Blazing hot tips to diagnose and treat hyperthyroidism with Dr Eve Bloomgarden, @evebmd (Northwestern). We cover a ton of ground including how to: interpret thyroid function tests, use your thumbs (or an ultrasound) to examine the thyroid, become an expert on Graves’ orbitopathy, prescribe methimazole and decide who needs surgery or radioactive iodine therapy. Plus, a bit on subclinical hyperthyroidism. This episode is on fire!
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Thyrotoxicosis is an umbrella term for undifferentiated hyperthyroidism with Graves’, thyroiditis and functional “hot” nodules as the top three causes. Think Graves’ disease in younger folks, hot nodules in older folks and thyroiditis at times of year when viral illnesses are making the rounds. Have a low threshold to refer patients to endocrinology if you’re unclear what’s going on, especially in pregnancy.
Thyroiditis: Ask about recent viral infection in patients with Subacute (painful) thyroiditis. Painless thyroiditis is thought to be autoimmune (Ross, Thyroid 2016). Trauma to the neck (e.g. strangulation) can be a precipitant. The spillover of thyroid hormone from thyroiditis is transient and can last 2-6 weeks before improvement. Patients should be monitored for development of hypothyroidism. Beta blockers are useful to mitigate symptoms as the disease runs its course.
Ask about neck pain or trauma, thyroid tenderness, use of immune checkpoint inhibitors (autoimmune thyroiditis), use of lithium or amiodarone, recent iodinated contrast load, history of afib or osteoporosis, weight changes, menstrual irregularities, eye discomfort (sandy or gritty feeling), or “awareness of their heartbeat when laying in bed”.
Thyrotoxicosis is signified by a low TSH and high free T4 and total T3. Order thyroid stimulating immunoglobulins (TSI) to diagnose Graves’. TSI antibodies can be tracked overtime to inform risk for recurrence and when antithyroid therapy can be discontinued (Ross, Thyroid 2016). Free T3 is hard to interpret and not routinely ordered.
Clues from physical exam: A thyroid bruit can be heard in Graves’. ‘Thyroid inferno’ or hypervascularity is the corresponding finding on ultrasound (Das, Indian J Endocrinol Metab 2011). Sometimes a thrill can be felt when laying 3-4 fingers gently over the thyroid. Use your thumbs to gently exam the thyroid while standing in front of the patient (expert opinion).
Assess for tremor: Ask the patient to close their eyes, straighten their arms and spread their fingers. Alternatively, you can put a piece of paper or pen between the fingers of outstretched arms/hands to look for shaking.
Reflexes: Use your fingers to tap the biceps tendon and feel for a brisk reflex.
Speech: Thyrotoxic patients often talk fast, which Dr Bloomgarden finds contagious.
Lid lag (whites of eye visible between iris and the eyelid) and stare (infrequent blinking) are signs of sympathetic overdrive. Looking for bulging eyes and chemosis as signs of Graves’ orbitopathy.
Thyroid ultrasound can be performed in the office to assess size, vascularity and presence of nodules. Many times thyroid scintigraphy can be avoided.
Thyroid scintigraphy can help differentiate between the causes of thyrotoxicosis. After Iodine-123 (I123) is given, scans are performed at 4 hours and 24 hours. Homogenous uptake is consistent with Graves’. Absent I123 uptake indicates either thyroiditis or recent iodine load (e.g. contrast, or taking amiodarone). This test can be useful in patients with suspected toxic nodules, but Dr. Bloomgarden orders it infrequently (maybe 2-3 times per year) since the diagnosis is often clear based on thyroid US, TSI antibodies and the clinical picture.
Biotin supplements for hair and nails have mega doses (10 mg of biotin) compared to the recommended daily intake, which is around 30 mcg. This interferes with the assays for TSH, free T4 and total T3 causing a pattern that looks like Graves’ with low TSH and high free T4 and total T3 (Elston, J Clin Endocrinol Metab 2016). Dr. Bloomgarden suspects this in patients who lack symptoms, but have labs suggesting thyrotoxicosis. Be sure to hold biotin supplements for 48 hours prior to thyroid function testing.
