Adrenal Disease Research Articles

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease.

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.

Incidence and Phenotypes of Endocrinopathies in Association With Immune Checkpoint Inhibitors: The Experience of Integrated Health Network

Introduction: Since 2011 FDA has approved several immune checkpoint inhibitors (ICI) as antineoplastic agents with very promising results. The side effects profile of ICI is different from that of conventional cancer therapies and predominated by immune-related adverse effects (IRAEs). Autoimmune endocrinopathies (AEs), such as disorders of the thyroid, pituitary, and adrenal glands are increasingly recognized IRAEs of ICI. If not diagnosed and treated early, AEs may cause serious harm in an already compromised patient by advanced malignancy. Therefore, it is necessary to recognize the incidence, phenotypes, and time to onset of various AEs in association with ICI. This retrospective study of a large cancer population treated at an integrated health network aims to do so. Methods: We conducted a retrospective chart review of adult patients treated with ICI as cancer therapy at Allegheny Health Network—a major healthcare provider in Western Pennsylvania—between 1/1/2016 and 6/30/2019. Inclusion criteria were ages 18-90 years who received one or more ICI within the study period, laboratory data available for a minimum of 6 months from date of the first ICI dose, and no pre-existing outcome of interest at the time of, or prior to, receiving the first ICI dose. Exclusion criteria were pre-existing thyroid, pituitary, or adrenal diseases. Results: We screened the records of 1200 patients who were treated for 47 different cancers for AEs. Of this sample, 57% were males 92.5% were White. Follow up period ranged between 6-57 months, during which 56% of patient died at a mean age of 67.1 years. The most common cancer diagnoses were non-small cell lung cancer (45.4%), malignant melanoma (11.7%), renal cell carcinoma (6.3%), and small cell lung cancer (6.2%). These patients received one or more agents from the three classes of ICI, including PD-1 (75.86%), PDL-1 (12.57%), and CTLA-4 (11.57%). The overall incidence of AEs was 18%. The distribution of AEs was as follows: primary hypothyroidism 15.3%, secondary hypothyroidism 0.5%, primary hyperthyroidism 3.5%, primary adrenal insufficiency 0.2%, secondary adrenal insufficiency 2.7%, and type 1 diabetes mellitus 0.2%. Of the 42 patients diagnosed with hyperthyroidism, 28 (66.7%) later developed primary hypothyroidism within a mean time of 9 weeks. There was no statistically significant association between the incidence of AEs and gender (P=0.748) or age (P=0.998). Conclusion: AEs are common sequelae of ICI and primary hypothyroidism is the most prevalent AEs among our study sample. This study should help increase awareness about the importance of routine screening of the AEs in cancer patients receiving ICI.

Endocrine Elective Primer for Medical Students

Background: Endocrine modules available online have shown improvement in student learning and increased student satisfaction with self-guided learning (Kirk, 2016). However, most available modules are geared towards preclinical medical students rather than clinical students. Therefore, we developed an endocrine primer, defined as a set of introductory preparatory material, in the form of a PowerPoint. The primer reviews commonly seen endocrine disorders in adults, including their presentation, diagnosis, and management, in order to offer students access to self-paced learning and help bridge the gap between the basic science curriculum and clinical experience. Methods: Third and fourth year medical students enrolled in the endocrine elective from Feb 2020-Oct 2020 completed a 15 question pre-and post-knowledge assessment, as well as an endocrine primer satisfaction survey. The knowledge assessments evaluated students’ knowledge of topics surrounding type 1 and 2 diabetes, hyper- and hypothyroidism, thyroid nodules, adrenal and pituitary disease, hyperparathyroidism, and osteoporosis. The pre-knowledge assessment was completed prior to starting the endocrine elective and viewing the endocrine primer. The post-knowledge assessment was completed at the end of the two or four week endocrine elective. Results: A paired-T test was used to compare the pre- and post-knowledge survey results. A total of 7 third- and fourth-year medical students completed the knowledge assessment and satisfaction survey. Knowledge results showed a nonsignificant mean improvement of 1.4 points, p=0.09, from the start of the elective to completion, with a decreased variability between student scores. Student satisfaction was high, with 100% of students who completed the primer agreeing it made them more prepared for the endocrine elective and all students recommending other electives create similar primers as well. Conclusion: The endocrine primer standardized students’ endocrinology knowledge and enhanced satisfaction with the endocrinology elective. This self-paced learning opportunity was well received by medical students and should be included in other clinical electives. This pilot study will be expanded to a larger sample size and incorporate internal medicine residents on the endocrinology elective. We also plan to review faculty satisfaction before and after the primer was initiated.

