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Background: The correlation between fibrinogen levels and adrenocortical carcinoma (ACC) remains unclear. This study aimed to explore the value of preoperative plasma fibrinogen as a biomarker for ACC. Methods: We identified 40 patients with ACC and 170 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2022. Plasma fibrinogen levels and postoperative tumor recurrence information of the patients were also recorded. For intergroup comparisons, data obtained from the AA and ACC groups were evaluated using a t -test. The cutoff value of fibrinogen level was determined using a receiver operating characteristic (ROC) curve. Results: Mean fibrinogen levels in the AA and ACC groups were 2.81 ± 0.59 g/L and 3.88 ± 1.75 g/L, respectively (P <.001). Fibrinogen level, which can help distinguish between AA and ACC, was evaluated using the ROC curve. The cutoff fibrinogen level was estimated as 3.87 g/L according to the Youden index. With this value, the sensitivity was 62.5%, specificity was 95.7%, and the area under the ROC curve (AUC) was 0.74 (P <.001). Fibrinogen level, which can help distinguish between recurrence and non-recurrence, was evaluated using the ROC curve. The cutoff fibrinogen level was estimated as 3.96 g/L according to the Youden index. The sensitivity, specificity, and AUC were 90%, 71.4%, and 0.85, respectively (P <.001). Conclusion: According to the data in this study, plasma fibrinogen could be used to distinguish ACC from AA. Most importantly, plasma fibrinogen may be used to identify recurrence of postoperative ACC. [ABSTRACT FROM AUTHOR]

Situs anomalies, including situs inversus and situs ambiguous (SAMB), are rare congenital conditions typically noted in pediatric populations, with SAMB being particularly uncommon in adults. This case study addresses the incidental discovery of situs ambiguous with polysplenia in a 65-year-old man evaluated for suspected adrenal adenoma. The patient's medical history included benign prostatic hyperplasia and tuberculous pleurisy. Methods included a thorough physical examination and laboratory tests, which showed normal cortisol levels and ACTH rhythm. Contrast-enhanced CT imaging revealed multiple spleens near the right adrenal region, altered liver positioning, a truncated pancreas, and a right-sided stomach, while the right adrenal gland was not visualized. Notably, the patient exhibited minimal symptoms despite these significant anatomical anomalies. The findings underscore the rarity of situs ambiguous in adults and its unexpected association with endocrine pathology. This case highlights the importance of comprehensive imaging and a multidisciplinary approach in managing patients with unusual anatomical presentations. It suggests that situs anomalies may be more prevalent in adult populations than previously recognized and emphasizes the need for increased clinical awareness and evaluation in similar cases. [ABSTRACT FROM AUTHOR]

Abstract Background The two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare. Case presentation The patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms. Conclusion Respiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient’s blood pressure and prevented the recurrence of life-threatening complications.

Background: The two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare. Case presentation: The patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms. Conclusion: Respiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient's blood pressure and prevented the recurrence of life-threatening complications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In cases of primary hyperaldosteronism, the aldosterone renin ratio (ARR) is crucial for determining the need for adrenal vein sampling (AVS). Our case highlights the importance of utilizing ARR with AVS, contextual interpretation of plasma renin and aldosterone levels, and stresses that sole reliance on imaging without AVS may result in unnecessary or contralateral adrenalectomy. [ABSTRACT FROM AUTHOR]

The differential diagnosis between malignant and benign adrenal cortical tumors is challenging, and concurrent androgen and cortisol production should raise  suspicion of a malignant tumor. We present the case of a 36-year-old woman who exhibited pronounced hirsutism, clitoromegaly, and secondary amenorrhea. A contrast-enhanced computed tomography (CT) scan revealed a 35 × 27 mm right adrenal mass with unenhanced CT attenuation of 40 Hounsfield units (HUs). The mass exhibited absolute and relative washout rates of 50% and 28%, respectively, and was accompanied by a 25 × 20 mm adenopathy located in the hepatogastric space. Total testosterone was elevated by 247 ng/dL (8.56 nmol/L) (normal reference range, 10-75 ng/dL; 0.34-2.6 nmol/L). A 1-mg dexamethasone suppression test revealed an elevated serum morning cortisol concentration of 10.57 μg/dL (291.58 nmol/L) (reference range, <1.8 μg/dL; < 49.66 nmol/L). A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan revealed increased uptake in both the adrenal mass and the adenopathy. Subsequently, the patient underwent an open right adrenalectomy and lymphadenectomy. Histological examination revealed the presence of an adrenal adenoma with myelolipomatous metaplasia, as well as a positive polymerase chain reaction (PCR) for Mycobacterium tuberculosis in the adenopathy. [ABSTRACT FROM AUTHOR]

