Iatrogenic hypoadrenocorticism following treatment with trilostane for hyperadrenocorticism in dogs: a description of 10 cases

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English. Trilostane is currently the medical treatment of choice for hyperadrenocorticism in dogs. Iatrogenic hypoadrenocorticism is considered infrequent, with most cases being transient. Only 8 cases of permanent hypoadrenocorticism have been described; adrenocortical necrosis was suspected based on post-mortem examination or adrenal changes on ultrasonography. The goal of this study was to report findings from 10 cases of iatrogenic hypoadrenocorticism following treatment with trilostane for hyperadrenocorticism. Medical records of dogs treated with trilostane since 2008 were reviewed. Dogs were included if they had clinical signs suggestive of hypoadrenocorticism and compatible ACTH stimulation test results and/or serum electrolytes abnormalities. Cases were considered as permanent if long term treatment of hypoadrenocorticism was required. Ten dogs met the inclusion criteria (5 males and 5 females) with an age ranging from 6.5 to 13 years. Nine dogs had a suspected pituitary-dependent hyperadrenocorticism. Clinical signs at the time of hypoadrenocorticism diagnosis were: lethargy (10/10), anorexia (10/10), vomiting (7/10), diarrhea (3/10), tremors (3/10) and polyuria-polydipsia (1/10). Time between beginning of trilostane treatment and hypoadrenocorticism occurrence ranged from 4 days to 13 months; trilostane dose ranged from 1 to 12 mg/kg/day. Five dogs had a suspicion of concurrent infectious disease at the time of hypoadrenocortism diagnosis. Sodium/potassium ratio was under 24 in 5 dogs and under 28 in 8 dogs. All 8 dogs having an ACTH stimulation test performed had pre- and post-stimulation cortisol concentration <55nmol/L. Trilostane dosage was decreased in 2 cases; trilostane was withdrawn in 1 case without further relapse of clinical signs of hyperadrenocorticism; 1 dog died at the time of diagnosis; glucocorticoids +/- mineralocorticoids supplementation was prescribed in 6 cases. Three out of these 6 dogs were lost to follow-up, the other 3 had a diagnosis of permanent hypoadrenocorticism. Adrenal gland ultrasonogaphy in these 3 dogs showed a progressive reduction in glands size with a heterogeneous echogenicity. Iatrogenic hypoadrenocorticism was also rare in our population, with 10 cases identified over 10 years. Dose and duration of treatment were variable. One dog died and at least 3 suffer from permanent hypoadrenocorticism. Progressive adrenal changes on ultrasonography were seen in 3 cases of permanent hypoadrenocorticism. The suspicion of concomitant infection in half of our cases at hypoadrenocorticism occurrence is an interesting finding. An impaired ability to synthesize cortisol in response to infection might trigger clinical signs appearance in dogs with previously subclinical hypoadrenocorticism.