Results of non‐selective adrenocorticolysis by O,p'‐DDD in 129 dogs with pituitary‐dependent hyperadrenocorticism

Abstract

One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of o,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first followup examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side-effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent CI: 71 to 87 per cent), the two-year survival was 69 per cent (95 per cent CI: 59 to 78 per cent), and the three-year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dog, and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time.

Long‐Term Survival of Dogs with Adrenal‐Dependent Hyperadrenocorticism: A Comparison between Mitotane and Twice Daily Trilostane Treatment

“…Five dogs were treated with mitotane using the NSAP described by den Hertog et al17 for the treatment of PDH. These animals received a PO initial dosage of mitotane3 of between 75 and 100 mg/kg/day for 25 days.…”

Selecting The Best Treatment Option For A Dog With Cushing’S Syndrome

“…With increasing pituitary size the survival and disease-free periods decrease and the incidence of central diabetes insipidus increases. The recurrence rate of 25% compares favorably with that after nonselective adrenocortical destruction with mitotane [36]. Hence transsphenoidal hypophysectomy can be expected to have the best outcome as the primary treatment in dogs with nonenlarged or only moderately enlarged pituitaries [33].…”

“…In order to avoid these complications, a treatment schedule aimed at complete destruction of the adrenal cortices and substitution for the induced hypoadrenocorticism was developed [38]. This nonselective destruction has been reported to result in fewer recurrences than does selective destruction [36]. Now o,p'-DDD is no longer used for treatment of PDH, but rather for treatment of inoperable and/or metastasized AT, with the intention of destroying all AT cells, including metastases [39].…”

“…Selective [37] or nonselective [36] destruction of the adrenal cortex with o,p'-DDD (mitotane) has long been the medical treatment of choice for PDH in dogs. Selective treatment aim at selective destruction of the zona fasciculata (ZF) and zona reticularis (ZR), sparing the zona glomerulosa (ZG).…”

Efficacy of Transsphenoidal Surgery on Endocrinological Status and Serum Chemistry Parameters in Dogs with Cushing's Disease

“…If a patient with Cushing's disease treated by TSS does not present remission or if the pituitary adenoma is difficult to resect, then radiotherapy is selected [14,31]. In contrast, in the treatment of canine Cushing's disease, most dogs are treated with mitotane and trilostane [1,5,8,13,16,27,38,40,43]. However, in human medicine, the use of mitotane and trilostane to decrease cortisol excess is limited and is selected only to improve hypercortisolemia before TSS, when re-operation is too difficult, when the localization of the corticotroph adenoma is not obvious, or as a short-term treatment until radiotherapy [6,10,21].…”