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The Journal of Clinical Endocrinology... Jul 2020The clinical spectrum and knowledge of the molecular mechanisms underlying primary aldosteronism (PA), the most frequent form of endocrine hypertension, has evolved over... (Review)
Review
CONTEXT
The clinical spectrum and knowledge of the molecular mechanisms underlying primary aldosteronism (PA), the most frequent form of endocrine hypertension, has evolved over recent years. In accordance with the Endocrine Society guidelines and in light of the growing evidence showing adverse cardiovascular outcomes, it is expected that a progressively wider population of patients affected by hypertension will be screened for PA, including the elderly.
EVIDENCE ACQUISITION
A systematic search of PubMed was undertaken for studies related to the renin-angiotensin-aldosterone system (RAAS), PA, and adrenal histopathology in the elderly population.
EVIDENCE SYNTHESIS
Several studies showed an age-dependent decrease in the activity of RAAS, together with a progressive decrease of the aldosterone response to sodium intake, particularly after the sixth decade of life. The positive correlation between age and serum aldosterone during liberal sodium intake over serum aldosterone during sodium restriction is paralleled by histological changes in adrenal aldosterone synthase (CYP11B2) expression patterns. Immunohistochemical studies showed a progressive loss of the continuous expression of CYP11B2 in the adrenal zona glomerulosa with aging and a concomitant increase of aldosterone-producing cell clusters, which might be responsible for relatively autonomous aldosterone production. Additionally, following PA confirmation and subtype diagnosis, older age is correlated with a lower benefit after adrenalectomy for unilateral PA.
CONCLUSIONS
Accumulating evidence suggests that RAAS physiology and regulation show age-related changes. Further studies may investigate to what extent these variations might affect the diagnostic workup of patients affected by PA.
Topics: Adrenal Glands; Age Factors; Aged; Aging; Aldosterone; Humans; Hyperaldosteronism
PubMed: 32303754
DOI: 10.1210/clinem/dgaa206 -
Biomedicine & Pharmacotherapy =... Nov 2021Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat...
AIM
Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat insomnia for more than thousands of years. Our previous study showed that MSZRD can improve the gastrointestinal discomfort related insomnia by regulating Orexin-A. This study is the first study to evaluate the effects and possible mechanisms of MSZRD in mice with insomnia caused by p-chlorophenylalanine (PCPA) combined with multifactor random stimulation.
METHODS
After 14 days of multifactor stimulation to ICR mice, a PCPA suspension (30 mg/mL) was injected intraperitoneally for two consecutive days to establish an insomnia model. Three different doses of MSZRD (3.6, 7.2, and 14.4 g/kg/day) were given to ICR mice for 24 days. The food intake and back temperature were measured, and behavioral tests and pentobarbital sodium-induced sleep tests were conducted. The levels of Orexin-A, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and adrenocortical hormones (CORT) in the serum and 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in hypothalamus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) were measured by high-performance liquid chromatography (HPLC). The expression of 5HT1A receptor (5-HTRIA) and orexin receptor 2 antibody (OX2R) was measured by Western blot (WB) and immunohistochemical staining (ICH). Hematoxylin and eosin (H&E) staining and Nissl staining were used to assess the histological changes in hypothalamus tissue.
RESULTS
Of note, MSZRD can shorten the sleep latency of insomnia mice (P < 0.05, 0.01), prolonged the sleep duration of mice (P < 0.05, 0.01), and improve the circadian rhythm disorder relative to placebo-treated animals. Furthermore, MSZRD effectively increased the content of 5-HT and 5-HTR1A protein in the hypothalamus of insomnia mice (P < 0.05, 0.01), while downregulated the content of DA and NE (P < 0.05, 0.01). Importantly, serum GABA concentration was increased by treatment with MSZRD (P < 0.05), as reflected by a decreased Glu/GABA ratio (P < 0.05). Moreover, MSZRD decreased the levels of CORT, ACTH, and CRH related hormones in HPA axis (P < 0.05, 0.01). At the same time, MSZRD significantly downregulated the serum Orexin-A content in insomnia mice (P < 0.05), as well as hypothalamic OX2R expression (P < 0.05). In addition, MSZRD also improved the histopathological changes in hypothalamus in insomnia mice.
CONCLUSION
MSZRD has sleep-improvement effect in mice model of insomnia. The mechanism may be that regulating the expression of Orexin-A affects the homeostasis of HPA axis and the release of related neurotransmitters in mice with insomnia.
Topics: Adrenal Glands; Animals; Behavior, Animal; Disease Models, Animal; Drugs, Chinese Herbal; Hypothalamo-Hypophyseal System; Male; Mice, Inbred ICR; Neurotransmitter Agents; Orexin Receptors; Orexins; Signal Transduction; Sleep; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Mice
PubMed: 34509822
DOI: 10.1016/j.biopha.2021.112141 -
Laeknabladid Jun 2023A 50-year old male presented to our emergency department with sudden abdominal pain. Upon arrival he was diaphoretic, pale and tachycardic. A CT showed retroperitoneal...
