Adrenalectomy Research Articles

OR04-4 Loss of KDM1A in Bilateral Macronodular Adrenal Hyperplasia With GIP-Dependent Cushing's Syndrome and in Acromegaly With Paradoxical GH Response to Oral Glucose

Abstract Context Primary bilateral macronodular adrenal hyperplasia (PBMAH) with glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome is caused by ectopic expression of GIP receptor (GIPR) in the adrenal lesions. Such ectopic expression of GIPR was also reported in other endocrine neoplasm, notably in somatotroph pituitary adenomas from acromegalic patients with paradoxical increase of GH after oral glucose load, suggesting a common molecular pathogenesis. We aimed to identify the driver event responsible for GIP-dependent PBMAH with Cushing's syndrome and ectopic GIPR expression in somatotropinomas. Methods We conducted an international, multicenter, cohort study. We collected blood and adrenal samples from patients who had undergone unilateral or bilateral adrenalectomy for GIP-dependent PBMAH with Cushing's syndrome. Adrenal samples from patients with PBMAH and Cushing's syndrome without food-dependent cortisol production were used as controls. We further collected somatotropinoma specimens from acromegaly patients followed at two expert endocrine centers in France. Results 17 patients with familial or sporadic GIP-dependent PBMAH with Cushing's syndrome were studied. We identified germline heterozygous mutations in the lysine demethylase 1A (KDM1A) gene in all 17 patients. We further identified a recurrent deletion of the short arm of chromosome 1 harboring the KDM1A locus in the adrenal lesions of affected patients. None of the 25 patients in the control group had KDM1A germline or somatic alterations. Concomitant genetic inactivation of both KDM1A alleles resulted in loss of KDM1A expression in the adrenal lesions. RNA-sequencing revealed the global impact of KDM1A loss in adrenal tissue on gene transcription and identified differentially regulated genes including those encoding for GIPR and other G-Protein-Coupled Receptors that may be involved in adrenal tumorigenesis and regulation of steroidogenesis. In vitro pharmacologic inhibition, silencing and knock-out by CRISPR-Cas9 genome editing of KDM1A led to an increase in GIPR transcripts and protein in human adrenocortical H295R cells. Somatotropinoma samples from 78 patients with acromegaly were studied. 24% of these patients presented with a paradoxical rise of GH after oral glucose load and expressed ectopically GIP-receptor in their somatotropinoma. None of the somatotropinomas harbored KDM1A pathogenic variants, but those from patients with paradoxical GH response displayed a recurrent chromosome 1p loss. Discussion We identified germline inactivating KDM1A mutations and loss of heterozygosity as a genetic predisposition to GIP-dependent PBMAH with Cushing's syndrome following a tumor suppressor gene model of tumorigenesis. We currently perform genetic screening in first-degree relatives of patients with GIP-dependent PBMAH with Cushing's syndrome and clinical examination with biochemical testing in asymptomatic KDM1A variant carriers. We did not identify somatic KDM1A mutations in somatotropinomas expressing GIPR ectopically, however their recurrent 1p chromosome loss suggests that KDM1A haploinsufficiency may contribute to GIPR expression in those tumors. Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.

PSAT041 A Rare Case of Severe Cyclical Cushing Syndrome Due to Ectopic ACTH Secretion by Appendiceal Carcinoid

