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Familial hypercholesterolemia (FH) is the most common monogenic metabolic disorder characterized by considerably elevated low-density lipoprotein cholesterol (LDL-C) levels leading to enhanced atherogenesis, early cardiovascular disease (CVD), and premature death. However, the wide phenotypic heterogeneity in FH makes the cardiovascular risk prediction challenging in clinical practice to determine optimal therapeutic strategy. Beyond the lifetime LDL-C vascular accumulation, other genetic and non-genetic risk factors might exacerbate CVD development. Besides the most frequent variants of three genes (

Absztrakt: A szerzők egy multiplex endokrin neoplasia-2A (MEN2A) szindrómában szenvedő beteg esetét ismertetik, akinél 55 éves korban hasi panaszok miatti részletes kivizsgálás részeként derült fény kétoldali mellékvese-térfoglalásra és pajzsmirigygöbre. Az utóbbi miatt végzett thyreoidectomia szövettani lelete medullaris pajzsmirigy-carcinomát igazolt. A mellékvese-térfoglalások hormon- és képalkotó vizsgálatok alapján bilaterális phaeochromocytomának bizonyultak. Tünetmentes primer hyperparathyreosisra is fény derült. Laparoszkópos adrenalectomia és mellékpajzsmirigy-adenoma eltávolítása történt. A beteg pozitív családi anamnézise és a klinikai kép alapján felmerülő MEN2A-szindrómát genetikai vizsgálattal bizonyítottuk. Az elsőfokú rokonok szűrése során a beteg 25 éves lánygyermeke génhordozónak bizonyult, nála preventív thyreoidectomiára került sor, és a szövettan többgócú medullaris carcinomát igazolt. Az eset kapcsán a szerzők áttekintik a MEN2A-szindróma klinikai jellemzőit, és hangsúlyozzák a genetikai vizsgálat és a családszűrés fontosságát. Orv Hetil. 2020; 161(2): 75–79.

Összefoglaló. Bevezetés: A pajzsmirigy-alulműködés gyakori betegség. Kezelésében a levotiroxin (LT4)-pótlás a szokásos eljárás, mely tabletta vagy gélkapszula formájában áll rendelkezésre Magyarországon. A nemzetközi trendeknek megfelelően az esetek korai felismerése miatt már a kevésbé kifejezett hormonális eltérések idején elindul a kezelés. Az endokrinológusok hypothyreosiskezelési szokásaival kapcsolatban Magyarországon és Európában felmérés eddig nem történt. Célkitűzés: A THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) célja, hogy felmérjük az európai és közte jelen munkánkban a magyar endokrinológusok hypothyreosiskezelési szokásait és az LT4 esetleges alkalmazását pajzsmirigy-működészavarral nem járó állapotokban. Módszer: A Magyar Endokrinológiai és Anyagcsere Társaság (MEAT) tagjainak e-mailben meghívót küldtünk az online kérdőíves vizsgálathoz. Eredmények: 165 magyar endokrinológus válaszai alapján végeztük az elemzést. A válaszadók többsége, 99,4%-uk első kezelésként LT4-pótlást alkalmaz. Az LT4 + LT3 kombinációt elsősorban olyan betegeknél alkalmazzák, akik LT4 szedése mellett euthyreoid hormonértékek ellenére hypothyreosisra jellemző tüneteket mutatnak (36,1%). Euthyreoid hormonértékek mellett, magas antitestszint és infertilitás esetén 60,3% megfontolná LT4 indítását, amit evidenciák jelenleg nem indokolnak. Számos kórállapot befolyásolja az LT4 felszívódását, ezekben az esetekben a magyar endokrinológusok 66,4%-a preferálja a lágy kapszula alkalmazását, jobb eredményt várva a gyógyszerformák közötti váltástól. Következtetés: A pajzsmirigy-alulműködés kezelésében a magyar endokrinológusok elsődlegesen az LT4-et választják. Az LT4 + LT3 kombinált alkalmazását a pajzsmirigy-stimuláló hormon normális szintjének elérése után perzisztáló hypothyreosisos tünetek esetén fontolják meg. Az újabb gyógyszerformákat a többség preferálja, ha az LT4 hagyományos tablettás formájának alacsonyabb biohasznosulása várható. Orv Hetil. 2022; 163(12): 463-472.Hypothyroidism has a high prevalence in the adult population. Levothyroxine (LT4) supplementation is considered to be the gold-standard treatment method. In Hungary, LT4 tablets and soft gel capsules are the available formulations. Similarly to the international trends, hypothyroidism is earlier recognised, leading to early LT4 supplementation. Up till now, there has been no survey on the treatment of hypothyroidism among Hungarian endocrinologists.THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) had been conducted to assess treatment preferences among European endocrinologists. Here we report the results on the use of thyroid hormones in hypothyroid patients and euthyroid individuals in Hungary.An e-mail invitation to participate, containing the link to the online survey was sent to members of the Hungarian Society for Endocrinology and Metabolism.There were 165 responses with full demographics which were included in the analysis. By the majority (99.4%) of them, LT4 was the first treatment of choice. LT4 + LT3 combination was considered an option in patients with persistent symptoms despite biochemical euthyroidism while on LT4 (36,1%). In euthyroid individuals, 60.3% of the respondents would consider starting LT4 in euthyroid infertile women with high antibody levels, which is hardly supported by evidence. In the presence of comorbidities and interfering medications which may hinder LT4 absorption, 66.4% of Hungarian endocrinologist anticipate significant improvement after switching from tablets to soft gel capsules.The treatment of choice for hypothyroidism is LT4 in Hungary. Combination therapy with LT4 + LT3 was considered for patients with persistent symptoms. In the presence of diseases and interfering medications affecting bioavailability, a high number of Hungarian endocrinologists prefer the new LT4 formulation. The administration of LT4 in euthyroid conditions awaits explanation and calls for intensive discussions at local conferences and courses. Orv Hetil. 2022; 163(12): 463-472.

