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Canine adrenal gland volume can be predicted based on body weight and computed tomography (CT) measurements using a validated algorithm. Use of this algorithm to detect adrenal pathology, including hyperplasia, hypoplasia and neoplasia, in clinical cases has not been described. The objective of this study was to illustrate application of the algorithm by estimating subject-specific adrenal gland volume in a historical cohort of dogs with known adrenal disease. Forty-six dogs that underwent CT and subsequent adrenalectomy were included. Clinical records and CT images from dogs that underwent adrenalectomy and histologic examination of the excised adrenal gland(s) were reviewed. Normal adrenal gland volumes for each dog were estimated using the algorithm, and compared with measured volumes of the affected glands. Linear measurement of the largest lesion diameter was also recorded. Fifty-eight adrenal glands were removed from 46 dogs, with pathology confirmed in all glands. Pathology included 28 adenomas, 13 carcinomas, 11 pheochromocytomas and 6 other benign pathologies. The volume of all removed adrenal glands was measured to be larger than the expected normal volume estimated by the algorithm, ranging from 1.1 to 212.9 times larger than estimated. Adrenal glands with malignant and benign pathology showed variable volumes with overlapping ranges recorded. Assessment of the dimensions of any focal lesion against a cut-off of 20 mm failed to discriminate malignancy. This study illustrates and supports the application of a validated volumetric algorithm for estimation of subject-specific adrenal gland volume to identify the presence of pathology and as a tool to assist clinical decision-making., (© 2024 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Background: Adrenal cysts are rare and appropriate management is unclear due to a lack of data on their natural history. Understanding adrenal cyst growth patterns would assist in clinical management., Methods: This single-institution study included all adult patients diagnosed with simple adrenal cysts between 2004 and 2021. Baseline characteristics and outcomes of those who underwent resection (ADX) or observation (OBS) were compared using the chi-squared test, student's t-test, and Wilcoxon rank-sum test. Growth curves and sensitivity analysis were plotted for all patients who had follow-up imaging., Results: We identified 77 patients with imaging-confirmed adrenal cysts. The majority were female (75.3%) and more than half were white (55.8%). One-third of patients underwent ADX, and the remaining were observed. ADX patients were younger (median age [IQR]: 55.5 y [45.0-68.2 y] vs. 44.2 y [38.7-55.0 y], p = 0.01) and more likely to be Hispanic (12% vs. 0%, p = 0.05). ADX patients presented with larger cysts (5.6 vs. 2.6 cm, p = 0.002). The median time from diagnosis to last follow-up was 1.1 y for ADX and 4.1 y for OBS. Average growth for OBS was 0.3 cm/y, while average growth for ADX was 3.9 cm/y. In ADX patients, cysts >10 cm grew significantly faster than cysts <10 cm (median growth rate 13.2 cm/y vs. 0.3 cm/y, p < 0.05). There was no adrenal malignancy diagnosis, hyperfunctionality, or observation-related complications (e.g., rupture)., Conclusion: While size >4-6 cm has guided surgical referral for solid adrenal masses, this study demonstrates a size threshold of 10 cm, below which asymptomatic, simple adrenal cysts can safely be observed., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Bilateral adrenal masses, increasingly encountered in clinical practice, manifest across diverse contexts, including incidental discovery, malignancy staging, and targeted imaging after hormonal diagnosis of adrenal disorders. The spectrum encompasses various pathologies, such as cortical adenomas, macronodular adrenal disease, pheochromocytomas, myelolipomas, infiltrative disorders, and primary and secondary malignancies. Notably, not all masses in both adrenal glands necessarily share the same etiology, often exhibiting diverse causes. Recently, the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors updated guidelines, introduced a 4-option schema based on imaging, aiding in targeted hormonal testing and management. This "Approach to the Patient" review delves into the latest advancements in imaging, biochemical, and genetic approaches for the diagnostic and management nuances of bilateral adrenal masses. It provides insights and a contemporary framework for navigating the complexities associated with this clinical entity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39 °C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease)., (© 2024. The Author(s).)

Adrenal cysts are rare lesions representing approximately 1-2% of adrenal incidentalomas. The majority of these rare lesions are benign. Rarely, phaeochromocytomas and adrenal malignant masses can present as cystic lesions and can occasionally be difficult to distinguish from benign cysts. Histologically, adrenal cysts are subdivided into pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. The radiological appearance of an adrenal cyst is generally similar to that of cysts in the kidney. They are thus well demarcated, usually rounded, with a thin wall and homogenous internal structure, low attenuating (<20 Hounsfield Units) on CT, low signalling on T1-weighted MRI sequences and high signalling on T2-weighted MRI sequences, and anechoic or hypoechoic on ultrasonography. Benign adrenal cysts have a slight female predominance and are usually diagnosed between the ages of 40 and 60. Most adrenal cysts are asymptomatic and are detected incidentally, although very large adrenal cysts can lead to mass effect symptoms, with surgery required to alleviate the symptoms. Thus, conservative management is usually recommended for asymptomatic cysts. However, when uncertainty exists regarding the benign nature of the cyst, additional work-up or follow-up is needed. The management of an adrenal cyst should preferably be discussed at an adrenal multidisciplinary team meeting., (© 2023. Springer Nature Limited.)

