Leonie H. A. Broersen
In a large percentage of patients with Cushing’s disease, medical therapy effectively induces cortisol normalization, suggesting the choice may serve as a useful first-line treatment vs. surgery for some, according to findings from a systematic review and meta-analysis published in Pituitary.
Cushing’s syndrome is generally approached by removal of the adrenocorticotropic hormone (ACTH)-producing tumor in ectopic disease and by adrenalectomy in ACTH-independent disease, Leonie H. A. Broersen, MD, of the department of medicine at Leiden University Medical Centre in Leiden, Netherlands, wrote in the study background. However, medical therapy can be used to control cortisol secretion preoperatively and as a “bridge” until control of hypercortisolism is achieved by radiotherapy, whereas use of medical therapy as a first-line treatment is increasing, they noted.
“Medical treatment is a reasonable treatment option for Cushing’s disease patients in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery,” Broersen told Endocrine Today. “In case of side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.”
Broersen and colleagues analyzed data from 35 studies with 1,520 patients reporting on six medical therapies for Cushing’s disease, including studies assessing pasireotide (n = 2; Signifor LAR, Novartis), mitotane (n = 5; Lysodren, Bristol-Myers Squibb), cabergoline (n = 3), ketoconazole (n = 8), metyrapone (n = 5; Metopirone, HRA Pharma), mifepristone (n = 2; Korlym, Corcept Therapeutics) and multiple medical agents (n = 10), all published between 1971 and 2017. Studies included 11 single-arm trials, two randomized controlled trials with two treatment arms, and 22 cohort studies. In 28 studies, normalization of cortisol was measured by urinary free cortisol, midnight salivary cortisol or a low-dose dexamethasone test, with 25 studies reporting on clinical improvement and three studies reporting on quality of life.
Across studies, medical treatment was effective in normalizing cortisol levels in Cushing’s disease in 35.7% (cabergoline) to 81.8% (mitotane) of patients, according to the researchers. In seven studies reporting data separately for medical therapy as primary (n = 4) or secondary therapy (n = 5), researchers found medication as primary therapy normalized cortisol levels in 58.1% of patients (95% CI, 49.7-66.2), similar to the effect of medication as a secondary therapy (57.8%; 95% CI, 41.3-73.6). In studies in which at least 80% of patients with Cushing’s disease were pretreated with medication before surgery, researchers observed a preoperative normalization of cortisol levels in 32.3% of patients (95% CI, 20-45.8). Patients using medical monotherapy experienced a lower percentage of cortisol normalization vs. patients using multiple agents (49.4% vs. 65.7%), according to researchers, with normalization rates higher among patients with concurrent or previous radiotherapy.
Across studies, 39.9% of patients experienced mild adverse effects, and 15.2% experienced severe adverse effects.
“Importantly, medical agents for hypercortisolism can cause severe side effects, leading to therapy adjustment or withdrawal in 4.8% (cabergoline) to 28.4% (mitotane) of patients,” the researchers wrote. “These results suggest that medical therapy can be considered a reasonable treatment alternative to the first-choice surgical treatment when regarding treatment effectiveness and side effects.” – by Regina Schaffer
For more information: Leonie H. A. Broersen, MD, can be reached at l.h.aA.firstname.lastname@example.org.
Disclosure: The authors report no relevant financial disclosures.