Purpose: To establish various radiomics models based on conventional CT scan images and enhanced CT images, explore their value in the classification of pheochromocytoma (PHEO) and lipid-poor adrenal adenoma (LPA) and screen the most parsimonious and efficient model Methods: The clinical and imaging data of 332 patients (352 lesions) with PHEO or LPA confirmed by surgical pathology in the Affiliated Hospital of Qingdao University were retrospectively analyzed. The region of interest (ROI) on conventional and enhanced CT images was delineated using ITK-SNAP software. Different radiomics signatures were constructed from the radiomics features extracted from conventional and enhanced CT images, and a radiomics score (Rad score) was calculated. A clinical model was established using demographic features and CT findings, while radiomics nomograms were established using multiple logistic regression analysis.The predictive efficiency of different models was evaluated using the area under curve (AUC) and receiver operating characteristic (ROC) curve. The Delong test was used to evaluate whether there were statistical differences in predictive efficiency between different models. Results: The radiomics signature based on conventional CT images showed AUCs of 0.97 (training cohort, 95% CI: 0.95~1.00) and 0.97 (validation cohort, 95% CI: 0.92~1.00). The AUCs of the nomogram model based on conventional scan CT images and enhanced CT images in the training cohort and the validation cohort were 0.97 (95% CI: 0.95~1.00) and 0.97 (95% CI: 0.94~1.00) and 0.98 (95% CI: 0.97~1.00) and 0.97 (95% CI: 0.94~1.00), respectively. The prediction efficiency of models based on enhanced CT images was slightly higher than that of models based on conventional CT images, but these differences were statistically insignificant(P>0.05). Conclusions: CT-based radiomics signatures and radiomics nomograms can be used to predict and identify PHEO and LPA. The model established based on conventional CT images has great identification and prediction efficiency, and it can also enable patients to avoid harm from radiation and contrast agents caused by the need for further enhancement scanning in traditional image examinations. [ABSTRACT FROM AUTHOR]

Object: Microwave ablation has been widely used in tumor treatment, and the antenna is a critical component of microwave ablation. We aimed to evaluate a single-slot antenna to generate a small volume ablation zone (0. 5 ∼ 4 cm 3) in adrenal tissue. Methods: A three-dimensional numerical model of the adrenal tissue was built and solved by the Finite Element Method. In the simulation model, the slot antenna was placed between the adrenal gland and fat, and the microwave ablation power and time were adjusted to obtain the target ablation zone. In ex vivo experiments, the length and width of the ablation zone were measured, and the significance of ablation parameters on it was determined using a multi-factorial analysis of variance method. The temperature versus time curves at 3 mm and 7 mm from the antenna were plotted to validate the simulation. Results: The simulation results showed that the combination of microwave ablation parameter settings 30 W/300 s, 40 W/180 s, and 40 W/300 s could create ablation zones in the adrenal tissue volumes of 1. 4 , 1. 1 7 and 3. 2 8 cm 3 , respectively, with minimal damage (less than 0. 1 8 cm 3) to the surrounding fat tissue. Both power and heating time significantly affected the length and width of the ablation zone. The temperature rise curves obtained in the simulation and ex vivo experiments were in good agreement. Conclusion: This work shows that utilizing a slot antenna can produce a small volume ablation zone in adrenal tissue for microwave ablation of benign adrenal adenomas. [ABSTRACT FROM AUTHOR]

The transformation of an adrenocortical adenoma (ACA) to an adrenocortical carcinoma (ACC) is extremely rare. Current guidelines suggest against further imaging studies and follow-up in patients with nonfunctional adrenal incidentalomas (NFAIs) with benign imaging characteristics. Herein, we present a 64-year-old male patient diagnosed initially with a NFAI of 3 cm in size with imaging characteristics consistent with an ACA. However, 13 years after initial diagnosis, this apparent ACA developed into a high-grade cortisol and androgen-secreting ACC with synchronous metastases. The literature review revealed a further 9 case reports of adrenal incidentalomas initially characterized as ACA that subsequently developed into ACC within a period ranging from 1 to 10 years. The pathogenesis of transformation of an initially denoted ACA to ACC is not fully delineated, although the existing literature focuses on the preexisting or changing genetic background of these lesions, highlighting the need to develop robust prognostic markers to identify patients at risk and individualize the follow-up of these unique cases. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim was to explore the preoperative and postoperative fibrinogen changes value (FCV) as a prognosis biomarker for in patients with adrenocortical carcinoma (ACC). Methods We identified 42 patients with ACC and 190 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2023. Preoperative fibrinogen, postoperative fibrinogen and follow-up information of the patients were recorded and analysed. The relationship between FCV and overall survival (OS)/ relapse-free survival (RFS) was evaluated. Results The mean level of preoperative and postoperative fibrinogen for ACC were 4.00 ± 1.64 g/L and 2.75 ± 0.59 g/L, respectively (p 1.25 g/L) (p = 0.007); however, the lower FCV (≤ 1.25 g/L) showed no poorer OS than the higher (> 1.25 g/L) (p = 0.243). On multivariate survival analyses, FCV remained a predictor of RFS (HR 3.138). Conclusion According to the data in this study, it can be said that FCV is correlated with prognosis of ACC. The FCV might be a new biomarker for predicting the RFS of ACC.