The adrenal is a small, anatomically unimposing structure that escaped scientific notice until 1564 and whose existence was doubted by many until the 18th century. Adrenal functions were inferred from the adrenal insufficiency syndrome described by Addison and from the obesity and virilization that accompanied many adrenal malignancies, but early physiologists sometimes confused the roles of the cortex and medulla. Medullary epinephrine was the first hormone to be isolated (in 1901), and numerous cortical steroids were isolated between 1930 and 1949. The treatment of arthritis, Addison's disease, and congenital adrenal hyperplasia (CAH) with cortisone in the 1950s revolutionized clinical endocrinology and steroid research. Cases of CAH had been reported in the 19th century, but a defect in 21-hydroxylation in CAH was not identified until 1957. Other forms of CAH, including deficiencies of 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 17α-hydroxylase were defined hormonally in the 1960s. Cytochrome P450 enzymes were described in 1962-1964, and steroid 21-hydroxylation was the first biosynthetic activity associated with a P450. Understanding of the genetic and biochemical bases of these disorders advanced rapidly from 1984 to 2004. The cloning of genes for steroidogenic enzymes and related factors revealed many mutations causing known diseases and facilitated the discovery of new disorders. Genetics and cell biology have replaced steroid chemistry as the key disciplines for understanding and teaching steroidogenesis and its disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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Context: The use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in the treatment of melanoma, renal carcinoma and non-small cell lung cancer; however, it is associated with frequent immune-related adverse events (irAE). Ipilimumab-induced hypophysitis (IIH) is a well-recognised and not infrequent endocrine irAE., Objective: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma., Design: Aretrospective review of hormone levels in consecutive adult patients treated with ipilimumab (3 mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor., Results: Of 189 patients, 24 (13%; 13 males; 60.5 ± 12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At the presentation of IIH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/L (≤3 μg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free thyroxine (fT4) levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with the recovery of thyroid hormone levels by 12 weeks after the presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH., Conclusion: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/L at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

Adrenal masses are frequently incidentally identified from cross-sectional imaging studies, which are performed for other reasons. The intensity of the approach to the patient with such a mass is tailored to the clinical situation, ranging from a quick evaluation to a detailed work-up. In all cases, the three components of the evaluation are clinical assessment, review of the images, and biochemical testing with the goal of ruling out malignancy and identifying hormonally active lesions. This article incorporates recent information to produce a logical, systematic assessment of these patients with risk stratification and proportionate follow-up., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Primary aldosteronism (PA) is the most common form of secondary and curable hypertension. Different germline and somatic mutations are found in aldosterone-producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with APA; however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH. The objective of this study was to analyze clinical data of patients with APA without biochemical success after adrenalectomy as well as the histological and genetic characteristics of their adrenal glands., Design and Methods: Clinical data of 12 patients with partial and absent biochemical cure were compared to those from 39 PA patients with hormonal cure after surgery. Histological, morphological, and genetic characterization of the adrenals was carried out by CYP11B2 and CYP11B1 immunostaining and by CYP11B2-guided NGS., Results: Patients with absent hormonal cure displayed a longer duration of arterial hypertension and lower lateralization index of aldosterone production. In ten patients, APAs expressing CYP11B2 were identified. No difference in histological and morphological characteristics was observed between patients with or without a hormonal cure. Somatic mutations in APA driver genes were identified in all CYP11B2 positive APAs; CACNA1D mutations were the most frequent genetic abnormality., Conclusions: Patients with partial and absent biochemical cure were diagnosed later and exhibited a lower lateralization index of aldosterone production, suggesting asymmetric aldosterone production in the context of BAH. Somatic mutations in adrenal glands from those patients indicate common mechanisms underlying BAH and APA.

Resident progenitor and/or stem cell populations in the adult adrenal cortex enable cortical cells to undergo homeostatic renewal and regeneration after injury. Renewal occurs predominantly in the outer layers of the adrenal gland but newly formed cells undergo centripetal migration, differentiation and lineage conversion in the process of forming the different functional steroidogenic zones. Over the past 10 years, advances in the genetic characterization of adrenal diseases and studies of mouse models with altered adrenal phenotypes have helped to elucidate the molecular pathways that regulate adrenal tissue renewal, several of which are fine-tuned via complex paracrine and endocrine influences. Moreover, the adrenal gland is a sexually dimorphic organ, and testicular androgens have inhibitory effects on cell proliferation and progenitor cell recruitment in the adrenal cortex. This Review integrates these advances, including the emerging role of sex hormones, into existing knowledge on adrenocortical cell renewal. An in-depth understanding of these mechanisms is expected to contribute to the development of novel therapies for severe endocrine diseases, for which current treatments are unsatisfactory.

Competing Interests: Declaration of interests We declare no competing interests.

Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.

