Diagnosis Of Subclinical Cushing's Syndrome Research Articles

Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas.

Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative 131I-6β-iodomethyl-norcholesterol (131I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection. The study included 90 patients with unilateral adrenal adenoma who fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol ≥3.0 μg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%) subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS group was comparable to that in the non-functioning adenoma group. In contrast, the uptake rate on the contralateral side was lower and the laterality ratio significantly higher in the SCS group. The two ACS indices were correlated with serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not. Tumor size was also important for the functional statuses of adrenal tumors and NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect SCS was 3.07. These results clearly indicate that contralateral adrenal suppression in ACS is good evidence showing subclinical cortisol overproduction.

Evaluation of the 1 mg overnight dexamethasone suppression test in the diagnosis of the subclinical Cushing's syndrome in patients with Adrenal Incidentaloma

To evaluate efficacy of the 1 mg overnight dexamethasone suppression test (1 mg overnight DST) in the diagnosis of subclinical Cushing's syndrome, and to explore the best diagnostic cut-off value. The clinical data of patients with adrenal incidentaloma in Chinese PLA General Hospital from 1995 to 2013 were gathered. The data of subclinical Cushing's syndrome (SCS) and non-functional adrenal adenoma (NFA) was retrospectively analyzed. The ROC curve was used to evaluate the efficacy of the 1 mg overnight DST and to explore the best cut-off value with high sensitivity and specificity. There were 447 patients with NFA (224 male and 223 female), and the mean age was 53±11 years old.49 patients were with SCS (19 male and 30 female), and the mean age was 47±12 years old. The area under the ROC of serum cortisol level after 1 mg overnight DST was 0.967 (95%CI: 0.942-0.993). The best cut-off value of serum cortisol after 1 mg overnight DST was 63.65 nmol/L, with a sensitivity of 100.0% and a specificity of 88.8%. The best cut-off value of the suppression ratio of serum cortisol was 85.64%, with a sensitivity of 83.3% and a specificity of 84.6%. The best criterion for 1 mg overnight DST in the diagnosis of SCS was serum cortisol level , and the recommend cut-off point was 63.65 nmol/L, with both a higher sensitivity and specificity. The suppression ratio of serum cortisol after 1 mg overnight DST was also considered as a suitable criterion in the diagnosis of SCS.

Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.

Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications

To investigate the possibility of a different prevalence of subclinical Cushing's syndrome (SCS) and potentially related morbidities between patients with unilateral adrenal incidentalomas (UAI) and bilateral adrenal incidentalomas (BAI), as existing data are few and controversial. Prospective observational study. Clinical examination, biochemical tests, and hormonal evaluation were performed in 298 consecutive patients with adrenal incidentalomas, unilateral in 224 patients (75.2%), bilateral in 74 patients (24.8%), with apparently benign masses based on imaging characteristics and after exclusion of overt endocrine disease. The diagnosis of SCS was based on a post-dexamethasone suppression test (2 mg dexamethasone/24 h for 48 h), with serum cortisol level ≥1.8 μg/dl combined with at least one abnormal result of the other hormonal measurements. SCS was diagnosed in 66 out of 298 (22.1%) patients, being more frequent in patients with BAI (35.1 vs 17.9%, P=0.003, for BAI and UAI respectively). Hypertension, type 2 diabetes mellitus, impaired glucose tolerance, and dyslipidemia were of a similar frequency in both groups. SCS patients with UAI and BAI did not differ in age, gender, BMI, waist circumference, and mass size. Factors related to SCS were the presence of BAI (OR, 3.24; 95% CI, 2.31-4.54) and mass size (OR, 2.63; 95% CI, 1.31-5.26). BAI patients present more often with SCS when compared with UAI patients; however, morbidities potentially related to subtle cortisol hypersecretion were of a similar frequency in both groups. Further studies are needed to clarify whether this difference in hormonal activity may be related to different pathophysiologies.

Subclinical Cushing's syndrome

Subclinical Cushing's syndrome (SCS) refers to subtle autonomous cortisol hypersecretion that is insufficient to generate the typical, clinically recognizable overt syndrome. Diagnosis of SCS is challenging. The combination of 1 mg overnight dexamethasone suppression test, serum ACTH level, and urinary cortisol level are used to diagnose SCS. Laparoscopic adrenalectomy is the treatment of choice for SCS. Patients with adrenal incidentalomas and SCS should be treated with perioperative steroids to prevent post-operative hypocortisolism.

Analysis of subclinical Cushing syndrome

Objective To evaluate subclinical Cushing syndrome cases and to improve the diagnosis.Methods A retrospective analysis was done on the data of 24 subclinical Cushing syndrome cases.Clinical data included clinical manifestations,endocrinal tests,imaging,treatments,light microscopic and electron microscopic results.Results No typical sign of Cushing syndrome was found in these 24 cases.Endocrine tests showed that 24-hour urine free cortisol increased in 18 cases (75%),cortisol rhythm disappeared in 12 cases(50%),high-dose dexamethasone suppression test was not inhibited in 11 cases (46%),and low-dose dexamethasone suppression test (LDDST) was not suppressed in all 24 cases (100%).CT scan showed the average tumor diameter was 3.1(1.8-4.5)cm.Laparoscopic resections of adrenal tumors were performed for all 24 patients.The light microscopic examination of the tumor specimens showed adrenocortical adenoma,and the electron microscopic examination found a greater number of cytoplasmic secretory granules.After 3 months' followup,patient's blood pressure was normal and the normal cortisol rhythm was detected.Conclusions Endocrine tests,especially LDDST,are important for the diagnosis of subclinical Cushing syndrome.Once a clear diagnosis of subclinical Cushing syndrome is established,the patient should be treated with surgery and will have a satisfactory result in both blood pressure control and endocrinal rhythm. Key words: Cushing syndrome; Subclinical; Diagnosis; Treatment; Microscopy,electron

American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: Executive Summary of Recommendations

American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: Executive Summary of Recommendations