A ZNRF3-dependent Wnt/ß-catenin signaling gradient is required for adrenal homeostasis.

Spatiotemporal control of Wnt signaling is essential for the development and homeostasis of many tissues. The transmembrane E3 ubiquitin ligases ZNRF3 (zinc and ring finger 3) and RNF43 (ring finger protein 43) antagonize Wnt signaling by promoting degradation of frizzled receptors. ZNRF3 and RNF43 are frequently inactivated in human cancer, but the molecular and therapeutic implications remain unclear. Here, we demonstrate that adrenocortical-specific loss of ZNRF3, but not RNF43, results in adrenal hyperplasia that depends on Porcupine-mediated Wnt ligand secretion. Furthermore, we discovered a Wnt/ß-catenin signaling gradient in the adrenal cortex that is disrupted upon loss of ZNRF3. Unlike ß-catenin gain-of-function models, which induce high Wnt/ß-catenin activation and expansion of the peripheral cortex, ZNRF3 loss triggers activation of moderate-level Wnt/ß-catenin signaling that drives proliferative expansion of only the histologically and functionally distinct inner cortex. Genetically reducing ß-catenin dosage significantly reverses the ZNRF3-deficient phenotype. Thus, homeostatic maintenance of the adrenal cortex is dependent on varying levels of Wnt/ß-catenin activation, which is regulated by ZNRF3.

Treatment of Primary Pigmented Nodular Adrenocortical Disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS), which mainly occurs in children and young adults. Treatment options with proven clinical efficacy for PPNAD include adrenalectomy (bilateral or unilateral adrenalectomy) and drug treatment to control hypercortisolemia. Previously, the main treatment of PPNAD is bilateral adrenal resection and long-term hormone replacement after surgery. In recent years, cases reports suggest that unilateral or subtotal adrenal resection can also lead to long-term remission in some patients without the need for long-term hormone replacement therapy. Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients with severe hypercortisolism. In addition, tryptophan hydroxylase inhibitor, COX2 inhibitor Celecoxib, somatostatin and other drugs targeting the possible pathogenic mechanisms of the disease are under study, which are expected to be applied to the clinical treatment of PPNAD in the future. In this review, we summarize the recent progress on treatment of PPNAD, in which options of surgical methods, research results of drugs acting on possible pathogenic mechanisms, and the management during gestation are described in order to provide new ideas for clinical treatment.

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome.

Bilateral hyperplasias of the adrenal cortex are rare causes of chronic endogenous hypercortisolemia also called Cushing syndrome. These hyperplasias have been classified in two categories based on the adrenal nodule size: the micronodular types include Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) and the macronodular also named Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). This review discusses the genetic and molecular causes of these different forms of hyperplasia that involve mutations and dysregulation of various regulators of the cAMP/protein kinase A (PKA) pathway. PKA signaling is the main pathway controlling cortisol secretion in adrenocortical cells under ACTH stimulation. Although mutations of the regulatory subunit R1α of PKA (PRKAR1A) is the main cause of familial and sporadic PPNAD, inactivation of two cAMP-binding phosphodiesterases (PDE11A and PDE8B) are associated with iMAD even if they are also found in PPNAD and PBMAH cases. Interestingly, PBMAH that is observed in multiple familial syndrome such as APC, menin, fumarate hydratase genes, has initially been associated with the aberrant expression of G-protein coupled receptors (GPCR) leading to an activation of cAMP/PKA pathway. However, more recently, the discovery of germline mutations in Armadillo repeat containing protein 5 (ARMC5) gene in 25-50% of PBMAH patients highlights its importance in the development of PBMAH. The potential relationship between ARMC5 mutations and aberrant GPCR expression is discussed as well as the potential other causes of PBMAH.

A Gene-Based Classification of Primary Adrenocortical Hyperplasias.

