Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing\'s disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P<0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L,n=18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n=15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group(P<0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.
目的： 探讨血清硫酸脱氢表雄酮（DHEAS）在原发性双侧肾上腺大结节样增生（PBMAH）与肾上腺无功能腺瘤（NFA）、肾上腺皮质腺瘤（ADA）、库欣病（CD）鉴别诊断中的价值。 方法： 横断面研究。回顾性分析解放军总医院第一医学中心2010年1月至2021年6月诊治的302例PBMAH、NFA、ADA、CD患者的临床资料，其中男97例，女205例，年龄（45.7±7.2）岁。采用受试者工作特征（ROC）曲线下面积评估DHEAS比值（血清DHEAS除以其相应年龄及性别正常参考值范围下限）及8点促肾上腺皮质激素（ACTH）水平鉴别诊断PBMAH与NFA、ADA、CD的效能，取约登指数最大值为cut-off值。 结果： 302例患者中PBMAH组33例，NFA组125例、ADA组67例和CD组77例。DHEAS比值在CD组、NFA组、PBMAH组及ADA组依次降低，分别为6.34（4.44，9.93）、3.37（2.24，4.79）、1.14（1.04，2.40）和0.58（0.27，1.05），各组间差异均有统计学意义（均P<0.01）。DHEAS比值将PBMAH与NFA、ADA、CD相鉴别的ROC曲线下面积分别为0.803、0.741、0.930，cut-off值分别为2.59、0.99、2.92，灵敏度分别为66.1%、64.2%、87.9%，特异度分别为81.8%、81.2%、85.7%。根据8点ACTH水平，将PBMAH分为ACTH抑制组（ACTH<2.2 pmol/L，n=18）和ACTH非抑制组（ACTH≥2.2 pmol/L，n=15），ACTH非抑制组DHEAS比值高于ACTH抑制组（P<0.01）。DHEAS比值鉴别ACTH非抑制PBMAH与CD的ROC曲线下面积为0.877，cut-off值为4.55，灵敏度93.3%，特异度75.3%。若DHEAS比值联合8点ACTH水平作为鉴别诊断指标，鉴别ACTH非抑制PBMAH与CD的ROC曲线下面积可达0.967，灵敏度100.0%，特异度81.8%。 结论： DHEAS比值在PBMAH、NFA、ADA、CD患者中存在差异，可协助PBMAH与NFA、ADA及CD的鉴别诊断，特别是在ACTH非抑制PBMAH与CD的鉴别诊断中更具有优势。.

BACKGROUND: Functioning adrenal adenoma during pregnancy is rare, and the diagnosis is challenging owing to unspecific symptoms and restricted investigations. The obstetric outcomes of patients who undergo surgery during pregnancy or who receive only medical treatment are poorly described.
OBJECTIVE: The aim was to investigate the associations between functioning adrenal adenomas and obstetric outcomes.
METHODS: A retrospective study was performed in a tertiary center over 20 years. The clinical characteristics, management and obstetric outcomes of the diagnosed pregnant women were reviewed.
RESULTS: A total of 12 women were diagnosed with functioning adrenal adenomas during pregnancy from January 2002 to September 2022. Eight women had cortisol-secreting adrenal adenomas, two had excessive catecholamine secretion, and two had primary aldosteronism. The initial symptoms of adrenal adenoma during pregnancy included hypertension or preeclampsia, gestational diabetes mellitus or prepregnancy diabetes mellitus, hypokalemia and ecchymosis. Four women underwent adrenalectomy during pregnancy, while 8 women received only medical therapy. Preterm birth occurred in all patients who received medicine, whereas 1 patient who underwent surgery experienced preterm birth. Among the 8 women in the medical treatment group, 3 had neonates who died.
CONCLUSIONS: Once hypertension, hyperglycemia and hypokalemia occur during the 1st or 2nd trimester, pregnant women with adrenal adenomas should be evaluated via laboratory and imaging examinations. The maternal and fetal outcomes were unpredictable owing to the severity of adrenal adenoma, particularly in patients who received only medical treatment. Adrenalectomy should be recommended during pregnancy.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to adrenal steroid biosynthesis, and mainly caused by mutations in the CYP21A2 gene encoding 21-hydroxylase. Adrenal tumors are common in CAH, but functional adrenal tumors are rare. Here, we report a 17-year-old female with virilized external genitalia and primary amenorrhea, accompanied by a right adrenal tumor. Her 17-OHP level was normal, cortisol and androgen levels were significantly elevated, and the tumor pathology showed adrenal cortical adenoma. Gene testing for CYP21A2 showed c.518T > A in exon 4 and c.29313C > G in intron 2. The possibility of untreated classic CAH with 21-OH deficiency causing functional adrenal cortical adenoma should be considered. When clinical diagnosis highly considers CAH and cannot rule out the influence of functional adrenal tumors\' secretion function on 17-OHP, gene mutation analysis should be performed.

BACKGROUND: Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy.
METHODS: A patient with primary aldosteronism (PA) associated with severe Cushing\'s syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings.
CONCLUSIONS: Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

The aim of this study was to determine the tissue expressions of vascular endothelial growth factor (VEGF) and endocan in adrenal cortical tumors and the factors associated with them. The study included 6 subjects with adrenocortical adenoma (ACA), 7 subjects with adrenocortical carcinoma (ACC), and 13 control subjects with a normal adrenal cortex. The status of VEGF and endocan expression was determined by the proportions of cells staining on a scale ranging from negative (not staining at all) to strongly positive. VEGF expression was detected in 1 (16.7%) of 6 subjects in the ACA group and in 6 (85.7%) of 7 subjects in the ACC group. VEGF expression was not detected in any of the subjects in the control group. Endocan expression was detected in 6 (100%) of 6 subjects in the ACA group and in 7 (100%) of 7 subjects in the ACC group, while it was detected in only 4 (30.7%) of 13 subjects in the control group. VEGF was expressed with a high frequency in subjects with ACC and with a low frequency in subjects with ACA, but it was not expressed in subjects with normal adrenal cortex tissue. Although endocan was expressed with a higher frequency in subjects with ACC and ACA, it was also expressed in subjects with normal adrenal cortex tissue. The percentage of cells expressed endocan in subjects with ACC was also significantly higher than in subjects with both ACA and normal adrenal cortex.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs).
METHODS: This is a single-center cohort study.
METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016.
RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P = .002).
CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

OBJECTIVE: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs).
METHODS: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram.
RESULTS: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000).
CONCLUSIONS: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.

BACKGROUND: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas.
METHODS: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis.
METHODS: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization.
CONCLUSIONS: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.

Adrenocortical tumours are rare in children and account for only 0.3%-0.4% of all neoplasms in childhood. They present with variable signs and symptoms, depending on the type of hormonal hypersecretion. The majority of the adrenocortical tumours in children are functional (90%) and malignant (88%). Here, we describe a functional plurihormonal oncocytic adrenal cortical adenoma in a young girl, that mimicked a malignant adrenal lesion, clinically as well as on imaging and biochemical features. This report bears the objective of being aware of the atypical biochemical as well as imaging characteristics of oncocytic adrenal tumours.

BACKGROUND: Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
METHODS: To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori\'s Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26.
RESULTS: ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, β-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival.
CONCLUSIONS: This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, β-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.