Akromegalie je vzácné onemocnění způsobené zvýšenou sekrecí růstového hormonu po uzavření růstových plotének kostí. Téměř vždy je způsobena adenomem hypofýzy (PitNET) produkujícím růstový hormon. Tato práce shrnuje aktuální poznatky umožňující co nejvíce personalizovaný přístup u pacienta s touto diagnózou. Rozebírá prediktivní faktory jako věk pacienta, charakter a rozsah adenomu na MR, histologickou specifikaci, nádorové změny, mutace; zkrátka vše, co ovlivňuje pravděpodobnost dalšího vývoje onemocnění a odpověď pacienta na léčbu.
Acromegaly is a rare condition caused by increased secretion of growth hormone after closure of the growth plates in bones. It is almost always caused by a pituitary adenoma (PitNET) producing growth hormone. This paper summarizes current knowledge enabling the most personalized approach possible for patients with this diagnosis. It discusses predictive factors such as patient age, the nature and extent of adenoma on MRI, histological specification, tumor changes, mutations, basically everything that influences the likelihood of further disease progression and the patient's response to treatment.
- MeSH
- adenom hypofýzy vylučující růstový hormon * chirurgie diagnostické zobrazování klasifikace radioterapie MeSH
- akromegalie * diagnóza farmakoterapie genetika MeSH
- glukózový toleranční test MeSH
- indukce remise MeSH
- lidé MeSH
- magnetická rezonance intervenční MeSH
- mutace MeSH
- prognóza MeSH
- somatostatin analogy a deriváty MeSH
- Check Tag
- lidé MeSH
SUMMARY: Severe Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare but often demands rapid diagnostics and treatment of hypercortisolism with its comorbidities. Pharmacotherapy of hypercortisolism by ketoconazole, metyrapone and osilodrostat is currently available. If unsuccessful or insufficient a bilateral adrenalectomy is an option. We present a 28-year-old female with severe Cushing's syndrome caused by a bronchial metastatic neuroendocrine tumour (NET). Hypercortisolism was efficiently treated by osilodrostat with block-replace and then titration regimen. A once-daily dose was finally used with normalised cortisol levels. Androgen levels measured by liquid chromatography-mass spectrometry were slightly elevated during the treatment but without any symptoms. A simple once-daily use of osilodrostat with titration regimen led to normalised cortisol levels in a severe Cushing's syndrome patient with an uncurable bronchial NET. Transient hypocortisolism during treatment appeared but was easily treated by hydrocortisone. LEARNING POINTS: Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare. Cortisol upregulation is often severe and rapid, though clinical signs are not always fully pronounced. Rapid treatment is a key for preventing and reducing complications such as fractures, thromboembolism, bleeding, hyperglycaemia, and arterial hypertension. The novel potent steroidogenesis inhibitor osilodrostat can be used as first-line treatment for reducing hypercortisolism.
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Background: Life-threatening cardiovascular complications significantly reduce the life expectancy in patients with Turner syndrome (TS). The genetic basis of cardiovascular disease in TS has not been defined yet. Aims: To determine the prevalence of cardiovascular disease in different cytogenetic subgroups of TS; to find out which germ layer is the most appropriate for genetic prediction of the cardiovascular risk in TS; to test the hypothesis of hidden chromosomal mosaicism in all TS individuals. Methods: The study group will comprise of approximately 100 to 150 TS individuals. Karyotype in all three germ layers will be done. If TS diagnosed, all participants will undergo a complete cardiac examination including cardiac magnetic resonance imaging. Conclusion: It is suggested that the cytogenetic evaluation undoubtedly plays beside other risk factors an important role in cardiovascular risk stratification in TS. Such an approach may enable the identification of the highest risk patients and subsequent individualisation of their cardiovascular monitoring.