A 50-year old male presented to our emergency department with sudden abdominal pain. Upon arrival he was diaphoretic, pale and tachycardic. A CT showed retroperitoneal hemorrhage with suspected tumor at the left adrenal gland. He was quickly stabilized with intravenous fluids and blood transfusion. Rebleed occurs roughly a week after discharge and a new CT showed a visceral pseudoaneurysm from the left middle adrenal artery. The pseudoaneurysm was embolized and the patient discharged in good condition. Follow-up MRI depicted reabsorption of the hematoma and no adrenal tumor. Thus, the etiology of the previous retroperitonal hemorrhage is considered spontaneous.
Topics: Male; Humans; Middle Aged; Aneurysm, False; Retroperitoneal Space; Hemorrhage; Hematoma; Adrenal Glands
PubMed: 37233620
DOI: 10.17992/lbl.2023.05.744 -
Frontiers in Endocrinology 2022Primary aldosteronism is the most common form of secondary arterial hypertension, due to excessive aldosterone production from the adrenal gland. Although somatic... (Review)
Review
Primary aldosteronism is the most common form of secondary arterial hypertension, due to excessive aldosterone production from the adrenal gland. Although somatic mutations have been identified in aldosterone producing adenoma, the exact mechanisms leading to increased cell proliferation and nodule formation remain to be established. One hypothesis is that changes in vascular supply to the adrenal cortex, due to phenomena of atherosclerosis or high blood pressure, may influence the morphology of the adrenal cortex, resulting in a compensatory growth and nodule formation in response to local hypoxia. In this review, we will summarize our knowledge on the mechanisms regulating adrenal cortex development and function, describe adrenal vascularization in normal and pathological conditions and address the mechanisms allowing the cross-talk between the hormonal and vascular components to allow the extreme tissue plasticity of the adrenal cortex in response to endogenous and exogenous stimuli. We will then address recent evidence suggesting a role for alterations in the vascular compartment that could eventually be involved in nodule formation and the development of primary aldosteronism.
Topics: Humans; Hyperaldosteronism; Adrenal Cortex Neoplasms; Adrenocortical Adenoma; Adrenal Glands; Aldosterone; Hypertension
PubMed: 36506065
DOI: 10.3389/fendo.2022.995228 -
International Journal of Molecular... Jan 2021Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and... (Review)
Review
Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.
Topics: Adrenal Glands; Androgens; Animals; Gonadal Steroid Hormones; Humans; Male; Prostate; Steroids; Testis
PubMed: 33466491
DOI: 10.3390/ijms22010466 -
Australian Journal of General Practice 2021Diseases of the adrenal gland occur rather more frequently than is appreciated and provide a series of challenges for the treating practitioner.
BACKGROUND
Diseases of the adrenal gland occur rather more frequently than is appreciated and provide a series of challenges for the treating practitioner.
OBJECTIVE
The aim of this article is to provide a practical approach to common adrenal disorders encountered in general practice, including adrenal incidentalomas, primary aldosteronism and adrenal insufficiency.
DISCUSSION
Adrenal incidentalomas are adrenal mass lesions >1 cm in diameter serendipitously discovered by radiological examination. They require structural assessment to distinguish common benign pathologies from the rare malignant ones, and biochemistry to exclude hypersecretion syndromes resulting from excess cortisol, aldosterone or catecholamines. Primary aldosteronism represents >5% of hypertension and may be cured or specifically treated, yet is rarely screened for in primary care. Low cortisol levels may reflect adrenal insufficiency due to either adrenal failure, where adrenocorticotropic hormone levels will be elevated, or secondary to hypothalamic-pituitary dysfunction resulting from structural lesions or, increasingly, prescribed exogenous synthetic glucocorticoids and nonconventional therapies.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Aldosterone; Humans; Hydrocortisone; Hyperaldosteronism
PubMed: 33543156
DOI: 10.31128/AJGP-09-20-5619 -
Cell Reports Jun 2022Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the...
Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class II macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.