Abstract 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.

Abstract 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. Case presentation 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. Conclusion 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.

Purpose: The aim was to explore the preoperative and postoperative fibrinogen changes value (FCV) as a prognosis biomarker for in patients with adrenocortical carcinoma (ACC). Methods: We identified 42 patients with ACC and 190 patients with adrenal adenoma (AA) who underwent surgery at our institution between 2015 and 2023. Preoperative fibrinogen, postoperative fibrinogen and follow-up information of the patients were recorded and analysed. The relationship between FCV and overall survival (OS)/ relapse-free survival (RFS) was evaluated. Results: The mean level of preoperative and postoperative fibrinogen for ACC were 4.00 ± 1.64 g/L and 2.75 ± 0.59 g/L, respectively (p < 0.001). The mean level of preoperative and postoperative fibrinogen for AA were 2.79 ± 0.59 g/L and 2.71 ± 0.58 g/L, respectively (p = 0.144). In ACC, the lower FCV (≤ 1.25 g/L) showed a significantly poorer RFS than the higher (> 1.25 g/L) (p = 0.007); however, the lower FCV (≤ 1.25 g/L) showed no poorer OS than the higher (> 1.25 g/L) (p = 0.243). On multivariate survival analyses, FCV remained a predictor of RFS (HR 3.138). Conclusion: According to the data in this study, it can be said that FCV is correlated with prognosis of ACC. The FCV might be a new biomarker for predicting the RFS of ACC. [ABSTRACT FROM AUTHOR]

Objective To explore the influencing factors for adrenal insufficiency after adrenalectomy in patients with adrenal adenoma-type subclinical Cushing's syndrome (SCS) and to analyze the predictive efficacy of relevant influencing factors on postoperative adrenal insufficiency. Methods Fifty-nine patients with adrenal adenoma-type SCS underwent laparoscopic unilateral adrenalectomy. Adrenal insufficiency was assessed one month postoperatively based on se- rum cortisol levels. Preoperative general data [gender, age, body mass index (BMI), blood pressure, metabolic comorbidities (overweight/obesity, hypertension, abnormal glucose metabolism, dyslipidemia, osteopenia/osteoporosis), tumor diameter], preoperative adrenal function-related hormone levels [adrenocorticotropic hormone (ACTH) and cortisol diurnal rhythm (8:00, 24:00), cortisol after 1 mg dexamethasone suppression test (1 mg-DST), cortisol after low-dose dexamethasone suppression test (LDDST), serum dehydroepiandrosterone sulfate (DHEAS), and 24-hour urine free cortisol(UFC)], and postoperative glucocorticoid use were compared between patients with adrenal insufficiency and those with normal adrenal function. We constructed a binary Logistic regression analysis model using indicators with intergroup com- parison of P<0. 10, analyzed the influencing factors of postoperative adrenal insufficiency in patients with SCS, and evaluated the predictive efficacy of relevant indicators by the receiver operating characteristic (ROC) curve. Results Adrenal insufficiency was observed in 25 out of 59 patients with SCS one month after surgery, accounting for 42. 37% of these cases. Compared with patients with normal adrenal function, patients with adrenal insufficiency had decreased plasma ACTH levels at 8:00, and increased serum cortisol levels at 24:00 and after 1 mg-DST before surgery. Logistic regression analysis showed that preoperative serum cortisol after 1 mg-DST was an independent influencing factor for the development of ad- renal insufficiency in patients with SCS postoperatively. The relative risk ratio of adrenal insufficiency after surgery in SCS patients with preoperative 1 mg-DST serum cortisol ≥233 nmol/L was 13.698 (95% CI: 2. 965-63. 274). Conclusions Patients with SCS are at risk of developing adrenal insufficiency after surgery. Preoperative serum cortisol after 1 mg-DST is an independent influencing factor for postoperative adrenal insufficiency and has good predictive efficacy on the occurrence of adrenal insufficiency after surgery. [ABSTRACT FROM AUTHOR]

