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The Lancet. Diabetes & Endocrinology Dec 2021Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it... (Review)
Review
Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it does not have a specific, easily identifiable feature and clinicians can be poorly aware of the disease. The diagnostic investigation is a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management. Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics. For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice. Bilateral forms are treated mainly with mineralocorticoid receptor antagonists. The goals of treatment are to normalise both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality. Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent. Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations drive autonomous aldosterone production in most adenomas. Many of these same mutations have been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease. In addition, germline mutations cause rare familial forms of aldosteronism (familial hyperaldosteronism types 1-4). Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients. In this Review, we discuss advances and future management approaches in the diagnosis of primary aldosteronism.
Topics: Adenoma; Adrenalectomy; Adrenocortical Adenoma; Aldosterone; Humans; Hyperaldosteronism; Hypertension; Quality of Life
PubMed: 34798068
DOI: 10.1016/S2213-8587(21)00210-2 -
JAMA Surgery Oct 2022Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal...
IMPORTANCE
Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered operative techniques and indications.
OBJECTIVE
To develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy.
EVIDENCE REVIEW
A multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included.
FINDINGS
Patients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics.
CONCLUSIONS AND RELEVANCE
Twenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Pheochromocytoma; Surgeons
PubMed: 35976622
DOI: 10.1001/jamasurg.2022.3544 -
Nature Jan 2020Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs), but so far there has been little scientific...
Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs), but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.
Topics: Adrenal Glands; Adrenalectomy; Animals; Autonomic Pathways; Cell Proliferation; Cells, Cultured; Denervation; Female; Hair Color; Humans; Male; Melanocytes; Mice; Norepinephrine; Psychological Trauma; Receptors, Adrenergic, beta-2; Stem Cell Niche; Stem Cells; Stress, Psychological; Sympathetic Nervous System
PubMed: 31969699
DOI: 10.1038/s41586-020-1935-3 -
Endocrinology and Metabolism (Seoul,... Aug 2023Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology... (Review)
Review
Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing's syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 μg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.
Topics: Pregnancy; Humans; Female; Adrenal Gland Neoplasms; Hydrocortisone; Cushing Syndrome; Adrenalectomy
PubMed: 37583083
DOI: 10.3803/EnM.2023.1779 -
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 -
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 -
Gland Surgery Jul 2019In the last three decades, endoscopic adrenalectomy has become the gold standard for the surgical treatment of most adrenal diseases. Gagner , first reported in 1992,... (Review)
Review
In the last three decades, endoscopic adrenalectomy has become the gold standard for the surgical treatment of most adrenal diseases. Gagner , first reported in 1992, the lateral trans-abdominal laparoscopic approach to adrenalectomy. Afterwards, several retrospective and comparative studies addressed the advantages of minimally invasive adrenalectomy specifically consistent in less postoperative pain, improved patients' satisfaction, shorter hospital stay and recovery time when compared to open adrenalectomy. The lateral transabdominal approach to the adrenals is currently one of the most widely used, since it allows an optimal comprehensive view of the adrenal region and surrounding structures, and provides and adequate working space. On the other hand, from a technical point of view, essential requirements for a successful laparoscopic adrenalectomy are an appropriate knowledge of retroperitoneal anatomy, a gentle tissue manipulation and a precise haemostasis technique in order to identify appropriately the structures of interest and avoid the troublesome 'oozing' that could complicate the surgical procedure.
PubMed: 31404184
DOI: 10.21037/gs.2019.06.07 -
Endocrinology and Metabolism (Seoul,... Dec 2020Since the introduction of minimally invasive surgery, laparoscopic adrenalectomy has become the main treatment option for adrenal masses. Various studies have reported... (Review)
Review
Since the introduction of minimally invasive surgery, laparoscopic adrenalectomy has become the main treatment option for adrenal masses. Various studies have reported that laparoscopic adrenalectomy showed fewer postoperative complications and faster recovery than conventional open adrenalectomy. Laparoscopic adrenalectomy can be performed through either the transperitoneal approach or the retroperitoneoscopic approach, which are widely used in most adrenal surgical procedures. Furthermore, with the development of minimally invasive surgery, organ-sparing adrenalectomy has recently emerged as a way to conserve functional adrenal gland tissue. According to recent data, organ-sparing adrenalectomy shows promising surgical, functional, and oncological outcomes including less intraoperative blood loss, maintenance of adrenal function, and low recurrence. Partial adrenalectomy was initially proposed for bilateral adrenal tumors in patients with hereditary disease to avoid chronic adrenal insufficiency. However, it has also gained popularity for the treatment of unilateral adrenal disease involving a small adrenal tumor because even patients with a unilateral adrenal gland may develop adrenal insufficiency in stressful situations. Therefore, partial adrenalectomy has become increasingly common to avoid lifelong steroid replacement and recurrence in most cases, especially in bilateral adrenal disease. This review article evaluates the current evidence on minimally invasive adrenalectomy and organ-preserving partial adrenalectomy.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Blood Loss, Surgical; Humans; Intraoperative Complications; Laparoscopy; Length of Stay; Minimally Invasive Surgical Procedures; Operative Time; Pain, Postoperative; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 33397038
DOI: 10.3803/EnM.2020.404 -
Gland Surgery Feb 2020Currently, laparoscopic adrenalectomy is considered as the preferred technique to manage adrenal tumors. However, there are no prospective randomized studies evaluating... (Review)
Review
Currently, laparoscopic adrenalectomy is considered as the preferred technique to manage adrenal tumors. However, there are no prospective randomized studies evaluating this strategy. With the recent advances in surgical equipment and the widespread of robotic technology, a robotic approach is considered as an interesting option in some medical centers. This approach seems to be feasible and safe but high-level evidence of its benefits is still lacking. This review summarizes indications, advantages and drawbacks of robotic adrenalectomy and describes its surgical technique.
PubMed: 32175258
DOI: 10.21037/gs.2019.12.11 -
Endocrine Journal Apr 2022Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has...
Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.
Topics: Adrenalectomy; Aldosterone; Humans; Hyperaldosteronism; Hypertension; Japan; Mineralocorticoid Receptor Antagonists; Renin
PubMed: 35418526
DOI: 10.1507/endocrj.EJ21-0508