Adrenocortical Disease Research Articles

Link between steroidogenesis, the cell cycle, and PKA in adrenocortical tumor cells

Adrenocortical tumors (ACTs) frequently cause steroid excess and present cell-cycle dysregulation. cAMP/PKA signaling is involved in steroid synthesis and play a role in cell-cycle regulation. We investigated, by cell synchronization in the different phases of the cell-cycle, the control of steroidogenesis and the contribution of PKA in adrenocortical cells (H295R and culture of primary pigmented nodular adrenocortical disease cells). Cells showed increased steroidogenesis and a maximal PKA activity at G2 phase, and a reduction at G1 phase. PRKACA overexpression, or cAMP stimulation, enhanced PKA activity and induced steroidogenesis in all synchronized groups but is not sufficient to drive cell-cycle progression. PRKAR1A inactivation enhanced PKA activity and induced STAR gene expression, only in cells in G1, and triggered cell-cycle progression in all groups.These findings provide evidence for a tight association between steroidogenesis and cell-cycle in ACTs. Moreover, PRKAR1A is essential for mediating the function of PKA activity on both steroidogenesis and cell-cycle progression in adrenocortical cells.

Corrigendum to: Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience.

Corrigendum to: Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience.

Illicit Upregulation of Serotonin Signaling Pathway in Adrenals of Patients With High Plasma or Intra-Adrenal ACTH Levels.

In the human adrenal, serotonin (5-HT), released by mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R). In primary pigmented nodular adrenocortical disease cells, activation of the cAMP/protein kinase A (PKA) pathway by PRKAR1A mutations triggers upregulation of the 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and the 5-HT4, 5-HT6, and 5-HT7 receptors. Because ACTH stimulates cortisol secretion through activation of PKA, adrenocortical tissues exposed to sustained stimulation by ACTH may harbor increased expression of TPH and 5-HT4/6/7 receptors. To investigate the effects of long-term ACTH stimulation on the serotonergic pathway in adrenals of patients with high plasma or intra-adrenal ACTH levels. Adrenal tissues were obtained from patients with Cushing disease, ectopic secretion of ACTH [paraneoplastic Cushing syndrome; (paraCS)], 21-hydroxylase deficiency (21-OHD), primary bilateral macronodular adrenal hyperplasia with intra-adrenal ACTH presence, or cortisol-producing adenomas. TPH and 5-HT4/6/7 receptor expression was investigated using RT-PCR and immunochemistry in comparison with normal adrenals. Primary cultured adrenocortical cells originating from a patient with paraCS were incubated with 5-HT and 5-HTR agonists/antagonists. TPH and/or 5-HT4/6/7 receptors were overexpressed in the different types of tissues. In paraCS cultured cells, the cortisol response to 5-HT was exaggerated compared with normal adrenal cells and the stimulatory action of 5-HT was reduced by 5-HT4R antagonist. Our results indicate that prolonged activation of the cAMP/PKA pathway by ACTH induces an aberrant serotonergic stimulatory loop in the adrenal cortex that likely participates in the pathogenesis of corticosteroid hypersecretion.

Corticotropinoma as the underlying cause of intermittent Cushing's syndrome in a patient previously diagnosed with primary pigmented adrenocortical disease (PPNAD) - a case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Adrenal tumors: when to search for a germline abnormality?

Over the last 20 years, the genetic landscape of adrenal tumours has been transformed by the identification of multiple susceptibility genes for the various tumour types. We review these recent developments here, and describe current recommendations for genetic testing in patients with tumours of the adrenal medulla and extra-adrenal paraganglia or the adrenal cortex. Phaeochromocytomas (adrenal medulla tumours) and paragangliomas, aldosterone-producing adenomas, primary macronodular adrenal hyperplasia, primary pigmented nodular adrenocortical disease and adrenocortical carcinoma (adrenal cortex tumours) may all be caused by a germline mutation in a specific gene, regardless of the presence/absence of a family history or syndromic disease at initial diagnosis. Dedicated genetic testing is now indicated in all these conditions, and in patients with clinical features suggestive of a specific inherited disease. Genetic testing should be considered in all patients with adrenal tumours, and is crucial for correct management. The identification of a germline mutation in a susceptibility gene guides treatment in patients with adrenal cancer and will facilitate risk-adapted screening/surveillance protocols in mutation carriers.

