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Endocrine Reviews Dec 2020An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients... (Review)
Review
An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients can be reassured and discharged, but a personalized approach based upon image analysis, endocrine workup, and clinical symptoms and signs are required in every case. Adrenocortical carcinoma remains a real concern but is restricted to <2% of all cases. Functional adrenal incidentaloma lesions are commoner (but still probably <10% of total) and the greatest challenge remains the diagnosis and optimum management of autonomous cortisol secretion. Modern-day surgery has improved outcomes and novel radiological and urinary biomarkers will improve early detection and patient stratification in future years to come.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Humans
PubMed: 32266384
DOI: 10.1210/endrev/bnaa008 -
Nature Reviews. Endocrinology Oct 2020Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular... (Review)
Review
Early diagnosis and appropriate treatment of primary aldosteronism, the most frequent cause of secondary hypertension, are crucial to prevent deleterious cardiovascular outcomes. In the past decade, the discovery of genetic abnormalities responsible for sporadic and familial forms of primary aldosteronism has improved the knowledge of the pathogenesis of this disorder. Mutations in genes encoding ion channels and pumps lead to increased cytosolic concentrations of calcium in zona glomerulosa cells, which triggers CYP11B2 expression and autonomous aldosterone production. Improved understanding of the mechanisms underlying the disease is key to improving diagnostics and to developing and implementing targeted treatments. This Review provides an update on the genetic abnormalities associated with sporadic and familial forms of primary aldosteronism, their frequency among different populations and the mechanisms explaining excessive aldosterone production and adrenal nodule development. The possible effects and uses of these findings for improving the diagnostics for primary aldosteronism are discussed. Furthermore, current treatment options of primary aldosteronism are reviewed, with particular attention to the latest studies on blood pressure and cardiovascular outcomes following medical or surgical treatment. The new perspectives regarding the use of targeted drug therapy for aldosterone-producing adenomas with specific somatic mutations are also addressed.
Topics: Adrenal Glands; Aldosterone; Animals; Humans; Hyperaldosteronism; Hypertension; Mutation
PubMed: 32724183
DOI: 10.1038/s41574-020-0382-4 -
Nature Oct 2021Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites (for example, suppressing severe systemic...
Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites (for example, suppressing severe systemic inflammation). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal-adrenal anti-inflammatory axis in mice. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal-adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2-marked nerve terminals through the ST36 site is sufficient to drive the vagal-adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2 nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways.
Topics: Acupuncture Points; Adrenal Glands; Animals; Autonomic Nervous System; Electroacupuncture; Hindlimb; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Reflex; Vagus Nerve
PubMed: 34646018
DOI: 10.1038/s41586-021-04001-4 -
Journal of the American College of... Dec 2019Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As... (Review)
Review
Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As timely diagnosis and treatment can provide a cure of hyperaldosteronism and hypertension, even when the latter is resistant to drug treatment, strategies to screen patients for PA early with a simplified diagnostic algorithm are justified. They can be particularly beneficial in some subgroups of hypertensive patients, as those who are at highest cardiovascular risk. However, identification of the surgically curable cases of PA and achievement of optimal results require subtyping with adrenal vein sampling, which, as it is technically challenging and currently performed only in tertiary referral centers, represents the bottleneck in the work-up of PA. Measures aimed at improving the clinical use of adrenal vein sampling and at developing alternative techniques for subtyping, alongside recommendations for drug treatment, including new development in the field, and for follow-up are discussed.
Topics: Adrenal Glands; Aldosterone; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension
PubMed: 31779795
DOI: 10.1016/j.jacc.2019.09.057 -
Nature Apr 2021Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we...
Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone-which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans-regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.
Topics: Adrenal Glands; Adrenalectomy; Animals; Cell Division; Corticosterone; Female; Hair Follicle; Intercellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Stem Cells; Stress, Psychological; Transcriptome; Up-Regulation
PubMed: 33790465
DOI: 10.1038/s41586-021-03417-2 -
Cancer Cell Nov 2020Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive...
Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Cell Differentiation; Cell Proliferation; Chromaffin Cells; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Neuroblastoma; Phenotype; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 32946775
DOI: 10.1016/j.ccell.2020.08.014 -
Endocrine Dec 2022In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment... (Review)
Review
BACKGROUND
In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment of endocrine glands. This induced regulatory authorities to ban some of these compounds and to carefully investigate others in order to prevent EDCs-related conditions. As a result, we witnessed a growing awareness and interest on this topic.
AIMS
This paper aims to summarize current evidence regarding the detrimental effects of EDCs on pivotal endocrine glands like pituitary, thyroid and adrenal ones. Particularly, we directed our attention on the known and the hypothesized mechanisms of endocrine dysfunction brought by EDCs. We also gave a glimpse on recent findings from pioneering studies that could in the future shed a light on the pathophysiology of well-known, but poorly understood, endocrine diseases like hormone-producing adenomas.
CONCLUSIONS
Although intriguing, studies on endocrine dysfunctions brought by EDCs are challenging, in particular when investigating long-term effects of EDCs on humans. However, undoubtedly, it represents a new intriguing field of science research.
Topics: Humans; Endocrine Disruptors; Thyroid Gland; Endocrine System Diseases; Pituitary Gland; Pituitary Diseases; Adrenal Glands
PubMed: 35604630
DOI: 10.1007/s12020-022-03076-x -
The Journal of Clinical Endocrinology... Jan 2021Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA).
OBJECTIVE
Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA).
CONTEXT
Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals.
PATIENTS AND METHODS
Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists.
RESULTS
Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists.
CONCLUSION
The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.
Topics: Adrenal Glands; Adrenalectomy; Adult; Cohort Studies; Consensus; Cytochrome P-450 CYP11B2; Cytodiagnosis; Diagnostic Techniques, Endocrine; Female; Germany; Histological Techniques; Humans; Hyperaldosteronism; Hypertension; Immunohistochemistry; Internationality; Male; Middle Aged; Practice Guidelines as Topic; Societies, Medical
PubMed: 32717746
DOI: 10.1210/clinem/dgaa484 -
Biomedica : Revista Del Instituto... May 2020Primary adrenal insufficiency is a defect in glucocorticoid, mineralocorticoid and sexual androgens production. Patients with this disorder have low cortisol levels and...
Primary adrenal insufficiency is a defect in glucocorticoid, mineralocorticoid and sexual androgens production. Patients with this disorder have low cortisol levels and aldosterone deficiency with concomitant hyponatremia and hyperkalemia. The most common etiology of this disease is the production of antibodies against the enzyme 21 hydroxylase. Another common cause, particularly in low income countries, are infectious diseases. Several micro-organisms have been reported as a causal agent in adrenal insufficiency including Mycobacterium tuberculosis, Mycobacterium avium complex, Neisseria meningitidis, Pseudomonas aeruginosa, Haemophilus influenzae, cytomegalovirus, Pneumocystis jirovecii, Histoplasma capsulatum, Blastomyces dermatiditis, Cryptococcus neoformans, Cocciodiodes immitis, Nocardia spp. and Paracoccidioides brasiliensis. In this article, we present the computerized tomography and the adrenal biopsy of a patient with adrenal insufficiency. The final diagnosis was paracoccidioidomycosis.
Topics: Adrenal Gland Diseases; Adrenal Insufficiency; Humans; Male; Middle Aged; Paracoccidioidomycosis
PubMed: 32463603
DOI: 10.7705/biomedica.4844