Project title
亞臨床庫欣氏症在腎上腺偶發瘤患者的診斷--橫斷面分析和縱向追蹤研究
Internal ID
MOST106-2314-B002-239
Principal Investigator
Start Date
August 1, 2017
End Date
July 12, 2018
Investigators
Organizations
Partner Organizations
The Diagnosis of Subclinical Cushing's Syndrome in Subjects with Adrenal Incidentaloma – Cross-Sectional Analysis and Longitudinal Follow-Up = 亞臨床庫欣氏症在腎上腺偶發瘤患者的診斷- 橫斷面分析和縱向追蹤研究
Description
Adrenal incidentalomas (AI) are defined as adrenal lesions discovered serendipitously on a radiological examination that has been performed for reasons others than suspected adrenal disease. Its mean prevalence is 2.3% without significant differences between females and males. The prevalence increases with the patient’s age, being less than 1% in young subjects as compared with 10-15% in subjects older than 70 years of age. There are two key points for AI, the first is the risk of malignancy, and the second is excess hormone production. The majority of AI are non-functioning benign cortical adenoma (NFAI). The lesions are characterized by autonomous cortisol production without specific signs and symptoms of Cushing’s syndrome (CS), a condition termed subclinical Cushing’s syndrome (SCS). It is the most common hormonal abnormality detected in patients with AIs. The diagnosis of SCS in patients with AI remains a challenge because in SCS the specific signs of hypercortisolism are absent, and there is no clinical gold standard to facilitate the diagnosis. Due to the standard biochemical tests used to screen for CS were not designed to reveal the subtle changes encountered in SCS, a combination of various parameters used to assess the integrity of the hypothalamus-pituitary-adrenal (HPA) axis have been employed. However, the use of a combination of different tests to assess the HPA axis has not shown to be superior to the 1mg overnight dexamethasone suppression test (DST). All published guidelines agree with the use of 1mg overnight DST for the screening of hypercortisolism. However, there is disagreement on the best cutoff for cortisol after DST, since the values of 1.8 μg/dL as well as 5.0 μg/dL are recommended as limits for normal cortisol suppression. In the case of symptomatic CS, the clinician’s index of suspicion is high and there is a high pretest probability of disease so therefore the likelihood of a false-positive test is reduced. In contrast, in patients with SCS, symptoms are subtle so the clinician’s index of suspicion is lower and therefore a test with greater specificity is preferable, despite the loss of sensitivity. The diagnostic flow-chart of SCS is highly challenging and clear standards are still lacking. We propose this projects to develop the best diagnostic test and cutoff to diagnose SCS in patients with AI. There are two specific aims in this project, including a retrospective cross-section analysis (specific aim A) and a prospective longitudinal follow-up cohort study (specific aim B). In specific aim A, we will collect 300 tissue samples, which are preserved from patients with AI who received adrenalectomy, and perform immunohistochemical (IHC) stain. Then we will use the results of IHC stain to define SCS, and search the best diagnostic test and cutoff to diagnose SCS in combination of the pre-operative adrenal hormonal data. In specific aim B, we will setup a long-term follow-up cohort of AI in Taiwan. In the first year, we will enroll 50 subjects with AI as pilot study. All subjects will receive routine hormonal evaluation for AI, and additional parameters and tests to assess the integrity of HPA axis and co-morbidities. We will analyze subjects undergo adrenalectomy first. By using of the results of IHC stain and post-adrenalectomy hypocortisolism to define SCS, we will validate the diagnostic performance of the cutoff developed from specific aim A, and also compare the diagnostic performance between the cutoff developed from specific aim A and previously used by studies.