Q.93 In Graves’ disease, the presence of auto antibodies against which ONE of the following molecules
is the direct cause of hyperthyroidism?
(A) Thyroperoxidase (B) Thyroxine
(C) Thyroid stimulating hormone (D) Thyroid stimulating hormone receptor
Graves’ Disease Autoantibodies: Direct Cause of Hyperthyroidism Explained
Graves’ disease triggers hyperthyroidism through specific autoantibodies that mimic TSH and overstimulate the thyroid. The correct answer is (D) Thyroid stimulating hormone receptor.
Correct Answer
In Graves’ disease, autoantibodies against the thyroid stimulating hormone receptor (TSHR) directly cause hyperthyroidism by binding and activating TSHR, leading to excessive thyroid hormone production. These thyroid-stimulating immunoglobulins (TSI or TRAb) act as TSH agonists.
Option Breakdown
| Option | Molecule | Role in Graves’ Disease | Why Not the Direct Cause? |
|---|---|---|---|
| (A) | Thyroperoxidase (TPO) | Enzyme for thyroid hormone synthesis; TPO antibodies common in Hashimoto’s thyroiditis (hypothyroidism). | Present in some Graves’ patients but causes thyroid damage, not stimulation; linked to remission, not hyperthyroidism. |
| (B) | Thyroxine (T4) | Main thyroid hormone produced in excess. | Hormone itself, not an immune target; autoantibodies don’t target hormones directly. |
| (C) | Thyroid stimulating hormone (TSH) | Pituitary hormone that normally stimulates TSHR. | TSH levels are low in Graves’ due to feedback; autoantibodies mimic TSH, suppressing it. |
| (D) | Thyroid stimulating hormone receptor | G-protein coupled receptor on thyroid cells. | Correct: Stimulating autoantibodies (TRAb/TSI) bind and activate it, causing uncontrolled T4/T3 release. |
Mechanism in Graves’ Disease
Autoantibodies to TSHR continuously stimulate thyroid follicles, bypassing normal TSH regulation, resulting in hyperthyroidism, goiter, and symptoms like weight loss and tachycardia. Unlike blocking antibodies (rare, cause hypo), stimulating types dominate in 90-100% of cases. TPO antibodies (A) may coexist but drive Hashimoto’s pathology.
This pathology question tests autoimmune thyroiditis differentiation, key for exams. TRAb assays confirm diagnosis with >95% specificity.
