Management of hyperglycaemia in Cushing's disease: Experts’ proposals on the use of pasireotide

Reznik, Yves; Bertherat, Jérôme; Borson‐Chazot, Françoise; Brue, Thierry; Chanson, Philippe; Cortet‐Rudelli, Christine; Delemer, Brigitte; Tabarin, Antoine; Bisot-Locard, S.; Vergès, Bruno

doi:10.1016/j.diabet.2012.10.005

Cited by 54 publications

(41 citation statements)

References 28 publications

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“…GLP1 analogues and dipeptidyl peptidase four inhibitors could be helpful in the management of GC-induced diabetes, increasing glucose dependent insulin secretion and reducing glucagon secretion as well as having positive effects on b-cell mass and function, appetite, adipocyte modulation, fat distribution, hyperlipidaemia, heart and bone (48,49). Incretin-based medications have been suggested for the management of pasireotide-induced hyperglycaemia, since somatostatin receptor inhibition leads to reduced secretion of GLP1, glucose-dependent insulinotropic polypeptide and insulin (50,51). Conventional tailored schemes of treatment with insulin analogues can be required when oral hypoglycaemic agents are not effective (24).…”

Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

146

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

146

121

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“…However, the major side effect of pasireotide is hyperglycemia, which is induced via inhibition of insulin secretion directly via binding to the sst5 receptor on pancreatic islet cells and indirectly via suppression of incretin hormone production by K and L cells (21). Pasireotideinduced hyperglycemia can be effectively managed with metformin and a dipeptidyl peptidase 4 inhibitor, switching to a glucagon-like peptide 1 receptor agonist and initiating insulin, as required (22,23).…”

Section: Discussionmentioning

confidence: 99%

Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

Yuen

Mercado

Moloney

et al. 2018

AACE Clinical Case Reports

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Objective: Pasireotide is approved for treatment of adults with Cushing disease (CD) with persistent hypercortisolism for whom surgery has failed or is not an option. Effective medical therapy for CD may increase the susceptibility of relative hypocortisolism during acute stress because of a patient's inability to compensate by increasing endogenous adrenocorticotropic hormone (ACTH) and cortisol secretion. We describe a patient with CD on pasireotide therapy for 7 years in whom biochemical eucortisolemia was achieved but subsequently experienced several distinct episodes of relative hypocortisolism during periods of acute illness.Methods: A 67-year-old man with biochemical confirmation of CD exhibited clinical and biochemical features of persistent hypercortisolism after transsphenoidal surgery despite pituitary magnetic resonance imaging showing no residual or recurrent tumor. He was enrolled into a phase 3 study (NCT00434148) and was initated on twice-daily subcutaneous pasireotide.Results: Long-term pasireotide therapy normalized 24-hour urinary free cortisol, serum cortisol, and ACTH levels. The patient subsequently developed type 2 diabetes mellitus and was managed effectively with oral hypoglycemic agents and insulin therapy. During a routine clinic assessment 79 months after study enrollment, he reported symptoms suggestive of relative hypocortisolism during three distinct substantially acute stressful health events in the preceding 18 months.Conclusion: Successful achievement of eucortisolemia with long-term medical therapy may increase susceptibility to relative hypocortisolism and precipitate symptoms of adrenal insufficiency during periods of acute stress in patients with CD. We recommend that such patients should be counseled on glucocorticoid stress dosing to prevent such events that could lead to adrenal crisis. (AACE Clinical Case Rep. 2018;4:e1-e6) Abbreviations: ACTH = adrenocorticotropic hormone; CD = Cushing disease; FPG = fasting plasma glucose; GH = growth hormone; HbA 1c = hemoglobin A 1c ; T2DM = type 2 diabetes mellitus; TSS = transsphenoidal surgery; UFC = urinary free cortisol

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“…Исследование у здоровых добровольцев показало выраженное снижение секреции инсулина, инкре-тинового ответа и в меньшей степени подавление глюкагона в ответ на введение пасиреотида без сни-жения чувствительности к инсулину [110]. Однако инсулинорезистентность является патогмоничным симптомом гиперкортицизма, поэтому для коррек-ции гипергликемии на фоне применения пасирео-тида эксперты рекомендуют использование мет-формина в сочетании с препаратами инкретинового ряда (ингибиторы DPP4 и агонисты GLP1) для ком-пенсации гипергликемии, а затем введение других средств для коррекции углеводного обмена или уве-личение дозы ранее назначенных препаратов [111,112].…”

Section: медикаментозная терапияunclassified