Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia.

Our aim is to update the topic of adrenal tumours (ATs) in congenital adrenal hyperplasia (CAH) based on a multidisciplinary, clinical perspective via an endocrine approach. This narrative review is based on a PubMed search of full-length, English articles between January 2014 and July 2023. We included 52 original papers: 9 studies, 8 case series, and 35 single case reports. Firstly, we introduce a case-based analysis of 59 CAH-ATs cases with four types of enzymatic defects (CYP21A2, CYP17A1, CYP17B1, and HSD3B2). Secondarily, we analysed prevalence studies; their sample size varied from 53 to 26,000 individuals. AT prevalence among CAH was of 13.3-20%. CAH prevalence among individuals with previous imaging diagnosis of AT was of 0.3-3.6%. Overall, this 10-year, sample-based analysis represents one of the most complex studies in the area of CAH-ATs so far. These masses should be taken into consideration. They may reach impressive sizes of up to 30-40 cm, with compressive effects. Adrenalectomy was chosen based on an individual multidisciplinary decision. Many tumours are detected in subjects with a poor disease control, or they represent the first step toward CAH identification. We noted a left lateralization with a less clear pathogenic explanation. The most frequent tumour remains myelolipoma. The risk of adrenocortical carcinoma should not be overlooked. Noting the increasing prevalence of adrenal incidentalomas, CAH testing might be indicated to identify non-classical forms of CAH.

Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd-Chiari-like syndrome.

BACKGROUND: Surgical resection is the treatment of choice for canine adrenal pheochromocytomas (PHEOs). Information on en bloc resection of adrenal PHEO with tumour thrombus, right hepatic division and segmental caudal vena cava (CVC) running through the adrenal tumour and right hepatic division is limited. OBJECTIVE: To describe the preemptively planned en bloc resection of an extensive right adrenal PHEO involving the right hepatic division, the caval thrombus and the segmental CVC in a dog with Budd-Chiari-like syndrome (BCLS). METHODS: A 13-year-old castrated male miniature dachshund was referred for surgical treatment due to anorexia, lethargy and severe abdominal distension caused by abundant ascites. Preoperative computed tomography (CT) revealed a large mass in the right adrenal gland with a large caval thrombus obstructing the CVC and hepatic veins, which caused BCLS. Additionally, collateral vessels were formed between the CVC and azygos veins. No findings suggested obvious metastases. Based on CT findings, an en bloc resection of the adrenal tumour with caval thrombus, right hepatic division and segmental CVC was planned. RESULTS: The preoperatively planned resection was feasible; the tumour was completely resected grossly. The operation time and total Pringle manoeuvre time were 162 min and 16 min 56 s, respectively. There was no postoperative hindlimb oedema, renal dysfunction, ascites or abdominal distention. The patient's clinical signs, including appetite, fully improved. Hospitalization lasted 16 days. However, the patient died on the 130th postoperative day due to suspected metastases and cachexia. CONCLUSIONS: Even in case of an extensive infiltration of adrenal PHEO causing BCLS, an en bloc resection might be successfully achieved based on the preoperative CT findings speculating the collateral vessels formed for caudal venous return.

Surgical findings and outcomes after unilateral adrenalectomy for primary hyperaldosteronism in cats: a multi-institutional retrospective study.

