Adrenal Adenoma Research Articles

Cushing's Syndrome in Pregnancy Secondary to Adrenocortical Adenoma: A Case Series and Review.

To present a case series of Cushing's syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes. We describe five pregnant women with CS, detailing clinical presentations and laboratory findings. Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas. Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.

Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Validation of the modified CT criteria for identifying non-adenomas.

Although adrenal computed tomography (CT) percentage washout is a potentially powerful imaging technique for differentiating adrenal adenomas from non-adenomas, its application to non-adenomas can be problematic. Recently, modified criteria for diagnosing pheochromocytomas using adrenal CT were developed based on data from 199 patients with surgically proven pheochromocytomas and adenomas. However, these criteria have not been thoroughly validated. The purpose of this study was to validate the performance of the modified criteria for diagnosing non-adenomas including pheochromocytomas. The conventional and modified criteria were applied to 266 patients from two cohorts who had surgically proven lipid-poor adenomas (155/266, 58.3%) and non-adenomas (111/266, 41.7%) and underwent adrenal CT. Two radiologists calculated the attenuation on each dynamic phase and percentage washout of adrenal masses. The final assessments based on the conventional and modified criteria were categorized into adenomas or non-adenomas. The diagnostic performance of each criterion for diagnosing non-adenomas was evaluated using the area under the receiver operating characteristic curve (AUC). False negatives and positives were also compared. The AUC for the diagnosis of non-adenomas was 0.806 for conventional criteria and 0.858 for modified criteria (p = 0.047). The false-negative rate of conventional criteria for the diagnosis of non-adenomas was 29.7%. Use of modified criteria could have reduced the false-negative rate by to 7.2%. The false-positive rate increased from 9% to 21.3% when using the modified criteria. The utilization of modified criteria has the potential to identify additional non-adenomas that would otherwise be misdiagnosed as adenomas using conventional criteria alone.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies

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 < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study

BackgroundLimited information exists on postoperative hypocortisolism and hypothalamus–pituitary–adrenal axis recovery in patients with adrenal incidentaloma following unilateral adrenalectomy. We evaluated frequency of postoperative hypocortisolism and predictors for recovery in non-aldosterone-producing adrenocortical adenoma patients after unilateral adrenalectomy.MethodsA retrospective analysis of 32 adrenal incidentaloma patients originally included in the ITACA trial (NCT04127552) with confirmed non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy from September 2019 to April 2023 was conducted. Preoperative assessments included adrenal MRI, anthropometrics, evaluation of comorbidities, adrenal function assessed via ACTH, urinary free cortisol, and 1 mg dexamethasone suppression test. ACTH and serum cortisol or Short Synacthen test were performed within 6 days, 6 weeks, 6 months, and a year after surgery.ResultsSix days postoperative, 18.8% of patients had normal adrenal function. Among those with postoperative hypocortisolism, 53.8% recovered by 6 weeks. Patients with earlier adrenal recovery (6 weeks) had lower preoperative 1 mg dexamethasone suppression test (median 1 mg dexamethasone suppression test 76.2 [61.8–111.0] nmol/L vs 260.0 [113.0–288.5] nmol/L, p < 0.001). Univariate analysis showed preoperative 1 mg dexamethasone suppression test negatively related with baseline ACTH levels (r = − 0.376; p = 0.041) and negatively associated with the 6-week baseline (r = − 0.395, p = 0.034) and 30-min cortisol levels during Short Synacthen test (r = − 0.534, p = 0.023). Logistic regression analysis demonstrated preoperative 1 mg dexamethasone suppression test as the only biochemical predictor for 6-week adrenal recovery: ROC curve identified a 1 mg dexamethasone suppression test threshold of 131 nmol/L predicting 6-week recovery with 89.5% sensitivity and 72.7% specificity (AUC 0.87; 95% CI 66.9–98.7, p < 0.001). Other preoperative assessments (tumor size, ACTH levels and anthropometrics) were not associated with postoperative hypothalamus–pituitary–adrenal axis function, but the presence of diabetes was associated with a lower probability of recovery (OR = 24.55, p = 0.036). ACTH levels increased postoperatively in all patients but did not predict hypothalamus–pituitary–adrenal axis recovery.ConclusionsThe preoperative 1 mg dexamethasone suppression test cortisol value and presence of diabetes are the only relevant predictor of hypothalamus–pituitary–adrenal axis recovery in patients with non-aldosterone- producing adrenocortical adenoma undergoing surgery, regardless other clinical and biochemical variables. Notably, pre- and postoperative ACTH levels did not predict hypothalamus–pituitary–adrenal axis recovery. These findings point towards the potential for saving resources by optimizing their allocation during follow-up assessments for patients with non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy.

