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
BACKGROUND: Thymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children. CASE PRESENTATION: We report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection. The patient underwent a diagnostic work-up which indicated the possibility of an ACTH-secreting pituitary neuroendocrine tumor. However, after a transsphenoidal surgery, the diagnosis was not confirmed on histopathological examination. Subsequent bilateral inferior petrosal sinus sampling showed strong indications of the presence of ectopic ACTH syndrome. Detailed rereading of functional imaging studies, including 18F-FDG PET/MRI and 68Ga DOTATOC PET/CT, ultimately identified a small lesion in the thymus. The patient underwent videothoracoscopic thymectomy that confirmed a neuroendocrine tumor with ACTH positivity on histopathological examination. CONCLUSION: This case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child. We can conclude that ketoconazole treatment was effective in managing hypercortisolemia in our patient. Further, a combination of functional imaging studies can be a useful tool in locating the source of ectopic ACTH secretion. Lastly, in cases of discrepancy in the results of stimulation tests, bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome.
- MeSH
- Cushingův syndrom etiologie diagnóza chirurgie MeSH
- dítě MeSH
- ektopický ACTH syndrom * diagnóza chirurgie MeSH
- ketokonazol terapeutické užití MeSH
- lidé MeSH
- nádory brzlíku * komplikace diagnóza chirurgie patologie MeSH
- neuroendokrinní nádory * komplikace diagnóza chirurgie patologie MeSH
- thymektomie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky 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
Jaterní cirhóza i Cushingův syndrom jsou izolovaná onemocnění s charakteristickým klinickým obrazem, který obvykle vede ke stanovení diagnózy. Prezentujeme případ 46letého pacienta, u kterého souběh jaterní cirhózy a Cushingovy nemoci významně ovlivnil jak diagnostický, tak zejména terapeutický postup obou onemocnění.
Liver cirrhosis as well as Cushing's syndrome have quite characteristic clinical picture that usually leads to an early diagnosis. Here we present a rather complex case of a 46-year-old patient with an unusual coincidence of Cushing's disease and cirrhosis causing complications during diagnostic evaluation and particularly during the treatment of both diseases.
- MeSH
- Cushingův syndrom * diagnóza etiologie terapie MeSH
- jaterní cirhóza * diagnóza terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory hypofýzy diagnóza komplikace terapie MeSH
- virová hepatitida u lidí diagnóza terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVE: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. DESIGN: A retrospective observational cohort study. METHODS: Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. RESULTS: Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. CONCLUSION: Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.
- MeSH
- Cushingův syndrom * komplikace epidemiologie chirurgie MeSH
- hydrokortison MeSH
- hypersekrece ACTH v hypofýze * komplikace MeSH
- lidé MeSH
- prevalence MeSH
- retrospektivní studie MeSH
- trombóza * MeSH
- žilní tromboembolie * etiologie komplikace MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