Most adrenal incidentalomas are benign neoplasms of the adrenal cortex. While the majority are nonfunctional, many secrete cortisol. Androgen- or estrogen-secreting adenomas are rare. A 44-year-old female, with history of hypertension and prediabetes, presented with worsening acne, hirsutism, secondary amenorrhea for 2 years, and a 40-pound weight gain. Laboratory evaluation showed high 24-hour urine free cortisol, suppressed adrenocorticotropic hormone (ACTH) level, indicative of ACTH independent Cushing syndrome, and elevated testosterone and androstenedione. Abdominal computed tomography (CT) revealed a 6.3 × 5.2 × 5.6 cm left adrenal mass. Patient underwent left open adrenalectomy. Pathology revealed benign adrenocortical adenoma. Postoperatively there was a significant improvement in her blood pressure and blood sugar levels, resumption of menses, and complete resolution of hyperandrogenism and hypercortisolism. We describe a patient with an adrenal adenoma cosecreting cortisol and androgen, leading to Cushing syndrome and significant virilization. Adrenal masses secreting androgens are less common and concerning for adrenocortical carcinoma (ACC). Patients with adrenal masses cosecreting multiple hormones should undergo workup expediently since ACC confers poor outcomes. [ABSTRACT FROM AUTHOR]

Key Clinical Message In cases of primary hyperaldosteronism, the aldosterone renin ratio (ARR) is crucial for determining the need for adrenal vein sampling (AVS). Our case highlights the importance of utilizing ARR with AVS, contextual interpretation of plasma renin and aldosterone levels, and stresses that sole reliance on imaging without AVS may result in unnecessary or contralateral adrenalectomy.

Magdalena Stasiak,1 Przemys&lstrok;aw Witek,2 Emilia Adamska-Fita,1 Andrzej Lewi&nacute;ski1,3 1Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital—Research Institute, Lodz, Poland; 2Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw; Mazovian Brodnowski Hospital, Warszawa, Poland; 3Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, PolandCorrespondence: Magdalena Stasiak, Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital—Research Institute, 281/289 Rzgowska Street, Lodz, 93-338, Poland, Tel +48502049292, Fax +48422711140, Email mstasiak33@gmail.comAbstract: Cushing’s disease (CD) is the most common cause of endogenous hypercortisolism. Osilodrostat was demonstrated to be efficient in treating CD, and the mean average dose required for CD control was < 11 mg/day. Potential differences in osilodrostat treatment between cortisol-producing adenoma (CPA) and CD have not been reported. The aim of this study was to present two patients with CPA in whom significant differences in the response to therapy compared to CD were found. We demonstrated a case of inverse response of cortisol levels with adrenal tumor progression during the initial dose escalation (Case 1). Simultaneously, severe exaggeration of hypercortisolism symptoms and life-threatening hypokalemia occurred. A further rapid dose increase resulted in the first noticeable cortisol response at a dose of 20 mg/day, and a full response at a dose of 45 mg/day. We also present a case that was initially resistant to therapy (Case 2). The doses required to achieve the first response and the full response were the same as those for Case 1. Our study demonstrated that osilodrostat therapy in patients with CPA may require a different approach than that in CD, with higher doses, faster dose escalation, and a possible initial inverse response or lack of response.Keywords: osilodrostat, adrenal adenoma, hypercortisolism, ACTH-independent, adverse events, hypokalemia

Primary aldosteronism (PA) is the most common cause of secondary hypertension, but its incidence during pregnancy is rare and less than 80 cases in pregnancy have been reported in literature to date. Here, we present a pregnant woman who delivered her first child in the presence of PA four years before, but in her second pregnancy, she developed severe hypertension associated with hypokalemia, and was admitted with preeclampsia. She lost her infant and received a diagnosis of PA due to an adrenal adenoma. After adrenalectomy, her blood pressure was normalized.