Adrenal insufficiency, the inability to produce adequate levels of corticosteroids, is a multi-causal disease that requires lifelong daily hormone replacement. Nevertheless, this cannot replace the physiological demand for steroids which are secreted following a circadian rhythm and vary in periods of stress; the consequences of under- or over-replacement include adrenal crisis and metabolic disturbances, respectively. Although clinical research has focused on enhancing the effectiveness/reducing side effects of current treatment modalities, only small improvements are deemed possible; thus, alternative solutions are urgently needed. Gene and cell therapy strategies have opened new possibilities for the cure of many diseases in a way that has never been possible before and could offer a viable option for the cure of adrenal diseases. The current state of cell- and gene-based approaches to restore adrenocortical function is discussed in this review., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Wnt signaling pathway is a critical mediator of the development and maintenance of several tissues. The adrenal cortex is highly dependent upon Wnt/β-catenin signaling for proper zonation and endocrine function. Adrenocortical cells emerge in the peripheral capsule and subcapsular cortex of the gland as progenitor cells that centripetally differentiate into steroid hormone-producing cells of three functionally distinct concentric zones that respond robustly to various endocrine stimuli. Wnt/β-catenin signaling mediates adrenocortical progenitor cell fate and tissue renewal to maintain the gland throughout life. Aberrant Wnt/β-catenin signaling contributes to various adrenal disorders of steroid production and growth that range from hypofunction and hypoplasia to hyperfunction, hyperplasia, benign adrenocortical adenomas, and malignant adrenocortical carcinomas. Great strides have been made in defining the molecular underpinnings of adrenocortical homeostasis and disease, including the interplay between the capsule and cortex, critical components involved in maintaining the adrenocortical Wnt/β-catenin signaling gradient, and new targets in adrenal cancer. This review seeks to examine these and other recent advancements in understanding adrenocortical Wnt/β-catenin signaling and how this knowledge can inform therapeutic options for adrenal disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report a case of adrenal extramedullary haematopoiesis in a 24-year-old women who presented with pallor and weakness. Ultrasonography of the abdomen detected moderate hepatosplenomegaly with multiple lesions in the spleen and an incidental right adrenal mass. There was no ascites or lymphadenopathy. CT scan revealed a heterogeneous right adrenal mass with multiple non-enhancing lesions in the spleen. Ultrasound guided trucut biopsy was performed after excluding a functioning tumour, which confirmed the diagnosis. Later, she was diagnosed to have haemoglobin E/beta thalassaemia and was put on hydroxyurea trial., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences such as acute adrenal insufficiency. Early adrenal axis testing, as well as directed imaging, is crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy and thromboembolic events., Case Description: A 66-year-old woman presented with acute COVID-19 infection and primary adrenal insufficiency due to bilateral adrenal hemorrhage (BAH). She also had a renal vein thrombosis. Her past medical history revealed primary antiphospholipid syndrome (APLS). Four weeks after discharge she had no signs of COVID-19 infection and her polymerase chain reaction test for COVID-19 was negative, but she still needed glucocorticoid and mineralocorticoid replacement therapy. The combination of APLS and COVID-19 was probably responsible of the adrenal event as a "two-hit" mechanism., Conclusions: COVID-19 infection is associated with coagulopathy and thromboembolic events, including BAH. Adrenal insufficiency is life threatening; therefore, we suggest that early adrenal axis testing for COVID-19 patients with clinical suspicion of adrenal insufficiency should be carried out., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adrenal pseudocysts are rare, nonfunctional, asymptomatic cystic masses that originate from the adrenal gland and are usually located in the suprarenal area. They are usually incidentally discovered during imaging, but diagnosis can be challenging because they are similar to benign and malignant cystic lesions of the adrenal gland and adjacent organs. We describe a giant, adrenal hemorrhagic pseudocyst that was atypically located, extending from the middle to the lower poles of the kidney, admixed with a renal cortical cyst.

Hemorrhage of the adrenal glands in the neonatal period happens secondarily to birth trauma and to changes in venous pressure. Neonatal jaundice has as an infrequent etiology the presence of an adrenal gland hematoma. Symptomatic cases are rare, and if they manifest, it is usually as prolonged jaundice. We present the case of a neonate who was admitted at 20 hours of life due to isoimmune jaundice. Due to an increase in conjugatedbi]irubin, an abdominal ultrasound was requested at 10 days of life, which showed a non-vascularized right adrenal mass, 50 x 21 mm, with cystic images inside, compatible with bleeding of the right adrenal gland. Serial ultrasound showed a progressive resolution until its disappearance, keeping the baby asymptomatic and withoutj aundice. In cases of prolonged jaundice in the neonatal period, the possibility of significant adrenal hemorrhage must be assessed., Competing Interests: None, (Sociedad Argentina de Pediatría.)

The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high- (as in Cushing's syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.

Cardiomyopathies are myocardial disorders in which heart muscle is structurally and/or functionally abnormal. Previously, structural cardiomyocyte disorders due to adrenal diseases, such as hyperaldosteronism, hypercortisolism, and hypercatecholaminism, were misunderstood, and endomyocardial biopsy (EMB) was not performed because was considered dangerous and too invasive. Recent data confirm that, if performed in experienced centers, EMB is a safe technique and gives precious information about physiopathological processes implied in clinical abnormalities in patients with different systemic disturbances. In this review, we illustrate the most important features in patients affected by primary aldosteronism (PA), Cushing's syndrome (CS), and pheochromocytoma (PHEO). Then, we critically describe microscopic and ultrastructural aspects that have emerged from the newest EMB studies. In PA, the autonomous hypersecretion of aldosterone induces the alteration of ion and water homeostasis, intracellular vacuolization, and swelling; interstitial oedema could be a peculiar feature of myocardial toxicity. In CS, cardiomyocyte hypertrophy and myofibrillolysis could be related to higher expression of atrogin-1. Finally, in PHEO, the hypercontraction of myofilaments with the formation of contraction bands and occasional cellular necrosis has been observed. We expect to clear the role of EMB in patients with cardiomyopathies and adrenal disease, and we believe EMB is a valid tool to implement new management and therapies.

