Cushing’s syndrome is one of the most common endocrine disorders in dogs and is typically managed with long-term medical treatment. Several pharmacological agents are available: trilostane, mitotane, ketoconazole, cabergoline, selegiline, and aminoglutethimide, but their comparative effects on survival remain unclear. This systematic review and meta-analysis compared the impact of these agents on survival outcomes in dogs with naturally occurring diseases. A comprehensive search of MEDLINE, Embase, Web of Science, Academic Search Complete, and the Cochrane Library was conducted between 1 September 2024 to 3 January 2025. Eligible studies included dogs diagnosed with Cushing’s syndrome that reported survival outcomes for at least one of the specified treatments. Five studies (n = 295 dogs) met the inclusion criteria, with trilostane and mitotane providing sufficient data for meta-analysis. Pooled mean difference in survival time across four studies was 85.1 days (95% CI: −255.9 to 85.7, p = 0.21) with substantial heterogeneity (I² = 89%), indicating no statistically significant difference between the drugs. In contrast, pooled survival rates at fixed intervals favored trilostane, with an 11% higher survival at 36 months (p = 0.005) and no heterogeneity observed (I² = 0%). These findings suggest trilostane may offer long-term survival benefits over mitotane.

Cushing’s syndrome is a common endocrine disorder in dogs managed with both medical and non-medical treatments; however, the effects of non-medical interventions on survival, perioperative, and clinical outcomes remain uncertain. A comprehensive search was conducted across MEDLINE, Embase, Web of Science, Academic Search Complete, and the Cochrane Library databases. Five studies (n = 248 dogs) met the inclusion criteria. Three studies evaluated laparoscopic and open adrenalectomy in dogs with adrenal-dependent hypercortisolism, whereas two studies evaluated radiotherapy in dogs with pituitary-dependent hypercortisolism. Meta-analysis demonstrated no significant differences in the survival rates between laparoscopic and open adrenalectomy at 12, 24, or 36 months. Fractionated radiotherapy improved survival rates at 12 months, while both fractionated and stereotactic radiotherapy improved survival rates at 24 months. This benefit, however, was not maintained at 36 months. Radiotherapy was also associated with improved neurologic outcomes (OR = 109.17, 95% CI 3.99–2985.49) and longer survival time (MD = 624.00 days, 95% CI 227.93–1020.07). Among dogs undergoing adrenalectomies; laparoscopic adrenalectomy was associated with shorter surgical times (MD = −28.38 min, 95% CI −41.39 to −15.38) and hospitalization (MD = −0.66 days, 95% CI −1.00 to −0.32) compared to open adrenalectomy.

In this article, we propose methods to determine sufficient sample sizes for applying the classical central limit theorem to skewed and heavy-tailed distributions. In doing so, we review the properties of an α−stable distribution and its domain of attraction. Then, we apply the general Edgeworth expansion for regularly varying distributions to t−distributions with degree freedom at least three. Motivated by the observed results, we propose a mathematical formula for determining enough sample sizes. The formula is valid for distributions with at least the fourth moment. Then, we propose an algorithm to apply this formula for a data set from general distributions. For distributions with infinite/undefined skew-ness/kurtosis, such as some heavy-tailed distributions, we could use Monte-Carlo simulation method to determine sample size. As an example, we propose an empirical method to determine the sample sizes for Pareto distributions. Both the algorithm and the empirical method are tested on simulated data.