Graves disease: Clinical Sciences

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Introduction0:00–0:32

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.

Unstable patient0:32–1:57

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.

Stable patient1:57–3:18

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.

Suspect hyperthyroidism3:18–5:01

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.

Treatment5:01–8:40

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.Speaking of radioactive iodine, let’s go all the way back and go over patients with contraindications to antithyroid medications, such as altered liver function.
These patients would go straight to radioactive iodine, which can be given as a single treatment. Afterwards, assess treatment response with labs including TSH and FT4.
If TSH and FT4 are normal, that’s euthyroidism, and only periodic follow-ups are needed. On the flip side, low TSH and high FT4 mean that hyperthyroidism persists, and alternative treatment options should be considered.
Finally, a high TSH with a normal or low FT4 means your patient is hypothyroid, and should receive thyroid hormone substitution therapy.As a clinical pearl, keep in mind that radioactive iodine treatment is absolutely contraindicated in pregnant patients and those actively breastfeeding.
Also, it’s relatively contraindicated in patients with Graves ophthalmopathy, as it may exacerbate the condition. Speaking of which, mild to moderate forms of Graves ophthalmopathy require only symptomatic treatment, such as artificial tears and eye patching, and usually resolve on their own once the hyperthyroid state has been adequately treated.
However, severe forms, namely those associated with diplopia, corneal damage, or optic nerve compression, typically require specific treatment, such as glucocorticoids or even surgical decompression.
Also, tobacco use is associated with a higher risk of ophthalmopathy, so don’t forget to encourage smoking cessation.Now, let’s go over for patients with severe Graves ophthalmopathy, large goiters, or suspicious thyroid nodules.
For patients with severe Graves ophthalmopathy, large goiters, or those with thyroid nodules that are suspicious for malignancy, surgery can be considered as a first line option.
If total thyroidectomy is performed, the patient will need lifelong thyroid hormone replacement therapy.And for one last clinical pearl… When you first diagnose hyperthyroidism, you can prescribe a beta-blocker, such as propranolol, to help control adrenergic symptoms like palpitations and tremors, until antithyroid medications or radioactive iodine treatment take effect or surgery can be performed.Alright, as a quick recap… Graves disease is an autoimmune cause of hyperthyroidism.

Review8:40–9:59

In patients with primary hyperthyroidism, order TSH-receptor antibodies. If antibodies are present, the diagnosis of Graves is confirmed; but, if antibodies are negative, proceed with a radioactive iodine uptake study, and diffusely elevated uptake confirms the diagnosis.
Now, first-line treatment for patients with high likelihood of remission is with antithyroid medications for 12 to 18 months, after which response is assessed with labs like TSH and free T4.
If hyperthyroidism persists, or if antithyroid medications are contraindicated, you can consider other options like radioactive iodine treatment.
Then, assess treatment response with labs including TSH & free T4; if hyperthyroidism persists, consider alternative treatments.
However, if your patient becomes hypothyroid after radioactive iodine, give thyroid hormone replacement therapy. Finally, in patients with severe Graves ophthalmopathy, large goiters, or thyroid nodules suspicious for malignancy, surgery can be a first-line option.