Wnt2b Is Essential for Adrenocortical Progenitor Cell Fate and Zona Glomerulosa Identity in Vivo

Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time. Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt/β-catenin signaling, but the cell-specific effects of individual WNT ligands in the adrenal cortex are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell fate and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization, which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed in the capsule with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice. Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying zG to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we first generated whole body Wnt2b knockout (KO) mice, which exhibit complete zG loss, as defined by known markers of zG identity (β-catenin and DAB2). To more fully determine the mechanism by which Wnt2b deletion results in zG loss, we crossed Wnt2b-floxed and capsule-specific Gli1-CreERT2 mice to generate a Wnt2b conditional knockout (cKO) model and study the effects of Wnt2b loss on the zG during homeostasis of the adult adrenal cortex. Gli1-CreERT2 activation by tamoxifen in 6-week-old mice significantly decreased Wnt2b expression and resulted in a lower adrenal-to-body weight ratio in Wnt2b cKOs compared to controls four weeks later. Adrenocortical proliferation (Ki67) was also significantly decreased in Wnt2b cKO mice, suggesting that WNT2B may promote progenitor cell self-renewal. To characterize the consequences of WNT2B loss on canonical Wnt signaling, we assessed activation of β-catenin, the primary Wnt signaling effector. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 and Hsd3b6. Together, these data reveal that capsule-derived WNT2B is required for zG differentiation and maintenance, potentially through activating adrenocortical Wnt/β-catenin signaling and downstream target gene expression involved in both progenitor cell fate and steroid-producing cell function. Studies to more fully elucidate the dynamic effects of WNT2B on the adrenal zG are ongoing as they have important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.

Cushing Syndrome in Carney Complex: Unilateral or Bilateral Adrenalectomy?

Abstract Carney Complex (CNC) is a rare multiple endocrine syndrome dueto PRKR1A germline mutations. Primary pigmented nodular adrenal disease (PPNAD), the most frequent manifestation of the disease is responsible for non-ACTH dependent Cushing syndrome and bilateral adrenalectomy is the recommended treatment. We had followed up a CNC family with mainly Cushing syndrome disease secondary to PPNAD for more than 40 years over 2 generations. Six members carry the disease and present a germline mutation of PRKR1A, 4 women and 2 men. One patient accidently died one year after surgery and the others 5 patients were regularly followed up. The index case, a 25 years woman, was diagnosed with Cushing syndrome in 1972 with hyperandrogenism, short stature and mild manifestations of hypercortisolism. Unilateral adrenalectomy was performed on the side of a nodular adrenal and pathology described PPNAD. Her sister was subsequently diagnosed and treated the same way. The 2 sisters did well, with pregnancies for both of them but different post surgery hormonal results. The index case had partial cortisol deficiency with persistent low cortisol level at 108 nmol/L. Her sister presented a moderate increase in cortisol in the evening or after dexamethasone at 306 nmol/L at last evaluation. The only events possibly associated to hypercortisolism in this patient were central overweight and three episodes of spontaneous pulmonary embolism and veinous thrombosis. Their 2 brothers were evaluated at 17 and 39 years while they developed cushing syndrome signs (round face, HTA, amyotrophy and fatigability). As CNC have been recognized at this time by Dr Carney, bilateral adrenalectomy was performed in one patient who died accidentally a few months later. His brother chose unilateral adrenalectomy on the side of the macronodular gland, recovered hypercortisolism signs and still needs adrenal substitution. The daughter of the index case demonstrated at 21 years old a mild Cushing syndrome and chose unilateral adrenalectomy like her mother. Symptoms resumed without any recurrence during 20 years follow up. The daughter of the patient II.2 was diagnosed earlier at seven years of age because she developed hyperandrogenism, central weight gain and growth arrest due to Cushing syndrome. Bilateral adrenalectomy was successfully performed and adrenal substitution was prescribed. Surprisingly, adrenal function seemed to recover 5 to 6 years post surgery and treatment was decreased then stopped. Adrenal CT scan did not show any residual gland but noriodocholesterol scintigraphy confirmed bilateral adrenal uptake. She is now mother of 2 and present a near normal cortisol circadian rythm without any treatment. Finally, we showed in this long-term study that unilateral adrenalectomy in PPNAD could be an option for the treatment of mild Cushing syndrome in adults. Recovery after bilateral adrenalectomy occurred in one patient.