The adrenal gland may exhibit a wide variety of pathologic conditions. A number of imaging techniques can be used to characterize these, although it is not always possible to attain a definitive diagnosis radiologically. Incorrect diagnoses may be made if radiologists are not attentive to technical parameters and interpretive factors associated with adrenal gland imaging. Hence, an appreciation of the intricacies of adrenal imaging strategies and characterization is required; this can be aided by understanding the pitfalls of adrenal imaging. Technical pitfalls at CT may relate to the imaging parameters, including region of interest characteristics, tube voltage selection, and the timing of contrast material-enhanced imaging. With MRI, imaging acquisition technique and evaluation of the reference tissues used in chemical shift MRI are important considerations that can directly influence image interpretation. Interpretive errors may occur when evaluating adrenal washout at CT without considering other radiologic features, including the size of adrenal nodules, the presence of fat or calcification, the attenuation of nodules, and atypical imaging features. The characterization of an incidental adrenal lesion as benign or malignant does not end the role of the radiologist; consideration as to whether an adrenal lesion is associated with endocrine dysfunction is required. While imaging may not be optimal for establishing endocrine activity, there are imaging features from which radiologists may infer function. In cases of known endocrine activity, imaging can guide clinical management, including further investigations such as venous sampling. © RSNA, 2020.

Adrenal pseudocysts are rare entities in clinical practice and many are picked up incidentally. 1 The incidence of congenital anomaly of inferior vena cava is estimated to range from 0.2% to 3.0% in the general population. 2 We report an exceptional case of a giant right-sided adrenal pseudocyst with inferior vena cava duplication to illustrate the clinical and histopathological features of this entity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Mass-like lesions are an uncommon presentation of cytomegalovirus (CMV) disease., Case: We report on a case of disseminated CMV disease with bilateral adrenal pseudotumors in a patient with a history of acute leukemia in remission., Conclusion: In the settings of advanced cancer therapy and organ transplantation, a high index of suspicion for CMV should be maintained for mass-like disease.

Adrenal hyperplasia is non-malignant enlargement of the adrenal glands, which is often bilateral. It can be incidental or related to indolent disease process and may be related to benign or malignant etiologies causing biochemical alterations in the hypothalamic-pituitary-adrenal axis which controls steroidogenesis and in particular cortisol production. Clinical significance of the adrenal hyperplasia is variable ranging from asymptomatic finding to serious manifestations of Cushing syndrome. This is often associated with anatomical changes in the adrenal glands, which typically manifests as diffuse and sometimes nodular enlargement of the adrenal glands radiologically. Approaching adrenal hyperplasia requires careful clinical and biochemical evaluation in correlation with imaging review to differentiate ACTH-dependent and ACTH-independent etiologies. CT is the primary modality of choice for adult adrenal imaging owing to reproducibility, temporal and spatial resolution and broader access, while MRI often serves a complimentary role. Ultrasound and MRI are most commonly used in pediatric cases to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation and imaging features of different types and mimics of adrenal cortical hyperplasia.

