A 30-year-old woman presents to the emergency department for palpitations. For 2 months, she has experienced intermittent palpitations along with menstrual irregularity and hair loss. At home, the air conditioner is at its coldest setting, but the patient still feels overheated. Her temperature is 99.5°F (37.5°C), blood pressure is 135/90 mmHg, pulse is 120/min, and respirations are 22/min. The patient is diaphoretic with tremulous hands, demonstrates thyromegaly, and protrusion of her eyes is noted. She is given atenolol in the emergency department with improvement of her palpitations and is instructed to follow up with her primary doctor for further management. Which of the following is most likely to be found in this patient after definitive treatment of her condition?
Exophthalmos
Hair loss
Heat intolerance
Thyromegaly
Exophthalmos
This patient presents with palpitations, tachycardia, tremor, heat intolerance, hair loss, menstrual irregularity, goiter, and exophthalmos concerning for hyperthyroidism due to Graves disease. Radioiodine ablation is the preferred definitive management for Graves disease, which can worsen exophthalmos.

Graves disease is an autoimmune hyperthyroid disorder caused by antibodies to the thyroid stimulating hormone receptor (TSHR), which induce production of T4 and triiodothyronine (T3). Overstimulation of the thyroid gland by TSHR antibodies results in diffuse enlargement of the thyroid gland, termed “goiter.” TSHR is also highly expressed in retro-ocular adipocytes and fibroblasts, where overstimulation by TSHR antibodies (and activated T-cells) leads to the expansion of retro-ocular connective tissue and extra-ocular muscle volume. This causes exophthalmos (bulging eyes) and is referred to as Graves ophthalmopathy or orbitopathy. Beta blockers are used to achieve acute sympathetic control in hyperthyroid Graves patients, and antithyroid medications (propylthiouracil or methimazole) are initiated to achieve a euthyroid state. Radioactive iodine ablation is first-line definitive management, particularly, for individuals with unsuccessful anti-thyroid medication management. Radioiodine ablation has been known to increase TSHR-antibodies, likely secondary to the leakage of thyroid antigens, and thus exophthalmos is often worsened after treatment. For this reason, corticosteroids are often co-administrated as a prophylactic measure.

Davies et al. review Graves disease including the pathophysiology and management. They note that Graves orbitopathy may be worsened by radioiodine ablation. They recommend further studies and advancements in care given this lasting complication.

Incorrect Answers:
Answer B: Hair loss can occur in hyperthyroid and hypothyroid states due to altered hair follicle stem cell function. However, this process is typically reversed, not worsened, after achieving a euthyroid state.

Answer C: Heat intolerance occurs in Graves disease due to hyperthyroid-induced sympathetic overactivity, which resolves after successful treatment.

Answer D: Menstrual irregularity occurs in hyperthyroidism through altered levels of sex hormone binding globulin, gonadotropin-releasing hormone, and prolactin. However, treatment of hyperthyroidism typically restores menstrual regularity. After ablation, patients will be hypothyroid; however, the standard of care is to start the patient on levothyroxine which should prevent this complication.

Answer E: Thyromegaly in Graves disease is caused by diffuse overactivation of the thyroid gland by the TSHR antibodies. Once treated with radioactive iodine (I-131), the thyroid gland gradually shrinks in size. Patients who undergo radioactive iodine ablation will later require life-long thyroxine supplementation due to resulting hypothyroidism.

Bullet Summary:
Definitive therapy for Graves disease is radioiodine ablation, which leads to increased TSHR antibodies and worsened exophthalmos from overactivation of TSHR-rich retro-ocular adipocytes and fibroblasts.