Abstract
PurposesPasireotide is the first medical therapy officially approved for adult patients with Cushing’s disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center.MethodsFourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis.ResultsFull or partial disease control was obtained in 85.7% of patients, according to a “per-protocol” methodology analysis, and in 42.9% of patients, according to an “intention-to-treat” methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose.ConclusionsThe current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.
Highlights
Cushing’s disease (CD), or pituitary-dependent Cushing’s syndrome (CS), is caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary tumor, leading to chronic hypercortisolism, which results in a typical clinical picture; this is characterized by weight gain with moon face, facial plethora, buffalo hump, supraclavicular and dorsal fat pads, Journal of Endocrinological Investigation (2020) 43:57–73 cutaneous purplish striae, bruising, proximal myopathy, and hirsutism and/or acne [1,2,3,4,5]
Regardless of dose increase, full or partial disease control was obtained in 34.2% (600 μg bid) and 41.3% (900 μg bid) of patients after 6 months, and in 29.3% (600 μg) and 27.5% (900 μg) of patients after 12 months [10]
It is noteworthy that full or partial disease control was obtained in 75% of patients after 6 months and in 85.7% after 12 months of treatment according to the “per-protocol” methodology analysis, whereas in 42.9% of patients, both at 6 and 12 months of treatment, according to the “intention-totreat” methodology analysis
Summary
Cushing’s disease (CD), or pituitary-dependent Cushing’s syndrome (CS), is caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary tumor, leading to chronic hypercortisolism, which results in a typical clinical picture; this is characterized by weight gain with moon face, facial plethora, buffalo hump, supraclavicular and dorsal fat pads, Journal of Endocrinological Investigation (2020) 43:57–73 cutaneous purplish striae, bruising, proximal myopathy, and hirsutism and/or acne [1,2,3,4,5]. The clinical picture is complicated by several comorbidities, including metabolic syndrome, characterized by visceral obesity, systemic arterial hypertension, impairment of glucose metabolism and dyslipidaemia, strictly associated with cardiovascular diseases, and additional clinical complications such as musculoskeletal diseases, impairment of reproductive and sexual function, neuropsychiatric diseases and immune disorders with higher susceptibility to infections [2]. The constellation of these comorbidities is associated with an increased morbidity and mortality, mainly for cardiovascular events and generalized sepsis, and with an impairment of quality of life (QoL) [1,2,3,4,5]. Additional second-line treatments are frequently required, such as repeat pituitary surgery, pituitary radiotherapy, bilateral adrenalectomy, and medical therapy [1, 6, 7]
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