Cushing's Disease
A specific form of Cushing's syndrome caused by an ACTH-secreting pituitary tumour. Pasireotide suppresses ACTH from the tumour via somatostatin receptor binding. Cushing's disease illustrates targeted peptide therapy for a specific endocrine disorder.
Technical Context
Cushing's disease accounts for approximately 70% of endogenous Cushing's syndrome. ACTH-secreting pituitary adenoma (usually microadenoma <10mm) → bilateral adrenal hyperplasia → excess cortisol. Diagnosis: confirm hypercortisolism (24h urinary free cortisol, midnight salivary cortisol, 1mg overnight dexamethasone suppression test) → confirm ACTH-dependent (plasma ACTH inappropriately normal/elevated) → localise source (pituitary MRI, inferior petrosal sinus sampling if MRI equivocal). First-line: transsphenoidal surgery (remission rate approximately 70-90% for microadenomas). Second-line medical therapy for surgical failure: pasireotide (Signifor — SC twice daily or LAR monthly) — targets SSTR5 (highly expressed on corticotroph adenomas) → suppresses ACTH secretion → cortisol reduction. Phase III PASPORT-CUSHINGS: approximately 26% of patients achieved urinary free cortisol normalisation at 6 months. Key side effect: hyperglycaemia (approximately 73% — due to SSTR5-mediated inhibition of insulin secretion), requiring glucose monitoring and management.