Cushing's Disease Cycling over Ten Years

Abstract

Cycles of excessive cortisol secretion have been reported interposed with phases of remission lasting from few days to several months. In this study we report a ten year follow up on a patient who had four episodes of hypercortisolism and Cushing's syndrome associated with hypokalemia and edema and three long lasting spontaneous remissions. This was all caused by corticotroph pituitary adenoma. She demonstrated the longest phase of remission yet recorded in this condition, 4.5 years. The precipitating factors for the recurrence in cyclical Cushing's syndrome are not well defined, but the last recurrence in our patient appeared two months after delivery. We have discussed the continuing uncertainty of the standard dynamic tests in the differential diagnosis of Cushing's syndrome.

Long-term Remission of Cyclic Cushing's Disease that was Diagnosed and Treated Surgically in Non-active Phase

“…A typical cyclic Cushing's disease has characteristic endocrinological features: 1) serum cortisol is not suppressed by high dose administration of dexamethasone [1-3, 9-12, 16, 25]; 2) plasma ACTH elevation is not blunted by an intravenous administration of CRH [15,17,21,22]. These endocrinological features were observed also in the present case.…”

“…The possible causes of periodicity of cortisol were reported to be infarcts [5], partial necrosis [8] or calcification [12] of the tumor, or patient stress [15]; however, the precise mechanism is still unclear. The fluctuation of cortisol and ACTH secretion makes it difficult to establish the diagnosis of cyclic Cushing's disease, especially in the remission phase.…”

“…Thus far, only 42 cases with cyclic Cushing's disease have been reported in the literature . This rare condition has distinctive endocrinological characteristics that are different from overt Cushing's disease without cyclicity: 1) no suppression of cortisol by high dose administration of dexamethasone [1-3, 9-12, 16, 25]; 2) blunted response of ACTH to an intravenous administration of corticotropin-releasing hormone (CRH) [15,17,21,22]; and 3) suppression of ACTH by bromocriptine [17,19,21,22,28]. Nevertheless, the diagnosis and surgical treatment of cyclic Cushing's disease are difficult.…”

Endocrine clinical update: Where are we in the therapeutic management of pituitary‐dependent hypercortisolism?

“…8 Cyclical or episodic CD is a potential trap for the unwary in terms of its diagnosis and treatment and is much more common than previously recognized. 2,[9][10][11][12][13] Delay in diagnosis is almost inevitable unless the index of suspicion is high, as traditional 24-h urine collections and blood tests are often within normal limits. Dexamethasone suppression tests may show either suppression or a paradoxical rise.…”

The 4‐mg intravenous dexamethasone suppression test in the diagnosis of Cushing’s syndrome

“…We acknowledge that a follow-up period of 2 years may not absolutely exclude some cases of mild or cyclical CS. 27 Follow-up information was used to distinguish LPC from CS, rather than the response to the IVDST, as the latter approach would have introduced bias, falsely increasing the specificity of the test. Twenty-six patients were excluded from the analysis, including some with a normal response to the IVDST, but insufficient followup data were available with respect to the final diagnosis.…”