Abstract Cushing syndrome (CS) secondary to ectopic ACTH secretion (EAS) is rare and accounts for 10% of CS with majority being bronchial or gut neuroendocrine tumors (NETs) and squamous cell lung cancer. There are only a few case reports of EAS due to appendiceal carcinoid. A 24-year-old woman was referred to endocrinology for 60-pound weight gain, acne, hirsutism, generalized weakness, heat intolerance, and hot flashes. She had secondary amenorrhea for 6 months prior to presentation. Family history was significant for bronchial carcinoid in mother. On examination, she had moon facies, wide purple striae on abdomen, hirsutism, dorsocervical and supraclavicular fat pads. She had normal blood pressure. Her laboratory workup showed potassium 3.2 mmol/L (N, 3.5-5.3), urine free cortisol (UFC) 539 mcg/24 hours (N<50), ACTH 54 pg/ml (N, 6-50) and post 1-mg dexamethasone suppression test cortisol 8.8 mcg/dL. CT abdomen revealed a 3-cm enhancing appendiceal mass, enlarged periappendiceal mesenteric lymph nodes and a 4-cm enhancing right hepatic lobe lesion. Ga-68 Dotatate PET/CT confirmed increased radiotracer uptake in appendiceal mass, lymph nodes and hepatic mass. On liver biopsy, pathology showed well differentiated NET Grade 1 and positive ACTH stain. Repeat UFC was 65 mcg/24 hrs and serum cortisol went down to <1 mcg/dL indicating severe cyclical CS. She was referred to surgical oncology for opinion on debulking surgery. Her genetic testing was negative. She was started on Lanreotide. Given severe cyclical CS with extensive tumor burden, she underwent robotic bilateral adrenalectomy with a plan for cytoreductive surgery once she is on physiologic doses of steroids. Appendiceal NET causing Ectopic CS is exceedingly rare. In 20 years’ experience at NIH, there was only one case of appendiceal NET reported. First reported case was in 1971, when CS was cured by resection of an appendiceal carcinoid incidentally detected on laparotomy for adrenalectomy. There are 3 additional case reports in literature of appendiceal carcinoid with ectopic CS. Management can be challenging particularly in patients with metastatic disease. Medical therapy should be individualized, and adrenalectomy should be considered early in patients with uncontrolled CS due to EAS. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Histopathologic Differences Between Adrenocorticotropic Hormone–Dependent and Adrenocorticotropic Hormone–Independent Adrenal Hyperplasia Causing Cushing Syndrome

A 64-year-old man with cushingoid features was found to have bilateral nodular adrenal masses (left > right). Laboratory studies showed elevated 24-hour urinary free cortisol level at 64 μg (reference range, 0-50 μg), abnormal levels for the 1-mg dexamethasone suppression test (cortisol, 4.8 μg/dL; dexamethasone level, 665 ng/dL), and suppressed adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone levels. ACTH-independent Cushing syndrome was diagnosed. He was treated with ketoconazole for 6 years, but owing to worsening symptoms including uncontrolled type 2 diabetes mellitus, bilateral adrenalectomy was performed.

SC144 - Robot-assisted partial adrenalectomy for conn syndrome: single center long term functional outcomes

SC144 - Robot-assisted partial adrenalectomy for conn syndrome: single center long term functional outcomes

Adrenal gland transplantation in clinical conditions

Chronic insufficiency of the cortical substance of the adrenal glands or hypocorticism until recently belonged to rare forms of endocrine pathology. This included a few cases of Addison’s disease of tuberculous etiology, a relatively small number of patients after bilateral adrenalectomy for Cushing’s disease, removal of bilateral, sometimes unilateral, hormonally active tumors of the cortex and medulla of the adrenal glands. Bilateral adrenalectomy is also practiced for some types of hormone‑dependent tumors of the mammary glands, ovaries, prostate, and malignant hypertension. The evolution of ideas about the pathophysiology of adrenal glands contributed to a significant expansion and increase in the number of patients suffering from hypocorticism. A decrease in the incidence of tuberculosis contributed to a decrease in the number of patients with classic Addison’s disease. However, an increasing number of patients with hypocorticism of autoimmune, genetically determined and other genesis are currently being discovered. The improvement of diagnostic methods contributes to the increase in the number of operations for adrenal glands tumors and, accordingly, the number of cases of post‑adrenalectomy hypocorticism. Operations on the pituitary gland for various types of tumors, the number of which is steadily increasing, also contribute to the increase in the number of cases of hypothyroidism. In the mid‑70s of the XX century. a new direction in the treatment of various forms of endocrine insufficiency by the method of transplanting cultures of cells and tissues of endocrine glands took shape. Disorders of the endocrine glands seem to be particularly suitable for the transplantation method of treatment, since it is expected that living and functionally active donor endocrine tissue, transplanted into a patient with endocrine insufficiency, will secrete hormones and provide the body’s physiological needs and clinical compensation of the insufficiency. Similar experimental studies have been conducted since the beginning of the 20th century. The methods of obtaining cultures of cells and tissues of various endocrine organs were developed in detail, the issue of their viability, morphological and hormonal characteristics, and the possibility of compensation of certain forms of endocrine insufficiency were studied.

TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

Tumor-to-tumor metastasis of colon cancer metastasizing to a pancreatic neuroendocrine tumor associated with von Hippel-Lindau disease: a case report

Von Hippel-Lindau disease (VHL) is frequently associated with pancreatic neuroendocrine tumors (PNETs). Here, we report a case of tumor-to-tumor metastasis in a VHL patient in whom colon cancer metastasized to the interior of a PNET. A 65-year-old man had undergone bilateral adrenalectomy for pheochromocytomas in both adrenal glands in his 50 s. Genetic screening was performed considering his family history of pheochromocytoma, and he was diagnosed with VHL. PNET was detected, for which the patient was regularly monitored by follow-up imaging. One year ago, the patient underwent right hemicolectomy to remove a tumor in the ascending colon (pT3N0M0, pStage IIA). He was admitted to our department for detailed examination because the pancreatic tumor had grown, and thus, pancreaticoduodenectomy was performed. Diagnostic imaging and histological findings indicated tumor-to-tumor metastasis, in which the patient’s previous colon cancer had metastasized to and proliferated within the PNET. Colon cancer metastasizing to a PNET is extraordinarily rare and has never been reported in the literature. Thus, practitioners should be vigilant for tumor-to-tumor metastasis when performing imaging surveillance of PNETs.

Pancreatic fluorescence using continuous indocyanine greeninfusion.

Pancreatic fluorescence using continuous indocyanine greeninfusion.

Treatment of ACTH-ectopic syndrome with long-acting octreotide: effective control of disease activity

ACTH — ectopic syndrome (ACTH-ES) is a severe multisystem disease caused by paraneoplastic secretion of ACTH itself and/or much less often corticoliberin (CL) by tumor tissue. The frequency of ACTH-ES is 12–20% of cases of endogenous hypercortisolism, i.e. about 1–2 cases per million population, and covers a range of tumors, from benign neoplasms to malignant tumors with widespread metastases, while the most common causes of ACTH-ES are tumors of the lung, pancreas and thymus, and more rare localizations are neuroendocrine tumors (NET) of the intestine, medullary thyroid cancer, pheochromocytoma and mesothelioma. The optimal treatment for ACTH-ES is to remove the ACTH-secreting tumor. For patients with an unidentified source of ectopic hormone secretion, the choice is narrowed to bilateral adrenalectomy followed by hormone replacement therapy with glucocorticoids and mineralocorticoids. Medication options are generally a low-effective/palliative treatment option. In this article, we present a clinical case of the successful use of long-acting octreotide in a 36-year-old woman with severe ACTH-ES for long-term control of paraneoplastic ACTH secretion, against which a clinical and biochemical improvement comparable to complete remission of the disease was achieved.

Cushing´s syndrome due to bilateral adrenal cortical disease: Bilateral macronodular adrenal cortical disease and bilateral micronodular adrenal cortical disease.

Cushing´s syndrome (CS) secondary to bilateral adrenal cortical disease may be caused by bilateral macronodular adrenal cortical disease (BMACD) or by bilateral micronodular adrenal cortical disease (miBACD). The size of adrenal nodules is a key factor for the differentiation between these two entities (>1cm, BMACD and <1cm; miBACD). BMACD can be associated with overt CS, but more commonly it presents with autonomous cortisol secretion (ACS). Surgical treatment of BMACD presenting with CS or with ACS and associated cardiometabolic comorbidities should be the resection of the largest adrenal gland, since it leads to hypercortisolism remission in up to 95% of the cases. Medical treatment focused on the blockade of aberrant receptors may lead to hypercortisolism control, although cortisol response is frequently transient. miBACD is mainly divided in primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD). miBACD can present at an early age, representing one of the main causes of CS at a young age. The high-dose dexamethasone suppression test can be useful in identifying a paradoxical increase in 24h-urinary free cortisol, that is a quite specific in PPNAD. Bilateral adrenalectomy is generally the treatment of choice in patients with overt CS in miBACD, but unilateral adrenalectomy could be considered in cases with asymmetric disease and mild hypercortisolism. This article will discuss the clinical presentation, genetic background, hormonal and imaging features and treatment of the main causes of primary bilateral adrenal hyperplasia associated with hypercortisolism.