PTU has a blackbox warning for fulminant hepatic failure (see LiverTox page) and is mainly used in the 1st trimester of pregnancy or when patients cannot tolerate methimazole.
Methimazole: Adherence is challenging and requires clear and frequent patient education. Patients must be counseled about the risk for agranulocytosis. Those who develop fever or sore throat need a CBC and hospital admission if low WBCs. Dr. Bloomgarden prefers once daily dosing (for adherence) often starting with 15-20 mg once daily and titrating down to the minimally effective dose over time. This may be as low as 2.5 mg every other day. Methimazole should not be stopped while TSI antibodies remain elevated. Note: When free T4 is above 7, Dr Bloomgarden may start with methimazole >30 mg daily (split between two doses) to speed recovery.
Beta blockers (BB): Can be used to mitigate symptoms, but do not modify the course of disease. Dr Bloomgarden may overlap BBs with the initiation of methimazole for ~4 weeks until levels and symptoms improve. She prefers atenolol due to once daily dosing. Propranolol and metoprolol are also options. Consider central access and an esmolol drip for inpatients with thyroid storm. Caution: Look out for signs of heart failure. Some patient’s cardiac output is dependent on tachycardia and BBs can precipitate cardiovascular collapse. Note: Propranolol only prevents T4 to T3 conversion at very high doses (200 mg per day).
Graves’ treatment: Treat with methimazole and monitor TSI antibodies. Therapy can be stopped if antibodies become undetectable. Radioactive iodine (RAI) can worsen or precipitate Graves’ orbitopathy (Shamasunder, Clin Endocinrol 2008). Thus, it is contraindicated in patients with existing Graves’ eye disease. Thyroidectomy can be considered in patients who wish to become pregnant and cannot take methimazole.
Subclinical hyperthyroidism is a biochemical diagnosis with low TSH and normal free T4 and total T3. Dr Bloodgarden recommends repeating labs (e.g. in 3 months) to confirm the diagnosis. Treatment of SH remains controversial, but expert consensus from the 2016 ATA guidelines recommend treatment when:
“When TSH is persistently <0.1 mU/L, treatment of SH is recommended in all individuals ≥65 years of age; in patients with cardiac risk factors, heart disease or osteoporosis; in postmenopausal women who are not on estrogens or bisphosphonates; and in individuals with hyperthyroid symptoms.” (Ross, Thyroid 2016)
Don’t forget to check a TSH in patients with osteoporosis to look for subclinical hyperthyroidism (expert opinion). It remains unclear whether or not treatment prevents fracture.
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Listeners will develop an approach to the diagnosis and management of hyperthyroidism and thyrotoxicosis.
After listening to this episode listeners will…
Dr Bloomgarden reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Bloomgarden E, Karginov T, Williams PN, Watto MF. “#228 Thyroid on Fire: Hyperthyroidism with Dr Eve Bloomgarden”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date August 3, 2020.
The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.
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I would like to ask Dr Bloomgarden about her views on " Block and replace " approach of treatment of Hyperthyroidism/Graves Disease. This entails administering a high dose of antithyroid drug like methimazole initially and blocking synthesis of thyroid hormones significantly. Later on if there is development of hyperthyroidism, a replacement dose of thyroxine is administered. This method is supposed to have advantages of taking benefit of adequate immunosuppressive actions of methimazole and at the same time avoids risk of under or overdosing of antithyroid medication. Best regards
Thanks for your feedback. You can try reaching out on Twitter: @evebmd
Thanks a lot for such amazing teaching.I work in India.Learning lot from the Curbsiders.Trying to listen to the episode everyday and show notes too.Too helpful.It has immensely improved my diagnosis skills.