We have studed in detail a group of patients repeatedly presenting over several years, on T4 only. Some of these complained of hypothyroid symptoms and some of hyper symptoms.What we wanted to find out is, how different are the complainers in each group different from those who were satisfied on T4 only. What seems to be the case is that, as we thought the response regarding FT3 production by conversion is detectably different in the subgroups from the rest. This is probably the first longterm analysis of a patient panel which divides patients into groups with different responses to an ongoing standardised T4 treatment. The idea is to present this study as a first step to the proper divising of clinical trials in future, recognising that a random panel of patients cannot be simply put together in one group, but must be first stratified according to their response to therapy. In this way those dissatisfied with T4 only could be identified in advance as probably needing more than T4 mono therapy. For your interest I present the abstract. It is of course rather complex, as the subject matter is. No guarantee of publication of course but if it is accepted it will be in Frontiers in Thyroid Endocrinology sometime later this year:
Background: For significant numbers of patients dissatisfied on standard levothyroxine (LT4) treatment for hypothyroidism, patient-specific treatment responses to levothyroxine could play a significant role.
Aim: To assess response heterogeneity to LT4 treatment, identifying confounders and hidden clusters within a patient panel, we performed a secondary analysis using a prospective cross-sectional and retrospective longitudinal study.
Methods: Multivariate and multivariable linear models adjusted for confounders (gender, age and BMI) were stratified by disease-specific treatment indication. During follow-up, pooled observations were compared from the same patient presenting either with or without self-reported symptoms. Statistical analysis was extended to multilevel models to derive intra-class correlation coefficients and reliability measures during follow-up.
Results: Equilibria between TSH, FT4 and FT3 serum concentrations in 342 patients were related to treatment indication (benign goitre, autoimmune thyroiditis, thyroid carcinoma), displaying complex interactive response patterns. 77 patients treated with LT4 and monitored for thyroid carcinoma presented, in association with changes in LT4 dose, either with hypothyroid symptoms or symptom-free. Significant biochemical differences appeared between the different presentations. Levelled trajectories by subject to relief from hypothyroid symptoms differed significantly, indicating distinct responses, and denying a single shared outcome. These were formally defined by a high coefficient of the intraclass correlation (ICC1) during follow-up on multiple visits at the same LT4 dose, when lacking symptoms, exceeding 0.60 in all thyroid parameters. Symptomatic change in these patients was strongly associated with serum FT3, but not with FT4 or TSH concentrations. In 25 patients transitioning from asymptomatic to symptomatically hyperthyroid, while their FT3 concentrations remained within the reference limits, biochemical differences were also marked between the presentations.
Conclusions: Considerable intra-individual clustering occurred in the biochemical and symptomatic responses to LT4 treatment, implying statistically heterogeneous response groups. Unmasking individual differences in the averaged treatment response hereby highlights clinically distinguishable subgroups. This, through well designed larger clinical trials will better target the different therapeutic needs of individual patients.
Time released thyroid hormone T4 and T3
U.S. Study Shows Combination Treatment Is Safe, Effective
thyroid hormone resistance? not getting better on t4 alone or t4/t3 