SUN-356 The Effects of Selective Serotonin Reuptake Inhibitors on Urinary Free Cortisol in Patients with Carney Complex and Primary Pigmented Nodular Adrenocortical Disease

PPNAD is a rare cause of ACTH-independent Cushing syndrome mainly associated with Carney complex (CNC). It is diagnosed by histologic examination or a 6-day Liddle test (LT) showing a paradoxical increase of >50% in 24-h urinary free cortisol (UFC) on the 2nd day of high-dose dexamethasone administration (Day 6 [D6]). PPNAD tissue has neuroendocrine features and can overexpress the serotonin (5-HT) synthesizing enzyme tryptophan hydroxylase type 2 and the 5-HT receptors types 4, 6, and 7, with formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production [1]. SSRIs inhibit the reuptake of 5-HT and are used as 1st-line antidepressants. This is a retrospective cohort study of patients with CNC and PPNAD that underwent a LT with the objective to evaluate the effect of SSRIs on UFCs in these patients. Of the 34 patients (4-65 y) with CNC and PPNAD that had a LT at our institution between 2004 and 2018, 4 patients took an SSRI during testing. No statistically significant differences were demonstrated between the SSRI (S) group and the non-SSRI (NS) group in baseline UFCs and urine 17-hydroxycorticosteroids (17OHS) and the percent increase in UFC and 17OHS on D6. Specifically, the median (IQR) baseline UFC in the S group was 36 (13-252) mcg/24h (nl 4-56) vs 35 (13-98) mcg/24h in the NS group (P=0.95). Baseline 17OHS were 11 (8-18) mg/mg creatinine (Cr) (nl ≤6) in the S group vs 8 (5-11) mg/mgCr in the NS group (P=0.27). The percent change in UFC was 208 (93-683)% in the S group and 185 (28-364)% in the NS group (P=0.89), while the percent change in 17OHS was 56 (40-87)% in the S group and 67 (16-92)% in the NS group (P=0.91). On D6, the S group appeared to have higher UFC [118 (63-635) mcg/24h vs 112 (58-201) mcg/24h; P=0.64] and 17OHS [16 (10-39) mg/mgCr vs 13 (7-17) mg/mgCr; P=0.25] than the NS group, but these were not statistically significant. Though these data do not confirm an effect of SSRIs on UFC and ultimately cortisol production in PPNAD, and the percent change in UFC during the LT was similar between both groups, the higher D6 UFC in the S group, when the baseline UFCs between the 2 groups were similar may suggest a degree of increased cortisol production in the S group. The data are limited by the small number of patients in the S group (n=4). In addition, 50% of patients in the S group vs 77% in the NS group underwent adrenalectomy, which is indicative of more severe disease in the NS group. More data are needed from this cohort to determine if SSRI use affects cortisol production in vivo, as this may have significant diagnostic and therapeutic implications for patients with CNC and PPNAD. Reference: 1. Bram, Z., et al., PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease. JCI Insight, 2016. 1(15): p. e87958.

SUN-369 Challenges in Diagnosing and Managing PPNAD in a Patient with Carney Complex