CASE SERIES SUMMARY: Twenty-nine cats from different institutions with confirmed or highly suspected primary hyperaldosteronism treated by unilateral adrenalectomy were retrospectively included in this study. The most frequent clinical signs were lethargy (n = 20; 69%) and neck ventroflexion (n = 17; 59%). Hypokalaemia was present in all cats, creatinine kinase was elevated in 15 and hyperaldosteronism was documented in 24. Hypertension was frequently encountered (n = 24; 89%). Preoperative treatment included potassium supplementation (n = 19; 66%), spironolactone (n = 16; 55%) and amlodipine (n = 11; 38%). There were 13 adrenal masses on the right side, 15 on the left and, in one cat, no side was reported. The median adrenal mass size was 2 × 1.5 cm (range 1-4.6 × 0.4-3.8); vascular invasion was present in five cats, involving the caudal vena cava in four cats and the renal vein in one. Median duration of surgery was 57 mins. One major intraoperative complication (3%) was reported and consisted of haemorrhage during the removal of a neoplastic thrombus from the caudal vena cava. In 4/29 cats (14%), minor postoperative complications occurred and were treated medically. One fatal complication (3%) was observed, likely due to disseminated intravascular coagulation. The median duration of hospitalisation was 4 days; 97% of cats survived to discharge. The potassium level normalised in 24 cats within 3 months of surgery; hypertension resolved in 21/23 cats. Follow-up was available for 25 cats with a median survival of 1082 days. Death in the long-term follow-up was mainly related to worsening of comorbidities. RELEVANCE AND NOVEL INFORMATION: Adrenalectomy appears to be a safe and effective treatment with a high rate of survival and a low rate of major complications. Long-term medical treatment was not required.

Case report: Misdiagnosis of accessory spleen in the left adrenal region as an adrenal tumour after splenectomy.

Background: Adrenal tumours are common in urology and endocrinology, and the diagnosis of adrenal tumours were mainly depends on imaging diagnosis. Howerver, misdiagnosis can still occur for some adrenal space-occupying lesions without specific manifestations or abnormal biochemical indexes. Methods: We report the case of a 55-year-old patient with a soft-tissue mass in the left adrenal region, and have no specific manifestations or abnormalities in biochemical indexes. The patient had undergone open splenectomy 20 years ago for splenic rupture caused by traffic-accident trauma, and had a 10-year special history of hypertension. Because of the uncertain nature of the mass, surgical treatment was recommended. Results: The surgeon managed to remove the left adrenal region mass. During the surgery, the adrenal source was excluded. In the histological examination, the splenic corpuscle and splenic medullary structure were seen under the microscope, and an accessory spleen was diagnosed. Conclusions: The accessory spleen was located in the adrenal region rarely, and can easily be misdiagnosed as an adrenal tumour. When the cases show abnormal adrenal space-occupying lesions in imaging examinations, non-adrenal diseases should be considered. we need to combine different imaging techniques for analysis, and think more about it, avoid misdiagnosis leading to unnecessary surgery.

A Rare Case of Cavernous Haemangioma of the Adrenal Gland: A Case Report and Review of Literature.

Cavernous haemangiomas, also known as cavernoma or cavernous angiomas, are clusters of vasculature malformations arising from the endothelial layer of blood vessels. They are commonly found in the central nervous systems, skin, or liver. Rarely, they can also affect adrenal glands, a phenomenon with only 66 cases since the first case was reported in the literature in 1955 and 2018. Adrenal cavernous haemangiomas are typically non-functioning and found incidentally on radiological imaging. Here, we present the case of a 79-year-old male who was referred by a district general hospital to our tertiary centre with an incidentaloma of the left adrenal gland which was first noted in 2014 measuring 6 cm. A repeat computed tomography in 2020 revealed the mass was 20.8 cm. In 2020, the growing mass was causing anaemia and abdominal discomfort due to displacement of the surrounding viscera. The initial radiological impression performed in another hospital of the indeterminate mass was highly suspicious of primary adrenal malignancy. The decision was made to operate prior to biopsy as biopsy was deemed high risk for dissemination of primary malignancy of the adrenal. The patient subsequently underwent a radical open left adrenalectomy in September 2020. The diagnosis of adrenal cavernous haemangioma was made on histopathological examination post-surgery. Published literature on this rare adrenal tumour between 2019 and 2021 is also reviewed in this paper.

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion.

Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4-10% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20-30% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.

