Primärer Hyperaldosteronismus – warum diagnostizieren wir immer noch so wenige Patienten?

2020 ◽  
Vol 145 (11) ◽  
pp. 716-721
Author(s):  
Laura Handgriff ◽  
Martin Reincke
Keyword(s):  
Diabetes Mellitus ◽  
Primary Aldosteronism ◽  
Outcome Study ◽  
Adrenal Hyperplasia ◽  
Primärer Hyperaldosteronismus ◽  
Oder Eine ◽  
Pet Ct ◽  
Jüngere Patienten ◽  
Bilateral Adrenal Hyperplasia ◽  
Captopril Test

Was ist neu? Definition, Klassifizierung und Prävalenz Der primäre Hyperaldosteronismus (PA) ist die häufigste chirurgisch therapierbare Form der sekundären Hypertonie. Hauptursachen des PA sind ein 1-seitiges Aldosteron-produzierendes Nebennierenadenom oder eine bilaterale idiopathische Nebennierenrindenhyperplasie (Bilateral Adrenal Hyperplasia, BAH). In den letzten Jahren ist das Phänomen der autonomen Kortisol-Co-Sekretion (ACS) im Rahmen des Conn-Syndroms in den Fokus gerückt. Während der Mineralokortikoidexzess für die Hypertonie verantwortlich ist, scheint die ACS vor allem zu metabolischen Komorbiditäten wie erhöhtem BMI, gestörter Glukosetoleranz und Diabetes mellitus Typ 2 zu führen. Das sogenannte „Connshing“-Syndrom (zusammengezogen von Conn- und Cushing-Syndrom) wird als neuer metabolischer Subtyp angesehen. Diagnose Folgende Hypertoniegruppen sollen unter anderem gescreent werden (etwa 50 % aller Hypertoniker): Patienten mit therapierefraktärer Hypertonie, mit arterieller Hypertonie und Hypokaliämien, mit arterieller Hypertonie und obstruktivem Schlafapnoe-Syndrom (OSAS), mit arterieller Hypertonie und adrenalem Nebennierenzufallstumor, mit Hypertonie und Blutdruck > 150/90 mmHg sowie jüngere Patienten mit Hypertonie. Das Screening erfolgt mittels des Aldosteron-Renin-Quotienten. Der nächste Schritt ist häufig die Bestätigung der Diagnose PA mittels Kochsalzbelastungs- und/oder Captopril-Test. Neu ist, dass bei sehr ausgeprägtem biochemischem Phänotyp, z. B. bei Patienten mit spontaner Hypokaliämie sowie maximal supprimierten Renin- und Aldosteron-Werten > 550 pmol/l, ohne weiteren Bestätigungstest direkt eine Subtypdifferenzierung erfolgen kann. Die Subtypdifferenzierung erfolgt mittels CT-Bildgebung der Nebennieren und (als Goldstandard) Nebennierenvenenkatheterisierung. Bei technisch nicht erfolgreichen Katheterisierungen werden nuklearmedizinische Verfahren (z. B. CXCR4-PET/CT) in Einzelfällen eingesetzt. Therapie Bei gesichertem unilateralem PA ist eine Adrenalektomie indiziert. Entsprechend der Primary-Aldosteronism-Surgical-Outcome-Study-Kriterien profitieren Frauen, jüngere Patienten (< 50 Jahre), Patienten mit geringerer Laufzeit der Hypertonie (< 5 Jahre) und Patienten mit geringerer Anzahl (< 2) von Antihypertensiva am meisten von einer Adrenalektomie. Im Fall einer BAH sollte eine Therapie mittels Spironolacton (initial 25–50 mg/d) eingeleitet werden, mit entsprechender Steigerungsoption zum Anheben des Renin als Ziel.

scholarly journals A Case of Primary Aldosteronism due to Bilateral Adrenal Hyperplasia with Hidden Undiagnosed Adrenal Adenoma for Eight Years