Severe Cushing Syndrome Due to Ectopic ACTH Secretion by Pheochromocytoma

Introduction: Ectopic ACTH production is a very unusual cause of Cushing Syndrome (CS). When it occurs, lung cancer is the main cause. Very rarely, this ectopic source of ACTH can arise from a Pheochromocytoma (Pheo). A recent literature review identified less than 100 cases described. We present a case of 28 years old woman who was referred for adrenalectomy for CS with notorious adrenal mass. However, during the investigation, ectopic ACTH due a Pheo was identified. Case Report: A 28-year-old woman required emergency care for ecchymosis and asymptomatic hypertension (BP: 230x130mmHg). Hyperpigmentation of the skin was evident on physical examination. Severe hypokalemia (K: 2.5mEq/liter) was detected. She denied taking any medication and was unaware of any previous illness. She always had normal BP measurements as well as laboratory tests. No family history of adrenal disease or secondary hypertension causes. During hospitalization, the hypothesis of CS was made and confirmed after: cortisol after 1mg dexamethasone: 44.5mcg/dl (<1.8mcg/dl) and 24h urinary free cortisol: 6228 mcg/dl (28-213mcg/dl). Concomitantly, a CT scan of the abdomen exhibited a left adrenal mass (3.1x2.8x3.5cm) of uncertain etiology and ACTH: 352pg/ml (<46pg/ml). Additionally, the patient presented hyperglycemia during hospitalization. After confirmation of the ACTH dependent CS, pituitary MRI was performed with normal results and a chest CT scan ruled out lung masses. As there was still no etiological confirmation and due to clinical deterioration, it was decided to start Ketoconazole 200mg/day, rising until 600mg and spironolactone with doses up to 250mg/day with a significant improvement in hypokalemia, decreased cortisol levels and optimal BP control. Due to the extremely high levels of ACTH and indeterminate adrenal mass, the hypothesis of ACTH ectopic due Pheo was postulated. Patient underwent abdomen MRI with left adrenal mass with hypersignal at T2 and urinary metanephrines levels: 6132mcg/24h (<289mcg/24h), urinary normetanephrines: 1808mcg/24h (<732mcg/24h). Once the diagnosis was elucidated, she received preoperative preparation with alpha blocker (Doxazosin) and underwent adrenalectomy without complications. After discharge, she received prednisone 10mg/day. The patient presented normalization of BP levels, as well as glycemic control with a slight improvement in skin hyperpigmentation. The pathology department confirmed Pheo and an ACTH expression was observed in immunohistochemistry. A genetic panel for Pheo is running with no results so far. Conclusion: Despite an extremely rare cause of CS, the ectopic production of ACTH by a Pheo has extremely high mortality rates, especially when not diagnosed or managed correctly. The clinicians must always remain alert and suspect this syndrome when the patient has a confirmed ACTH dependent CS associated with adrenal masses.

Pheochromocytoma Presenting in a Elderly Female With a History of Uterine Leiomyoma and Renal Cell Carcinoma