Abstract The clinical characteristics of Cushing’s syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients

Objective Glucocorticoid resistance is a rare endocrine disease caused by variants of the NR3C1 gene encoding the glucocorticoid receptor (GR). We identified a novel heterozygous variant (GRR569Q) in a patient with uncommon reversible glucocorticoid resistance syndrome. Methods We performed ex vivo functional characterization of the variant in patient fibroblasts and in vitro through transient transfection in undifferentiated HEK 293T cells to assess transcriptional activity, affinity, and nuclear translocation. We studied the impact of the variant on the tertiary structure of the ligand-binding domain through 3D modeling. Results The patient presented initially with an adrenal adenoma with mild autonomous cortisol secretion and undetectable adrenocorticotropin hormone (ACTH) levels. Six months after surgery, biological investigations showed elevated cortisol and ACTH (urinary free cortisol 114 µg/24 h, ACTH 10.9 pmol/L) without clinical symptoms, evoking glucocorticoid resistance syndrome. Functional characterization of the GRR569Q showed decreased expression of target genes (in response to 100 nM cortisol: SGK1 control +97% vs patient +20%, P <.0001) and impaired nuclear translocation in patient fibroblasts compared to control. Similar observations were made in transiently transfected cells, but higher cortisol concentrations overcame glucocorticoid resistance. GRR569Q showed lower ligand affinity (Kd GRWT: 1.73 nM vs GRR569Q: 4.61 nM). Tertiary structure modeling suggested a loss of hydrogen bonds between H3 and the H1–H3 loop. Conclusion This is the first description of a reversible glucocorticoid resistance syndrome with effective negative feedback on corticotroph cells regarding increased plasma cortisol concentrations due to the development of mild autonomous cortisol secretion. [ABSTRACT FROM AUTHOR]

This article presents a rare case of postmenopausal hyperandrogenism, which is characterized by an excess of male hormones in women after menopause. The condition can be caused by various factors, including ovarian or adrenal neoplasia, Cushing's syndrome, or polycystic ovary syndrome. The article emphasizes the importance of thorough endocrine investigation and diagnostic tools such as serum hormone levels, imaging, and venous sampling. The case study discussed in the article highlights the challenges in diagnosing and localizing the source of hyperandrogenism and suggests the potential usefulness of venous sampling in certain patients. The study was conducted by a team of medical professionals, including radiologists, a histopathologist, an endocrine surgeon, and a gynecologist. [Extracted from the article]

Context: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. Objective: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. Design: Cross-sectional study. Patients: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. Methods: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. Main outcome measure: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. Results: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. Conclusion: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Purpose: Transient pregnancy-induced Cushing's syndrome is a rare condition characterized by the manifestation of symptoms solely during pregnancy, which typically resolve spontaneously following delivery or miscarriage. While it has been established that GNAS is associated with adrenal tumors, its specific role in the pathogenesis of pregnancy-induced Cushing's syndrome remains uncertain.This work aims to examine the association between GNAS mutation and pregnancy-induced Cushing's syndrome. Methods: DNA was extracted from patients' peripheral blood and tumor tissues for whole-exome sequencing (WES) and Sanger sequencing. We used AlphaFold to predict the protein structure of wild-type and mutant GNAS and to make functional predictions, and immunohistochemistry was used to detect disease-associated protein expression. A review and summary of reported cases of transient pregnancy-induced Cushing's syndrome induced by pregnancy was conducted. Results: Using WES, we identified a somatic mutation in GNAS (NM_000516, c.C601T, p.R201C) that was predicted to have a deleterious effect using computational methods, such as AlphaFold. Human chorionic gonadotropin (hCG) stimulation tests had weakly positive results, and immunohistochemical staining of adrenal adenoma tissue also revealed positivity for luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and cytochrome P450 family 11 subfamily B member 1 (CYP11B1). We reviewed 15 published cases of transient Cushing's syndrome induced by pregnancy. Among these cases, immunohistochemical staining of the adrenal gland showed positive LHCGR expression in 3 case reports, similar to our findings. Conclusion: Transient pregnancy-induced Cushing's syndrome may be associated with somatic GNAS mutations and altered adrenal pathology due to abnormal activation of LHCGR. [ABSTRACT FROM AUTHOR]

This case report describes the surgical management of a giant left adrenal mass (27 x 26 × 27 cm, 9.370 kg) in a 69-year-old female. We review the multidisciplinary decision-making process for pre-operative preparation, embolization, resection feasibility, and strategies to mitigate intra-operative complications. This is the largest adrenal adenoma removal reported to date. The case highlights the importance of meticulous surgical planning and execution in managing rare and challenging cases, with significant implications for patient outcomes.

