Study the effect of combination therapy with levothyroxine and leiothyronine in comparison with levothyroxine on Well-Being, Quality of Life, or Cognitive Function in Patients with Primary Hypothyroidism

the present RCT will be conducted to evaluate the effect of combined LT4+LT3 therapy vs LT4 alone on the quality of life.

A randomized, double-blind, parallel-group comparison trial in a 1:1 ratio including the baseline (April- Oct 2020 ) and the 6-months follow-up

Hypothyroid patients with levothyroxine monotherapy and normal TSH In this double blind study, patients divided in two groups Place of study: Sayad Shirazi Hospital Endocrinology Clinic, Gorgan

Inclusion Criteria Age over 16 years Being able to read and understand Persian Diagnosis of overt hypothyroidism at least 6 months before inclusion Stable and regular LT4 monotherapy for at least 3 months before inclusion Patient-reported signs and symptoms of hypothyroidism including fatigue, mood change, weight gain, lethargy, decreased psychomotor performance conative, depression, and disturbances despite normal thyroid hormone levels Exclusion criteria Pregnancy or planned pregnancy within the next 6 months Patients with drug or alcohol addiction Patients with Malignancy, cardiovascular disease ,renal, or hepatic disease, chronic liver disease ,depression, anxiety Patients with mental illness and had been on psychiatric medicine for 6 months before inclusion

Patients will be randomized to continue receiving their usual dose of LT4 (100 µg/day) in the combination of placebo for 6 months (Group 1), or change their usual treatment to the combination therapy of LT4 50 µg and LT3 6.25 µg twice a day (Group 2) The placebo will be “liothyronine” and labeled “approved for research purposes only”.

changes in quality of life between baseline and follow-up visits of the

Change questionnaire

We will design a randomized, double-blind (both patients and physicians), parallel-group comparison trial in a 1:1 ratio, and patients are randomly assign following procedures to LT4+placebo or LT4+LT3 treatment groups. The list of random allocation cards will be generated by an independent trained researcher using computer-generated random numbers. To avoid the confusion of coding A or B, the researcher will keeps the original random allocation sequences in an inaccessible third place and works with a copy.

The placebo will be placed into envelopes according to the allocation orders by another independent nurse who was not aware of the study. The patient's ID, visit date, and other information will be recorded on each envelope. Neither the patients nor the physicians who will assess the patients are aware of the treatment. After 6 months, another independent researcher who is not aware of the treatment will assess the patient's health-related quality of life scores.

All data in this study can be shared without identifying individuals.

Start access 3 months after printing the results

Data from this study will only be available to researchers working at academic and research institutes and specialist physicians

There are no restrictions on data analysis

Dr. Fatemeh Talebi / Email: Fahajtalebi@yahoo.com/ Phone Number: 09151042897

The applicant will be able to access the document after submitting documents regarding the reason for requesting the data file and determining the identity of the person (specialist or researcher).