Graves disease: Clinical Sciences

Graves disease is an autoimmune condition characterized by the production of TSH-receptor antibodies, or TRAb, for short. These antibodies mimic thyroid-stimulating hormone, or TSH, so they bind to TSH receptors on thyroid cells and stimulate them to produce thyroid hormone, causing hyperthyroidism. In fact, Graves disease is the most common cause of hyperthyroidism.

Now, if your patient presents with a chief concern suggesting Graves disease, you should first perform an ABCDE assessment to determine if they are unstable or stable. If the patient is unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including heart rate, blood pressure, and pulse oximetry; as well as cardiac telemetry. Finally, if needed, provide supplemental oxygen.

Now, here’s a high-yield fact to keep in mind! If your patient presents with fever, tachycardia, delirium, or coma, you should suspect thyrotoxic crisis, also called thyroid storm. This is a severe, life-threatening presentation of Graves disease that typically occurs in patients with untreated or undertreated hyperthyroidism, and it’s triggered by an inciting event, such as major illness or surgery.

Treatment includes the four Ps: Propranolol or other beta-blockers, Propylthiouracil, Prednisolone or other glucocorticoids, and Potassium iodide. These patients need close monitoring, and may require intensive measures such as volume resuscitation and whole-body cooling.

Okay, now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss the stable ones. First, obtain a focused history and physical examination. Your patient may report palpitations, heat intolerance, anxiety, and insomnia, as well as digestive issues, such as increased appetite associated with unintentional weight loss, and diarrhea.

On the other hand, physical exam findings typically include the classic triad of Graves disease, which includes goiter, ophthalmopathy, and thyroid dermatopathy. Goiter refers to a smooth, firm, and diffusely enlarged thyroid gland, while ophthalmopathy refers to eyelid retraction, periorbital edema, and protrusion of the eyeballs due to retro-orbital inflammation. This condition is often described as Graves ophthalmopathy.

Finally, thyroid dermatopathy, also known as pretibial myxedema, refers to non-pitting edema and skin thickening over the shins, that occurs due to stimulation of fibroblasts in the dermis and subsequent deposition of glycosaminoglycans. Other physical exam findings include tachycardia, tremor, warm, moist skin, and muscle weakness.

At this point, you should suspect hyperthyroidism, so your next step is to order TSH and free T4 levels. If the TSH is normal or high and if the free T4 is normal or low, consider an alternative diagnosis. However, if the TSH is low and the free T4 is high, this is diagnostic of primary hyperthyroidism.

Next, check if your patient has TSH receptor antibodies. If they are present, no additional workup is required, and a Graves disease diagnosis can be made. If no antibodies are present, proceed with radioactive iodine uptake. If the pattern of iodine uptake reveals findings inconsistent with Graves disease, such as unifocal or multifocal iodine uptake, you should consider alternative diagnoses, such as solitary or even multiple thyroid nodules. On the other hand, diffusely elevated uptake confirms the diagnosis of Graves disease.

Now, here’s a clinical pearl to keep in mind! Sometimes, TSH-receptor antibodies can cause hypothyroidism! See, even though hypothyroidism is most commonly associated with antithyroid peroxidase and antithyroglobulin antibodies, rarely, TSH receptor antibodies can actually work as antagonists of the TSH receptor. In this case, they block thyroid hormone production, causing hypothyroidism!

Alright, now that you’ve diagnosed Graves disease, your goal is to treat hyperthyroidism by reducing thyroid hormone synthesis. Let’s look at patients with a high likelihood of remission. Patients with a high likelihood of remission, such as females, those with small goiters, as well as those with negative or low titer TSH-receptor antibodies or TRAb, are usually managed with antithyroid medications, such as propylthiouracil, carbimazole, or methimazole, for an initial 12 to 18 months.

Afterwards, assess treatment response with labs including TSH and FT4. If your patient has a normal TSH and FT4, that’s euthyroidism, and only periodic follow-ups are needed. On the other hand, low TSH and high FT4 mean that hyperthyroidism persists, and alternative treatment options should be considered, typically radioactive iodine.