In this episode, we discuss an overview of inpatient management of can’t miss endo emergencies. Our esteemed guest, Dr. Sara Markley Webster (Emory University, @smarkleywebster) walks us through identification, workup and management of adrenal crisis, myxedema coma, and thyroid storm.
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● Written, Produced, and Hosted by: Monee Amin, MD and Meredith Trubitt, MD
● Show Notes, Infographic and Cover Art: Caroline Coleman, MD
● Reviewer: Emi Okamoto, MD
● Showrunner: Matthew Watto MD, FACP; Paul Williams MD, FACP
● Technical Production: PodPaste
● Guest: Sara Markley Webster, MD
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● Intro, disclaimer, guest bio
● Guest one-liner, Picks of the Week*
● Case 1 from Kashlak
● Adrenal crisis identification, workup and management
● Case 2 from Kashlak
● Myxedema identification, workup and management
● Case 3 from Kashlak
● Thyroid storm identification, workup and management
Hypoadrenalism (or adrenal insufficiency) occurs when a patient cannot create enough cortisol, and can be due to a primary (pituitary issue) or secondary (adrenal gland issue) etiology. Adrenal crisis is defined by adrenal insufficiency with resulting organ failure (eg, nausea/vomiting, hypotension). Common etiologies include missing home steroid doses, being chronically underdosed outpatient, psychological stressors, or physiologic stressors like infection or trauma (Rushworth 2019). Dr. Markley-Webster reminds us that even mild stressors, like psychological stress, can cause deterioration into adrenal crisis as well, especially if they were underdosed outpatient prior to presentation. It’s of great importance to be able to identify adrenal crisis early as it can have up to 6% mortality (Rushworth 2019).
Often times a diagnosis of hypoadrenalism will be known, and making diagnostic work-up less important. However, at times it may not be known, and further diagnosis may be necessary. Therefore, depending on severity of illness at presentation, you can consider performing a random cortisol level or ACTH stimulation test prior to treatment. Dr. Markley Webster points out though, that if a patient is severely ill, and suspicious of adrenal crisis to just start steroids and can perform ACTH stimulation test in an outpatient setting after acute illness.
If there is suspicion for adrenal crisis, the threshold for starting stress dose steroids should be low. Risk of untreated adrenal crisis should drive the clinical decision making, rather than concerns about risk of IV hydrocortisone. If the patient has known adrenal insufficiency and is on home steroids, Dr. Markley Webster recommends tripling their home dose. Alternatively, she recommends giving 100 mg IV hydrocortisone once followed by 50 mg every 6 hours (Bornstein 2016).
It’s worth noting that a dose of ≥50mg of hydrocortisone covers both glucocorticoid and mineralocorticoid receptors, so stress dose steroids will cover both and the distinction is less important as she’ll be treating both anyways (Puar 2016). Notably, dexamethasone doesn’t have mineralocorticoid activity, which makes it less helpful for treating adrenal insufficiency or crisis. Dr. Markely Webster also points out that these doses are so high that they are not significantly affected by CYP inducers/inhibitors.
Other treatment pearls for inpatient management are to vigorously fluid resuscitate and manage electrolyte derangements (eg, hyponatremia, hyperkalemia, hypercalcemia), as they are frequently very volume-depleted (Rushworth 2019) . Notably, the hypercalcemia usually corrects with fluid resuscitation, and patients with mild cases should have correction of all electrolyte abnormalities within about a day.
Tapering the Steroids
The subsequent hydrocortisone taper then depends on the patient’s response–if they clinical improve in about a day, Dr. Markley Webster will start tapering quickly, but if they remain sick, she’ll keep them on the same 50 mg every 6 hours dosing as the team looks for other treatable inciting factors like infections (Rushworth 2019).
Regarding mineralocorticoid replacement, Dr. Markley Webster evaluates this as an outpatient and considers whether the patient also needs fludrocortisone. You can consider discharge when they are back on their home dose of hydrocortisone, or they are on acceptable oral doses to complete the taper to their home dose outpatient. Note that you do not need PCP prophylaxis until you reach daily doses that exceed 80 mg of hydrocortisone a day for greater than one month, which is the equivalent of 20mg of prednisone per day, but that the average patient will be on much lower doses than this.
Important counseling prior to discharge is to emphasize the importance of not missing steroid doses and to also review sick dosing. Dr. Markley Webster tells her patients to double their dose with mild illness (eg, sore throat, runny nose) and to triple their dose if they have a temperature ≥38C. She will often give them an extra 50-70 tablets per 90-day supply to ensure that they have adequate stress dosing at home.
Myxedema coma is a clinical, not biochemical, diagnosis . It is characterized by a general slowing of metabolic function, including both heart and skeletal muscle contractions and relaxation, neuro conductions, core temperature, and GI motility. Common etiologies include missing home levothyroxine doses or being chronically underdosed outpatient, as well as stressors like infection (Ylli, 2019).