Comparison of the effectiveness and safety of robotic-assisted and laparoscopic in adrenalectomy: A systematic review and meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of robot-assisted adrenalectomy (RA) and laparoscopic adrenalectomy (LA). METHODS: We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines. Five databases, including Medline, PubMed, Cochrane Library, Scopus, and Web of Science, were systematically searched. The search timeframe was set from the creation of the database to December 2021. RESULTS: There were 26 studies including 2985 patients. Our study found that the robotic technique was superior to conventional laparoscopy for estimated blood loss (WMD = -18.25, 95% CI [-27.85, -8.65], P < 0.01), length of stay (WMD = -0.45, 95% CI [-0.57, -0.33], P < 0.01), and conversion to open (OR = 0.31, 95% CI [0.12, 0.78], P = 0.01), while complications and readmissions were comparable. Interestingly, there was no difference in operative time between the two surgical modalities, but subgroup analysis found that the retroperitoneal route robotic technique took longer (WMD = 14.64, 95% CI [0.04, 29.24], P < 0.05), whereas the study of the mixed surgical modality (RA versus LA with mixed transabdominal and retroperitoneal surgical routes) found that the robot required less time (WMD = -12.29, 95% CI [-22.86, -1.72], P < 0.05). For pheochromocytoma, RA was superior to LA in terms of length of stay (WMD = -0.49, 95% CI [-0.83, -0.15], P < 0.01), with no difference in other indicators. CONCLUSION: robotic-assisted adrenalectomy is a superior technique to conventional laparoscopy in managing adrenal tumors, even in the case of a specific adrenal tumor - pheochromocytoma.

ProSAAS peptide of the granin protein family in biochemical diagnostics of pheochromocytoma.

INTRODUCTION: Pheochromocytoma is a hormonally active tumour originating from neuroendocrine cells of the adrenal medulla. Chromogranin A (CgA) and peptide proSAAS belong to the family of granins and are present in neuroendocrine cells of adrenal medulla, from where they are released to circulation, along with catecholamines. The aim of this study was to assess the usability of proSAAS peptide assay in patients with adrenal pheochromocytoma. MATERIAL AND METHODS: 23 patients (13 females and 10 males) with adrenal pheochromocytoma (benign in 18 patients and malignant in 5) confirmed by histopathology examination, and 35 blood donors as a control group. Plasma free metanephrines, CgA, and proSAAS peptide levels were measured in all participants. RESULTS: CgA and proSAAS levels in the group of pheochromocytoma patients vs. the control were: 209 ng/mL and 0.8 ng/mL vs. 59 ng/mL and 0.3 ng/mL (p < 0.001), respectively. The following sensitivity and specificity indexes were obtained from ROC curves for CgA: 83% and 92%, respectively, and for the proSAAS peptide: 39% and 88%, respectively. The combination of 2 parameters: normetanephrine and proSAAS (96% and 100%) had a high diagnostic value, and the value of all determined parameters together (metanephrine, normetanephrine, CgA, and proSAAS) was 100%. CONCLUSION: A single determination of the proSAAS peptide level is associated with a rather low diagnostic value. But collective determination of CgA and proSAAS may be an additional, valuable tool in biochemical diagnostics of pheochromocytoma.

Gynaecomastia in a male neutered cat with an adrenal tumour and associated hyperprogesteronism, hypercortisolism and hyperaldosteronism.

CASE SUMMARY: A 7-year-old male neutered domestic longhair cat was presented with chronic progressive gynaecomastia, polydipsia, polyphagia, weight loss and poor fur regrowth. Sexualised behavioural changes were not reported and virilisation was not present on physical examination. Pertinent haematology, biochemistry and urinalysis findings at the time of referral included mild hypokalaemia. Left adrenomegaly and mild prostatomegaly were identified on a CT scan. Evaluation of adrenal hormones with a low-dose dexamethasone suppression test, serum progesterone, testosterone, oestradiol, plasma aldosterone, renin, plasma metanephrine and normetanephrine measurement supported a diagnosis of hyperprogesteronism, hyperaldosteronism and hypercortisolism. Adrenalectomy was performed and histopathology was consistent with an adrenocortical tumour. Clinical signs and hormone elevations resolved postoperatively. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the second report of gynaecomastia secondary to an adrenal tumour in a male neutered cat and the first associated with hyperprogesteronism.

Ganglioneuroma presenting as an adrenal incidentaloma: Feasibility of adrenal-sparing surgery.

