Dexamethasone Infusion Testing in the Diagnosis of Cushing's Syndrome

Abstract

Abstract. Cushing's syndrome and its various aetiologies is a markedly difficult diagnosis to make given its subtle signs, sometime cyclical nature, and the lack of a single definitive diagnostic test. Although a great variety of diagnostic tests have been developed to assist in the diagnosis, even with the best clinical acumen, biochemistry and medical imaging the diagnosis can remain elusive. The long low and high dose oral dexamethasone suppression test is cumbersome, costly and often requiring an extended inpatient stay. The utility of the dexamethasone suppression test would be greatly enhanced if it could be performed as a short outpatient procedure. In this study we sought to confirm and refine the clinical utility of the high dose 4 mg intravenous dexamethasone suppression test as an alternative diagnostic test for Cushing's syndrome. There were a total of 31 subjects: 8 patients with proven pituitary Cushing's disease, 3 with primary adrenal tumors, 10 with pseudo-Cushing's syndrome and 10 healthy controls. All subjects with pseudo-Cushing's syndrome suppress serum cortisol at +5 and at +24 hours. In subjects with pituitary Cushing's disease, 7 out of 8 (88%) had serum cortisol suppressed at +5 hours but rebounded at +24 hours to at least 70% of the original serum level. Primary adrenal tumors showed a pattern of non-suppression throughout. The 4 mg intravenous dexamethasone suppression test is excellent in ruling out pseudo-Cushing's syndrome. This test is much simpler and more convenient than the oral dexamethasone suppression test in confirming clinical suspicion of pituitary Cushing's disease.

A Very Low Dose Intravenous Dexamethasone Suppression Test as an Index of Glucocorticoid Sensitivity

“…Thus, by avoiding the intestinal absorption and liver passage, intravenous dexamethasone may be a useful and more consistent alternative. However, this test has not been routinely used and it was previously reported only for differential diagnosis of Cushing’s syndrome using higher doses of dexamethasone [13,14,15]. …”

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

“…Abou Samra et al 11 reported that Day 2 cortisol was >276 nmol/l in 10 patients with CS and <83 nmol/l in 21 normal subjects. Tran et al 12 reported Day 2 cortisol of ‡350 nmol/l in 11 patients with CS. Furthermore, Abou Samra et al 11 used a competitive protein-binding method for the estimation of cortisol, which is less specific compared to modern immunoassays.…”

“…11,12 We have also quantified the response in overweight/obese subjects with type 2 diabetes. These results are consistent with two previous studies demonstrating a sustained suppression of the HPA axis in normal subjects using the same IVDST protocol.…”

“…3,4 These conditions can result in clinical and biochemical features of hypercortisolism without true CS. 2,6 To overcome these problems, several intravenous DST (IVDST) regimens have been evaluated over the past 40 years, including 8-mg bolus, 7 5 lg/kg/h for 5 h, 8 and fixed dose infusions (1-1AE5 mg/h) administered over 3-7 h. [9][10][11][12][13][14][15][16] All the studies have assessed the plasma cortisol response on the day of the infusion. For any oral DST, variable absorption of dexamethasone, as well as poor compliance, may influence the results.…”

“…5,6 Various forms of the dexamethasone suppression test (DST) are used to establish the diagnosis of CS and to differentiate the aetiology which can be divided into ACTH-independent [adrenal Cushing's (AC)] and ACTH-dependent CS caused by pituitary [Cushing's disease (CD)] or ectopic tumours [ectopic ACTH syndrome (EAS)]. Four studies 7,8,11,12 have also assessed the cortisol response on the following morning (Day 2), including a study by Abou Samra et al 11 which reported that in nine normal weight and 12 obese subjects, plasma cortisol decreased to <83 nmol/l at +5 h (5 h after the commencement of the infusion) and remained suppressed on Day 2. 2,6 To overcome these problems, several intravenous DST (IVDST) regimens have been evaluated over the past 40 years, including 8-mg bolus, 7 5 lg/kg/h for 5 h, 8 and fixed dose infusions (1-1AE5 mg/h) administered over 3-7 h. [9][10][11][12][13][14][15][16] All the studies have assessed the plasma cortisol response on the day of the infusion.…”