Introduction: Cyclic Cushings Syndrome (CCS) is a rare disorder in which rhythmic fluctuations in the secretion of ACTH trigger cyclic variations in the production of adrenal steroids and an extremely variable clinical presentation. It should be considered when clinical hypercortisolism coexists with normal cortisol levels and a paradoxical response to the dexamethasone test, and when selective transsphenoidal adenomectomy fails after an uncomplicated intervention.
Clinical case: A 34-year-old woman was evaluated from 2000 to 2005 in another hospital and diagnosed with cyclic Cushings syndrome without evidence of primary adrenal pathology or ectopic ACTH production. In December 2004 and February 2005 hypercortisolism was confirmed, but previous studies were not conclusive because the hormonal determinations were normal in most cases although the patient presented Cushingoid features, and dexamethasone suppression tests were starting from practically normal values of cortisol. Pituitary magnetic resonance (MR), performed in 2000, revealed a possible microadenoma in the left half of the pituitary, not confirmed in subsequent studies. Computed tomography thoracoabdominal and catecholamines, 5-OH-indole acetic acid, histamine in 24-hour urine were normal. For years she followed therapy with ketoconazole, suspended in January 2004 for inoperability. In 2006 the patient was sent to our hospital to perform petrosal sinus catheterization with stimulation of CRH showing these results: central/peripheral ACTH ratio <2:1 (basal) and >3:1 after stimulation. Further tests included: basal ACTH (with hypercortisolism): 32.9 pg/ml; In-111 Octreoscan and all the biochemical tests repeatedly performed did not show significant alterations; bone densitometry showed very mild osteopenia in the spine; adrenal MR bilateral hypertrophy without nodular images and pituitary MR repletion defects inside the adenohypophysis, of right and left location, in possible relation to microadenomas. Given the impossibility of controlling the episodes of hypercortisolism with cabergoline and ketoconazole, in March 2010 a bilateral adrenalectomy was performed. Histopathological diagnosis corresponded to a combined bilateral adrenal cortical hyperplasia, diffuse and micronodular with several nodules, the largest one being 1 cm, in the right adrenal. Clinical and biochemical hypercortisolism disappeared in the postoperative period and is still the case >8 years later. In September 2018, basal ACTH was 376 pg/ml (046). In control pituitary MR a pituitary gland with normal characteristics is observed.
Discussion: The high degree of recurrence of CCS after pituitary surgery often conditions new interventions and/or combined pharmacological therapy. Despite the risk of developing Nelson syndrome, bilateral adrenalectomy could be the best initial surgical option
18 - 21 May 2019
European Society of Endocrinology