Background Carney complex (CNC) is a rare disorder associated with endocrine, cardiac, cutaneous and neural tumors. Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation in patients with CNC and can be challenging to diagnose and manage. Case A 35 yo female with CNC diagnosed at the age of 3 yrs presented with a 20 lb. weight gain over last 1 year associated with easy bruising, anxiety, dorsocervical and supraclavicular fat pad. She had no other comorbidities and had normal bone density. Her morning cortisol after 8 mg dexamethasone was not suppressed (cortisol 14.9 mcg/dl, dexamethasone 1920 ng/dl); however, urine cortisol values were high normal to only mildly elevated (42.7, 48.4; n-3.5-45 mcg/24hr). Loss of circadian rhythm was noted on comparing midnight and morning cortisol level (8.4, 8.3 mcg/dl respectively), ACTH was suppressed (<5 pg/ml) and DHEAS was low (0.26; n-0.35-4.30 mcg/ml). Her Liddle’s test was not consistent with PPNAD. Adrenal CT was suggestive of possible focal enlargement of medial limb of left adrenal. She was offered bilateral adrenalectomy, but has deferred it at this time. Discussion CNC was first described by Dr. Carney in 1985 as ‘the complex of myxomas, spotting pigmentation and endocrine over-reactivity’. It is a rare disorder with 750 known cases. It has autosomal dominant inheritance with almost 100% penetrance. PPNAD is seen clinically in 25-60% of patients with CNC, however, it has been found in almost every individual with CNC who underwent autopsy, suggesting significant variability in presentation. Symptoms may evolve over a span of many years, making it difficult to determine the appropriate timing of treatment. Diagnosing PPNAD can be challenging as cortisol production can be cyclical, periodic or subclinical. The paradoxical rise in glucocorticoids in response to dexamethasone (Liddle’s test) is reported in 69% of patients but is not pathognomonic. Radiological diagnosis is also challenging as most nodules are less than 4 mm in size, so the adrenals may appear normal on CT scan. Recommended treatment for PPNAD is bilateral adrenalectomy, but this introduces a lifelong burden of steroid replacement and risk of adrenal crisis. Recently, Xu et al performed unilateral adrenalectomy in patients with PPNAD with remission of disease in 12/13 patients with mean follow-up of 3.9 yrs. Longer follow up is needed to determine if unilateral adrenalectomy is an acceptable treatment in PPNAD. Conclusion Diagnosing PPNAD and deciding appropriate time of surgery can be challenging. Unilateral adrenalectomy as a treatment modality needs to be further studied. References Correa et al. Carney Complex: An Update. Eur J Endocrinol 2015. Xu et al. The Role of Unilateral Adrenalectomy in Corticotropin-Independent Bilateral Adrenocortical Hyperplasias. World J Surg 2013.

SAT-350 Comparative Proteomic Analysis of Various Forms of Bilateral Adrenocortical Hyperplasia

Bilateral Adrenal Hyperplasias (BAH) are responsible for approximately 10% of ACTH-independent Cushing syndrome and are classified as either micronodular or macronodular. Whereas Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) are subtypes of micronodular hyperplasia, Primary Macronodular Adrenal Hyperplasia (PMAH) is the most common form of macronodular BAH. These tumors are classified differently based on clinical, histological and genetic features but they all share a dysregulation of the cyclic AMP/protein kinase (PKA) pathway, a molecular signaling system that is essential for the synthesis and secretion of glucocorticoids. In this project, we investigated the molecular differences between the various types of BAHs using a proteomic approach on normal tissue, iMAD, PPNAD and PMAH. In total, we identified 37 proteins differentially expressed between these diagnostic groups. Most of these proteins were involved in metabolism and mitochondrial function, which is consistent with prior transcriptomic data as well as the secretory status of BAH. We are currently comparing all "-omics" for consistency and/or important differences. Interestingly, each BAH (iMAD, PPNAD and PMAH) has its own proteomic signature and can be separated by primary component analysis highlighting differences in molecular pathways. We propose that the 37 proteins identified herein may provide new clues for the formation of these neoplasms, how they link to the PKA pathway, and importantly assist in their clinical diagnosis.

Cushing syndrome: uncovering Carney complex due to novel PRKAR1A mutation.

SummaryCarney complex (CNC) is a rare multiple neoplasia syndrome characterized by spotty pigmentation of the skin and mucosa in association with various non-endocrine and endocrine tumors, including primary pigmented nodular adrenocortical disease (PPNAD). A 20-year-old woman was referred for suspected Cushing syndrome. She had signs of cortisol excess as well as skin lentigines on physical examination. Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. Unenhanced computed tomography scan of the abdomen did not reveal an obvious adrenal mass. She subsequently underwent bilateral laparoscopic adrenalectomy, and histopathology was consistent with PPNAD. Genetic testing revealed a novel frameshift pathogenic variant c.488delC/p.Thr163MetfsX2 (ClinVar Variation ID: 424516) in the PRKAR1A gene, consistent with clinical suspicion for CNC. Evaluation for other clinical features of the complex was unrevealing. We present a case of PPNAD-associated Cushing syndrome leading to the diagnosis of CNC due to a novel PRKAR1A pathogenic variant.Learning points:PPNAD should be considered in the differential for ACTH-independent Cushing syndrome, especially when adrenal imaging appears normal.The diagnosis of PPNAD should prompt screening for CNC.CNC is a rare multiple neoplasia syndrome caused by inactivating pathogenic variants in the PRKAR1A gene.Timely diagnosis of CNC and careful surveillance can help prevent potentially fatal complications of the disease.