Introduction Thyroid eye disease (TED) is an autoimmune disease of the orbits. Once developed, complete cure is rare. Plasminogen activator inhibitor type 1 (PAI-1) contributes to remodeling of connective tissue and has a central role in the pathogenesis of TED. We aimed to test if the 4G/5G polymorphism of PAI-1 is a predictor of the development of moderate-to-severe TED. Methods A total of 185 patients with Graves’ disease, 87 of them with TED, 98 without TED, as well as 201 healthy controls, were studied. Genomic DNA was isolated from peripheral blood samples. The 4G/5G polymorphism of the PAI-1 gene was analyzed by allele-specific PCR, and the distribution of genotypes was calculated in each group. Plasma PAI-1 and thyroid hormone levels were measured by ELISA and ECLIA, respectively. Results The 4G/4G genotype was associated with the development of moderate-to-severe TED (OR = 2.54; 95% CI: 1.26–5.14; p < 0.01). The 4G/5G polymorphism of PAI-1 was not a predictor of plasma PAI-1 levels. Conclusion The 4G/4G genotype of PAI-1 is a risk factor for the development of moderate-to-severe TED. Patients with Graves’ disease who harbor this genotype may be candidates for special attention towards the development of TED.

Purpose Hyaluronan (HA) overproduction by orbital fibroblasts (OFs) is a major factor in the pathogenesis of Graves’ orbitopathy (GO). 4-methylumbelliferone (4-MU) is an inhibitor of HA synthesis in different cell types in vitro and has beneficial effects in animal models of autoimmune diseases. Methods HA production and mRNA expression of HA synthases (HAS1, HAS2, and HAS3) and hyaluronidases (HYAL1 and HYAL2) were measured in the presence and absence of 4-MU in unstimulated and transforming growth factor–β–stimulated fibroblasts from GO orbital (n = 4), non-GO orbital (n = 4), and dermal origin (n = 4). Results The 4-MU treatment (1 mM) for 24 hours resulted in an average 87% reduction (P < 0.001) of HA synthesis, decreased the expression of the dominant HAS isoform (HAS2) by 80% (P < 0.0001), and increased the HYAL2 expression by 2.5-fold (P < 0.001) in control OFs, GO OFs, and dermal fibroblasts (DFs) regardless of the origin of the cells. The proliferation rate of all studied cell lines was reduced to an average 16% by 4-MU (P < 0.0001) without any effects on cell viability. HA production stimulated by transforming growth factor–β was decreased by 4-MU via inhibition of stimulated HAS1 expression in addition to the observed effects of 4-MU in unstimulated cases. Characteristics of HA synthesis inhibition by 4-MU did not differ in OFs compared with DFs. Conclusions 4-MU has been found to inhibit the HA synthesis and the proliferation rate in OFs in vitro, adding it to the list of putative therapeutic agents in a disease the cure of which is largely unresolved.