Background/objective: This study aims to evaluate the current surgical approach to adrenal masses in the pediatric age group., Methods: We retrospectively analyzed cases that underwent surgery for adrenal masses between 2007 and 2017. Patients were assessed regarding age, sex, primary diagnosis, image defined risk factors (IDRF), surgical treatment method, complications, duration of hospital stay, and follow-up., Results: We examined 50 patients who underwent surgery for adrenal mass (mean age: 4.8 years; range: 5 days-14 years). For IDRF assessment, Ultrasonography was used in 42, Computed Tomography in 36, and Magnetic Resonance Imaging in 36 patients. Lesions were present on the right in 25, left in 21, and bilateral in 4 patients. Histopathological findings were neuroblastoma (n = 29), ganglioneuroma (n = 6), adrenal cortex tumor (n = 5), ganglioneuroblastoma (n = 4), pheochromocytoma (n = 3), cyst (n = 1), and adrenal hematoma (n = 2). Laparotomy was performed on 37 patients, and laparoscopy on 13 patients. None of the cases had any operative complications., Conclusion: The crucial factors determining the surgical approach to adrenal masses in pediatric cases are the histopathology of the mass, volume, and IDRF. Minimally invasive procedures could be reliably performed in appropriate cases., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Adrenal gland infarction resulting from adrenal vein thrombosis is an infrequently recognised entity with a limited differential diagnosis. When bilateral, it can result in acute life-threatening adrenal failure. Heparin-induced thrombocytopenia (HIT) is an antibody-mediated, prothrombotic state that represents an important cause of adrenal vein thrombosis leading to associated infarction. Sometimes, the clinical picture of HIT-including the presence of HIT antibodies-occurs despite absence of proximate heparin exposure ('spontaneous HIT syndrome'). We report a case of nearly missed adrenal failure secondary to bilateral adrenal infarction that evolved during the second week following knee arthroplasty (a known trigger of spontaneous HIT syndrome). The combination of bilateral adrenal infarction, thrombocytopenia and presence of platelet-activating HIT antibodies not explainable by preceding heparin exposure led to a diagnosis of postknee arthroplasty spontaneous HIT syndrome. The case also highlights the clinical and laboratory findings associated with rapidly progressive acute adrenal failure., Competing Interests: Competing interests: TEW has received lecture honoraria from Instrumentation Laboratory and royalties from Informa (Taylor & Francis); has provided consulting services to Aspen Global, Bayer, Octapharma and WL Gore; has received research funding from Instrumentation Laboratory and WL Gore; and has provided expert witness testimony relating to HIT and non-HIT thrombocytopenic and coagulopathic disorders. The other authors report no competing interests., (© BMJ Publishing Group Limited 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bilateral adrenal hemorrhage (BAH) is a rare but potentially catastrophic condition. Its clinical manifestation is often non-specific and sometimes difficult to be diagnosed in time. A 57-year-old woman, who presented with severe fatigue, nausea and vomiting after left hip arthroplasty due to her femoral neck fracture in a local hospital, was transferred to our medical center. Laboratory results revealed significant hyponatremia, low serum cortisol and elevated serum ACTH. Computed tomography (CT) showed a bilateral adrenal mass, measured 3.6 × 2.7 cm on the left and 3.4 × 2.3 cm on the right. Further magnetic resonance imaging (MRI) confirmed the diagnosis of BAH. The patient was prescribed with oral prednisolone acetate, 5 mg, tid, and her condition improved gradually. Nine months after, the patient was in good condition with 5 mg prednisolone acetate per day. CT revealed a clearly shrunken adrenal mass compared with 9 months ago., Conclusions: This case illustrates the difficulty in making the diagnosis of BAH with atypical presentation. Such cases necessitate greater alertness on the part of the clinician and require rapid diagnosis and prompt glucocorticoid replacement for better clinical outcomes.

Chromaffin cells (CCs) of the adrenal gland and the sympathetic nervous system produce the catecholamines (epinephrine and norepinephrine; EPI and NE) needed to coordinate the bodily "fight-or-flight" response to fear, stress, exercise, or conflict. EPI and NE release from CCs is regulated both neurogenically by splanchnic nerve fibers and nonneurogenically by hormones (histamine, corticosteroids, angiotensin, and others) and paracrine messengers [EPI, NE, adenosine triphosphate, opioids, γ-aminobutyric acid (GABA), etc.]. The "stimulus-secretion" coupling of CCs is a Ca 2+ -dependent process regulated by Ca 2+ entry through voltage-gated Ca 2+ channels, Ca 2+ pumps, and exchangers and intracellular organelles (RE and mitochondria) and diffusible buffers that provide both Ca 2+ -homeostasis and Ca 2+ -signaling that ultimately trigger exocytosis. CCs also express Na + and K + channels and ionotropic (nAChR and GABA A ) and metabotropic receptors (mACh, PACAP, β-AR, 5-HT, histamine, angiotensin, and others) that make CCs excitable and responsive to autocrine and paracrine stimuli. To maintain high rates of E/NE secretion during stressful conditions, CCs possess a large number of secretory chromaffin granules (CGs) and members of the soluble NSF-attachment receptor complex protein family that allow docking, fusion, and exocytosis of CGs at the cell membrane, and their recycling. This article attempts to provide an updated account of well-established features of the molecular processes regulating CC function, and a survey of the as-yet-unsolved but important questions relating to CC function and dysfunction that have been the subject of intense research over the past 15 years. Examples of CCs as a model system to understand the molecular mechanisms associated with neurodegenerative diseases are also provided. Published 2019. Compr Physiol 9:1443-1502, 2019., (Copyright © 2019 American Physiological Society. All rights reserved.)