Život ohrožující kardiovaskulární komplikace (KV) signifikantně zkracují předpokládanou délku života u pacientek s Turnerovým syndromem (TS). Dosud nebyla jednoznačně definována genetická příčina KV onemocnění u TS. Cíle: Stanovení prevalence KV onemocnění u pacientek s Turnerovým syndromem rozdělených do podskupin dle cytogenetického nálezu; zhodnocení korelace KV rizika s karyotypem ze všech třech zárodečných listů; otestování hypotézy skrytého mozaicismu u TS. Metody: Do studie bude zahrnuto přibližně 100-150 pacientek s TS. Bude vyšetřen karyotyp ve všech třech zárodečných listech. Všechny nositelky TS podstoupí komplexní kardiologické vyšetření včetně magnetické rezonance (MRI) srdce. Závěr: Je pravděpodobné, že cytogenetické vyšetření hraje významnou roli při stratifikaci KV rizika u nositelek TS. Podrobné cytogenetické vyšetření spolu s MRI srdce by mohlo pomoci při identifikaci pacientek s nejvyšším KV rizikem a následně vést k individualizaci jejich kardiologického sledování.
- MeSH
- bikuspidální aortální chlopeň MeSH
- disekce aorty MeSH
- kardiovaskulární nemoci epidemiologie genetika MeSH
- karyotyp MeSH
- karyotypizace MeSH
- koarktace aorty MeSH
- magnetická rezonanční tomografie MeSH
- mozaicismus MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- srdce diagnostické zobrazování MeSH
- Turnerův syndrom komplikace MeSH
- zárodečné listy MeSH
- Check Tag
- ženské pohlaví MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- genetika, lékařská genetika
- kardiologie
- epidemiologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
BACKGROUND: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. OBJECTIVE: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin), and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. DESIGN AND PATIENTS: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. RESULTS: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% vs. 70.0%; p < 0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p < 0.01), but the predictive power was insufficient. CONCLUSION: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.
Acromegaly is a rare condition typically caused by benign pituitary adenomas, resulting in excessive production of growth hormone. Clinical manifestations of acromegaly are diverse, varying from the overgrowth of body tissue to cardiovascular, metabolic, and osteoarticular disorders. Symptoms may emerge slowly, overlapping with other diseases and often involve many different healthcare specialists. In the last decade, efforts to provide an accurate and timely diagnosis of acromegaly have improved disease management and clinical experience. Despite this progress, marked differences in the diagnosis, treatment, and management of acromegaly exist from country-to-country. To address these inconsistencies in the region comprising Central and Eastern Europe, Israel, and Kazakhstan, a panel of acromegaly experts from 13 of these countries was convened. Acromegaly experts from each country provided available information on the approaches from their country, including regional treatment centers and multidisciplinary teams, treatment access, reimbursement and availability, and physician education, disease awareness, and patient advocacy. Across several areas of acromegaly management, divergent approaches were identified and discussed, including the provision of multidisciplinary care, approved and available treatments, and disease awareness programs. These were recognized as areas of potential improvement in the management of acromegaly, in addition to participation in national and regional acromegaly registries. Further experience exchange will facilitate the identification of specific strategies that can be adapted in each country, and widespread participation in acromegaly registries will enable their evaluation. It is anticipated that this approach will support the optimization of acromegaly patient care across this region.
- MeSH
- akromegalie * diagnóza epidemiologie terapie MeSH
- lidé MeSH
- růstový hormon MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Izrael MeSH
- Kazachstán MeSH
- východní Evropa MeSH
AIMS: Turner syndrome is the only chromosome monosomy that is postnatally compatible with life. The reported incidence of TS is 1 in 2500 liveborn girls. The phenotype of these girls is highly variable, with cardiac abnormalities being life-threatening defects. The aim of the study was to reveal the possible influence of the parental origin of the X chromosome in these patients on a selected phenotype that is associated with Turner syndrome. Selected symptoms and parameters were: a bicuspid aortic valve, aortic coarctation, lymphoedema, pterygium colli, coeliac disease, thyroiditis, otitis media, diabetes mellitus 2, renal abnormalities, spontaneous puberty, and IVF. METHODS: The X chromosome haplotype was determined for a group of 45,X patients verified by native FISH. A molecular diagnostic method based on the detection of different lengths of X chromosome-linked STR markers using the Argus X-12 QS kit was used to determine the X haplotype. RESULTS: Our results, analysed by Fisher's exact (factorial) test, suggest independence between the maternal/paternal origin of the inherited X chromosome and the presence of the anomalies that were studied (P=1 to P=0.34). CONCLUSION: In the group of 45,X patients, who were precisely selected by means of the native FISH method, no correlation was demonstrated with the parental origin of the X chromosome and the observed symptom.