1996 ◽  
Vol 19 (1) ◽  
pp. 47
Author(s):  
Seock Ah Im ◽  
Eun Mi Nam ◽  
Si Hoon Park ◽  
Gil Ja Shin ◽  
Woo Hyung Lee ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Adrenal Adenoma ◽  
Adrenal Hyperplasia ◽  
Bilateral Adrenal Hyperplasia

scholarly journals Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

2020 ◽  
Vol 52 (06) ◽  
pp. 379-385
Author(s):  
Lucie S. Meyer ◽  
Siyuan Gong ◽  
Martin Reincke ◽  
Tracy Ann Williams
Keyword(s):  
Angiotensin Ii ◽  
Primary Aldosteronism ◽  
Functional Role ◽  
Adrenal Hyperplasia ◽  
Endocrine Hypertension ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma ◽  
Agonistic Autoantibodies

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

scholarly journals MON-LB036 Uncommon Findings in Beckwith-Wiedemann Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jéssica M E S Martins ◽  
Tamires S Garcia ◽  
Juliana S Lee ◽  
Edson Cechinel ◽  
Genoir Simoni ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Large For Gestational Age ◽  
Abdominal Wall Defects ◽  
Adrenal Hyperplasia ◽  
Abdominal Ct ◽  
Cell Hyperplasia ◽  
Basal Cortisol ◽  
Pet Ct ◽  
Bilateral Adrenal Hyperplasia ◽  
Urinary Metanephrines

Abstract Introduction: Beckwith-Wiedemann syndrome (BWS) is characterized by variable phenotypes that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy and predisposition to embryonal tumours. Some features are more specific, including adrenal cytomegaly. BWS increases risk for several tumors, including adrenocortical tumor (ACT). Some protocols recommend screening with adrenal ultrasonography and serum DHEAS every 4–6 months. Case report: A 1-month-old male, preterm (34 weeks 4 days), large for gestational age (weight 3670g), presented with macrosomia, macroglossia, umbilical hernia and auricular pits, with clinical diagnosis of BWS. In newborn screening 17 alpha hydroxyprogesterone (17OHP): 70,15 ng/mL (&lt;15ng/mL) and 66,32 ng/mL in second sample. Presented basal cortisol 11.4 mcg/L (6,70 a 22,60 µg/dL), normal electrolytes, dehydroepiandrosterone sulphate (DHEAS) &gt; 1000 mcg/dL (30,0 - 250,0 mcg/dL), testosterone 637 ng/dL (60-400 ng/dL), leading to ACT suspicion. No suppression of cortisol (2,8 mcg/dL) after dexamethasone 10 mcg/kg. Urinary metanephrines were normal, plasmatic normetanephrine 554 pg/mL (&lt;196 pg/mL) and plasmatic norepinephrine 2094 pg/mL (&lt; 420 pg/mL). Abdominal CT showed increased adrenal glands, with normal contrast uptake. MRI and PET/CT DOTA-68Ga did not identify tumors. Eight months later: 17OHP 0,88 ng/mL (0,8-5ng/mL), DHEAS 37 mcg/dL (&lt;30,0 mcg/dL), testosterone 13 ng/mL (&lt; 30 ng/dL), normal urinary metanephrines and plasmatic catecholamines. Conclusion: In this case congenital adrenal hyperplasia was ruled out and ACT was suspected. Imaging did not identify tumors and biochemical findings (hypercortisolism and high androgens levels) had progressive improvement. Bilateral adrenal hyperplasia may be present in BWS as a result of fetal adrenal gland delay maturation. Permanent adrenal cortex cytomegaly may be responsible for hypercortisolism. Transient cortex persistence can lead to androgens elevation and produces large amounts of DHEA, that could explain DHEAS elevation similar to that in ACT. Bilateral adrenal hyperplasia is described as a feature of BWS, but, to our knowledge, there is no similar case in literature with these biochemical findings. References: 1) Beckwith JB. Extreme cytomegaly of the adrenal fetal cortex, omphalocele, hyperplasia of kidneys and pancreas, and Leydig-cell hyperplasia: Another syndrome. West Soc Pediatr Res. 1963; 11 2) Carney JA, Ho J, Kitsuda K, et al. Massive neonatal adrenal enlargement due to cytomegaly, persistence of the transient cortex, and hyperplasia of the permanent cortex: findings in Cushing syndrome associated with hemihypertrophy. Am J Surg Pathol. 2012