Background: Adrenal incidentaloma are masses that are found coincidentally on radiologic imaging usually performed for indications other than evaluation for adrenal disease. Pheochromocytomas are rare, usually sporadic catecholamine-producing adrenal tumors and represent 5% of adrenal incidentalomas. While pheochromocytomas can present on their own, they can also present as part of a spectrum of disease found in certain familial syndromes. We present a case of pheochromocytoma found in a patient with a history of renal cell carcinoma and fallopian tube leiomyoma.Case Presentation: A 67 year old female with a past medical history of diabetes mellitus type II, end stage renal disease on hemodialysis, hypertension, skin cancer, right fallopian tube leiomyoma, and right renal mass suspected for renal cell carcinoma presented to the clinic for evaluation of a left adrenal mass. Left adrenal mass was incidentally found 3 years ago on CT abdomen for evaluation for renal transplant and noted to be 2.2 cm in diameter. There were also incidental findings of a 1.3cm right renal mass and a 5.6x4.8cm right adnexal mass. Patient underwent robot assisted total laparoscopic hysterectomy with bilateral salpingo-oophrectomy and surgical pathology results showed leiomyoma of the myometrium. Surveillance CT imaging done 3 years after showed the left adrenal mass and right renal mass increased in size with the adrenal mass increasing to 4.3 cm in diameter with central necrosis and right renal mass increasing to 3.2 x 1.3 cm. Screening biochemical test were done, and initial test and confirmatory test confirmed pheochromocytoma. Dexamethasone suppression test and aldosterone/renin ratio results were normal. Surgical pathology confirmed pheochromocytoma and biopsy of the right renal mass 8 months later confirmed renal cell carcinoma.Conclusion: Majority of pheochromocytomas are sporadic but up to 40% have been identified as inherited in origin due germline mutations. They have been known to present as a part of a spectrum of disease pathologies specific for certain familial syndromes such as Neurofibromatosis Type 1, Von Hippel Lindau Syndrome, Multiple Endocrine Neoplasia Type 2, and Familial Paragangliomas. One relatively uncommon syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome due to a mutation in the fumarate hydratase gene, has been known to present with pheochromocytoma in rare cases. Our patient presented with pheochromocytoma, renal cell carcinoma, and uterine leiomyoma which is suspicious for Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. The diagnosis was not confirmed as genetic testing was not done. Due to a high rate of inherited patterns of pheochromocytoma, routine genetic testing should be done as identification of gene mutations may lead to diagnosis, treatment, and surveillance for patients and their relatives.

RNA-Binding Protein Musashi-2 Inhibits Aldosterone Production

The adrenal cortex is the site of steroid hormone synthesis. These hormones control important physiological processes like metabolism, blood pressure and volume, and sexual characteristic development. While the signaling pathways, transcription factors, and steroidogenic enzymes are well-characterized, surprisingly little is known about the contribution RNA-binding proteins (RBPs). RBPs exert post-transcriptional control by interacting with specific elements within target mRNAs. Here we focus on the RBP, Mushashi-2 (MSI2), which binds to UAG sequences in the 3’UTR of its target transcripts. MSI2 is required for development of steroidogenic tissues which is consistent with its higher mRNA levels in human ovaries and testis. MSI2 also exhibits high expression levels in human adrenal tissue and the immortalized human adrenocortical cell line (H295R). Based on the compelling MSI2 expression pattern, we set out to determine the role of MSI2 on aldosterone production. Depletion of MSI2 using siRNA led to significantly lower aldosterone levels in H295R cells stimulated with AngII. We also employed an orthogonal loss-of-function approach by co-treating cells with AngII and increasing concentrations of Ro-08-2750 (Ro), a direct and selective inhibitor of MSI2-RNA interactions. Ro inhibited aldosterone production in a dose-dependent manner at 1 µM with almost complete inhibition at 5 µM. The molecular mechanism by which MSI2 regulates target RNA translation and/or decay is unknown. Moreover, whether MSI2 acts as a repressor or activator appears to be context dependent. Our goal is to determine the precise molecular mechanism by which MSI2 promotes aldosterone production. Specifically, we will identify MSI2 targets, temporally resolved consequences of MSI2 inhibition, and protein interaction partners. This work will impact our understanding of fundamental principles of RBP-mediated regulation, as well as novel regulatory mechanisms underlying human steroid hormone synthesis. Indeed, Ro (or further optimized compounds) may represent new therapeutic avenues for adrenal disease.

Single-cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

P12: PREDICTORS OF CONVERSION FROM MINIMALLY INVASIVE TO OPEN ADRENALECTOMY: A SYSTEMATIC REVIEW &amp; META-ANALYSIS OF OBSERVATIONAL STUDIES