- MeSH
- chromozom X MeSH
- fenotyp MeSH
- haplotypy MeSH
- lidé MeSH
- Turnerův syndrom * genetika MeSH
- vrozené srdeční vady * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.
- MeSH
- akromegalie komplikace genetika metabolismus MeSH
- biologické markery MeSH
- dospělí MeSH
- imunohistochemie MeSH
- kadheriny genetika MeSH
- klinické rozhodování MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- management nemoci MeSH
- mladý dospělý MeSH
- nádory hypofýzy diagnóza etiologie terapie MeSH
- prognóza MeSH
- protein - isoformy MeSH
- receptory somatostatinu genetika metabolismus MeSH
- regulace genové exprese * MeSH
- ROC křivka MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
CONTEXT: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. OBJECTIVE: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. DESIGN: Retrospective multicenter study. SETTING: Eight participating European centers. METHODS: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. RESULTS: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormone concentration at diagnosis were associated with absolute IGF-1 reduction (β = 0.90, standard error (SE) = 0.02, P ≤ .0001 and β = 0.002, SE = 0.001, P = .014, respectively). CONCLUSION: Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients were more likely to achieve nonresponse.
- MeSH
- akromegalie krev diagnóza farmakoterapie MeSH
- biologické markery analýza metabolismus MeSH
- biomarkery farmakologické * analýza metabolismus MeSH
- cyklické peptidy terapeutické užití MeSH
- dospělí MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský růstový hormon krev MeSH
- ligandy MeSH
- multivariační analýza MeSH
- oktreotid terapeutické užití MeSH
- prognóza MeSH
- receptory somatostatinu agonisté MeSH
- retrospektivní studie MeSH
- somatostatin analogy a deriváty terapeutické užití MeSH
- teoretické modely * 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
- metaanalýza MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Pathologies involving the pituitary stalk (PS) are generally revealed by the presence of diabetes insipidus. The availability of MRI provides a major diagnostic contribution by enabling the visualization of the site of the culprit lesion, especially when it is small. However, when only an enlarged PS is found, the etiological workup may be difficult, particularly because the biopsy of the stalk is difficult, harmful and often not contributive. The pathological proof of the etiology thus needs to be obtained indirectly. The aim of this article was to provide an accurate review of the literature about PS enlargement in adults describing the differences between the numerous etiologies involved and consequent different diagnostic approaches. The etiological diagnostic procedure begins with the search for possible other lesions suggestive of histiocytosis, sarcoidosis, tuberculosis or other etiologies elsewhere in the body that could be more easily biopsied. We usually perform neck, thorax, abdomen, and pelvis CT scan; positron emission tomography scan; bone scan; or other imaging methods when we suspect generalized lesions. Measurement of serum markers such as human chorionic gonadotropin, alpha-fetoprotein, angiotensin converting enzyme, and IgG4 may also be helpful. Obviously, in the presence of an underlying carcinoma (particularly breast or bronchopulmonary), one must first consider a metastasis located in the PS. In the case of an isolated PS enlargement, simple monitoring, without histological proof, can be proposed (by repeating MRI at 3-6 months) with the hypothesis of a germinoma (particularly in a teenager or a young adult) that, by increasing in size, necessitates a biopsy. In contrast, a spontaneous diminution of the lesion is suggestive of infundibulo-neurohypophysitis. We prefer not to initiate steroid therapy to monitor the spontaneous course when a watch-and-see attitude is preferred. However, in many cases, the etiological diagnosis remains uncertain, requiring either close monitoring of the lesion or, in exceptional situations, trying to obtain definitive pathological evidence by a biopsy, which, unfortunately, is in most cases performed by the transcranial route. If a simple surveillance is chosen, it has to be very prolonged (annual surveillance). Indeed, progression of histiocytosis or germinoma may be delayed.