scholarly journals Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology

Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4129-4138 ◽  
Author(s):  
Leticia Aragao-Santiago ◽  
Celso E Gomez-Sanchez ◽  
Paolo Mulatero ◽  
Ariadni Spyroglou ◽  
Martin Reincke ◽  
...  
Keyword(s):  
Mouse Models ◽  
Primary Aldosteronism ◽  
Genetic Basis ◽  
Plasma Renin ◽  
Adrenal Hyperplasia ◽  
Endocrine Hypertension ◽  
Bilateral Adrenal Hyperplasia ◽  
Human Disorder ◽  
Aldosterone Producing Adenoma ◽  
Functional Mechanisms

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype–phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.

scholarly journals Mass Spectrometry–Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

2016 ◽  
Vol 62 (3) ◽  
pp. 514-524 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Tanja Dekkers ◽  
Mirko Peitzsch ◽  
Anna S Dietz ◽  
Martin Bidlingmaier ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Plasma Concentrations ◽  
Adrenal Hyperplasia ◽  
Peripheral Plasma ◽  
Steroid Profiling ◽  
Bilateral Adrenal Hyperplasia ◽  
Potential Use ◽  
Venous Plasma

Abstract BACKGROUND Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS–based steroid profiling to stratify patients with primary aldosteronism. METHODS Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with primary aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios. RESULTS Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS–derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P &lt; 0.0001) than immunoassay-derived ratios. The hybrid steroids, 18-oxocortisol and 18-hydroxycortisol, also showed lateralized secretion in 76% and 35% of patients with APAs. Adrenal venous concentrations of glucocorticoids and androgens were bilaterally higher in patients with BAH than in those with APAs. Consequently, peripheral plasma concentrations of 18-oxocortisol were 8.5-fold higher, whereas concentrations of cortisol, corticosterone, and dehydroepiandrosterone were lower in patients with APAs than in those with BAH. Correct classification of 80% of cases of APAs vs BAH was thereby possible by use of a combination of steroids in peripheral plasma. CONCLUSIONS LC-MS/MS–based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.

scholarly journals Molecular mechanisms in primary aldosteronism

2019 ◽  
Vol 242 (3) ◽  
pp. R67-R79 ◽  
Author(s):  
Kelly De Sousa ◽  
Alaa B Abdellatif ◽  
Rami M El Zein ◽  
Maria-Christina Zennaro
Keyword(s):  
Arterial Hypertension ◽  
Adrenal Cortex ◽  
Primary Aldosteronism ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Type I ◽  
Adrenal Hyperplasia ◽  
New Genes ◽  
Aldosterone Production ◽  
Bilateral Adrenal Hyperplasia

Primary aldosteronism (PA) is the most common form and an under-diagnosed cause of secondary arterial hypertension, accounting for up to 10% of hypertensive cases and associated to increased cardiovascular risk. PA is caused by autonomous overproduction of aldosterone by the adrenal cortex. It is mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Excess aldosterone leads to arterial hypertension with suppressed renin, frequently associated to hypokalemia. Mutations in genes coding for ion channels and ATPases have been identified in APA, explaining the pathophysiology of increased aldosterone production. Different inherited genetic abnormalities led to the distinction of four forms of familial hyperaldosteronism (type I to IV) and other genetic defects very likely remain to be identified. Somatic mutations are identified in APA, but also in aldosterone-producing cell clusters (APCCs) in normal adrenals, in image-negative unilateral hyperplasia, in transitional lesions and in APCC from adrenals with bilateral adrenal hyperplasia (BAH). Whether these structures are precursors of APA or whether somatic mutations occur in a proliferative adrenal cortex, is still a matter of debate. This review will summarize our knowledge on the molecular mechanisms responsible for PA and the recent discovery of new genes related to early-onset and familial forms of the disease. We will also address new issues concerning genomic and proteomic changes in adrenals with APA and discuss adrenal pathophysiology in relation to aldosterone-producing structures in the adrenal cortex.

scholarly journals The syndromes of low-renin hypertension: "separating the wheat from the chaff"