Objective: The clinical significance of immunohistochemistry (IHC) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow‐up of PA patients could be in sight. Long‐term outcomes of patients, classified based on IHC, need further investigation. We aimed to assess long‐term clinical outcomes for unilateral PA, classifying patients based on IHC. Design: A nationwide observational study, with up to 16 years follow‐up, executed in 2007–2016 at Landspitali University Hospital, tertiary referral center. Patients were diagnosed and treated in line with the current guidelines. Haematoxylin and eosin (H&E) tissue slides were stained using CYP11B1 and ‐B2 antibodies. All cases were re‐evaluated and classified according to the HISTALDO consensus. Outcomes were assessed using the PASO criteria. Patients: All unilateral PA patients diagnosed in 2007‐2016 in Iceland, 26 patients aged 28–73 years, who underwent adrenalectomy, were included. Measurements: Aldosterone, renin, and cortisol values, use and dosage of antihypertensives, potassium supplementation, blood pressure and serum potassium pre‐intervention and throughout follow‐up, and histopathology results post‐adrenalectomy. Results: Following IHC, an aldosterone‐producing nodule was seen in 12 adrenals, an aldosterone‐producing adenoma in 10 and multiple aldosterone‐producing micronodules in four. IHC altered histopathology from previous H&E diagnosis in 23% (6/26) of the patients. In total, 81% (21/26) of the patients had partial clinical success. Eight percent (2/26) of the patients needed potassium supplementation during follow‐up. In the classical group, the AVS results were more determinative with significantly higher lateralization index (median 10.1 vs. 5.3, p =.04) and more contralateral suppression (median nondominant ratio 0.4 vs. 1.0, p =.03). One out of five patients with complete clinical success at 12 months post‐op had severe relapse later, the other four were normotensive without antihypertensives for up to 10 years. Conclusions: We found IHC mandatory for accurate histopathologic diagnosis of PA. Our results support the importance of contralateral suppression when interpreting AVS results. Also, the study highlights the complicated assessment of clinical outcome and importance of aldosterone and renin measurements during follow‐up. [ABSTRACT FROM AUTHOR]

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Objective: To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). Design: Systematic review and meta-analysis. Methods: Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). Results: In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. Conclusions: The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities [ABSTRACT FROM AUTHOR]

Background: Abnormalities of the adrenal gland include primary neoplasm, metastases, hemorrhage, or enlargement of the adrenal gland from external hormonal stimulation. Adrenal masses can be divided into two physiologic categories based on whether they hypersecrete a hormone. Hyperfunctioning adrenal masses produce a hormone that results in a chemical imbalance and include pheochromocytomas, aldosteronomas, and cortisol or androgen-producing tumors. Aim & Objective:1. Characterization of adrenal masses using contrast enhanced CT scan. Methods: Study design: Prospective Observational study. Study setting: Department of Radio-diagnosis, Study population: Patients with adrenal masses, measuring more than 1cm, with Hounsfield Unit more than 10. Sample size: 50. Results: The pathological diagnosis was 25 adenomas and 29 non adenomas. Absolute percent washout diagnosed 24 of 25 adenomas and 27 of 29 non adenomas. It had a Sensitivity of 96.00%, Specificity of 93.10%, Positive Predictive Value of 92.31% and Negative Predictive Value of 96.43%. Relative percent washout diagnosed 23 of 25 adenomas and 26 of 29 non adenomas. It had a sensitivity of 92%, specificity of 89.66%, Positive Predictive value of 88.46% and Negative Predictive Value of 92.86%. Both were found to be statistically significant. Conclusions: CT contrast washout study is helpful in categorising adenomas and non-adenomas in adrenal masses with high degree of accuracy, sensitivity and specificity and helps guide clinical management [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA) is the most common cause of secondary hypertension, but its incidence during pregnancy is rare and less than 80 cases in pregnancy have been reported in literature to date. Here, we present a pregnant woman who delivered her first child in the presence of PA four years before, but in her second pregnancy, she developed severe hypertension associated with hypokalemia, and was admitted with preeclampsia. She lost her infant and received a diagnosis of PA due to an adrenal adenoma. After adrenalectomy, her blood pressure was normalized. [ABSTRACT FROM AUTHOR]

