/kg, p ¼ 0.038) and menopausal women (1.34 mg/kg vs. 1.49 mg/ kg, p ¼ 0.023). When examining IBW using a model incorporating age, men also required lower LT 4 doses than both premenopausal women (1.64 mg/kg vs. 1.92 mg/kg, p ¼ 0.0033) and menopausal women (1.64 mg/kg vs. 1.90 mg/kg, p ¼ 0.0024). Serum TSH concentrations were not significantly different in any of the gender groups. There was no relationship between serum TSH and either age or BW. The initial serum TSH concentration was by design with the normal range, but the concentration within that range was not a significant predictor of the LT 4 replacement dose in any of the models. Conclusion: In contrast to previous studies suggesting that age affects LT 4 replacement requirements, we found that age-based differences in doses are secondary to differences in BW and gender. In addition, in contrast to prior studies showing that lean body mass, but not gender, affected LT 4 dose, we instead found a significant impact of gender. Gender-based differences in dose requirement only became apparent either when IBW was used to correct for the dose or when degree of overweight was included in the model. Gender differences in LT 4 dose requirement exist, but are masked unless gender-based differences in degree of overweight are also considered.

Comparison Among the Daily Levothyroxine Doses According to the Etiology of Hypothyroidism

“…On the other hand, Franklyn et al suggested that increasing age alone does not significantly influence thyroid hormone measurements [12]. A more recent study also suggested that age does not directly affect FT4 replacement requirements, and age-based differences in doses are secondary to differences in body weight and gender [13]. These findings correlate to the results of our categorical analyses.…”

“…The data presented above explain the findings of previous studies (13) in which doses of levothyroxine needed for patients in menopause were smaller (1.49 μg/kg/day) than those of premenopausal patients (1.51 μg/kg/day). In our study, considering women under and over 50 years old, the dose was higher for the younger patients (< 50 years), but the difference was not statistically significant.…”

Clinical practice guidelines for the management of hypothyroidism

“…Initial recommended daily dose for clinical hypothyroidism in < 60 years old patients is 1.6-1.8 μg/ kg ideal body weight (190) (B). No differences were found between slow or full starting dose (191) …”

Factors Associated with the Stability of Thyroid-stimulating Hormone Values in Hypothyroidism

“…Two studies by Jonklaas et al [26] and Devdhar et al [27] suggest that the levothyroxine dose required by pre-and postmenopausal women disappear are the same if they are assessed using ideal weight, rather than using current body weight. These authors attributed the alterations that occur during aging to the change in weight.…”