Abstract: Thyroid stimulating hormone receptor (TSHR) is a vital thyrocyte membrane protein in the thyroid gland. Thyroid Stimulating Hormone (TSH) which is a pituitary hormone is the main stimulator of thyroid gland to produce thyroid hormones, it binds with high affinity to the TSHR through weak bonds including hydrophobic, ionic, hydrogen bonds and trigger the initial steps in thyroid gland stimulation to produce the related hormones. This study was carried out at department of biochemistry of Golestan university of medical sciences. All the related articles related to TSHR modification happened due to mutations and any other alterations which affect the level of TSH-TSHR complex were studied and the main points were extracted out of the pile of information and were organized as present review. TSH-TSHR is the initial and vital step of a long process of thyroid hormone production within the thyroid gland. Any alteration on the TSH-TSHR affinity which may happen due to the direct effect of TSHR modification eventually lead to the serious adverse effects of either hypothyroidism or hyperthyroidism if the TSH-TSHR level are suppressed or elevated, respectively. The prime cause of the thyroid disorders relay on the possible modification on the biochemical structure of TSHR with subsequent alteration on the level of TSH-TSHR complex. TSHR mutation accompanied by biochemical modification, unable it to bind properly to TSH. In some other conditions such mutation leave a TSHR with either of higher affinity towards to TSH or even TSHR which can be activated in the absence of TSH. The structural modification of TSHR and alteration in the level of TSH-TSHR in the thyroid gland eventually lead to thyroid disorders either of hypothyroidism or hyperthyroidism.