Demographic Characteristics, Etiology, and Comorbidities of Patients with Cushing's Syndrome: A 10-Year Retrospective Study at a Large General Hospital in China.

Purpose To investigate the demographic characteristics, etiology, and comorbidities of Cushing's syndrome (CS) patients at a large medical center in China. Methods Records on CS patients discharged from 2008 to 2017 were retrieved from the hospital discharge abstract database (DAD) using ICD-10 codes. Demographic characteristics, etiology, and comorbidity data were analyzed. Results Cushing's disease (CD) accounted for 63.0% of CS patients, followed by adrenocortical adenoma (ACA) (20.9%), primary bilateral macronodular adrenal hyperplasia (BMAH) (6.2%), ectopic ACTH syndrome (EAS) (5.9%), primary pigmented nodular adrenocortical disease (PPNAD) (1.8%), and adrenocortical carcinoma (ACC) (1.0%). CD, ACA, ACC, and PPNAD presented marked preponderances in women (4.1 : 1, 10.5 : 1, 4.3 : 1, and 2.3 : 1, respectively), while BMAH (59.8%) and EAS (51.0%) showed slightly higher preponderances in men. CD patients were younger than ACA and EAS patients (36.1 ± 12.9 years vs. 39.4 ± 12.7 years and 36.1 ± 12.9 years vs. 41.0 ± 15.8, P < 0.001); PPNAD patients were the youngest (24.2 ± 10.8 years, P < 0.001), and BMAH patients were the oldest (51.3 ± 9.9 years, P < 0.001). Hypertension, diabetes mellitus, osteoporosis without fractures, osteoporotic fractures, dyslipidemia, and fatty liver occurred more frequently in CD patients than in ACA patients (P < 0.001 for all). Osteoporotic fractures were observed more frequently in PPAND than in ACA (26.7% vs. 9.0%, P < 0.001) and BMAH (26.7% vs. 4.9%, P < 0.001) patients. EAS patients had more severe and diverse comorbidities, with higher prevalences of hypokalemia (52.0%), diabetes mellitus (61.2%), and osteoporotic fractures (28.6%). When adjusted for age, male CD patients were associated with hypertension (OR = 2.266, 95% CI: 1.524–3.371, and P < 0.001), osteoporotic fractures (OR = 2.274, 95% CI: 1.568–3.298, and P < 0.001), fatty liver (OR = 1.435, 95% CI: 1.028–2.003, and P = 0.034), and hypokalemia (OR = 1.944, 95% CI: 1.280–2.951, and P = 0.002). Conclusions The proposed method efficiently evaluates CS patients' epidemiological profiles using hospital DADs with ICD-10 codes and thus may enrich the limited epidemiological data and contribute to clinical practice for CS.

A case of autonomous cortisol secretion in a patient with subclinical Cushing\u2019s syndrome, GNAS mutation, and paradoxical cortisol response to dexamethasone

BackgroundIncreased urinary free cortisol in response to the oral administration of dexamethasone is a paradoxical reaction mainly reported in patients with primary pigmented nodular adrenocortical disease. Here, we describe the first case of subclinical Cushing’s syndrome represented by autonomous cortisol secretion and paradoxical response to oral dexamethasone administration, harboring an activating mutation in the α subunit of the stimulatory G protein (GNAS).Case presentationA 65-year-old woman was diagnosed with subclinical Cushing’s syndrome during an evaluation for bilateral adrenal masses. Tumors of unknown origin were found in the heart, brain, thyroid gland, colon, pancreas, and both adrenal glands. Adenocarcinoma of the sigmoid colon and systemic brown-patchy skin pigmentation were also present. Her urinary cortisol levels increased in response to oral dexamethasone, while serum dehydroepiandrosterone-sulfate was not suppressed. After right adrenalectomy, genetic analysis of the resected tumor revealed the somatic GNAS activating mutation, p.R201H. Paradoxical urinary cortisol response persisted even after unilateral adrenal resection, although serum and urinary cortisol levels were attenuated.ConclusionsThis patient harbored a GNAS activating mutation, and presented with a mild cortisol- and androgen-producing adrenal adenoma. Administration of oral dexamethasone paradoxically increased cortisol levels, possibly via the stimulation of the cyclic adenosine monophosphate-dependent protein kinase A signaling pathway, which is seen in patients with pigmented nodular adrenocortical disease or Carney complex. GNAS mutations may provide clues to the mechanisms of hyper-function and tumorigenesis in the adrenal cortex, especially in bilateral adrenal masses accompanied by multiple systemic tumors. Examining GNAS mutations could help physicians detect extra-adrenal malignancies, which may contribute to an improved prognosis for patients with this type of Cushing’s syndrome.