Abstract Introduction Minimally invasive adrenalectomy has become the standard of care internationally in benign adrenal disease. Intra-operative conversion to open surgery is associated with significantly increased morbidity and prolonged hospital stay. The aim of this systematic review is to identify risk factors associated with intra-operative conversion of minimally invasive adrenalectomy. Method This systematic review was conducted according to MOOSE guidelines. PubMed, EMBASE and Cochrane library were systematically searched for observational studies evaluating risk factors for intra-operative conversion of minimally invasive adrenalectomy to open surgery. Specific risk factors of interest included patient demographics, patient co-morbidities, tumour characteristics and histology. Result Eight studies met the inclusion criteria for analysis with a total of 2939 patients. 6.02% (n=177) required intra-operative conversion. 67.5% (n=1983) underwent laparoscopic transperitoneal adrenalectomy. There were no significant associations between any patient demographics or co-morbidities and intra-operative conversion. Tumour characteristics such as right sided tumours (pooled odds ratio (OR), 1.51; 95% Confidence Interval (CI), 0.98-2.32; p=0.06) and increasing tumour size (OR, 2.29; 95% CI, 1.4-3.74; p=0.001) were shown to be significantly associated with an increased risk of conversion. Pheochromocytoma (OR, 2.21; 95% CI, 1.89-2.58; p&amp;lt;0.0001) and malignancy (OR, 5.38; 95% CI, 2.1-13.81; p=0.005) were also significant predictors of intra-operative conversion. Conclusion Minimally invasive adrenalectomy has significantly reduced post-operative morbidity in patients requiring adrenal surgery but the need for intra-operative conversion remains significant. Identifying patients at increased risk of conversion pre-operatively may assist intra-operative decision making and contribute to improved patient outcomes. Take-home message Minimally invasive adrenalectomy carries a significant risk of conversion. Recognising patients with known risk factors for conversion aids risk stratification and may contribute to better outcomes.

Spectrum of adrenal disorders in a referral hospital of Bangladesh

Background: Adrenal diseases are common and their presentations are variable. This study aimed to determine the frequency and presenting features of various adrenal diseases in a tertiary care hospital of Bangladesh.&#x0D; Methods: This retrospective descriptive study was carried out in Endocrinology in-patient department of BIRDEM General Hospital, Dhaka, Bangladesh, from October 2017 to December 2018. During this time, total 745 patients were screened; out of whom 91 had adrenal diseases.&#x0D; Results: Mean age of the study population was 39.6±11.5 years. Among them, 65.9% were male. Most (75.8%) cases had adrenal insufficiency, followed by endogenous Cushing’s syndrome (8.8%), Conn’s syndrome (6.6%), non-functioning adenoma (3.3%), congenital adrenal hyperplasia (CAH) (2.2%), pheochromocytoma (1%), myelolipoma (1%) and adrenal carcinoma (1%). According to functional status, most (75.8%) were hypofunctional. Of the patients with adrenal insufficiency, secondary adrenal insufficiency was the most common (78.3%). Among the secondary adrenal insufficiencies, 75.9% had iatrogenic adrenal insufficiency and 24.1% had pituitary diseases. Regarding the cases of primary adrenal insufficiency, 20% cases were due to adrenal tuberculosis, 6.6% were due to adrenal histoplasmosis and 73.3% were idiopathic. Most of the adrenal insufficiency patients presented with hypotension (66.7%), followed by gastrointestinal symptoms (76.8%), weight loss (55.1%), hyponatraemia (42%), pigmentation (13%) and hypoglycemia (10%). In this study, 9.9% patients had adrenal incidentaloma. Most of them (88.9%) were benign. Causes of Cushing’s syndrome among the study population were, iatrogenic (66.7%), adrenal (16.7%) and pituitary cause (16.7%). In this study, 16.5% patients had endocrine hypertension and the causes were endogenous Cushing’s syndrome (53.3%), Conn’s syndrome (40%) and pheochromocytoma (6.7%). Of the hypertensive patients, 60% had co-existing hypokalemia.&#x0D; Conclusion: Adrenal insufficiency was the most common adrenal disorder followed by endogenous Cushing’s syndrome, Conn’s syndrome, non-functioning adenoma and other adrenal disorders. Presentations of adrenal disorders are variable. Among the cause of adrenal insufficiency iatrogenic adrenal insufficiency was the most common.&#x0D; Birdem Med J 2021; 11(2): 103-107