Adrenal ganglioneuromas (GNs) are very rare tumours that originate from neural crest cells. Most of the time, they are diagnosed incidentally as they are usually non-functional and remain asymptomatic. Nowadays, they are being detected more often due to better availability of imaging facilities such as computed tomography (CT)/magnetic resonance imaging (MRI). Minimally invasive adrenalectomy (laparoscopic or robotic) remains the standard of care for such lesions. Hereby, we report a case of a 15-year-old young girl with right adrenal incidentaloma which was diagnosed on CT with the features suggestive of GN. She underwent robot-assisted excision of the mass with adrenal-sparing surgery. Histopathology revealed benign GN and no adjuvant treatment was required. As GN is not known for recurrence or metastasis, minimal invasive adrenal-sparing surgery should be a preferred modality of choice.

Large adrenal tumours mimicking hepatic malignancy: the role of concurrent adrenalectomy and anterior approach hepatectomy.

BACKGROUND: Large right adrenal tumours may invade the liver and mimic primary hepatic malignancy, presenting diagnostic and management challenges. The 'anterior approach hepatectomy' (AAH) using hanging manoeuvre may be safe for resection of such tumours. METHODS: Prospectively maintained database was analysed to identify the large tumours of adreno-hepatic region subjected to hepatectomy. Clinico-biochemical, radiological and surgical details were reviewed. AAH and hanging manoeuvre was adopted for the patients requiring right hepatectomy. RESULTS: Out of the eight patients with adreno-hepatic tumour, four had indeterminate origin of the mass, two had complex cysts, and two were diagnosed as hepatocellular carcinoma on the pre-operative imaging. The median age was 38 years (23-66); male:female ratio was 5:3. AAH was performed in four patients, while others underwent non-anatomical resection of involved segment(s). This accounted for 1.01% of 789 hepatectomies performed during the study period. The median intra-operative blood loss was 525 mL (150-2200 mL) and the median tumour size was 9 cm (6-17 cm). All patients underwent R0 resection. The final histopathological diagnoses were: three phaeochromocytomas (two malignant and one benign), two adrenocortical carcinomas, one malignant paraganglionomas and two adrenal cysts. Major complication (grade IVa) was experienced in one patient. On median follow-up of 67.5 months (7-84), all were alive and one patient had tumour recurrence. CONCLUSION: Adrenal tumours mimicking primary hepatic malignancy are rare but pose diagnostic challenges. The AAH is a safe approach with acceptable R0 resection, blood loss, surgical complications and overall outcome for the patients requiring right hepatectomy.

H19 in Endocrine System Tumours.

Long non-coding RNAs (lncRNAs) are over 200 nucleotides long recently discovered RNA molecules that are not involved in the translation process. Accumulating evidence shows that H19 lncRNA is an important regulator of gene expression and its altered expression contributes to carcinogenesis. The aim of this review was to reveal current knowledge about H19 lncRNA and its impact on tumours of the endocrine system. We present findings about H19 altered regulation and its association with tumorigenesis, cancer progression and differentiation, and its potential use in diagnostics, prognostics and therapy. The mechanism and molecular pathways involved in these processes are discussed.

Laparoscopic adrenalectomy for giant adrenal tumours: Technical considerations and surgical outcome.

BACKGROUND: Giant adrenal tumours are tumours with size ≥6 cm. These are rare cancer associated with malignancy in 25% of cases. PATIENTS AND METHODS: A retrospective review was conducted on the medical records of patients admitted to our high-volume centre of Careggi University Hospital with a giant adrenal tumour and submitted to adrenalectomy between January 2008 and December 2018. The group of patients who underwent to laparoscopic adrenalectomy was compared with a group of patients that was submitted to open adrenalectomy. RESULTS: In the past 10 years, we performed about 245 adrenalectomies for benign and malignant adrenal tumours. Fifty (20.4%) of these were giant tumours. The medium size was 9.9 cm (7-22 cm). The mean age was 57 years (21-81 years). Thirty-four (68%) of these cancers were laparoscopically removed and 16 (32%) with an open approach. The surgical outcomes in these patients were optimal if compared to the group of patients submitted to open approach in terms of good pain control, hospital stay, mean operative time and bloodless. No difference was observed about post-operative complications in the two groups. The follow-up after 30 months for malignant tumours did not show local recurrences. CONCLUSION: Our results pinpoint the advantages of performing a laparoscopic adrenalectomy for giant adrenal tumours. The tumour size is only a predictive parameter of possible malignancy, and the laparoscopic approach is a safe and feasible method in terms of surgical and oncological, only if performed by expert surgeons and in high-volume centres.

