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Acute Presentations

Endocrine immune-related adverse events

VENESSA H. TSANG, Bernard Champion
OPEN ACCESS

Long-term maintenance dose titration depends on the patient’s blood pressure and energy levels, and is usually the equivalent of 2.5 to 5.0 mg prednisone daily.10 Hydrocortisone (10 to 20 mg daily) or cortisone acetate (12.5 to 25 mg daily) can also be used and is particularly useful in patients requiring split dosing, or varying dosing during the day. In addition, hydrocortisone and cortisone have the advantage of less long-term effects on bone mineral density but require careful titration to the lowest required dose. Hydrocortisone and cortisone should be given in two to three split doses during the day. Doses should be uptitrated, taking into account the patient’s symptoms and weight. However, there is a lack of evidence on the optimal regimen to provide a patient, balancing improving clinical symptoms with prevention of side effects of over-replacement.11 

It is important to discuss stress management of glucocorticoids with patients, particularly those with infective illnesses, gastrointestinal illness where oral glucocorticoids may not be easily absorbed, and elective surgery where patients have fasted. Most patients who have developed hypophysitis do not recover pituitary function and require long-term hormone replacement.

Jack also likely requires thyroxine replacement given his low free T4, free T3 and inappropriately low TSH levels. It is important to replace this after glucocorticoids, as unopposed thyroxine replacement in patients with hypophysitis can lead to adrenal crisis due to increased basal metabolic rate and increased cortisol clearance. The dose of thyroxine would be about 1.6 mcg/kg daily (i.e. a full replacement dose is required).

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Testosterone replacement may be required, but low levels can sometimes be a stress response and recover to normal levels in several months time.

 

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How should Jack be followed up in the  long term?
Answer: It is important to assess Jack’s glucocorticoid replacement and ensure the dose is adequate. The importance of stress dosing should be reiterated and intramuscular injection of hydrocortisone should be prescribed with an appropriate family member taught how to administer this.

Even if patients do not develop hypothyroidism at onset they may lose other axes later, so it is important, particularly with ACTH and TSH, to monitor these regularly later on.

 

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What is the prognosis of endocrine irAEs?
Answer: There are currently no reliable markers to predict the onset of endocrine irAEs and the presentation of hypophysitis is often rapid. It is important to note that once a gland fails due to ICIs it does not recover, and patients are on lifelong glucocorticoid, thyroxine or gonadal replacement. However, most patients only have mild grade 1 and 2 symptoms and many can be appropriately managed in the outpatient setting. (See Practice Points box for handy tips.)

 

COMPETING INTERESTS: None.

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Dr Tsang is Staff Specialist in the Department of Endocrinology at the Royal North Shore Hospital, Sydney; and Senior Lecturer in the Northern Clinical School, Faculty of Medicine and Health at The University of Sydney, Sydney, NSW. Associate Professor Champion is an Endocrinologist and Associate Professor in Medicine at Macquarie University; and Honorary Associate Professor at Nepean Clinical School, The University of Sydney, Sydney, NSW.