Cushing’s Disease of Unknown Etiology: A Clinical Case Report

Abstract

Cushing’s disease (CD) remains a diagnostic and therapeutic challenge. Different subtypes may be recognized that will offer insight in this complex situation. We describe an atypical case that we assume is a common variation albeit with no previous formal description. A young female patient presented with minimal clinical features of CD, but increased adrenocorticotropic hormone (ACTH) and cortisol levels, with maintained circadian rhythm that was not suppressed either after the rapid dexamethasone or the prolonged low-dose dexamethasone tests, but suppressed with the prolonged high-dose dexamethasone test and presented a flat ACTH and cortisol response after the corticotropin-releasing hormone (CRH) test. A diffuse enlarged pituitary gland with thickened pituitary stalk was present and a mixed corticotroph adenoma was removed. CD persisted despite now normal pituitary morphology, except for pituitary stalk widening. Plasma levels of CRH were low and no abnormalities were found in the coding region or flanking introns of glucocorticoid receptor (GCR) gene ( NR3C1 ). Somatostatin receptors were not present in the octreoscan, and treatment with cabergoline or somatostatin analogs was ineffective. Morbidity and mortality are increased in CD even in patients successfully treated and in remission. Despite early success in over 80% of the patients, in the long term CD recurs in almost 50% of the patients. Defining subtypes of CD may help elucidate mechanisms of the disease. We propose a new variant that we assume is common. Furthermore adaptation to chronic hypercortisolism is present. J Endocrinol Metab. 2022;12(1):40-48 doi: https://doi.org/10.14740/jem784