Fluorescence-guided minimally-invasive resection of abdominal paragangliomas using indocyanine green

This retrospective study explores the utility of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in enhancing the intraoperative identification and guidance for the resection of abdominal paragangliomas. They can be challenging to detect during minimally invasive surgery, due to their anatomical location, varying size and similar appearance in regard to their surrounding tissue. Patients with suspected abdominal paragangliomas planned for a minimally-invasive resection were included. As part of standard of care they received single intravenous dose of 5 mg ICG after abdominal exploration. NIR fluorescence imaging of the anatomical region of the suspected lesion was performed immediately following intravenous administration, to assess fluorescence signals, intraoperative identification, and histopathological correlation. Out of five resected suspicious lesions, four were imaged with NIR fluorescence, pathology confirming four as paragangliomas, the latter turned out to be an adrenal adenoma. NIR fluorescence identified all four lesions, surpassing the limitations of white-light visualization. Homogeneous fluorescence signals appeared 30–60 s post-ICG administration, which lasted up to 30 min. The study demonstrates the feasibility and potential clinical value of fluorescence-guided minimally-invasive resections of abdominal paragangliomas using a single intravenous ICG dose. These findings support the scientific basis for routine use of ICG-fluorescence-guided surgery in challenging anatomical cases, providing valuable assistance in lesion detection and resection.

Adrenal Myelolipoma: Case Report

Introduction: Myelolipomas were first described in 1905 as an adrenal tumor composed of mature fat mixed with myeloid and erythroid cells. Adrenal myelolipomas are the second most common benign type of tumor in the adrenals, following after adrenocortical adenomas. It is mostly discovered incidentally on imaging of abdomen done for non-adrenal related reasons or at autopsy. Symptomatic tumors, growing tumors or tumors larger than 10 cm should be excised surgically. We report the case of 1 male patient presenting with flank pain and upper pole renal masse, treated surgically with adrenalectomy. Myelolipoma was confirmed on histology. Case presentation: a 46-years-old male, with a history of blood hypertension, presented with persistent abdominal discomfort and occasional pain in the right flank region. Physical examination revealed a non-tender palpable mass in the right upper quadrant of the abdomen. The abdominal CT scan revealed a large well-defined retroperitoneal tumor, which compressed and displaced the right kidney downward, the mass was heterogeneous with areas of soft-tissue attenuation. The patient underwent open left adrenalectomy. The pathological study confirmed the diagnosis of adrenal myelolipoma. The differential diagnosis of fat-containing retroperitoneal masses would include retroperitoneal lipoma or liposarcoma and renal angiomyolipoma. Discussion: Adrenal myelolipomas are the second most common adrenal incidentalomas comprising 6 to 16% of adrenal incidentalomas. The size of adrenal myelolipomas is variable and can range from a few millimeters to greater than 10 cm. These are called giant adrenal myelolipomas. The largest adrenal myelolipoma reported to date weighed 6 kg. Extra-adrenal sites for myelolipomas include the retroperitoneum, thorax, and pelvis. Usually unilateral however they can also involve both adrenals. The most common symptoms observed are abdominal discomfort/pain, hypochondrial pain, and flank pain. Ultrasonography (USG), ......

The improvement of postoperative blood pressure and associated factors in patients with hormone-negative adrenal adenoma and hypertension.

To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.

