AIM: The aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations. MATERIALS AND METHODS: Simulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing. RESULTS: With the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients. CONCLUSION: Consideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.
- MeSH
- adherence k farmakoterapii * MeSH
- antagonisté mineralokortikoidních receptorů farmakokinetika MeSH
- dospělí MeSH
- hyperaldosteronismus farmakoterapie krev MeSH
- hypertenze * farmakoterapie MeSH
- kanrenon * farmakokinetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- senioři MeSH
- spironolakton * farmakokinetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Adrenálne incidentalómy (AI) zahŕňajú všetky lézie nadobličiek s priemerom ≥ 1 cm zistené náhodne počas zobrazovacích vyšetrení indikovaných z inej indikácie ako podozrenie na patológiu nadobličiek. Na základe hormonálnej aktivity sa AI rozdeľujú na hormonálne afunkčné a hormonálne funkčné. Afunkčné AI a adenómy s miernou hormonálnou produkciou môžu byť klinicky asymptomatické. Avšak AI, ktoré vykazujú významnú hormonálnu aktivitu, sa často prejavujú charakteristickými príznakmi Cushingovho syndrómu, primárneho hyperaldosteronizmu alebo hyperandrogenizmu. Hodnotenie AI nadobličiek si vyžaduje komplexný prístup zahŕňajúci hormonálne a zobrazovacie vyšetrenia na presné určenie povahy nádoru. Najčastejšie sú AI afunkčné adenómy kôry nadobličiek, ale môžu to byť aj karcinómy kôry nadobličiek, feochromocytóm, metastatické a infekčné lézie, atď. Terapeutický manažment AI (adrenalektómia / klinické pozorovanie) závisí najmä od charakteru lézie a prípadnej hormonálnej aktivity. Nasledujúci článok je zhrnutím etiológie, klinických prejavov, diagnostických a terapeutických postupov AI s ohľadom na aktuálne odporúčania Európskej endokrinologickej spoločnosti (ESE) z roku 2023.
Adrenal incidentalomas (AI) include all adrenal lesions ≥ 1 cm in diameter found incidentally during radiological examinations indicated for other than adrenal pathologies. Based on hormonal activity, AI are divided into hormonally non-functional and hormone active (functional). Nonfunctional AI and those with mild hormonal secretion can remain asymptomatic. However, AI that exhibit significant hormonal activity often present with characteristic symptoms of Cushing syndrome, primary hyperaldosteronism, or hyperandrogenism. Evaluation of AI requires a comprehensive approach involving hormonal examinations as well as imaging examinations to accurately determine the nature of the tumour. The most common etiology of AI is hormonally inactive adenoma of the adrenal cortex, but others can also be carcinoma of the adrenal cortex, pheochromocytoma, metastatic and infectious lesions, etc. Therapeutic management of AI (adrenalectomy/clinical observation) depends mainly on the nature of the lesion as well as its hormonal activity. The following article is a summary of etiology, clinical manifestations, diagnostic and therapeutic procedures of AI according to revised 2023 European Society of Endocrinology (ESE) guideline.
- MeSH
- adenom kůry nadledvin chirurgie diagnóza patofyziologie MeSH
- adrenalektomie metody MeSH
- Cushingův syndrom etiologie MeSH
- diabetes mellitus etiologie MeSH
- diagnostické zobrazování metody MeSH
- hyperaldosteronismus etiologie MeSH
- hyperandrogenismus etiologie MeSH
- lidé MeSH
- nádory nadledvin * chirurgie diagnóza patologie MeSH
- náhodný nález * MeSH
- Check Tag
- lidé MeSH
Bartterov syndróm zahŕňa skupinu vzácnych geneticky podmienených tubulopatií sprevádzaných zvýšenými močovými stratami solí. Patogenetickým podkladom je porucha transportných systémov zodpovedných za reabsorpciu solí predovšetkým v hrubom segmente vzostupného ramienka Henleho kľučky. Medzi základné charakteristiky Bartterovho syndrómu patrí hypokaliemická, hypochloremická metabolická alkalóza a sekundárny (hyperrenínový) hyperaldosteronizmus pri normálnom alebo nízkom systémovom krvnom tlaku. Klinické prejavy sa líšia v závislosti od postihnutého génu, pričom rozoznávame 5 rôznych génovo-špecifických fenotypov ochorenia. V článku uvádzame súbor 8 pacientov z Českej republiky a Slovenska s geneticky potvrdeným Bartterovým syndrómom a ich klinický a laboratórny fenotyp.