Primary or adrenocorticotropin-independent adrenocortical tumors and hyperplasias represent a heterogeneous group of adrenocortical neoplasms that arise from various genetic defects, either in isolation or familial. The traditional classification as adenomas, hyperplasias, and carcinomas is non-specific. The recent identification of various germline and somatic genes in the development of primary adrenocortical hyperplasias has provided important new insights into the molecular pathogenesis of adrenal diseases. In this new era of personalized care and genetics, a gene-based classification that is more specific is required to assist in the understanding of their disease processes, hormonal functionality and signaling pathways. Additionally, a gene-based classification carries implications for treatment, genetic counseling and screening of asymptomatic family members. In this review, we discuss the genetics of benign adrenocorticotropin-independent adrenocortical hyperplasias, and propose a new gene-based classification system and diagnostic algorithm that may aid the clinician in prioritizing genetic testing, screening and counseling of affected, at risk individuals and their relatives.

Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review.

Hypercortisolemia in females may lead to menstrual cycle disturbances, infertility, hirsutism and acne. Herewith, we present a 18-year-old patient, who was diagnosed due to weight gain, secondary amenorrhea, slowly progressing hirsutism, acne and hot flashes. Thorough diagnostics lead to a conclusion, that the symptoms was the first manifestation of primary pigmented nodular adrenocortical disease (PPNAD). All symptoms of Cushing syndrome including hirsutism and menstrual disturbances resolved after bilateral adrenalectomy. Our report indicates that oligo- or amenorrhea, hirsutism, acne in combination with weight gain, growth failure, hypertension and slightly expressed cushingoid features in a young woman requires diagnostics towards hypercortisolemia. Despite PPNAD is a very rare cause of ACTH-independent Cushing syndrome, it has to be taken into consideration, especially when adrenal glands appear to be normal on imaging and paradoxical rise in cortisol level in high-dose dexamethasone test is observed. Unlike in our patient, in vast majority of patients, PPNAD is associated with Carney complex (CC). Therefore, these patients and their first-degree relatives should be always carefully screened for symptoms of PPNAD, CC and genetic mutations of PRKAR1A, PDE11A, and PDE8B genes.

mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).

Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating mutations of the PRKAR1A tumor suppressor gene that encodes the regulatory subunit R1α of the cAMP-dependent protein kinase (PKA). In human and mouse adrenocortical cells, these mutations lead to increased PKA activity, which results in increased resistance to apoptosis that contributes to the tumorigenic process. We used in vitro and in vivo models to investigate the possibility of a crosstalk between PKA and mammalian target of rapamycin (mTOR) pathways in adrenocortical cells and its possible involvement in apoptosis resistance. Impact of PKA signaling on activation of the mTOR pathway and apoptosis was measured in a mouse model of PPNAD (AdKO mice), in human and mouse adrenocortical cell lines in response to pharmacological inhibitors and in PPNAD tissues by immunohistochemistry. AdKO mice showed increased mTOR complex 1 (mTORC1) pathway activity. Inhibition of mTORC1 by rapamycin restored sensitivity of adrenocortical cells to apoptosis in AdKO but not in wild-type mice. In both cell lines and mouse adrenals, rapid phosphorylation of mTORC1 targets including BAD proapoptotic protein was observed in response to PKA activation. Accordingly, BAD hyperphosphorylation, which inhibits its proapoptotic activity, was increased in both AdKO mouse adrenals and human PPNAD tissues. In conclusion, mTORC1 pathway is activated by PKA signaling in human and mouse adrenocortical cells, leading to increased cell survival, which is correlated with BAD hyperphosphorylation. These alterations could be causative of tumor formation.

Diurnal Plasma Cortisol Measurements Utility in Differentiating Various Etiologies of Endogenous Cushing Syndrome.

Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia.

Current views on the diagnosis and management of hypokalaemia in children.

UNLABELLED: Hypokalaemia is a common electrolyte disorder in children, caused by decreased potassium intake, increased gastrointestinal and urinary losses or transcellular shift. Patients with severe hypokalaemia may suffer from symptoms such as life-threatening cardiac arrhythmias. The aim of our study was to review the aetiology of hypokalaemia, suggest a diagnostic algorithm and discuss the management of patients with various aetiologies of hypokalaemia. CONCLUSION: Understanding the pathophysiology of hypokalaemic states, along with a detailed medical history, physical examination and specific laboratory tests are required for proper diagnosis and appropriate treatment.