Topics: Adrenal Glands; Animals; Female; Histocompatibility Antigens Class II; Leukocyte Count; Macrophages; Male; Mice; Monocytes; Sex Characteristics
PubMed: 35705045
DOI: 10.1016/j.celrep.2022.110949 -
Frontiers in Endocrinology 2022Mixed corticomedullary tumor (MCMT) of the adrenal gland is an extremely rare tumor characterized by an admixture of steroidogenic cells and chromaffin cells in a single... (Review)
Review
Mixed corticomedullary tumor (MCMT) of the adrenal gland is an extremely rare tumor characterized by an admixture of steroidogenic cells and chromaffin cells in a single tumor mass simultaneously producing adrenocortical hormones and catecholamines; it is associated with ectopic adrenocorticotropic hormone (ACTH) in some cases. We reviewed and summarized clinicopathological data of 28 MCMTs, including four metastatic tumors in 26 previous reports. These reports included 21 females and 7 males, and the average tumor sizes were 4.8 ± 2.5 cm and 12.6 ± 6.4 cm in the non-metastatic and metastatic groups, respectively (P<0.001). The clinical manifestations and laboratory data were as follows: Cushing or subclinical Cushing syndrome, 58% (14/24); hypertension, 71% (17/24); elevated adrenocortical hormones, 75% (18/24); elevated catecholamines, 75% (18/24); and ectopic ACTH, 71% (10/14). All four patients with metastatic MCMTs had poor prognoses and elevated adrenocortical hormone levels; however, only two patients had elevated catecholamine levels. Immunohistochemistry was essential for the pathologic diagnosis of MCMTs. In this study, using an improved technique, we detected ectopic ACTH-producing cells in the same paraffin-embedded sections reported to be negative in our previous reports. As MCMT is composed of cells with embryologically different origins, its pathogenesis has been explained by various hypotheses. We compared MCMT to the adrenal gland of birds and the early stage of human fetuses, in which nests of chromaffin cells and steroidogenic cells admix without the formation of cortex and medulla. MCMT is characterized by the immaturity of organogenesis and might be classified as an adrenal embryonal tumor.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Catecholamines; Female; Humans; Male; Pheochromocytoma
PubMed: 36187098
DOI: 10.3389/fendo.2022.1026918 -
Frontiers in Endocrinology 2023The adrenal glands are small endocrine glands located on top of each kidney, producing hormones regulating important functions in our body like metabolism and stress.... (Review)
Review
The adrenal glands are small endocrine glands located on top of each kidney, producing hormones regulating important functions in our body like metabolism and stress. There are several underlying causes for adrenal insufficiency, where an autoimmune attack by the immune system is the most common cause. A number of genes are known to confer early onset adrenal disease in monogenic inheritance patterns, usually genetic encoding enzymes of adrenal steroidogenesis. Autoimmune primary adrenal insufficiency is usually a polygenic disease where our information recently has increased due to genome association studies. In this review, we go through the physiology of the adrenals before explaining the different reasons for adrenal insufficiency with a particular focus on autoimmune primary adrenal insufficiency. We will give a clinical overview including diagnosis and current treatment, before giving an overview of the genetic causes including monogenetic reasons for adrenal insufficiency and the polygenic background and inheritance pattern in autoimmune adrenal insufficiency. We will then look at the autoimmune mechanisms underlying autoimmune adrenal insufficiency and how autoantibodies are important for diagnosis. We end with a discussion on how to move the field forward emphasizing on the clinical workup, early identification, and potential targeted treatment of autoimmune PAI.
Topics: Humans; Addison Disease; Adrenal Insufficiency; Adrenal Glands; Autoantibodies; Kidney
PubMed: 38027140
DOI: 10.3389/fendo.2023.1285901 -
Current Opinion in Endocrinology,... Jun 2022Renin-independent aldosterone production from one or both affected adrenal(s), a condition known as primary aldosteronism (PA), is a common cause of secondary... (Review)
Review
PURPOSE OF REVIEW
Renin-independent aldosterone production from one or both affected adrenal(s), a condition known as primary aldosteronism (PA), is a common cause of secondary hypertension. In this review, we aimed to summarize recent findings regarding pathophysiology of bilateral forms of PA, including sporadic bilateral hyperaldosteronism (BHA) and rare familial hyperaldosteronism.
RECENT FINDINGS
The presence of subcapsular aldosterone synthase (CYP11B2)-expressing aldosterone-producing micronodules, also called aldosterone-producing cell clusters, appears to be a common histologic feature of adrenals with sporadic BHA. Aldosterone-producing micronodules frequently harbor aldosterone-driver somatic mutations. Other potential factors leading to sporadic BHA include rare disease-predisposing germline variants, circulating angiotensin II type 1 receptor autoantibodies, and paracrine activation of aldosterone production by adrenal mast cells. The application of whole exome sequencing has also identified new genes that cause inherited familial forms of PA.
SUMMARY
Research over the past 10 years has significantly improved our understanding of the molecular pathogenesis of bilateral PA. Based on the improved understanding of BHA, future studies should have the ability to develop more personalized treatment options and advanced diagnostic tools for patients with PA.
Topics: Adrenal Glands; Aldosterone; Cytochrome P-450 CYP11B2; Humans; Hyperaldosteronism
PubMed: 35621175
DOI: 10.1097/MED.0000000000000729