Bartter syndrome includes a group of rare genetically determined tubulopathies accompanied by increased urinary salt losses. The pathogenetic basis is a disorder of transport systems responsible for the reabsorption of salts, primarily in the thick ascending limb of the loop of Henle. The basic characteristics of Bartter syndrome include hypokalemic, hypochloremic metabolic alkalosis and secondary (hyperreninemic) hyperaldosteronism with normal or low systemic blood pressure. Clinical manifestations vary depending on the affected gene, with five different gene-specific phenotypes of the disease being recognized. In the article, we present a group of 8 patients from the Czech Republic and Slovakia with genetically confirmed Bartter syndrome and their clinical and laboratory phenotype.
- MeSH
- Bartterův syndrom * genetika klasifikace patofyziologie patologie MeSH
- dítě * MeSH
- lidé MeSH
- Check Tag
- dítě * MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
Few studies have investigated the hemodynamic mechanism whereby primary hyperaldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. Recently, we investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we found that aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. In addition, we validated mathematical models of human integrative physiology, derived from Guyton's classic 1972 model - Quantitative Cardiovascular Physiology-2005 and HumMod-3.0.4. Neither model accurately predicted the usual changes in sodium balance, CO, and SVR that normally occur in response to clinically realistic increases in salt intake. These results demonstrate significant limitations with the hypotheses inherent in the Guyton models. Together these findings challenge the traditional view of the hemodynamic mechanisms that cause salt-sensitive hypertension in primary aldosteronism. Key words: Aldosterone, Blood pressure, Salt, Sodium, Rat.
- MeSH
- aldosteron krev metabolismus MeSH
- hemodynamika * účinky léků MeSH
- hyperaldosteronismus * patofyziologie metabolismus MeSH
- hypertenze * patofyziologie etiologie MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl * škodlivé účinky MeSH
- modely kardiovaskulární MeSH
- modely nemocí na zvířatech * MeSH
- potkani Sprague-Dawley * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.
- MeSH
- adrenalektomie metody MeSH
- aldosteron krev MeSH
- antagonisté mineralokortikoidních receptorů * terapeutické užití MeSH
- dospělí MeSH
- hyperaldosteronismus * krev diagnóza farmakoterapie chirurgie MeSH
- krevní tlak fyziologie účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- nadledviny * MeSH
- renin krev MeSH
- retrospektivní studie MeSH
- studie případů a kontrol MeSH
- tendenční skóre MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Sekundární hypertenze představuje příležitost, jak nabídnout cílenou terapii pacientům s arteriální hypertenzí. Léčba může vést ke zlepšení kompenzace hypertenze a v některých případech i k úplnému vyléčení. Podmínkou pro úspěšnou léčbu je včasná diagnostika, která při vysokém počtu pacientů s arteriální hypertenzí musí být cílená. Nejdůležitější částí v diagnostickém procesu je na možnost sekundární etiologie myslet, a to především ve skupině pacientů s rezistentní hypertenzí a při specifických projevech sekundární hypertenze. Pokud se podezření potvrdí, je vhodné pacienta referovat do specializovaného centra.
Secondary hypertension represents an opportunity to offer targeted therapy to patients with arterial hypertension. The treatment, in some cases, can lead to a complete cure or an improvement in the compensation of hypertension. However, it's crucial to diagnose this early, as in the case of a larger group of patients with hypertension, the diagnostic process must be targeted. The most important when diagnosing is to acknowledge secondary etiology as a possibility, especially in patients with resistant hypertension and specific manifestations of secondary hypertension. If the suspicion is confirmed, we refer the patient to a specialized centre.
- Klíčová slova
- sekundární hypertenze,
- MeSH
- feochromocytom diagnóza komplikace MeSH
- hyperaldosteronismus diagnóza komplikace MeSH
- hypertenze * diagnóza etiologie farmakoterapie klasifikace MeSH
- krevní tlak účinky léků MeSH
- lidé MeSH
- obstrukční spánková apnoe diagnóza komplikace MeSH
- renovaskulární hypertenze diagnóza komplikace MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation. OBJECTIVES: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. METHODS: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined. RESULTS: We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55. CONCLUSIONS: With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01234220.
Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.
- MeSH
- adenom kůry nadledvin * MeSH
- adrenokortikální nádory * MeSH
- aldosteron MeSH
- buněčná adhezní molekula 1 MeSH
- cytochrom P450 CYP11B2 MeSH
- hyperaldosteronismus * MeSH
- hypertenze * MeSH
- lidé MeSH
- mezerový spoj MeSH
- mutace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