Association of urinary free cortisol with bone formation in patients with mild autonomous cortisol secretion.

CONTEXT: Mild autonomous cortisol secretion (ACS) is associated with an increased risk of vertebral fractures (VFx). However, the influence of this condition on bone turnover or its association with mild ACS is still controversial. OBJECTIVE: This study aimed to evaluate the impact of mild ACS on bone quality among patients living with the disease. DESIGN AND SETTING: A retrospective study was conducted using data from 55 mild ACS and 12 nonfunctioning adrenal tumour (NFT) patients who visited Chiba University Hospital, Japan, from 2006 to 2018. PATIENTS AND MAIN OUTCOME MEASURES: We analysed clinical features and bone-related factors, including bone mineral density (BMD) and VFx, performed blood tests to assess bone metabolism markers in patients with mild ACS and NFT, and assessed the associations between bone-related markers and endocrinological parameters in patients with mild ACS. RESULTS: No significant differences between mild ACS and NFT patients were observed with respect to the presence or absence of VFx and BMD. Urinary free cortisol (UFC) was higher in mild ACS patients with VFx than those without (p = .037). The T-score and young adult mean (YAM) of the BMD of the femoral neck in mild ACS patients with a body mass index <25 were positively correlated with dehydroepiandrosterone sulphate levels (ρ: 0.42, p = .017; ρ: 0.40, p = .024, respectively). Pearson's correlation analysis showed that bone-specific alkaline phosphatase was negatively correlated with UFC in the patients with mild ACS (ρ: -0.37, p = .026). CONCLUSIONS: These results suggest that urinary free cortisol may be useful for predicting bone formation in mild ACS patients.

Excision of a huge adrenal pheochromocytoma resembling a pancreatic tumor: A case report.

INTRODUCTION: Pheochromocytoma is a rare disease. Adrenal gland tumors make intraoperative blood pressure control difficult. If the tumor is large, it may need to be differentiated from pancreatic tumors and may require combined resection of other organs. PRESENTATION OF CASE: A 73-year-old Japanese woman presented to our hospital with abdominal pain. Computed tomography revealed a left abdominal tumor of 15 cm diameter. Magnetic resonance imaging, abdominal ultrasonography, and fractionated catecholamine test results led to strong suspicions of pheochromocytoma. A surgery was performed to remove the large tumor while controlling the blood pressure in the perioperative period and preparing for the possibility of combined resection of other organs. DISCUSSION: Left adrenal tumors can be difficult to differentiate from pancreatic tumors if the lesion is large. Pheochromocytoma is a catecholamine-producing tumor, and surgery to remove the tumor can be risky if the blood pressure is not controlled in the perioperative period. CONCLUSION: Careful preparations must be made to resect a giant pheochromocytoma. Adrenal tumors should always be considered as a differential diagnosis for any lesion suspected of being a large pancreatic body tail tumor.

Is robot-assisted retroperitoneal adrenalectomy safe? An investigation of perioperative hypertensive crisis among hypertensive and normotensive patients.

BACKGROUND: Objective: We examined the incidence of perioperative hypertensive crisis in robot-assisted retroperitoneal laparoscopic adrenalectomy. METHODS: A consecutive series of 120 patients with adrenal tumours undergoing robot-assisted retroperitoneal laparoscopic adrenalectomy were included. Patients were divided into two groups: group A (hypertension group, 58 cases, mean age 43.59 years) and group B (normotension group, 62 cases, mean age 48.01 years). General anaesthesia was applied using endotracheal intubation and haemodynamic changes were closely monitored. RESULTS: A total of nine (7.5%) hypertensive crisis cases were observed. After intravenous infusion of sodium nitroprusside, seven cases of them were quickly controlled and two cases experienced transient severe hypertension. The incidence of hypertensive crisis was 13.7% and 1.6% in groups A and B, respectively (p < 0.05). CONCLUSION: These findings highlight the importance of strengthening the monitoring of anaesthesia and taking various measures to effectively control the blood pressure in robot-assisted retroperitoneal laparoscopic adrenalectomy, especially among hypertensive patients.