Outcomes of Bilateral Adrenalectomy in Cushing's Syndrome.

Context:The literature on outcomes of bilateral adrenalectomy (BADx) in Cushing's syndrome (CS) is scant.Aims:The aim of this study is to analyze the short- and long-term outcomes of patients who underwent BADx and to compare the outcomes among different etiologies of CS.Settings and Design:This is a retrospective analysis of patients who underwent BADx for CS at our center between 2005 and 2018.Materials and Methods:In all, 33 patients were studied for clinical outcomes, survival rates, and long-term complications.Statistical Analysis:All analyses were performed with SPSS software (version 21.0).Results:The mean age at surgery was 39.33 ± 15.67 years. The primary etiology for CS was Cushing's disease (CD) in 42.42%, ectopic source in 36.36%, primary pigmented nodular adrenocortical disease (PPNAD) in 12.12%, and adrenocorticotrophin hormone–independent macronodular adrenal hyperplasia (AIMAH) in 9.09% of patients. The median follow-up time was 72.77 months. Improvement in hypertension and diabetes status after surgery was seen in 78% and 76.19% of patients, respectively. Proximal myopathy improved in 68% of patients. Nelson's syndrome and adrenal crisis were seen in 21.4% of patients each on long-term follow-up. Total mortality after BADx was 33.3%. Mortality in the first 30 days after surgery was seen in five patients (15.15%). Higher cortisol levels at presentation and age more than 40 years were predictors of mortality. Among the Cushing's subtypes, PPNAD had the best prognosis followed by CD. Perioperative Infections were a major cause of mortality.Conclusion:BADx is an effective treatment for CS especially in patients with PPNAD and CD but carries a significant mortality rate too.

Carney Complex.

Carney complex is a rare, autosomal dominant, multiple endocrine neoplasia and lentiginosis syndrome, caused in most patients by defects in the PRKAR1A gene, which encodes the regulatory subunit type 1α of protein kinase A. Inactivating defects of PRKAR1A lead to aberrant cyclic-AMP-protein kinase A signaling. Patients may develop multiple skin abnormalities and a variety of endocrine and non-endocrine tumors. Endocrine manifestations include primary pigmented nodular adrenocortical disease, that may cause Cushing syndrome, growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia which can result in acromegaly, as well as gonadal and thyroid tumors. Non-endocrine tumors associated with Carney complex include myxomas of the heart, breast, and other sites, psamommatous melanotic schwannomas, breast ductal adenomas, osteochondromyxomas, and a predisposition to a number of malignancies from adrenal to pancreatic and liver cancer.

Genetics of micronodular adrenal hyperplasia and Carney complex

Micronodular bilateral adrenal hyperplasia (MiBAH) is a rare cause of adrenal Cushing syndrome (CS). The investigations carried out on this disorder during the last two decades suggested that it could be divided into at least two entities: primary pigmented nodular adrenocortical disease (PPNAD) and isolated micronodular adrenocortical disease (i-MAD). The most common presentation of MiBAH is familial PPNAD as part of Carney complex (CNC) (cPPNAD). CNC, associated with multiple endocrine and non-endocrine neoplasias, was first described in 1985 in 40 patients, 10 of whom were familial cases. In 2000, we identified inactivating germline mutations of the PRKAR1A gene, encoding the regulatory subunit type 1α (RIα) of protein kinase A (PKA), in the majority of patients with CNC and PPNAD. PRKAR1A mutations causing CNC lead to increased PKA activity. Since then, additional genetic alterations in the cAMP/PKA signaling pathway leading to increased PKA activity have been described in association with MiBAH. This review summarizes older and recent findings on the genetics and pathophysiology of MiBAH, PPNAD, and related disorders.