Evolution has resulted in profound differences between males and females that extend to non-reproductive organs and are reflected in the susceptibility and progression of diseases. However, the cellular and molecular basis for these differences remains largely unknown. Here we report that adrenal gland tissue renewal is highly active and sexually dimorphic, with female mice showing a 3-fold higher turnover than males. Moreover, in males, homeostasis relies on proliferation of cells within the steroidogenic zone, but females employ an additional stem and/or progenitor compartment situated in the adrenal capsule. Using lineage tracing, sex reversal models, gonadectomy, and dihydrotestosterone treatments, we further show that sex-specific stem cell activity is driven by male hormones that repress recruitment of Gli1 + stem cells from the capsule and cell proliferation. Taken together, our findings provide a molecular and cellular basis for adrenal sex dimorphism that may contribute to the increased incidence of adrenal diseases in females., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy., Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy., Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p<0.001) and BMI (p=0.009) were independent predictors of intra-operative complications. Pathological diagnosis (p<0.001) and Charlson score (p=0.013) were independent predictors of death., Conclusion: Diligent care is needed with older patients, with multiple comorbidities and harboring unfavorable adrenal disorders (adrenocortical carcinoma and pheocromocytoma), who have greater risk of post-operative complications. Patients with elevated BMI and larger tumors have higher risk of intra, but not of post-operative complications., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: During follow-up in cancer patients, adrenal lesions are frequently found by computer tomography imaging. In these patients, the frequency of subclinical Cushing's syndrome (SCS) has not been fully explored. The aim of the present study was to investigate the presence of SCS in cancer patients with adrenal lesions in comparison to patients with true adrenal incidentalomas., Design: We studied 95 patients with adrenal lesions: 57 patients (group A, 20 males and 37 females) had a history of extra-adrenal malignancy and adrenal lesions were discovered during staging of the primary cancer, and 38 patients (group B, 6 males and 32 females) had adrenal incidentalomas. The two groups had similar BMI. All patients had unenhanced HU < 10 in computed tomography to ensure low risk of adrenal metastatic disease. Patients' morning plasma cortisol levels and ACTH were measured. An overnight 1 mg dexamethasone suppression test (ODST) was performed in all participants; in case of abnormal results, 24-h urine cortisol and the low-dose dexamethasone suppression test were additionally conducted. The cutoffs of morning cortisol values used for ODST were 1.8 and 5 μg/dl., Results: When the cutoff of 1.8 μg/dl for suppressed morning cortisol was used, 42.1% of group A and 39.5% of group B had abnormal results (p = 0.95). By using the threshold of 5 μg/dl after ODST, 5.3% of group A and 13.2% of group B did not have suppressed cortisol levels with the 1 mg ODST (p = 0.18). The main factors found to influence suppressed cortisol levels after ODST in both groups were BMI and size of the adrenal lesion., Conclusions: Patients with extra-adrenal malignancies and adrenal lesions had similar rates of subclinical hypercortisolemia compared to patients with true adrenal incidentalomas.

Glucocorticoids play a major factor in fetal maturation and fate decision after birth. We have previously demonstrated that prenatal caffeine exposure (PCE) resulted in adrenal dysplasia. However, its molecular mechanism has not been clarified. In the present study, a rat model of intrauterine growth retardation (IUGR) was established by PCE, and offspring were sacrificed. Moreover, NCI-H295 A cells were used to confirm glucocorticoid-related molecular mechanism. Results showed that PCE fetal weight decreased, and the IUGR rate increased, while serum corticosterone levels increased but insulin-like growth factor 1 (IGF1) levels decreased. Fetal adrenals exhibited an activated glucocorticoid-activation system, and the downregulated expression of IGF1 signal pathway and steroidal synthetases. For adult rats, there was no significant change in the glucocorticoid-activation system in the PCE group, the IGF1 signal pathway showed increased trend, and the expression levels of adrenal steroidal synthetases were close to normal. The data in vitro showed that the cortisol of 1200 nM can inhibit the expression of adrenocortical cell steroidal synthetases and IGF1 signal pathway when compared with the control. Meanwhile, the glucocorticoid-activation system was activated while GR inhibitor mifepristone can reverse the effect of cortisol. Furthermore, cortisol can also promote GR into the nucleus after its activation. Based on these findings, we speculated that high concentrations of glucocorticoid in utero led to GR in the nucleus through its activation and then inhibited the IGF1 signaling pathway by activating the glucocorticoid-activation system, which could further downregulate steroid synthesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objectives: The adrenal gland is a frequent site for metastasis, and a solitary adrenal mass is often observed during staging workup or imaging follow-up in patients with extra-adrenal malignancy. To create an appropriate management plan, it is essential to distinguish between benign adrenal lesions and metastasis in patients with extra-adrenal cancer having solitary adrenal masses. Therefore, here we evaluated the predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass., Materials and Methods: From September 2003 to June 2016, we retrospectively reviewed patients with extra-adrenal malignancy having solitary adrenal mass on a cancer staging workup or follow-up study who subsequently underwent adrenalectomy at our institution. All patients underwent preoperative functional studies; those with positive results were excluded from this study. Characteristics of oncology patients with adrenal mass including age, sex, body mass index, smoking, mass location, mass size, hypertension, diabetes mellitus, precontrast Hounsfield unit (HU), and synchronous or metachronous adrenal mass based on the time of the extra-adrenal cancer diagnosis were analyzed., Results: Of the total 68 patients with extra-adrenal cancer having solitary adrenal mass, 22 had pathologically confirmed adrenal metastasis. Primary cancers consisted of hepatocellular cell carcinoma (n = 7), renal cell carcinoma (n = 7), lung cancer (n = 4), colon cancer (n = 3), and breast cancer (n = 1). On multivariate analysis, a higher precontrast HU (P = 0.001, odds ratio [OR] = 1.105, 95% confidence interval [CI] = 1.042-1.172), male sex ( P = 0.019, OR = 9.782, 95% CI = 1.462-65.461), and metachronous adrenal mass ( P = 0.007, OR = 11.090, 95% CI = 1.937-63.490) were observed as predictive factors for adrenal metastasis in patients with extra-adrenal cancer having solitary adrenal mass. The cut-off value of precontrast HU to distinguish between metastasis and benign lesions was 36.2 (sensitivity = 81.8%; specificity = 91.3%)., Conclusion: High precontrast HU (> 36), male sex, and metachronous adrenal mass are predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass., (© 2018 Wiley Periodicals, Inc.)

Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands. NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.

A 67-year-old man was adrenalectomized due to a tumor measuring 100 mm. Specimens revealed an inflammation with slight fibrosis and moderate infiltrates of lymphocytes and plasmacytes with immunoreactivity for IgG and IgG4 resulting in the diagnosis of an active IgG4-associated adrenalitis. To our knowledge, this is the first reported active adrenalitis of this type. It should be the precursor lesion of the adrenal calcifying fibrous tumor that was reported once before.