Biochemical and clinical characteristics of patients with primary aldosteronism: Single centre experience.

BACKGROUND: Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. METHODS: Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). RESULTS: Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. CONCLUSIONS: Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity.

Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour.

It is widely believed that adrenal tumours and ovarian luteomas in pregnant women cause virilisation of female foetuses through overproduction of testosterone and/or androstenedione. However, this notion raises a fundamental question as to how these classic androgens pass through the placenta without being converted by aromatase into oestrogens. Here, we report a case of maternal adrenal tumour, in which overproduction of 11-oxygenated C19 steroids (11ox C19s), newly characterised non-aromatisable androgens in humans, caused foetal virilisation. The female proband presented with severely virilised external genitalia at birth. The mother exhibited hirsutism, hyperglycaemia and hypertension and was diagnosed as having adrenal tumour. The mother was subjected to comprehensive steroid measurement. Serum levels of 11ox C19s were markedly elevated. In contrast, testosterone and androstenedione levels remained within the normal range, and levels of most other steroids in the conventional and backdoor androgenic pathways were normal or only mildly elevated. After tumour removal, levels of 11ox C19s were markedly reduced. These results provide the first evidence that 11ox C19s can be synthesised in adrenal adenomas and, due to their non-aromatisable nature, can pass through the placental barrier to cause foetal virilisation. These findings highlight a unique pathogenic property of these newly specified androgens in humans.

Bilateral pheochromocytoma: Clinical characteristics, treatment and longitudinal follow-up.

OBJECTIVE: Comprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma. DESIGN: A retrospective study at a tertiary care centre. PATIENTS: All patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015. MEASUREMENTS: Tumour size, genetic testing, plasma/urine metanephrines and catecholamines. RESULTS: A total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4-70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1-38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical-sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow-up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy. CONCLUSIONS: Bilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.

Clinical course of adrenal myelolipoma: A long-term longitudinal follow-up study.

OBJECTIVE: We aimed to describe clinical course of myelolipoma and to identify predictors of tumour growth and need for surgery. DESIGN: A retrospective study. PATIENTS: Consecutive patients with myelolipoma. RESULTS: A total of 321 myelolipomas (median size, 2.3 cm) were diagnosed in 305 patients at median age of 63 years (range, 25-87). Median follow-up was 54 months. Most myelolipomas were incidentally detected (86%), whereas 9% were discovered during cancer staging and 5% during workup of mass effect symptoms. Thirty-seven (12%) patients underwent adrenalectomy. Compared to myelolipomas <6 cm, tumours ≥6 cm were more likely to be bilateral (21% vs 3%, P < .0001), cause mass effect symptoms (32% vs 0%, P < .0001), have haemorrhagic changes (14% vs 1%, P < .0001) and undergo adrenalectomy (52% vs 5%, P < .0001). Among patients with ≥6 months of imaging follow-up, median size change was 0 mm (-10, 115) and median growth rate was 0 mm/y (-6, 14). Compared to <1 cm growth, ≥1 cm growth correlated with larger initial size (3.6 vs 2.3 cm, P = .02), haemorrhagic changes (12% vs 2%, P = .007) and adrenalectomy (35% vs 8%, P < .0001). CONCLUSIONS: Most myelolipomas are incidentally discovered on cross-sectional imaging. Myelolipomas ≥6 are more likely to cause mass effect symptoms, have haemorrhagic changes and undergo resection. Tumour growth ≥1 cm is associated with larger myelolipoma and haemorrhagic changes. Adrenalectomy should be considered in symptomatic patients with large tumours and when there is evidence of haemorrhage or tumour growth.