Common incidental urological lesions on computed tomography images: What to do with renal and adrenal computed tomography incidentalomas in a primary care setting.

The widespread use of cross-sectional imaging has led tothe increased detection of urological incidentalomas. Incidental renal and adrenal masses are the most commonly detected urological incidentalomas and areoften encountered by general practitioners. This review aims to provide an evidence-based approachto managing renal and adrenal masses. Renal lesions occur in 14% of computed tomography (CT) scans. Differentials include cysts (benign or malignant), angiomyolipomas, oncocytomas and renal cell carcinomas (RCCs). The Bosniak classification should be used for cystic renal lesions. Active treatment should be considered for RCCs that are >4 cm, symptomatic or rapidly growing. Patients with adrenal lesions should undergo functional work-up. If clinically concerned, screening tests include 1 mg overnight dexamethasone suppression test and plasma or urinary metanephrines. Inthe presence of hypertension or hypokalaemia, screening for hyperaldosteronism with the plasma aldosterone-to-plasma renin ratio should be considered. Benign adrenal adenomas on CT are <4 cm, homogenous and hypodense (Hounsfield unit <10).

Liver mass masquerading as adrenal space-occupying lesion: A rare presentation

Adrenal pseudotumors have been described in the literature; however, liver mass masquerading as adrenal space occupying lesion is a rare entity. Here, we describe the case of a 40-year-old female who presented with right-sided abdominal pain for 1 year and was provisionally diagnosed as non-functioning adrenal adenoma after evaluation. She was planned for laparoscopic adrenalectomy. On laparoscopy, a mass arising from the liver was found. The procedure was abandoned and a computed tomography-guided tru-cut biopsy of liver mass was done, which showed the feature of benign liver tissue suggestive of hepatic adenoma. Later, she underwent an excision of the liver mass. Adrenal pseudotumor should always be kept in mind during surgery for any suspected adrenal mass.

Clinical, Biochemical, and Radiological Retrospective Analysis in Patients with Adrenal Incidentaloma – A Secondary Publication

Objective: To evaluate the epidemiological, demographic, clinical features, treatment approaches, and survival of patients followed up for adrenal incidentaloma. Methods: Data from 46 patients who were treated and followed up due to adrenal incidentaloma in the Endocrinology Department of Mersin University Health Research and Application Hospital between 2010 and 2014 were retrospectively analyzed. Results: Of the cases included in the study, 13 were male, 33 were female, and the mean age was 54.09 ± 10.7 years. The most common reason for admission was abdominal pain in 34.78% of the patients, the most commonly diagnosed radiological method was dynamic adrenal CT in 60.87%, and the most common location was the left adrenal gland. The mean lesion diameter was between 26.8 ± 16.5 mm. The frequency of hypertension was 50%, obesity 47.8%, type 2 diabetes 21.7%, osteoporosis 42.8%, and metabolic syndrome 41.3%. According to hormonal evaluation results, non-functional adrenal adenoma (NFAA) was found in 82.61%, subclinical Cushing’s syndrome (SCS) in 15.21%, and aldosteronoma in 2.1%. Myelolipoma, pheochromocytoma, and adrenocortical adenoma were diagnosed in 8 cases undergoing adrenalectomy. One patient died due to liver failure. No hormonal activation or growth in lesion size was detected during the follow-up of the patients. Conclusion: Due to the very different pathological and radiological appearances of adrenal incidentaloma, it is important to evaluate demographic, etiological, clinical, laboratory, and radiological data as a whole in the treatment and follow-up.

Diverse presentations of Cushing's syndrome during pregnancy - A case series.

Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

Adrenal Incidentaloma Prevalence and Clinical Management- A Retrospective Study

This study aims to investigate the characteristics and prevalence of adrenal incidentalomas and subsequent clinical practice among patients in Armed Forces Hospital Southern Region -Saudi Arabia, 2021. An observational retrospective study was conducted in Armed Forces Hospital Southern Region -Saudi Arabia on the medical records of 383 consecutive patients. Patients with incidental adrenal tumors who underwent abdominal CT scans with intravenous contrast during the period from January 2013 and December 2021. A total of 300 patients were included in this study. However, the data were analyzed using statistical tests. The results revealed that most patients with adrenal incidentalomas were above 60 (53.3%%). The gender distribution was nearly equal, with 50.3% females and 49.7% males. Most observed tumors were unilateral (96.0%), while a small percentage was bilateral (4.0%). In terms of size, the majority were less than 1 cm (59.0%), followed by sizes greater than 4 cm (31.0%) and 1-4 cm (10.0%). Further analysis indicated that 49.3% were found to have functioning tumors, while 50.7% had non-functioning tumors. The specific types of functioning tumors included non-functioning adrenal adenoma (50.7%), pheochromocytoma (16.9%), Cushing’s syndrome (5.8%), and other functional tumor types (28.0%). Most of these patients were not referred to endocrine clinics. Adrenal incidentalomas are prevalent in the above-60 age group, with most tumors being non-functional. Further research into adrenal incidentalomas associated with diabetes and hypertension is required.

Steroid metabolites producing adenoma: a case report

Hyperandrogenism is the most prevalent cause of menstrual cycle abnormalities and infertility in women. Here, we present a case of a 32-year-old woman with a 7-year history of menstrual irregularity and infertility. Laboratory test results revealed elevated 17-hydroxyprogesterone, progesterone 21-deoxycortisol. Abdominal computed tomography found a 3,9х2,9х2,6 cm left adrenal tumor. Non-classic congenital adrenal hyperplasia was diagnosed initially, however, treatment with supraphysiological doses of dexamethasone proved ineffective and progesterone and 17-hydroxyprogesterone levels remained high. Genetic testing revealed no 21-hydroxylase deficiency. Laparoscopic adrenalectomy was performed with subsequent pathological report being compatible with an adrenal cortical adenoma. 17-hydroxyprogesterone, progesterone 21-deoxycortisol levels returned to the normal range postoperatively and the patient’s menstrual cycle normalized without additional medication. Steroid metabolites producing adenomas are also extremely rare with only a few cases found in patients without previous CAH diagnosis. When a patient with clinically and biochemically diagnosed NCCAH demonstrate no typical features and shows poor response to steroid therapy, the patient should receive multisteroid LC–MS/MS assay for glucocorticoids and androgens, adrenal and ovarian imaging and undergo CYP21A2 gene mutation analysis.

P-07 Unraveling the Mystery-Conn's Syndrome

Abstract Background Conn's syndrome, also known as primary aldosteronism, is a rare disease that can manifest at a young age. Resolving the underlying cause of hypertension is crucial, as seen in this case report. Clinical Case A 17-year-old female patient was admitted with a history of recurrent fever over the past 6 months, bifrontal headaches, palpitations, and myalgia for the past 4 months. Examination revealed resistant hypertension, and laboratory results showed persistent hypokalemia and an elevated aldosterone/renin ratio. CT imaging revealed a left adrenal adenoma. A laparoscopic intervention successfully addressed the uncontrolled hypertension. Histological examination confirmed a diagnosis of a benign adrenal cortical adenoma. Conclusion Post-surgery, the patient's overall condition significantly improved, and blood pressure was effectively controlled. This case report underscores the rare presentation of Conn's syndrome in young individuals and emphasizes the importance of investigating specific underlying causes of hypertension to prevent associated morbidity and mortality.Figure 1.Conns syndrome, CT scan, histology section gross.CECT scan of abdomen and pelvis - left adrenal adenoma gross section - cut section adrenal gland -showing 2 cysts one on medial side 1*1cm and inferiolateral side 1*0.5cm histology of the removed adrenal confirmed diagnosis of benign adrenal cortical adenoma Table 1.Conns syndrome investigations Table 2.Conns syndrome investigations

P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome

Abstract Introduction The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules. Clinical Case A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome. Conclusion In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.

