Iatrogenic Hypoadrenocorticism Following Treatment With Trilostane

In the Literature

Lamoureux A, Cadoré JL, Hugonnard M, Chabanne L, Krafft E. Iatrogenic symptomatic hypoadrenocorticism after treatment with trilostane for hyperadrenocorticism in dogs: eight cases (2008-2019). J Small Anim Pract. 2023;64(6):409-414. doi:10.1111/jsap.13594 

The Research …

Canine hyperadrenocorticism is a common endocrine disorder characterized by excessive cortisol production. Most of these cases are managed with trilostane, a synthetic steroid analogue that prevents cortisol and, to a lesser extent, aldosterone synthesis by inhibiting the enzyme 3-beta-hydroxysteroid dehydrogenase. Response to therapy should be assessed and adverse effects monitored for via clinical sign evaluation and ACTH stimulation testing during trilostane treatment. Adverse effects, including iatrogenic hypoadrenocorticism, can be caused by a variety of dosages and be temporary or permanent. In one study, 76.3% of dogs with iatrogenic hypocortisolemia secondary to trilostane administration demonstrated adrenal recovery within 6 months.¹

This retrospective study described 8 cases of clinical iatrogenic hypoadrenocorticism in a population of 127 dogs given trilostane for treatment of hyperadrenocorticism over an 11.5-year period. Dosages ranged from 1 to 8 mg/kg in a 24-hour period. One dog had stopped receiving trilostane 2 months prior to iatrogenic hypoadrenocorticism crisis. The remaining 7 dogs had received trilostane for 4 days to 13 months and were receiving this medication at the time of iatrogenic hypoadrenocorticism crisis.

Lethargy (n = 8) and anorexia (n = 8) were the most common clinical signs at presentation, followed by vomiting (n = 5), tremors (n = 3), and diarrhea (n = 1). Two dogs were presented with signs of hypovolemic shock. Electrolytes were measured in 6 dogs, all of which had a sodium:potassium ratio <28. ACTH stimulation testing was performed in all dogs, with pre- and post-ACTH cortisol concentrations <2 µg/dL. Six dogs were presented with concurrent disease, which may have caused stress that precipitated a hypoadrenocorticism crisis.

Treatment of hypoadrenocorticism signs included trilostane dosage decrease, withdrawal of trilostane, hospitalization, fluid therapy, and administration of a glucocorticoid and/or mineralocorticoid. Three dogs required permanent treatment for hypoadrenocorticism; ultrasonography in these dogs revealed progressive reduction in adrenal gland size compatible with adrenal necrosis.

… The Takeaways

Key pearls to put into practice:

• Although iatrogenic hypoadrenocorticism is an uncommon complication of trilostane therapy, this condition is an important differential in patients that develop new signs of illness during treatment. Iatrogenic hypoadrenocorticism may occur at any stage of therapy and is not associated with dosage or duration of treatment. Dogs that develop clinical hypoadrenocorticism may recover adrenal function over time, even dogs that require treatment with mineralocorticoids.

• Not all dogs with iatrogenic hypoadrenocorticism are presented in a crisis. Pet owners should be instructed to monitor for more subtle clinical signs (eg, anorexia, lethargy, vomiting) suggestive of hypoadrenocorticism. Trilostane administration should be stopped and the dog evaluated by a clinician if any of these clinical signs are present.

• Dogs treated with trilostane that have other concurrent diseases should be monitored closely due to the possibility of endogenous stress precipitating a crisis in a subclinical dog.