While both pathologies will have elevated TSH levels, myxedema coma is distinguished from hypothyroidism by having end organ damage, which notably includes altered mental status. This altered mental status can range from something as mild as lethargy to something more noticeable like the characteristic finding of slurred speech or even as pronounced as somnolence or coma. Other notable findings are abnormal vital signs (eg, bradycardia, hypotension) and lab derangements (eg, hyponatremia). Similarly to adrenal crisis, it has a high mortality rate if left untreated (Ylli, 2019).
Similarly to adrenal crisis, the risk of not treating myxedema coma often outweighs the risk of treating with IV levothyroxine. IV is preferred to PO dosing due to the risk of patients having gut edema and not having adequate PO absorption (Jonklaas, 2014). The loading dose is 200-400 micrograms, and Dr. Markley Webster uses the patient’s age and comorbidities to help guide the dose (ie, lower doses if older and certain comorbidities like heart disease). Following the loading dose, the patient should receive 75% of their oral dose in IV form.
You can monitor response clinically as well as with serum free T4 levels every 3 or so days (expert opinion). You can consider giving liothyronine or T3, the active form of thyroid hormone, as well (Jonklaas, 2014). Lastly, many endocrinopathies run together, and due to the risk of concomitant adrenal insufficiency, Dr. Markley Webster also recommends that these patients receive stress dose steroids.
Again, similar to adrenal crisis, patients with myxedema coma can clinically improve within a few days, but may take longer if they have other medical comorbidities. You can transition to PO levothyroxine once the patient is feeling back to their baseline and/or their free T4 levels have normalized, but IV is often more convenient than PO due to the absorption challenges of dosing levothyroxine with other medications, breakfast, etc (expert opinion).
Regarding anticipatory guidance, it is paramount for patients to take their levothyroxine, but due to the drug’s long half life, you can double up a dose the next day if you forget to take a tablet.
Similarly to the other endocrine emergencies, thyroid storm is differentiated from hyperthyroidism by the presence of end organ damage (eg, arrhythmia, heart failure). Dr. Markley Webster points out that the Burch-Wartofsky score is very non-specific for thyroid storm and not very helpful clinically.
Thyroid storm is precipitated by underdosing of medication and/or a significant stressor, and carries a high mortality rate if untreated (Devereaux 2016). Notably, if a patient with hyperthyroidism requires a physiologically stressful procedure like a large surgery, Dr. Markley Webster notes that they can decompensate at any point throughout the operation, which makes management especially challenging.
Management begins with medications that shut off thyroid hormone production, such as methimazole and propylthiouracil, or PTU. You can also transiently shut off thyroid production with iodine, with formulations like Lugol’s solution (Ylli, 2019). Again, autoimmune endocrinopathies like to run together, so Dr. Markley Webster recommends high dose glucocorticoids (300mg IV hydrocortisone load, then 100mg q8h) for these patients as well in case there is concomitant adrenal insufficiency (Ross, 2016). The steroids also help inhibit peripheral conversion of T4 to the active T3, which helps directly manage the hyperthyroidism as well. Lastly, management includes beta blockade, commonly with propranolol as it also inhibits peripheral conversion of T4 to T3. You can also consider supportive management with cooling if they are hyperthermic (Ylli, 2019).
With appropriate medical management, patients should improve within 24-48 hours. If their symptoms persist, the patient will need thyroidectomy or plasmapheresis due to the high mortality risk, so it’s prudent to involve consultants early for these patients (Chiha, 2013).
Once the patient’s symptoms are controlled, Dr. Markley Webster usually tapers PTU and transitions to methimazole due to a more favorable side effect profile (PTU has risks of liver injury). The patient will also need a beta blocker to keep their heart rate under 90.
Lastly, they will require rapid (<1 month) endocrine clinic follow up as these medications will be tapered quickly outpatient (expert opinion). Notably, it will take several weeks for their biochemical markers to normalize, so Dr. Markley-Webster encourages providers to NOT check TFTs within a week or so of hospital discharge.
Listeners will develop a framework to approach the identification, workup, and management of three endocrine emergencies: adrenal crisis, myxedema coma, and thyroid storm.
After listening to this episode listeners will…
Dr. Markley Webster reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Amin MR, Trubitt ME, Coleman C, Markley Webster S. “#372 Endocrine Emergencies”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list December 19, 2022.
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Hypoadrenalism definitions - Primary(adrenal gland issue) Secondary(pituitary issue) Thank you for this excellent review of this important topic.
Of course! We love hearing feedback from our listeners :)
I believe the above commenter might have been pointing out that under, “Hypoadrenalism & Adrenal Crisis; Definition and Diagnosis,” it says, “…can be due to a primary (pituitary issue) or secondary (adrenal gland issue)…” but that these definitions should be the other way around 🤓 Also, yes, thank you for all that you do to make medicine (much) more manageable!!
Thank you for your comment. I will be sure to check back and share with the team who worked on this episode. Regards, The Curbsiders