O-03 Adrenalectomy for Cushing's syndrome during pregnancy

Abstract Introduction Cushing's syndrome (CS) is rare in pregnancy because CS itself is a cause of anovulatory infertility due to excess cortisol secretion. Moreover it is also difficult to diagnose CS in pregnancy because placental production of corticotropin releasing and adrenocorticotropic hormone (ACTH), increased maternal production of estrogen induced corticosteroid binding globulin leads to physiological hypercortisolism during pregnancy. So physicians face a clinical overlap in many features of CS such as weight gain, fatigue, edema, hypertension, hyperglycemia, stretch marks, mood changes that can also be attributed to pregnancy. Thus their coexistence represents a diagnostic challenge. Herein we report a case of CS that was diagnosed and successfully treated during pregnancy. Clinical Case A 43-year-old gravida 3 female was consulted at the 21st week of gestation with persistent high blood pressure and hyperglycemia for a month. She had an obstetric history of 2 spontaneous first term abortion, 2 healthy labor 18 years ago and she was healthy after. She was in such a depressive mood that she was consulted with psychiatry many times. On physical examination edema, proximal weakness of lower extremities and hirsutism (modified Ferriman–Gallwey score of 9) was detected. Initial laboratory tests were all within normal range except potassium level (2.7 mmol/L), the results were not consistent with preeclampsia and there was a suspicious adrenal mass detected on ultrasound. She was currently receiving high dose antihypertensive treatment with methyldopa, calcium channel blockers, rapid acting and detemir insulin for diabetes and i.v. potassium replacement. We ruled out conns syndrome with normal plasma aldosterone renin ratio and found catecholamine levels normal. Hormonal analyses revealed with high plasma cortisol levels, increased nocturnal cortisolemia, a suppressed plasma ACTH and dehydroepiandrosterone sulfate level and distinctly elevated 24-hour urinary cortisol greater than 3-fold the upper normal reference range. Non contrast magnetic resonance imaging demonstrated a 47×32 mm left adrenal mass. Laparoscopic adrenalectomy was performed in the 26th week of gestation and the following histopathology revealed an adrenocortical adenoma. Antihypertensive medication was progressively reduced, glycemic control and hypokalemia reversal were achieved. She was followed up with appropriate glucocorticoid replacement. At 34 weeks of gestation, after sudden labor pain and regular uterine contractions a 2586 g male infant with Apgar scores of 8 was born by cesarean section. They were discharged in good health. Conclusion CS should be kept in mind especially in the case of hypertension and diabetes that started before the 20th gestational age. Analysis of the urinary free cortisol level and circadian rhythm of cortisol is necessary to diagnose. Despite the diagnostic challenge we can achieve better maternal and fetal outcomes with proper management.Figure 1.Non-contrast magnetic resonance imaging of the patient Table 1.Patient's laboratuary test results Table 2.Patient's laboratory test results

O-05 A novel mutation of MEN1 gene in familial Multiple Endocrine Neoplasia Type 1 (MEN1): A report of two cases