PURPOSEThis study aimed to determine the accuracy of texture analysis in differentiating adrenal lesions on unenhanced computed tomography (CT) images.METHODSIn this single-center retrospective study, 166 adrenal lesions in 140 patients (64 women, 76 men; mean age 56.58 ± 13.65 years) were evaluated between January 2015 and December 2019. The lesions consisted of 54 lipid-rich adrenal adenomas, 37 lipid-poor adrenal adenomas (LPAs), 56 adrenal metastases (ADM), and 19 adrenal pheochromocytomas (APhs). Each adrenal lesion was segmented by manually contouring the borders of the lesion on unenhanced CT images. A texture analysis of the CT images was performed using Local Image Feature Extraction software. First-order and second-order texture parameters were assessed, and 45 features were extracted from each lesion. One-Way analysis of variance with Bonferroni correction and the Mann–Whitney U test was performed to determine the relationships between the texture features and adrenal lesions. Receiver operating characteristic curves were performed for lesion discrimination based on the texture features. Logistic regression analysis was used to generate logistic models, including only the texture parameters with a high-class separation capacity (i.e., P < 0.050). SPSS software was used for all statistical analyses.RESULTSFirst-order and second-order texture parameters were identified as significant factors capable of differentiating among the four lesion types (P < 0.050). The logistic models were evaluated to ascertain the relationships between LPA and ADM, LPA and APh, and ADM and APh. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the first model (LPA vs. ADM) were 85.7%, 70.3%, 81.3%, 76.4%, and 79.5%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of the second model (LPA vs. APh) were all 100%. The sensitivity, specificity, PPV, NPV, and accuracy of the third model (ADM vs. APh) were 87.5%, 82%, 36.8%, 98.2%, and 82.7%, respectively.CONCLUSIONTexture features may help in the characterization of adrenal lesions on unenhanced CT images.

ABSTRACT Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Abstract Background Functioning and non-functioning adrenocortical adenoma are two subtypes of benign adrenal adenoma, and their differential diagnosis is crucial. Current diagnostic procedures use an invasive method, adrenal venous sampling, for endocrinologic assessment. Methods This study proposes establishing an accurate differential model for subtyping adrenal adenoma using computed tomography (CT) radiomic features and machine learning (ML) methods. Dataset 1 (289 patients with adrenal adenoma) was collected to develop the models, and Dataset 2 (54 patients) was utilized for external validation. Cuboids containing the lesion were cropped from the non-contrast, arterial, and venous phase CT images, and 1,967 features were extracted from each cuboid. Ten discriminative features were selected from each phase or the combined phases. Random forest, support vector machine, logistic regression (LR), Gradient Boosting Machine, and eXtreme Gradient Boosting were used to establish prediction models. Results The highest accuracies were 72.7%, 72.7%, and 76.1% in the arterial, venous, and non-contrast phases, respectively, when using radiomic features alone with the ML classifier of LR. When features from the three CT phases were combined, the accuracy of LR reached 83.0%. After adding clinical information, the area under the receiver operating characteristic curve increased for all the machine learning methods except for LR. In Dataset 2, the accuracy of LR was the highest, reaching 77.8%. Conclusion The radiomic features of the lesion in three-phase CT images can potentially suggest the functioning or non-functioning nature of adrenal adenoma. The resulting radiomic models can be a non-invasive, low-cost, and rapid method of minimizing unnecessary testing in asymptomatic patients with incidentally discovered adrenal adenoma.

Simple Summary: The information obtained in the CT and MRI allows adequate differentiation of adrenal adenomas and pheochromocytomas (PHEOs) with a high diagnostic accuracy. Our study confirms that our predictive model combining tumor size and lipid content has high re-liability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis. We observed that in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. Purpose: to perform an external validation of our predictive model to rule out pheochromocytoma (PHEO) based on unenhanced CT in a cohort of patients with PHEOs and adenomas who underwent adrenalectomy. Methods: The predictive model was previously developed in a retrospective cohort of 1131 patients presenting with adrenal lesions. In the present study, we performed an external validation of the model in another cohort of 214 patients with available histopathological results. Results: For the external validation, 115 patients with PHEOs and 99 with adenomas were included. Our previously described predictive model combining the variables of high lipid content and tumor size in unenhanced CT (AUC-ROC: 0.961) had a lower diagnostic accuracy in our current study population for the prediction of PHEO (AUC: 0.750). However, when we excluded atypical adenomas (with Hounsfield units (HU) > 10, n = 39), the diagnostic accuracy increased to 87.4%. In addition, in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. The probability of PHEO was <0.3% for adrenal lesions <20 mm with >10 HU and without hyperintensity in T2. Conclusion: Our study confirms that our predictive model combining tumor size and lipid content has high reliability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Although there is growing evidence associating nonfunctioning adrenal incidentalomas (NFAI) with cardiovascular risk factors, there are limited data whether NFAI and autonomous cortisol secretion (ACS) groups have similar or different clinical and metabolic features. The aim of this study is to compare cardiometabolic clinic parameters among patients with ACS and NFAI, as well as controls. Design: Cross‐sectional study. Patients: Eighty nine NFAI, 58 ACS and 64 controls were evaluated. Measurements: Diagnosis of NFAI (1 mg dexamethasone suppression test [1 mg‐DST] ≤50 nmol/L [≤1.8 μg/dl]) and ACS (1 mg‐DST > 50 nmol/L [> 1.8 μg/dl]) was established according to current guidelines. The control group was selected based on a normal adrenal imaging exam. Results: There were no differences between groups regarding age, gender, ethnicity, menopause or body mass index. Patients with adrenal incidentaloma presented higher frequency of hypertension (74.1 vs. 57.8%; p =.02), resistant hypertension (45.4 vs. 9.4%; p <.001), dyslipidemia (80.1 vs. 63.9%; p =.01), as well as metabolic syndrome (84.2 vs. 61.7%; p =.001) compared to the controls, respectively. NFAI and ACS patients presented similar frequency of arterial hypertension (70.8 vs. 79.3%) and resistant hypertension (41.3 vs. 51.1%), dyslipidemia (79.3 vs. 81.5%) and metabolic syndrome (83.3 vs. 85.7%); also, levels of HbA1c were similar between the groups. Binary logistic regression showed that NFAI (p =.004) and ACS (p =.001) were independent predictors for resistant hypertension (p =.003); also, ACS was an independent predictor for metabolic syndrome (p =.04). Conclusions: NFAI and ACS presented a higher frequency of cardiometabolic morbidities in comparison with individuals with normal adrenal glands. Additionally, we demonstrated that both ACS and NFAI groups have similar cardiometabolic conditions. [ABSTRACT FROM AUTHOR]