Unilateral or bilateral adrenalectomy in PPNAD: six cases from a single family followed up over 40 years

The most frequent endocrine Carney complex manifestation is a bilateral primary pigmented nodular adrenocortical disease and bilateral adrenalectomy (BA) is therefore its main treatment. In this study, a 40 years follow-up of six members of the same family with heterozygous PRKAR1A germline mutation, is reported over two generations. The first cases, two sisters with severe hyperandrogenism and Cushing syndrome (CS) diagnosed in 1972 at age 14 and 25, were successfully treated with unilateral adrenalectomy (UA). Their two brothers were then diagnosed, one with a CS-related severe osteoporosis treated with BA and the other with CS treated with UA. The second generation was diagnosed with CS signs at 7 and 21 years of age and were treated with BA and UA respectively. Out of the four patients treated with UA, the only event possibly related to CS was spontaneous episode of pulmonary embolism, 30 years after surgery. Hormonal evaluation revealed either eucortisolism in one patient or partial adrenal deficiency in two and mild hypercortisolism in one patient. For the two patients with BA, one of them accidentally died. The second one, surprisingly, recovered progressively normal cortisol secretion and circadian variation. Steroid substitution was stopped 6 years after her surgery and we demonstrated by iodocholesterol scintigraphy the presence of bilateral adrenal remnants. In conclusion, our results of long term evolution of PPNAD patients show that UA in this subset of patients could be considered to treat CS.

Cushing's disease: role of bilateral adrenalectomy.

Laparoscopic bilateral adrenalectomy (BAD) is one of the treatments of Cushing's Disease (CD), but its indications and outcome is debated. The literature on BAD was reviewed as part of a work performed for the Cushing's disease guideline. The surgical morbidity of BAD is reported between 10 and 18% and no mortality has been reported in the largest series. Because of the endocrine sacrifice it will be mostly performed after a multidisciplinary team discussion in selected cases of refractory CD (mostly after failure of pituitary surgery and/or medical treatment). It is also frequently discussed in female patients desiring pregnancy. Corticotroph tumor progression occurs in 40% of the patients but is in most patients manageable when detected early by a careful long term monitoring with pituitary MRI and ACTH assays after BAD. BAD is a safe and effective treatment of CD used in specific situations and requiring long term monitoring.

Characterization of Adrenal miRNA-Based Dysregulations in Cushing's Syndrome.

MiRNAs are important epigenetic players with tissue- and disease-specific effects. In this study, our aim was to investigate the putative differential expression of miRNAs in adrenal tissues from different forms of Cushing’s syndrome (CS). For this, miRNA-based next-generation sequencing was performed in adrenal tissues taken from patients with ACTH-independent cortisol-producing adrenocortical adenomas (CPA), from patients with ACTH-dependent pituitary Cushing’s disease (CD) after bilateral adrenalectomy, and from control subjects. A confirmatory QPCR was also performed in adrenals from patients with other CS subtypes, such as primary bilateral macronodular hyperplasia and ectopic CS. Sequencing revealed significant differences in the miRNA profiles of CD and CPA. QPCR revealed the upregulated expression of miR-1247-5p in CPA and PBMAH (log2 fold change > 2.5, p < 0.05). MiR-379-5p was found to be upregulated in PBMAH and CD (log2 fold change > 1.8, p < 0.05). Analyses of miR-1247-5p and miR-379-5p expression in the adrenals of mice which had been exposed to short-term ACTH stimulation showed no influence on the adrenal miRNA expression profiles. For miRNA-specific target prediction, RNA-seq data from the adrenals of CPA, PBMAH, and control samples were analyzed with different bioinformatic platforms. The analyses revealed that both miR-1247-5p and miR-379-5p target specific genes in the WNT signaling pathway. In conclusion, this study identified distinct adrenal miRNAs as being associated with CS subtypes.

