‘I feel like I‘m jumping out of my skin’: Could this be Graves’ disease?

Clinical pearls for frontline PCPs

A generally healthy 42-year-old female presents for evaluation of anxiety, tremors, weight loss, loose stools and heart racing. Symptoms began shortly after she was let go at work about 4 months ago.

She is the primary breadwinner in a family of five. She is very stressed about her job loss.

The medical assistant (MA) rooms the patient and checks her vital signs:

• BP = 135 mm Hg /90 mm Hg;
• heart rate (HR) = 105;
• respiratory rate = 16; and
• body weight = 110 lbs (down from 125 lbs a year ago).

She is very “fidgety.” She is taking no medications and has no significant past medical history.

The MA presents the patient’s history to the physician. “Doc, this lady is really anxious. She told me, ‘I feel like I’m jumping out of my skin.’ She reports weight loss, shakiness and always being too warm. These symptoms began soon after she got laid off at work. If you ask me, doc, I think that she is just super stressed.”

Philip A. Bain

The physician enters the room and notes a very anxious-appearing patient. When asked to hold both arms outstretched, a fine bilateral upper extremity resting tremor is noted. Thyroid exam reveals a diffusely nodular, nontender, enlarged thyroid estimated to be about 30 g on exam. No discreet nodules are noted. Her eyes show mild to moderate exophthalmos. A cardiac exam is notable for the tachycardia and a precordial heave. Extremities show diffuse, nonpitting edema of both lower extremities.

Labs show a thyroid-stimulating hormone (TSH) that was nondetectable. Additional results show the following:

• free thyroxine (T4) = 17 ug/dL (elevated);
• triiodothyronine (T3) = 300 ng/dL (elevated);
• complete blood count = normal;
• comprehensive metabolic panel = normal; and
• thyrotropin receptor antibody (Ab) test = 8 IU/L (elevated).

She is started on metoprolol 25 mg twice daily for the tremor and tachycardia. A radioactive uptake and scan is ordered, and this shows significantly increased uptake. She is referred to a local endocrinologist for definitive recommendations. They make the diagnosis of Graves’ disease. The physician and patient discuss medication options and I-131 radioactive iodine (RAI) ablation, and they decide through shared decision-making to move forward with RAI treatment. In the meantime, she is referred to a local ophthalmologist for the exophthalmos. Her Clinical Activity Score (see Table) — calculated by the ophthalmologist — is 5, indicative of Graves’ orbitopathy.

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In about 3 months, the patient returns for reevaluation. Most of her symptoms have improved significantly or resolved, although she still feels tired. TSH is now 40 mU/L. She is started on levothyroxine 75 µg daily and asked to follow up in 3 months. At that visit, her HR is 75 and her metoprolol is stopped. She sees the ophthalmologist once more, and that time, her exophthalmos is barely perceptible.

Lessons learned

1. Hyperthyroidism is a relatively common condition of the thyroid, occurring in about 1% of the U.S. population. It is more common in women than men. While there are many causes of hyperthyroidism, the three most common are Graves’ disease, toxic multinodular goiter, and toxic adenoma, with Graves’ being the most common cause in the U.S.
2. Classic symptoms include anxiety, tremor, emotional lability, palpitations, heat intolerance, weight loss, diaphoresis, change in menstrual periods and frequent bowel movements.
3. Hyperthyroidism in older patients can present quite differently, either as “apathetic hyperthyroidism,” generally presenting as weakness, or as atrial fibrillation, dyspnea on exertion and/or new-onset edema.
4. Subclinical hyperthyroidism is common and can present with minimal symptoms or in the context of new-onset atrial fibrillation.
5. Physical exam findings in a patient with hyperthyroidism can include eye signs such as exophthalmos (protruding eyes), prominent “lid lag” and periorbital edema. A patients’ skin may be warm and moist, and they may experience hair thinning and/or hair loss. Their vital signs can include tachycardia, or an irregular rhythm due to atrial fibrillation. Hyperthyroidism is also associated with systolic hypertension. A precordial heave may be noted due to a hyperdynamic heart. A patient can also present with myxedema, a condition with four types — diffuse, plaque, nodular and elephantiasic. A thyroid exam can offer clues as well: a single palpable nodule may be an autonomously functioning adenoma. It can be tender in subacute (or granulomatous) thyroiditis. Painless (eg, lymphocytic) thyroiditis can have no, minimal or moderate thyroid enlargement. In Graves’ disease, the thyroid can be significantly enlarged and with bruits due to increased blood flow. In older adults with Graves’ disease, the thyroid may not even be palpable.
6. Regarding lab results, patients with primary hyperthyroidism will have a low TSH and elevated free T4 and T3. Checking the thyrotropin receptor Ab test can be very helpful because it is very often positive in Graves’ disease.
7. Once serological hyperthyroidism has been established, the cause of the hyperthyroidism should be determined. Sometimes, such as with Graves’ disease, the clinical presentation will make the diagnosis obvious. Clinicians usually rely on RAI uptake for nonpregnant patients, but RAI is absolutely contraindicated in pregnant or breastfeeding patients. If the uptake is low, this is indicative of either inflammation or destruction of thyroid tissue.
8. An indeterminate uptake and scan may be due to an autonomously functioning nodule and would be best served with a referral to a thyroid specialist.
9. In both pregnant and nonpregnant patients with hyperthyroidism without nodular goiter — especially without obvious clinical signs of Graves’ disease — measuring thyrotropin receptor Ab can help to determine the cause of the hyperthyroidism, because autoantibodies to the thyrotropin receptor are highly suggestive of Graves’ disease.
10. Treatment of hyperthyroidism depends on the etiology. Symptomatic treatment of tachycardia, tremor and anxiety usually includes a beta blocker like metoprolol. Definitive treatment for the three most common diagnoses includes RAI therapy, medical therapy with propylthiouracil or methimazole, or subtotal thyroidectomy. The choice of treatment depends on the etiology of the hyperthyroidism, comorbid conditions, age and patient preference.

References:

• American Thyroid Association. Hyperthyroidism. https://www.thyroid.org/wp-content/uploads/patients/brochures/hyperthyroidism.pdf. Accessed July 14, 2024.
• Kravets I. Am Fam Physician. 2016;93(5):363-370.
• Lee SY, et al. JAMA. 2023;doi:10.1001/jama.2023.19052.
• University of Michigan Health. Hyperthyroidism and Graves’ Disease. https://www.uofmhealth.org/conditions-treatments/endocrinology-diabetes-and-metabolism/hyperthyroidism-and-graves-disease. Accessed July 14, 2024.