Panic attacks and panic disorders are common in the general population. However, the presence of panic attacks associated with primary hyperaldosteronism has been rarely documented. We describe a patient with new-onset hyperaldosteronism secondary to adrenal adenoma who presented with recurrent panic attacks. The patient underwent adenoma resection, which was the definitive cure for the patients hyperaldosteronism and panic attacks. Clinicians should include hyperaldosteronism on the differential for medical etiologies of panic attacks. Further research is needed to elucidate the mechanistic relationship between primary hyperaldosteronism and panic attacks.

Purpose: The current clinical discrimination of the dominant side of primary aldosteronism (PA) mainly relies on invasive adrenal venous sampling (AVS) examination. This study investigated the feasibility of dual-energy CT energy imaging parameters as a novel biomarker in identifying bilateral adrenal dominant lesions. Methods: Fifty PA patients with bilateral lesions who underwent CT and AVS of the adrenal glands at Shaanxi Provincial People's Hospital from October 2019 to June 2021 were retrospectively analyzed. Forty-eight patients had successful bilateral blood collection and two failed right-sided blood collection due to venous variation. Forty patients who were classified based on AVS underwent unilateral adrenalectomy and pathological findings confirmed adenoma in all cases. Quantitative dual-energy CT parameters were measured for all adrenal lesions, and the differences in dual-energy CT energy spectrum imaging parameters between the dominant and nondominant adrenal lesions were compared. Results: Among forty-eight PA patients with bilateral lesions, forty patients with preoperative AVS-determined lesions on the dominant side underwent unilateral adrenalectomy, and eight patients without the dominant side were treated with medication. The iodine concentration difference (ICD) in the arteriovenous phase was more significant in the 40 cases of primary aldosteronism with dominant adrenal lesions than in the nondominant adrenal lesions (1.18 ± 0.45 vs 0.41 ± 0.42). The NICAP was higher in the dominant adrenal lesions than in the non-dominant lesions (0.39 ± 0.39 vs 0.14 ± 0.05). The sensitivity and specificity of the diagnosis of the dominant adrenal lesion were 88.2% and 82.4% using the ICD of 0.68 as the threshold value. Conclusion: Conventional CT has lower diagnostic value for dominant adrenal lesions, and CT-based energy imaging can be a new assessment method as a complement to AVS in identifying bilateral dominant adrenal lesions. [ABSTRACT FROM AUTHOR]

A 38-year-old transgender man with advanced metastatic functional pancreatic neuroendocrine neoplasm (PanNEN) gastrinoma was admitted to the Department of Endocrinology due to severe ACTH-dependent hypercortisolemia. An ectopic production of ACTH by PanNEN was suspected. The patient qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent resection of the left adrenal glandwith the tumor only, which surprisingly resulted in a significant decrease in ACTH and cortisol levels, leading to clinical improvement. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. We looked for a correlation between gender-affirming hormone treatment and the onset of the disease and its rapid progression. This may be the first case describing the coexistence of gastrinoma and ectopic Cushing disease in a transsexual patient. [ABSTRACT FROM AUTHOR]