Comparison of Laparascopic and Open Adrenalectomy

An Erratum to this article was published on 01 January 2022. http://journal.acibadem.edu.tr/en/pub/issue/65423/1049054 Purpose Laparoscopic adrenalectomy, which was performed successfully for the first time in 1992, has become the preferred method in adrenal surgery especially in benign adrenal diseases. In this study, our aim is to compare the postoperative results of laparoscopic and open adrenalectomies performed in the general surgery clinic of our hospital. Methods The records of the patients who were operated in hospital due to a surrenal mass between August, 2006 and December 2012 have been retrospectively assessed. Demographic characteristics of the patients, such as age, sex, the size and location of tumors were included. Surgical indications were classified in terms of their radiologic and biochemical investigations. Type of the surgery (lateral transperitoneal laparoscopic or open approach), the incision used in these surgeries (midline, subcoastal and paramedian), the length of operation, the length of hospital stay, postoperative complications and the final pathology results were all examined. Results During the afformentioned period, unilateral adrenalectomy was performed in 106 patients. Eighty of these patients (%75,4) were operated by open surgery and 26 of them (%24,6) were operated by lateral transperitoneal laparoscopic surgery. Subcostal incision was used 61 of 80 patients (% 82,4), whereas 17 patients (% 22,9) were operated by midline incision and 2(% 2,7 were by paramedian incision. No mortality was encountered. The length of operation was statistically significantly shorter in the open group (p<0,0166).The length of hospital stay was statistically significantly longer in open group (p<0,0083). The length of hospital stay was statistically significantly longer in midline incision group(p<0,0083). No statistically meaningful difference was found in terms of age, sex and patological diagnosis releated to postoperative complications. Conclusion In carefully selected group of patients laparoscopic adrenalectomy offered lesser postoperative hospital stay and lesser postoperative complications than the open adrenalectomy. The longer operative time can be decreased when more experience is gained in laparascopic adrenalectomy. Complication rates of laparoscopic adrenalectomies are lower than conventional adrenalectomy and should be preferred as the gold standard in centers with completed learning curve. An Erratum to this article was published on 01 January 2022. http://journal.acibadem.edu.tr/en/pub/issue/65423/1049054

CT measures of adrenal gland length and caudal pole diameter are reproducible in large breed dogs: A pilot study.

Computed tomography (CT) is increasingly available to evaluate dogs with suspected adrenal disease, however, published studies describing the reproducibility of CT methods for quantifying adrenal gland (AG) measurements are lacking. This prospective, pilot, observer agreement study aimed to evaluate reproducibility and repeatability of two different methods of measurement of AGs on CT to establish a usable technique and define standard reference ranges. Multiplanar reformatted (MPR) CT images of both AGs of six large breed dogs were obtained with the MPR axis parallel to the spine and parallel to the long axis of the AG. Ten measurements were performed: maximal length and diameter at cranial and caudal poles on dorsal, sagittal, and transverse images; and minimal diameter of cranial and caudal poles on transverse images. Three observers with different levels of experience repeated these measurements three times for each dog. Intra‐ and interobserver variability were calculated through intraclass correlation coefficient (ICC). The differences in time to perform measurements between the two methods were tested with Student's t‐test. Regardless of the measurement method used, length of AGs on dorsal and sagittal MPR images had the lowest intra‐ and inter‐observer variability (ICC = 0.93‐0.99), diameter of caudal pole on transverse plane showed low intra‐ and interobserver variability (ICC = 0.77‐0.80) and diameter of cranial pole had the highest variability (ICC = 0.12‐0.61). Although length was the less variable measurement, its use may be unrealistic in daily practice. Interestingly measurement of caudal pole on transverse plane was characterized by low intra‐ and interobserver variability. No difference in time performing the measurements was noted between the two methods.

Usefulness of salivary cortisol as a marker of secondary adrenal insufficiency in paediatric patients

Background: The main cause of adrenal insufficiency (AI) in paediatric patients is prolonged treatment with corticosteroids. Determination of plasma cortisol (PC) during ACTH test is the most used adrenal function indicator in clinical practice. However, determination of salivary cortisol (SC), a simple test especially useful in children in order to avoid invasive procedures, can be used as an alternative technique for the diagnosis of adrenal disease. Methods: A two-year prospective study (January 2014-January 2016) in paediatric patients (2-18 years of age) treated with corticosteroids for more than fifteen days, who were investigated for suspected AI. Low-dose ACTH test was used to determine adrenal function and samples for SC and PC were obtained simultaneously in basal situation and during the test (at 30, 60 and 90 minutes). Results: 230 samples (118 PC-112 SC) of 30 studies belonging to 20 patients (4 males), mean age 10.93 years ± 3.69 SD. Pearson’s correlation coefficient showed a positive correlation between PC and SC (r = 0.618, p &lt; 0.001). All the studies with some determination of PC higher than 18 μg/dL (n = 8) had a SC peak higher than 0.61 μg/dL with a specificity of 66.67% and a sensitivity of 93.94% (ROC analysis). Conclusion: Measurement of SC is a less invasive, easier and quicker test than PC to measure plasma free cortisol levels. In our study, a SC peak in low-dose ACTH test higher than 0.61 μg/dL was able to discriminate patients without AI, and proved to be a useful tool in the initial evaluation of children with suspected AI.