2004 ◽  
Vol 48 (5) ◽  
pp. 674-681 ◽  
Author(s):  
Claudio E. Kater ◽  
Edward G. Biglieri
Keyword(s):  
Receptor Antagonist ◽  
Myocardial Fibrosis ◽  
Cardiac Remodeling ◽  
Primary Aldosteronism ◽  
Renin Activity ◽  
Adrenal Hyperplasia ◽  
Test Characteristics ◽  
Low Renin Hypertension ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma

Primary aldosteronism (PA) is characterized by hypertension and suppressed renin activity with or without hypokalemia and comprises the aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia or idiopatic hyperaldosteronism (IHA). In recent series employing the aldosterone (aldo, ng/dL):renin (ng/mL·h) ratio (ARR) for screening, prevalence of PA among hypertensives soars to 8-20%; current predominance of IHA (>80%) over APA suggests the inclusion of former low-renin essential hypertensives (LREH), in whom plasma aldo can be reduced by suppressive maneuvers. We evaluated the test characteristics of the ARR obtained retrospectively from 127 patients with PA (81 APA; 46 IHA) and 55 with EH (30 LREH; 25 NREH) studied from 1975 to 1990. Using the combined ROC-defined cutoffs of 27 for the ARR and 12ng/dL for aldo, we obtained 89.8% sensitivity (Ss) and 98.2% specificity (Sp) in discriminating PA from EH: all APA and 72% of the IHA patients had values above these limits, but only one (3%) with LREH. Among the 46 IHA patients, 10 (21.7%) had ARR <27, four of whom with aldo <12ng/dL, virtually indistinguishable from LREH. Use of higher cutoff values (ARR >100; aldo >20) may attain 84%Ss and 82.6%Sp in separating APA from IHA. Because IHA and LREH ("the chaff") may be spectrum stages from the same disease, definite discrimination between these entities seems immaterial. However, precise identification of the APA ("the wheat") is critical, since it is the only surgically curable form of PA. Thus, while patients who may harbor an APA must be thoroughly investigated and surgically treated, non-tumoral disease (IHA and LREH) may be best treated with an aldo-receptor antagonist that will also prevent the aldo-mediated inflammatory effects involved in myocardial fibrosis and abnormal cardiac remodeling.

scholarly journals Primary Aldosteronism: The Next Five Years

2017 ◽  
Vol 49 (12) ◽  
pp. 977-983 ◽  
Author(s):  
John Funder
Keyword(s):  
Primary Aldosteronism ◽  
Germline Mutations ◽  
Adrenal Hyperplasia ◽  
Bilateral Disease ◽  
The Past ◽  
Wide Range ◽  
Unilateral Disease ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma ◽  
Current Guidelines

AbstractThe management of primary aldosteronism is widely varied within various published guidelines, with very little in the way of data supporting the choice of one variation over others. Current estimates of prevalence are probably accurate for aldosterone producing adenoma, but fall very short of that for bilateral adrenal hyperplasia. Discovery at the level of basic science has proven illuminating over the past 6 years in terms of unilateral disease and both somatic and germline mutations, with much less focus on the much more common bilateral disease; Attempts at harmonization have begun – for example, criteria for complete/partial/absent cure after adrenalectomy for unilateral disease; again focus on bilateral disease is muted. A number of possibilities are suggested as agenda for active consideration and change, across a wide range of areas – referral patterns, screening, confirmation and lateralization, what will be needed is discussion and agreement, to fill the lacunae within the current guidelines. Those involved will want to change to make such an agenda possible.

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

2020 ◽  
Vol 52 (06) ◽  
pp. 394-403
Author(s):  
Zsófia Tömböl ◽  
Péter István Turai ◽  
Ábel Decmann ◽  
Peter Igaz
Keyword(s):  
Rna Interference ◽  
Primary Aldosteronism ◽  
Expression Profiles ◽  
Microrna Expression ◽  
Circulating Microrna ◽  
Adrenal Hyperplasia ◽  
Aldosterone Secretion ◽  
Adrenocortical Tumors ◽  
Bilateral Adrenal Hyperplasia ◽  
Aldosterone Producing Adenoma

AbstractMicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.

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