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Carney complex review: Genetic features

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms.In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex.This review will address the genetic aspects related to Carney complex.

Adrenal venous sampling as used in a patient with primary pigmented nodular adrenocortical disease

Background: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause for hypercortisolism, and it diagnosis is highly challenging as the symptoms are often mild and the patients usually visit doctors long after the onset of their symptoms. Methods: Present herein is a rare case of PPNAD which was diagnosed thanks to adrenal venous sampling. A 21-year-old woman presented with centripetalism lumbodynia, hypertension, osteoporosis, and amenorrhea. Plasma cortisol concentrations were elevated, and there was a loss of circadian rhythms. Laboratory reports indicated her plasma adrenocorticotropic hormone (ACTH) as normal and brain imaging showed no delayed enhancement in the saddle region of the pituitary gland, confirming a diagnosis of ACTH-independent Cushing’s syndrome. Enhancement CT scan showed tiny nodules on her left adrenal gland. Adrenal venous sampling (AVS) discoverer elevated plasma cortisol in left adrenal vein and the left part of the inferior vena cava mesial side, indicating increased cortisol secretion in the left adrenal. Results: Following an adrenalectomy taken on her left adrenal, immunohistochemistry revealed PPNAD on the left adrenal. Conclusions: Adrenal venous sampling contributes to the diagnosis of PPNAD and that of Cushing’s syndrome as well. Adrenal venous sampling, an effective diagnostic of PPNAD, proves useful in diagnosis of Cushing’s syndrome.

Ultrasonographic Findings of 1385 Adrenal Masses: A Retrospective Study of 1319 Benign and 66 Malignant Masses.

To evaluate the features of adrenal masses on ultrasonography and correlate the findings with the pathologic diagnoses to help distinguish benign from malignant adrenal lesions. Ultrasonography was performed in 1363 patients with adrenal lesions. The following ultrasonographic parameters were recorded: size, shape, margin, echogenicity, echo texture, cystic necrosis, calcifications, and blood supply. The sensitivity and specificity of aggressive features for predicting malignancy were calculated. Of 1385 adrenal lesions, 66 (4.8%) were malignant: 33 malignant pheochromocytomas, 20 adrenal cortical carcinomas, 10 metastases, 2 leiomyosarcomas, and 1 primitive neuroectodermal tumor. The remaining 1319 (95.2%) lesions were benign: 832 adenomas, 182 pheochromocytomas, 153 nodular adrenal hyperplasia, 54 myelolipomas, 42 cysts, 23 ganglioneuromas, 10 schwannomas, 8 cortical tumor eosinophils, 4 teratomas, 4 tuberculosis, 4 primary pigmented nodular adrenocortical disease, and 3 Castleman disease. Most of the tumors were regular and hypoechoic. The malignant lesions were significantly larger than the benign lesions (mean ± SD, 6.3 ± 2.4 versus 4.6 ± 1.7 cm; P < .01). Significant differences between malignant and benign tumors were observed when comparing the shape, margins, echo texture and vascularization of the analyzed lesions (P < .01). An irregular shape, poor definition of margins, heterogeneous echo texture, and vascularization indicated malignancy, with sensitivity and specificity of 45.5% and 97.0%, 34.8% and 99.2%, 92.4% and 97.3%, and 15.2% and 97.5%, respectively. Ultrasonography could be an effective diagnostic supplementary tool for adrenal tumors. A large size, irregular shape, poorly defined margins, heterogeneous echo texture, and vascularization of adrenal lesions could be effective indicators of malignancy.

Adrenal venous sampling as used in a patient with primary pigmented nodular adrenocortical disease

Background: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause for hypercortisolism, and it diagnosis is highly challenging as the symptoms are often mild and the patients usually visit doctors long after the onset of their symptoms.

Revisión del complejo de Carney: Aspectos genéticos

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms.In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex.This review will address the genetic aspects related to Carney complex.