Analogues of etomidate: modifications around etomidate's chiral carbon and the impact on in vitro and in vivo pharmacology.

BACKGROUND: R-etomidate possesses unique desirable properties but potently suppresses adrenocortical function. Consequently, efforts are being made to define structure-activity relationships with the goal of designing analogues with reduced adrenocortical toxicity. The authors explored the pharmacological impact of modifying etomidate's chiral center using R-etomidate, S-etomidate, and two achiral etomidate analogues (cyclopropyl etomidate and dihydrogen etomidate). METHODS: The γ-aminobutyric acid type A receptor modulatory potencies of drugs were assessed in oocyte-expressed α1(L264T)ß3γ2L and α1(L264T)ß1γ2L γ-aminobutyric acid type A receptors (for each drug, n = 6 oocytes per subtype). In rats, hypnotic potencies and durations of action were measured using a righting reflex assay (n = 26 to 30 doses per drug), and adrenocortical potencies were quantified by using an adrenocorticotropic hormone stimulation test (n = 20 experiments per drug). RESULTS: All four drugs activated both γ-aminobutyric acid type A receptor subtypes in vitro and produced hypnosis and suppressed adrenocortical function in rats. However, drug potencies in each model ranged by 1 to 2 orders of magnitude. R-etomidate had the highest γ-aminobutyric acid type A receptor modulatory, hypnotic, and adrenocortical inhibitory potencies. Respectively, R-etomidate, S-etomidate, and cyclopropyl etomidate were 27.4-, 18.9-, and 23.5-fold more potent activators of receptors containing ß3 subunits than ß1 subunits; however, dihydrogen etomidate's subunit selectivity was only 2.48-fold and similar to that of propofol (2.08-fold). S-etomidate was 1/23rd as potent an adrenocortical inhibitor as R-etomidate. CONCLUSION: The linkage between the structure of etomidate's chiral center and its pharmacology suggests that altering etomidate's chiral center may be used as part of a strategy to design analogues with more desirable adrenocortical activities and/or subunit selectivities.

Distinguishing cystic degeneration from other aging lesions in the adrenal cortex of Sprague-Dawley rats.

Cystic degeneration of the adrenal cortex is a common age-related finding in the Sprague-Dawley (SD) rat strain occurring more frequently in females. Compression of the adjacent cortex, a common hallmark of benign adrenal cortical tumors, often accompanies foci of cystic degeneration, creating a diagnostic challenge. Accurately differentiating these relatively common degenerative changes from proliferative lesions is critical in safety assessment studies. Cystic degeneration typically arises in the zona fasciculata of the adrenal cortex and often causes compression along the margin of the lesion. The degenerating cells are large, with abundant eosinophilic cytoplasm, or contain clear cytoplasmic vacuoles. Mitotic figures are generally uncommon. In many cases, cystic degeneration appears to arise in areas of hypertrophy in the zona fasciculata. In contrast, adrenal cortical hyperplasia and adrenal cortical adenoma are frequently comprised of smaller cells that cause compression of adjacent cortex, and in some cases mitotic figures are observed. Cytological detail and growth patterns should be considered more useful criteria than compression alone for separating degenerative cystic lesions from proliferative lesions in the adrenal cortex of SD rats.

[A pedigree study of a patient with primary pigmented nodular adrenocortical disease and familial gene mutation].

