Objective: To explore the nature and extent of possible residual complaints among Dutch hypothyroid patients
using thyroid replacement therapy, we initiated a comprehensive study measuring health-related quality of life
(QoL), daily functioning, and hypothyroidism-associated symptoms in patients and control persons.

Methods: An online survey measuring thyroid-specific QoL (ThyPRO), daily functioning, and hypothyroidismassociated
symptoms (ThySHI) was distributed among treated hypothyroid patients and control individuals.
The advertising text was formulated in an open-ended manner. Patients also provided their most recent thyroid
blood values and their thyroid medication.

Results: There was a large-sized impairment of QoL (Cohen’s d = 1.04, +93 % ThyPRO score) in hypothyroid
patients on thyroid replacement therapy (n = 1195) as compared to controls (n = 236). Daily functioning was
significantly reduced i.e., general health (-38 %), problems with vigorous- (+64 %) and moderate activities (+77
%). Almost 80 % of patients reported having complaints despite thyroid medication and in-range thyroid blood
values, with 75 % expressing a desire for improved treatment options for hypothyroidism (total n = 1194).
Hypothyroid patients experienced 2.8 times more intense hypothyroidism-associated symptoms than controls (n
= 865, n = 203 resp). Patients’ median reported serum concentrations were: TSH 0.90 mU/L, FT4 17.0 pmol/L,
and FT3 2.67 pmol/L, with 52 % having low T3 levels (<3.1 pmol/L). The QoL was not found to be related to
age, sex, BMI, menopausal status, stress, serum thyroid parameters, the origin and duration of hypothyroidism,
the type of thyroid medication, or the LT4 dose used.

Conclusions: Our study revealed major reductions in quality of life and daily functioning, and nearly three times
more intense hypothyroidism-associated symptoms in treated hypothyroid patients as compared to controls,
despite treatment and largely in-range serum TSH/FT4 concentrations. The QoL was not associated with serum
thyroid parameters. We recommend future research into the origin of persisting complaints and the development
of improved treatment modalities for hypothyroidism.