Patient tailored levothyroxine dosage with pharmacokinetic/pharmacodynamic modeling: a novel approach after total thyroidectomy.

Abstract

Background After seven decades of levothyroxine replacement therapy, dosage adjustment still takes several months. We have developed a decision aid tool (DAT) that models levothyroxine pharmacometrics and enables patient tailored dosage. The aim was to speed up dosage adjustments for patients after total thyroidectomy. Methods The DAT computer program was developed with a group of 46 post thyroidectomy patients, and then applied in a prospective randomized multicenter validation trial in 145 unselected patients admitted for total thyroidectomy for goiter, differentiated thyroid cancer or thyrotoxicosis. The levothyroxine dosage was adjusted after only two weeks, with or without application of the DAT, which calculated individual thyroxine (FT4) targets based on four repeated measurements of FT4 and TSH levels. The individual TSH target was either < 0.1, 0.1 - 0.5 or 0.5 - 2.0 mIU/L, depending on the diagnose. Initial postoperative levothyroxine dosage was determined according to clinical routine without using algorithms. A simplified DAT with a population based FT4 target was used for thyrotoxic patients who often went into surgery after prolonged TSH suppression. Subsequent levothyroxine adjustments were carried out every six weeks until target TSH was achieved. Results When clinicians were guided by the DAT, 40 % of goiter patients and 59 % of cancer patients satisfied the narrow TSH targets eight weeks after surgery, as compared to only 0 % and 19 % of the respective controls. The TSH was within the normal range in 80 % of DAT/goiter patients eight weeks after surgery as compared to 19 % of controls. The DAT shortened the average dosage adjustment period by 58 days in the goiter group and 40 days in the cancer group. For thyrotoxic patients, application of the simplified DAT did not improve the dosage adjustment. Conclusions Application of the DAT in combination with early post-operative TSH and FT4 monitoring offers a fast approach to levothyroxine dosage after total thyroidectomy for patients with goiter or differentiated thyroid cancer. Estimation of individual TSH-FT4 dynamics was crucial for the model to work, as removal of this feature in the applied model for thyrotoxic patients also removed the benefit of the DAT.