Adrenal cysts are a rare entity which makes their treatment somewhat tough. Discovered in a fortuitous way or in the course of explorations for very aspecific symptoms, it is necessary to decide on a case-by-case basis, and after a careful clinical examination, whether the lesion is to be treated through surgery or if a follow-up iconography is sufficient. Three main parameters will influence this choice: the functional status of the cyst, its malignant potential and the potential complications related to the cyst. Current recommendations suggest a surgical treatment for all symptomatic cysts, for functional cysts, for cysts with a diameter exceeding 5 cm, for hemorrhagic cysts and for cysts with malignant imaging potential. The progress and surgical advantages brought by the development of laparoscopy make it the first technique to be chosen.

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.

Objective: The purpose of this study was to determine the rate of malignancy in incidentally detected bilateral adrenal masses in patients with no known history of cancer., Materials and Methods: A retrospective search of CT reports of patients with incidentally detected bilateral adrenal nodules was performed from January 1, 2002, to January 1, 2014. Patients were excluded if they had a known cancer or suspected functioning adrenal tumor; 161 patients were included. Nodules were characterized as benign or malignant on the basis of imaging features at the index CT examination, imaging features at subsequent adrenal protocol CT or MRI, imaging stability for a minimum of 1 year, or clinical follow-up of a minimum of 2 years., Results: Mean nodule size was 1.8 cm (range, 0.7-4.9 cm). There were no cases of primary or secondary adrenal malignancy (95% CI, 0.00-0.023). The nodules diagnosed on index CT scans were 73 adrenal adenomas and two myelolipomas. Seventy-four nodules were subsequently characterized as adrenal adenomas on the basis of imaging findings. Of the 113 indeterminate nodules that had imaging follow-up, 111 were stable at the latest follow-up examination. One nodule grew 26% over 8.1 years, and the other grew 59% over 12.4 years. Clinical follow-up of patients with 60 indeterminate nodules revealed no evidence of adrenal malignancy., Conclusion: No case of malignancy was found in 322 incidentally detected bilateral adrenal nodules at CT of patients without known cancer. Imaging follow-up of such lesions may be unnecessary.

Background: Fine-needle aspiration (FNA) of adrenals is needed in patients with pyrexia of unknown origin (PUO) and adrenal enlargement in absence of other diagnostic clues. Adrenals are easily accessible by endoscopic ultrasound (EUS) due to proximity; however, there is no systemic study available on FNA of adrenals in patients with PUO. The aim of this study was to evaluate the diagnostic yield and safety of EUS-FNA of enlarged adrenal in patients with PUO., Methods: Data was analyzed from October 2010 to September 2016 at a single tertiary care center in northern India. EUS-FNA of enlarged adrenals was done in 52 patients for the etiological diagnosis of PUO in whom a definitive diagnosis could not be made with other means., Results: The mean age was 48±14 years; 36 were males and 16 were females. EUS-FNA was done from the left adrenal in 50 patients and from the right sample in 2 patients. A technical success was achieved in 100% cases. The 19-G needle was used in the majority (75%) to the presence of necrotic areas in adrenals; median numbers of passes were 2. The cytopathological diagnoses were tuberculosis (n = 36), histoplasmosis (n = 13), lymphoma (n = 2), and metastasis from undiagnosed neuroendocrine tumor of lung (n = 1). Thus, a diagnosis could be made in 52/52 (100%) patients. None of the patients had any procedure-related complications., Conclusions: EUS-FNA is a safe and effective method for evaluating etiology of PUO in patients with adrenal enlargement.

Neuroblastoma (NB) is a tumor of the sympathoadrenal system arising in children under 15 years of age. In Germany, NB accounts for 7% of childhood cancer cases, but 11% of cancer deaths. It originates from highly migratory progenitor cells that leave the dorsal neural tube and contribute neurons and glial cells to sympathetic ganglia, and chromaffin and supportive cells to the adrenal medulla and paraganglia. Clinically, histologically and molecularly, NBs present as extremely heterogeneous, ranging from very good to very poor prognosis. The etiology of NB still remains unclear and needs to be elucidated, however, aberrant auto- and paracrine embryonic cell communications seem to be likely candidates to initiate or facilitate the emergence, progression and regression of NB. The wingless-type MMTV integration site (WNT) family of proteins represents an evolutionary highly conserved signaling system that orchestrates embryogenesis. At least 19 ligands in the human, numerous receptors and co-receptors are known, which control not only proliferation, but also cell polarity, migration and differentiation. Here we seek to interconnect aspects of WNT signaling with sympathoadrenal and paraganglionic development to define new WNT signaling cues in the etiology and progression of NB.