Complex treatment of invasive corticotropic pituitary macroadenoma - Case report

Introduction: Cushing's disease is a hypercortisolemic state caused by the excess secretion of corticotropin by the pituitary adenoma. Cushing's disease is diagnosed on the basis of clinical and laboratory signs of hypercortisolemia and the presence of an MRI pituitary adenoma. Pituitary surgery represents the first-line therapy, but it is non-curative in one third of patients, requiring additional treatments. Second-line treatments include pharmacotherapy, pituitary radiotherapy and bilateral adrenalectomy.&#x0D; Case report: A 57-year-old patient with clinical symptoms of hypercortisolemia was admitted to the Endocrinology Clinic due to dizziness and headache. Laboratory tests and MRI confirmed Cushing's disease caused by invasive pituitary macroadenoma. The tumor was not completely resected through the sphenoid sinus. Disease symptoms were remitted and hormone levels were stabilized. After 2 years, the underlying disease was relapsed. A second tumor removal operation was performed. The tumor was incompletely removed. The disease has progressed.. The patient was referred for stereotaxic CyberKnife radiotherapy.&#x0D; Conclusion: Cushing's disease should be diagnosed and treated in a specialized endocrinology center, and the success of treatment depends on a multidisciplinary team of physicians consisting of an endocrinologist, neurosurgeon and neuroradiologist.About 50% of untreated patients die within 5 years of the disease due to complications of hypercortisolemia. Surgical treatment is effective in the case of microadenomas, while in the case of macroadenomas, it may turn out to be ineffective when the tumor is highly invasive. If subsequent surgeries are unsuccessful, treatment with radiotherapy or pharmacotherapy should be given.

Cushing's disease: role of preoperative and primary medical therapy.

Transsphenoidal surgery is the first-line treatment for Cushing's disease. However, some situations may require the use of a primary medical treatment, such as in patients with severe life-threatening hypercortisolism, a situation which can be handled by fast-acting steroidogenesis inhibitors, instead of classical bilateral adrenalectomy. Primary medical treatment could also be considered in patients with non-severe hypercortisolism, but the evidence is far less convincing for its systematic use. The aim of this short review is to explain briefly the different circumstances in which primary medical therapy could be considered, the limits of this approach, and the way in which to initiate and monitor the treatment.

Cushing Syndrome Secondary to Ectopic ACTH Production in Pregnancy: A Case Report

Ectopic adrenocorticotropic hormone production is an extremely rare cause of Cushing syndrome in pregnancy and is associated with significant morbidity. A 37-year-old multiparous woman at 32 weeks’ gestation presented with hypertension, anasarca, hypokalemia, and fetal distress requiring an urgent cesarean section. Her adrenocorticotropic hormone and cortisol levels were elevated, and high-dose dexamethasone failed to suppress them, suggesting ectopic adrenocorticotropic hormone production. Multimodality imaging did not identify a source, and she had urgent bilateral adrenalectomy for refractory severe hypercortisolism. Ectopic Cushing syndrome in pregnancy requires a high index of suspicion for diagnostic testing and prompt treatment to minimize maternal and fetal complications.

Anesthesia and Outcome of 33 Surgeries in 24 Multiple Endocrine Neoplasia Type 2A (MEN2A) Patients: A National Rare Disease Center's Experience.

BackgroundMultiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome that presents as medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Experience is lacking in the anesthetic management of patients with this syndrome, particularly in those who present with pheochromocytoma receiving nonpheochromocytoma resection. We aimed to share our experience with the anesthetic management of MEN2A patients.MethodWe retrospectively enrolled 24 MEN2A patients who had received different types of surgery at Peking Union Medical College Hospital from January 1, 2015, to December 31, 2021. All the medical records were reviewed and analyzed.ResultIn total, 33 surgeries were performed in 24 MEN2A patients, with 20 surgeries comprising pheochromocytoma resection in 17 patients. Most of these patients who had received pheochromocytoma resection had typical hemodynamic changes during surgery and anesthesia. Regarding the other 13 nonpheochromocytoma resections in 13 patients, 10 were performed in patients without pheochromocytoma, and 3 surgeries were performed with either functional primary (1, bilateral tumor whose patient refused adrenalectomy) or metastatic pheochromocytoma (2, unresectable and malign tumors developed years after bilateral adrenalectomy). Regarding the latter 3 patients, 1 showed hypertension and tachycardia during anesthesia induction, 1 showed tachycardia during surgery and the other showed stability during surgery. Patients who had received pheochromocytoma resection (n=17) required longer postoperative hospital stays than those who had received nonpheochromocytoma resection without pheochromocytoma (n=10) (5.8 ± 1.8 vs. 4.3 ± 1.6; P = 0.031).ConclusionsWhenever MEN2A patients are diagnosed with pheochromocytoma, surgical resection of the pheochromocytoma remains the primary choice for MEN2A treatment. Nonpheochromocytoma surgeries performed with existing pheochromocytoma could be risky and require full caution and preparation.

Primary Aldosteronism: State-of-the-Art Review.

We are witnessing a revolution in our understanding of primary aldosteronism (PA). In the past 2 decades, we have learned that PA is a highly prevalent syndrome that is largely attributable to pathogenic somatic mutations, that contributes to cardiovascular, metabolic, and kidney disease, and that when recognized, can be adequately treated with widely available mineralocorticoid receptor antagonists and/or surgical adrenalectomy. Unfortunately, PA is rarely diagnosed, or adequately treated, mainly because of a lack of awareness and education. Most clinicians still possess an outdated understanding of PA; from primary care physicians to hypertension specialists, there is an urgent need to redefine and reintroduce PA to clinicians with a modern and practical approach. In this state-of-the-art review, we provide readers with the most updated knowledge on the pathogenesis, prevalence, diagnosis, and treatment of PA. In particular, we underscore the public health importance of promptly recognizing and treating PA and provide pragmatic solutions to modify clinical practices to achieve this.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

The Relationship Between Baseline Cortisol Levels and Surgery Method of Primary Bilateral Macronodular Adrenal Hyperplasia.

Aim was to explore the associations between baseline cortisol levels and surgery method of primary bilateral macronodular adrenal hyperplasia (PBMAH). We retrospectively reviewed the clinical features and management of 30 patients (18 females and 12 males) who were diagnosed with PBMAH in our center between 2005 and 2019. Based on surgery method, we divided the patients into two groups: unilateral adrenalectomy (UA) group; and bilateral adrenalectomy (BA) group. Serum cortisol rhythm and 24-hour urinary free cortisol (UFC/24 h) levels were assayed using chemiluminescence method. Associations between baseline cortisol levels and BA were assessed using logistic regression. The predictive value of baseline cortisol levels for BA was calculated using receiver operating characteristic (ROC) curves. Twenty patients (66.7%) underwent UAs and ten patients (33.3%) underwent BAs. After adjusting for age, sex, BMI, SBP, and adrenal volume, the concentrations of baseline serum cortisol (8 AM, 4 PM, and 0 AM) and UFC/24 h were associated with bilateral adrenalectomy (all p<0.05). The area under the ROC curve based on 8 AM serum cortisol level model was larger than that in models based on 4 PM, 0 AM serum cortisol levels and UFC/24 h, but the differences were non-significant (all p>0.05). According to maximum Youden index criteria, the optimal cutoffs of 8 AM serum cortisol level and UFC were 26.89 μg/dl and 406.65 μg/24 h, respectively, for BA. The baseline cortisol levels are positively associated with BA. Increased levels of baseline cortisol levels may predict higher possibility of BA, which should be confirmed by prospective studies.