Abstract Introduction Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare (1-9/100000) autosomal dominant disease. It is characterized by primary hyperparathyroidism (90%), enteropancreatic tumor (60-70%), non-functional adrenal adenomas (30%) and pituitary tumors (10-20%). Herein, we present two cases in the same family with MEN1 syndrome caused by a novel mutation. Clinical Case 1: 49-year-old male presented to our clinic with fasting hypoglycemia. Fasting serum glucose (FSG) was 51 mg/dl and serum cortisol was 18 ug/dl. During the hypoglycemia in prolonged fasting test, the serum levels of glucose, insulin and C-peptide were 37 mg/dl, 17.3 mu/l, 7.75 ng/ml respectively (Table 1). Abdominal MRI revealed mass lesions in the pancreas (Figure 1). Ultrasonography of the neck and MIBI scintigraphy performed because of the high levels of calcium and parathyroid hormone (PTH), were consistent with parathyroid adenoma (Table 2). Pituitary MRI showed a 12 mm macroadenoma. He underwent parathyroidectomy and distal pancreatectomy simultaneously. The resected specimens revealed a well-differentiated neuroendocrine tumor (NET) of the pancreas and parathyroid adenoma. The patient had no new hypoglycemic episodes after surgery and serum calcium remained within the normal range (Table 2). Central hypothyroidism and hypogonadotropic hypogonadism which was resulted from the pressure of the adenoma was managed medically. Genetic testing revealed a heterozygous mutation in NM_001370251.1:c.949del(HET). First degree relatives of the patient were screened for MEN. Clinical Case 2: The son of case 1, an 18-year-old male, presented with fasting hypoglycemia. He had a BMI of 37 kg/m2 and underwent gastric botox 3 months prior to his presentation. FPG was 52 mg/dl and serum cortisol was 20 ug/dl. Prolonged fasting test confirmed the diagnosis of insulinoma (Table 1). Abdominal MRI showed a pancreatic tail mass 37×22 mm in size. Gallium 68 PET/CT DOTATATE revealed increased uptake in multiple lesions in the pancreas. Ultrasonography and MIBI scintigraphy showed a parathyroid adenoma. A nonfunctional microadenoma was detected in pituitary MRI. The patient underwent distal pancreatectomy. Following pancreatectomy, right superior and left inferior parathyroidectomies were performed. Since his serum calcium levels started to increase in 48 hours after the operation, the patient has had second operation for left superior parathyroidectomy. After the operation, the serum calcium and parathyroid hormone levels were 9.2 mg/dl, 58 pg/ml respectively. Specimens revealed well-differentiated NET and atypical parathyroid adenoma. The patient was found to have the same genetic mutation with his father and during the follow up the serum glucose and calcium levels remained within the normal range (Table 2). Conclusion In the genetic examination the heterozygous mutation NM_001370251.1:c.949del(HET) in exon 7/11 of the MEN1 gene found in our patients represents a novel mutation.Figure 1.MRI showing pancreatic masses Table 1.Laboratory findings Table 2.Prolonged fasting test

What We Know about and What Is New in Primary Aldosteronism.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.

Unveiling the Significance of NCAP Family Genes in Adrenocortical Carcinoma and Adenoma Pathogenesis: A Molecular Bioinformatics Exploration.

Adrenocortical carcinoma (ACC), a rare and aggressive adrenal cortex cancer, poses significant challenges due to high mortality, poor prognosis, and early post-surgery recurrence. Variability in survival across ACC stages emphasizes the need to uncover its molecular underpinnings. Adrenocortical adenoma, a benign tumor, adds to diagnostic challenges, highlighting the necessity for molecular insights. The Non-SMC Associated Condensin Complex (NCAP) gene family, recognized for roles in chromosomal structure and cell cycle control. This study focuses on evaluating NCAP gene functions and importance in ACC through gene expression profiling to identify diagnostic and therapeutic targets. Microarray datasets from ACC patients, obtained from the Gene Expression Omnibus database, were normalized to eliminate batch effects. Differential expression analysis of NCAP family genes, facilitated by the GEPIA2 database, included survival and pathological stage evaluations. A Protein-Protein Interaction network was constructed using GeneMANIA, and additional insights were gained through Gene Ontology enrichment analysis, correlation analysis, and ROC curve analysis. ACC samples exhibited elevated levels of NCAPG, NCAPG2, and NCAPH compared to normal and adenoma samples. Increased expression of these genes correlated with poor overall survival, particularly in advanced disease stages. The Protein-Protein Interaction network highlighted interactions with related proteins, and Gene Ontology enrichment analysis demonstrated their involvement in chromosomal structure and control. Differentially expressed NCAP genes showed positive associations, and ROC curve analysis indicated their high discriminatory power in identifying ACC from adenoma and normal samples. The study emphasizes the potential importance of NCAPG, NCAPG2, and NCAPH in ACC, suggesting roles in tumor aggressiveness and diagnostic relevance. These genes could serve as therapeutic targets and markers for ACC, but further exploration into their molecular activities and validation studies is imperative to fully harness their diagnostic and therapeutic potential, advancing precision medicine approaches against this rare but lethal malignancy.