Primary aldosteronism: from diagnosis to therapy in clinical practice

Primary aldosteronism (PA) is the single most common cause of secondary hypertension and is associated with increased target organ injury. It can be can either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. The diagnostic work-up of PA is a sequence of three phases comprising screening tests, confirmatory tests and the differentiation of unilateral from bilateral forms. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements. In patients with PA, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension.

Blood Tests for the Diagnosis of Adrenal Diseases

Blood Tests for the Diagnosis of Adrenal Diseases

Cross-sectional imaging features of unusual adrenal lesions: a radiopathological correlation.

The detection rates of adrenal masses are increasing with the common and widespread use of cross-sectional imaging. Adrenal adenomas, myelolipomas, metastases, pheochromocytomas, and adrenocortical tumors are well-known and relatively common adrenal tumors. However, there are many less-known neoplastic and nonneoplastic adrenal diseases that might affect the adrenal glands in addition to these common lesions. These rare entities include, but are not limited to, hydatid cysts, congenital adrenal hyperplasia, Wolman disease, adrenal tuberculosis, primary adrenal lymphoma. This article aims to present imaging findings of these unusual lesions in accordance with their pathologic characteristics. We think that the simultaneous presentation of the pathological findings with the imaging features may facilitate the learning process and may potentially enhance the recognition of these entities.

Chronic kidney disease in adrenal disorders.

This review will focus on hypertension due to underlying adrenal disorders in chronic kidney disease (CKD). Diagnosis of adrenal hypertension and particularly primary aldosteronism (PA) in CKD is frequently not pursued. We outline limitations that advanced kidney disease poses on the diagnostic work up of these disorders and provide a framework for approaching CKD patients suspected of having an adrenal disorder. Recognition of these disorders is important as they are often underdiagnosed which leads to poorer outcomes. Adrenal disease associated with hypertension in CKD is most commonly due to PA whereas pheochromocytoma and Cushing's disease are important but less common. Diagnosis of these diseases is important as their identification leads to better blood pressure control and can possibly mitigate the risk of progression of CKD. Work up and treatment of PA has been shown to be safe and is associated with less antihypertensive medication requirement for the associated hypertension and slower progression of CKD. This chapter summarizes the importance of recognizing adrenal hypertension in CKD and reinforces the need for physicians to pursue these diagnoses in CKD patients as this is safe and improves both BP control and delays progression of CKD.

Best Achievements in Pituitary and Adrenal Diseases in 2020.

Significant progress in pituitary and adrenal diseases was made in 2020. This review presents major translational and clinical advances in research on pituitary and adrenal diseases, encompassing their epidemiology, pathogenesis, diagnosis, and clinical management. We address the controversy regarding the nomenclature of pituitary neuroendocrine tumors, omics-based molecular classification of pituitary adenomas, and novel drugs for Cushing’s disease in the field of pituitary diseases. In the field of adrenal diseases, we cover big data-driven epidemiology of adrenal tumors, steroid profiling as a new diagnostic tool, and the utility of scoring systems in the decision-making process of managing primary aldosteronism. This brief article will broaden readers’ understanding of pituitary and adrenal diseases.

Multiple Hepatic and Pulmonary Tumors Combined with Bilateral Adrenal Masses in a Young Woman with von Hippel–Lindau Disease

Question: A 37-year-old woman was admitted to our center for adrenal diseases with bilateral adrenal tumors and multiple hepatic and pulmonary lesions for surgery. She was first diagnosed with von Hippel–Lindau (VHL) syndrome in April 2000, with proof of heterozygous point mutation c.292T>C in exon 1 of the VHL gene. Her father was diagnosed with a VHL gene mutation as well. She complained of a 4- to 5-kg weight loss in 4 months, increased daytime fatigue, and anxiety. She reported occasional nicotine abuse in the past.