Thyroid Axis Changes After Long-term Levothyroxine Therapy
Thyroid Axis Changes After Long-term Levothyroxine Therapy
Table 1 contains the details of the patients, as well as the various laboratory measurements at time1 and time2 and the results of tests for differences between the two time points. As can be seen in Table 1, there were no significant differences in levothyroxine dose or bodyweight between time1 and time2, nor were there significant differences in rT3 levels. TT3, TT4 and TSH levels were however significantly reduced at time2 as compared to time1.
To exclude a relevant influence on thyroid hormone levels resulting from changes in LT4 doses, we analysed the relationship between these two variables. At time2, there were no significant changes in the relationship between the dose of LT4/kg bodyweight taken by patients and the resulting TT4 levels (P = 0·14) compared with time1.
At time2, the TT3 levels were significantly decreased compared with time1, which reflects itself in a considerable, significant increases in the TT4/TT3 (P < 0·001); this effect is also illustrated in Fig. 1a.
(Enlarge Image)
Figure 1.
Graphic depiction of changes in the relationship between total T4, total T3 and reverse T3. (a) the relationship between total T4 and total T3 levels at time1 and time2. (b) the relationship between total T4 levels and reverse T3 levels at time1 and time2. (c) The relationship between reverse T3 and total T3 levels at time1 and time2.
There was a significant 16% decrease in the TT4/rT3 ratio (P < 0·001; see also Fig. 1b), indicating a relative increase in the production of rT3. As is also illustrated in Fig. 1c, the TT3/rT3 ratio shows a considerable and significant decrease over time (P < 0·001).
Although we did not have enough serum available to perform direct measurements of the thyroxin binding globulin (TBG) levels, these levels can nonetheless be deduced from the ratio of bound-to-free thyroid hormone levels, which is solely dependent on the TBG level. As the TT3/FT3 ratio showed no significant changes (P = 0·52) between time1 and time2, major changes in the TBG levels can practically be excluded.
As the interval between time1 and time2 is considerable, we wanted to rule out a possible influence of increasing age of the patients. Therefore, we analysed the relationship between age and thyroid hormone ratios. As is illustrated in Fig. 2 for the TT4/TT3 ratio, we found that the ratios changed similarly along all age groups for each ratio, with regression lines for time1 and time2 being parallel, indicating that the changes were independent from age.
(Enlarge Image)
Figure 2.
Graphic depiction of the changes in the relationship between total T4 and total T3 as a function of age at time1 and time2, with corresponding regression lines.
Results
Table 1 contains the details of the patients, as well as the various laboratory measurements at time1 and time2 and the results of tests for differences between the two time points. As can be seen in Table 1, there were no significant differences in levothyroxine dose or bodyweight between time1 and time2, nor were there significant differences in rT3 levels. TT3, TT4 and TSH levels were however significantly reduced at time2 as compared to time1.
Influence: Dose of LT4/kg on Thyroid Hormone Levels
To exclude a relevant influence on thyroid hormone levels resulting from changes in LT4 doses, we analysed the relationship between these two variables. At time2, there were no significant changes in the relationship between the dose of LT4/kg bodyweight taken by patients and the resulting TT4 levels (P = 0·14) compared with time1.
Relationship Between Thyroid Hormone Levels
At time2, the TT3 levels were significantly decreased compared with time1, which reflects itself in a considerable, significant increases in the TT4/TT3 (P < 0·001); this effect is also illustrated in Fig. 1a.
(Enlarge Image)
Figure 1.
Graphic depiction of changes in the relationship between total T4, total T3 and reverse T3. (a) the relationship between total T4 and total T3 levels at time1 and time2. (b) the relationship between total T4 levels and reverse T3 levels at time1 and time2. (c) The relationship between reverse T3 and total T3 levels at time1 and time2.
There was a significant 16% decrease in the TT4/rT3 ratio (P < 0·001; see also Fig. 1b), indicating a relative increase in the production of rT3. As is also illustrated in Fig. 1c, the TT3/rT3 ratio shows a considerable and significant decrease over time (P < 0·001).
Exclusion of Changes in Thyroxin Binding Globulin Levels
Although we did not have enough serum available to perform direct measurements of the thyroxin binding globulin (TBG) levels, these levels can nonetheless be deduced from the ratio of bound-to-free thyroid hormone levels, which is solely dependent on the TBG level. As the TT3/FT3 ratio showed no significant changes (P = 0·52) between time1 and time2, major changes in the TBG levels can practically be excluded.
Influence of Age
As the interval between time1 and time2 is considerable, we wanted to rule out a possible influence of increasing age of the patients. Therefore, we analysed the relationship between age and thyroid hormone ratios. As is illustrated in Fig. 2 for the TT4/TT3 ratio, we found that the ratios changed similarly along all age groups for each ratio, with regression lines for time1 and time2 being parallel, indicating that the changes were independent from age.
(Enlarge Image)
Figure 2.
Graphic depiction of the changes in the relationship between total T4 and total T3 as a function of age at time1 and time2, with corresponding regression lines.