Background: Adrenal gland trauma is a rare condition that typically stems from blunt force trauma, and is associated with multiple organ injuries. Alternatively, isolated adrenal gland trauma is extremely rare, accounting for only 1.5 to 4% of all adrenal trauma cases. While isolated adrenal trauma is a mostly self-limiting condition, it is potentially life-threatening, representing a significant cause of bleeding, and/or hypotension due to adrenal insufficiency and adrenal crisis. Due to its rare occurrence, there are no reported guidelines for monitoring and observing isolated adrenal trauma., Case Presentation: Here we report on an isolated adrenal hemorrhage from a blunt trauma without associated injuries. A 53-year-old white man presented with abdominal pain after a high-speed motor vehicle accident. An initial evaluation revealed minimal abdominal pain and negative focused assessment with sonography for trauma examination; computed tomography imaging revealed a significant fluid collection consistent with adrenal hemorrhage. He was observed in our intensive care unit for 24 hours, and had stable hemoglobin and vital signs, after which he was discharged. At 1-month follow-up, he reported persistent intermittent abdominal pain, which was completely resolved by the 4-month follow-up., Conclusions: This case report demonstrates isolated adrenal gland injury resulting from significant blunt trauma to the abdomen. There are no current guidelines for monitoring isolated adrenal hemorrhage. Recognizing possible adrenal injury in blunt trauma cases is important due to potentially severe adrenal hemorrhage; therefore, we recommend follow-up with serial abdominal computed tomography until the resolution of hemorrhage and symptoms.

A 70-year-old man with history of heart transplant performed in 1986, presented with altered mental status. CT scan of brain showed ring-enhancing lesions, raising suspicion for metastatic malignancy. Work-up revealed bilateral adrenal masses, biopsy showed granulomatous changes consistent with histoplasmosis. The possibility of histoplasmosis was less likely as the patient had no prior history of symptomatic disease and had lived in the endemic area 30 years prior to presentation. Brain biopsy confirmed central nervous system involvement. Amphotericin B was initiated for disseminated disease but his hospital course was complicated by renal failure and new liver hypodensities on follow-up imaging. Acute progressive disseminated histoplasmosis can manifest after decades of initial exposure and should always be in differential diagnosis even in non-endemic areas for prompt diagnosis and better clinical outcome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

True epithelial-lined cysts are rare forms of adrenal cystic lesions, the pathogenesis of which is still not fully understood. In this report we present a case of an adrenal cyst diagnosed incidentally on imaging in a 31-year-old, previously healthy, obese woman. Due to non-specific hormonal disorders and enlargement of the lesion, a right-sided laparoscopic adrenalectomy was performed. The cyst was lined predominantly by ciliated cuboidal-to-columnar, Müllerian-type epithelium, and focally by flat-to-cuboidal, mesothelium-like lining. Immunohistochemistry demonstrated a strong positive reaction in the cells of both types of lining for CKAE1+E3, CK19, CK7 and WT1, and both had a negative reaction for CK20, CD34, Melan-A, SF1, TTF1, SMA and CDX2. The cells of the ciliated cuboidal-to-columnar epithelium were strongly positive for PAX8, ER, Ep-CAM and EMA, focally positive for PR, and were negative for calretinin, whereas the cells of the flat-to-cuboidal lining were positive for calretinin and podoplanin and showed only a weak positive response in individual cells for PAX8, EMA and Ep-CAM, but were negative for ER and PR. This is the first reported case of an adrenal ciliated epithelial cyst with Müllerian differentiation (confirmed immunohistochemically) in the English literature. The differences in morphology and immunophenotype of the two types of lining (epithelial Müllerian phenotype versus mesothelial phenotype), suggest that some adrenal epithelial cysts probably form due to metaplasia of mesothelium-derived lining. A similar mechanism may also be involved in the pathogenesis of at least some of the so-called Müllerian cysts (or inclusions) in other locations.

The adrenal glands in children can be affected by a variety of benign lesions. The diagnosis of adrenal lesions can be challenging, but assessment of morphologic changes in correlation with the clinical presentation can lead to an accurate diagnosis. These lesions can be classified by their cause: congenital (eg, discoid adrenal gland, horseshoe adrenal gland, and epithelial cysts), vascular and/or traumatic (eg, adrenal hemorrhage), infectious (eg, granulomatous diseases), enzyme deficiency disorders (eg, congenital adrenal hyperplasia [CAH] and Wolman disease), benign neoplasms (eg, pheochromocytomas, ganglioneuromas, adrenal adenomas, and myelolipomas), and adrenal mass mimics (eg, extralobar sequestration and extramedullary hematopoiesis). Multimodality cross-sectional imaging helps to define the origin, extent, and relationship of these lesions to adjacent structures, as well as to guide treatment management. The anatomic and functional imaging modalities used to evaluate pediatric adrenal lesions include ultrasonography, computed tomography (CT), magnetic resonance imaging, and iodine 123 metaiodobenzylguanidine scintigraphy. Identifying the imaging features of nonmalignant adrenal lesions is helpful to distinguish these lesions from malignant adrenal neoplasms. Identifying characteristic imaging findings (eg, enlarged adrenal glands, with cerebriform surface, and stippled echogenicity in CAH; a T2-hyperintense mass with avid contrast enhancement in pheochromocytoma; low CT attenuation [<10 HU] and signal intensity drop on opposed-phase chemical shift images in adenoma; and enhancing suprarenal mass supplied by a systemic feeding artery in extralobar sequestration) can aid in making the correct diagnosis. In addition, clinical features (eg, ambiguous genitalia in CAH and hypertension in pheochromocytoma) can also guide the radiologist toward the correct diagnosis. © RSNA, 2017.