OBJECTIVE: To clarify the clinical features and genetic background of a kindred of primary pigmented nodular adrenocortical disease (PPNAD). METHODS: Detailed clinical characteristics and laboratory test results from a ten-year old girl diagnosed as PPNAD were collected. Seven members of her family were screened for Cushing syndrome and Carney complex, and their blood DNA was extracted and sequenced for PRKAR1A, PDE11A, PDE8B and CTNNB1 mutations with ABI3730. RESULTS: The girl presented with symptoms and signs of hypercortisolism, while no features of Carney complex were observed. Hypercortisolemia, suppressed corticotrophin and high urinary free cortisol level were revealed. Cortisol level could not be suppressed both in high and low dose dexamethasone suppression test. The diagnosis of adrenocorticotrophic hormone (ACTH)-independent Cushing syndrome was established. Image and pathology of adrenal glands were in accordance with PPNAD. Other family members showed no evidence of Cushing syndrome or Carney complex. DNA sequencing showed that the patient harbored a missense mutation, C18G. Her father and younger sister were proved to be carriers of this mutation. CONCLUSION: A Chinese PPNAD family was identified clinically and genetically, and a novel missense mutation of PRKAR1A was found.

[Clinical characteristics of adrenocorticotropic hormone independent macronodular adrenal hyperplasia: a report of 30 cases].

OBJECTIVE: To explore the clinical characteristics of adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH). METHODS: A total of 30 AIMAH patients from January 2001 to December 2011 at our hospital were reviewed retrospectively and their clinical data collected. RESULTS: AIMAH was equally distributed between genders. Their mean age was 44 ± 9 years and median course of disease 5 years. Hypertension was the most common clinical manifestation. Circadian rhythm of plasma cortisol disappeared in all patients, and the level of 24 hour urinary free cortisol (24 hUFC) was normal only in 4 (13.3%) patients. Both low and high dose dexamethasone suppression tests were not suppressed in 30 (100.0%) and 28 (93.3%) patients respectively. The stimulation tests for detecting aberrant expression of hormone receptors were performed in 14 patients. At least one aberrant cortisol response was identified in 12 patients. Twenty-five patients underwent adrenalectomy. Among 7 patients of bilateral adrenalectomy, 6 achieved remission while 8 patients did so among 14 patients of unilateral adrenalectomy. CONCLUSIONS: AIMAH should be considered in patients with massively enlarged bilateral adrenal glands. Treatment modalities should be decided according to clinical manifestations and cortisol level so as to relieve symptoms and improve prognosis.

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review.

Aims: Primary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing's syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD. Methods: Databases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles. Results: A total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations (PRKAR1A, PDE11A, PRKACA, CTNNB1, PDE8B, and ARMC5) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD (p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period. Conclusions: For young patients with Cushing's syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023416988.

The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias.

BACKGROUND: The objective of the present study was twofold: to demonstrate our experience with unilateral adrenalectomy in the treatment of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) caused by bilateral adrenocortical hyperplasias, and to evaluate the long-term results as evidenced by the main laboratory and clinical findings. METHODS: From February 2000 to August 2009, unilateral adrenalectomy was performed on 27 patients with ACTH-independent CS and bilateral adrenocortical hyperplasias, including 14 patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and 13 patients with primary pigmented nodular adrenocortical disease (PPNAD). Signs and symptoms of CS, endocrine examinations, and radiographic imaging were evaluated preoperatively and postoperatively. RESULTS: At a median follow-up of 69 months (range: 23-120 months) for AIMAH and 47 months (range: 16-113 months) for PPNAD, 25 patients were cured by unilateral adrenalectomy. Serum cortisol level, daily urinary free cortisol (UFC), and plasma ACTH regained the normal range in both AIMAH and PPNAD patients at monthly follow-up visits; the circadian serum cortisol rhythm returned to normal, and a normal responsiveness to overnight low-dose dexamethasone administration (LDDST) became obvious. Both systolic and diastolic blood pressure (BP) levels were significantly reduced: 85 % of patients recovered normal BP levels, and the remaining patients need antihypertensive drugs, but at a reduced dose. No surgery-related morbidity occurred, and there was no sign of further enlargement of the residual adrenal gland after successful unilateral adrenalectomy. One patient with PPNAD and another patient with AIMAH with similar weights and sizes of the bilateral adrenals needed contralateral adrenalectomy. CONCLUSIONS: Unilateral adrenalectomy may be the suitable treatment for selected patients with AIMAH and PPNAD. It can achieve long-term remission of CS and improve glycemic control and BP values.

Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

An unusual presentation of Carney complex with diffuse primary pigmented nodular adrenocortical disease on one adrenal gland and a nonpigmented adrenocortical adenoma and focal primary pigmented nodular adrenocortical disease on the other.

A 24-year-old female patient with cushingoid appearance was admitted in May 2000. The endocrine studies showed ACTH-independent Cushing's syndrome. A 2-day high-dose dexamethasone suppression test (HDDST) revealed paradoxical increase of 24 h urinary free cortisol (UFC). Abdominal computed tomography demonstrated a left adrenal nodule (3 x 2 cm in diameter). An adrenal scintigram with ¹³¹I-6ß-iodomethyl-19-norcholesterol showed uptake of the isotope in the left adrenal gland and non-visualization in the right adrenal gland throughout the examination course. A retroperitoneoscopic left total adrenalectomy was performed in July 2000. The cut surface of the left adrenal was yellow-tan grossly. Microscopically, the left adrenal nodule contained a nonpigmented adrenocortical adenoma (NP) and another focal primary pigmented nodular adrenocortical disease (PPNAD, FP) mixed lesion. The immunohistochemical studies of CYP17 demonstrate positive in NP and FP of the left adrenal gland. Very low baseline morning plasma cortisol (0.97 µg/dL) and subnormal ACTH (8.16 pg/mL) levels were measured 1.5 months after left adrenalectomy. Right adrenal gland recovered its function 6 months after left adrenalectomy. Plasma cortisol could be suppressed to 3.47 µg/dL by overnight low-dose dexamethasone suppression test 65 months after left adrenalectomy. Cushingoid features still did not appear 122 months after left adrenalectomy. In May 2011, this patient was readmitted due to cushingoid characteristics. Paradoxical rise of 24-h UFC to 2-day HDDST was demonstrated. Ultrasonography of thyroid showed bilateral thyroid cysts. Subtotal right adrenalectomy about 80% of right adrenal was performed. Diffuse PPNAD of the right adrenal was proved pathologically. Immunohischemical stain for CYP17 is positive in the right adrenal gland but weaker positive than that in the left adrenal gland. The genetic study of the peripheral blood, left adrenocortical nodule, and right PPNAD all showed p.R16X (c.46C>T) mutation of the PRKAR1A gene.

Recurrent left atrial myxomas in Carney complex: a genetic cause of multiple strokes that can be prevented.

BACKGROUND: Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical, and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described. The regulatory subunit (R1A) of the protein kinase gene (PRKAR1A) is mutated in >60% of patients with Carney complex. METHODS: We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere; a total of 7 patients with 16 recurrent atrial myxomas and >14 episodes of strokes were identified. RESULTS: Neurologic deficits were reported; in 1 patient, an aneurysm developed at the site of a previous stroke. All patients were females, were also diagnosed with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, and c.177+1G>A) were located in exons 3 to 5 and introns 2 to 3, and all led to a non-sense PRKAR1A mRNA. CONCLUSIONS: Female patients with Carney complex appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes.

[Post-resuscitation syndrome. Role of inflammation after cardiac arrest]. / Postreanimationssyndrom. Rolle der Entzündung nach Herz-Kreislauf-Stillstand.

Cardiac arrest with subsequent cardiopulmonary resuscitation causes an ischemic reperfusion syndrome of the whole body resulting in localized damage of particularly sensitive organs, such as the brain and heart, together with systemic sequelae. The main factor is a generalized activation of inflammatory reactions resulting in symptoms similar in many aspects to those of sepsis. Systemic inflammation strengthens organ damage due to disorders in the macrocirculation and microcirculation due to metabolic imbalance as well as the effects of direct leukocyte transmitted tissue destruction. The current article gives an overview on the role of inflammation following cardiac arrest and presents in detail the underlying mechanisms, the clinical symptoms and possible therapeutic approaches.