The authors present the case of a multiplex endocrine neoplasia type 2A (MEN2A). The 55-year-old woman underwent detailed examinations for abdominal complaints. Bilateral adrenal masses and thyroid nodular goiter were found. Based on metanephrine excretion and MIBG imaging, bilateral phaeochromocytomas were diagnosed. The thyroid nodules were confirmed by thyroidectomy as bilateral medullary thyroid carcinoma. Asymptomatic primary hyperparathyroidism was also detected. Laparoscopic adrenalectomy and parathyroid adenoma removal were performed. Based on family history and the characteristic clinical presentation, MEN2A syndrome was confirmed by genetic testing. During genetic screening of first-degree relatives, the patient's 25-year-old daughter was shown to be a gene carrier. Preventive thyroidectomy was performed and histology proved multifocal medullary thyroid cancer. In addition to the importance of genetic testing, the authors emphasize the guideline-based, but individualized approach to patients with suspected MEN2A syndrome. Orv Hetil. 2020; 161(2): 75-79.Absztrakt: A szerzők egy multiplex endokrin neoplasia-2A (MEN2A) szindrómában szenvedő beteg esetét ismertetik, akinél 55 éves korban hasi panaszok miatti részletes kivizsgálás részeként derült fény kétoldali mellékvese-térfoglalásra és pajzsmirigygöbre. Az utóbbi miatt végzett thyreoidectomia szövettani lelete medullaris pajzsmirigy-carcinomát igazolt. A mellékvese-térfoglalások hormon- és képalkotó vizsgálatok alapján bilaterális phaeochromocytomának bizonyultak. Tünetmentes primer hyperparathyreosisra is fény derült. Laparoszkópos adrenalectomia és mellékpajzsmirigy-adenoma eltávolítása történt. A beteg pozitív családi anamnézise és a klinikai kép alapján felmerülő MEN2A-szindrómát genetikai vizsgálattal bizonyítottuk. Az elsőfokú rokonok szűrése során a beteg 25 éves lánygyermeke génhordozónak bizonyult, nála preventív thyreoidectomiára került sor, és a szövettan többgócú medullaris carcinomát igazolt. Az eset kapcsán a szerzők áttekintik a MEN2A-szindróma klinikai jellemzőit, és hangsúlyozzák a genetikai vizsgálat és a családszűrés fontosságát. Orv Hetil. 2020; 161(2): 75–79.

Purpose Graves’ orbitopathy (GO) is a complication of Graves’ disease (GD), the development of which cannot be predicted at the time of diagnosis of GD. Our aims were (i) to test if orbital 99mTc-labelled diethylenetriamine pentaacetic acid single-photon emission computer tomography (DTPA SPECT) can predict development of GO later during the course of the disease and (ii) to study whether orbital immune activity can be detected in GD patients who do not develop GO during follow-up. Methods Fifty-four orbits of 27 patients with newly diagnosed GD were entered into the case-control study. Individuals showing signs of GO at enrolment were excluded. During the two-year follow-up, eye signs were recorded every 3 months. Orbital DTPA uptakes on SPECT images were measured when entering the study and at the end of the follow-up period, or when clinical signs of GO developed, whichever occurred first. Results During the follow-up, 6 patients (22%) were diagnosed with GO. There was no significant difference between the initial DTPA uptakes of the patients with or without later developing GO (10.45±1.72 MBq/cm3 vs. 9.18±1.18 MBq/cm3 respectively). However, the DTPA uptakes of both GD groups (ie. with and without GO) were higher than that of the control group (7.45±1.36 MBq/cm3, p Conclusions We have shown that GD is accompanied by moderate orbital immune activity in GD patients without GO, irrespective of later development of GO. Why this orbital autoimmunity remains subclinical in the majority of the cases, and progresses into clinically detectable GO in others, remains unclear.

Graves' orbitopathy is the most common extrathyroidal manifestation of Graves' disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves' orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves' orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted.Az endokrin orbitopathia a Graves-kór leggyakoribb extrathyreoidalis manifesztációja. A súlyos – látást veszélyeztető – esetek kezelése a mai napig nem megoldott probléma. A szerzők a közleményben a nemzetközi ajánlásokban is szereplő, elfogadott kezelési módok bemutatása mellett az elmúlt évtizedek terápiás próbálkozásait, a közelmúlt új kezelési lehetőségeit, valamint saját klinikai tapasztalataikat foglalják össze. Kiemelik, hogy az endokrin orbitopathia kezelésében a biológiai terápiák közül elsősorban az anti-CD20 antitesttel végzett terápiával kedvező irodalmi adatok állnak rendelkezésre. A szelén enyhe esetekben egyértelműen pozitív hatású. További, nagyobb esetszámú prospektív vizsgálatok szükségesek a biológiai terápiák alkalmazhatóságáról endokrin orbitopathiában. Orv. Hetil., 2014, 155(33), 1295–1300.

Graves' orbitopathy is the extrathyroidal manifestation of Graves' disease, which is the most common cause of exophthalmos. As eye symptoms usually coincide with the development of thyrotoxicosis, the diagnosis of the disease is rarely difficult. The aim of the authors was to summarize the differential diagnosis of Graves' orbitopathy based on literature review and presentation of their own four problematic cases on this topic. They conclude that symptoms similar to endocrine orbitopathy are present in other disorders. Endocrinologists need to be aware of these other conditions to avoid treatment failures.

Graves’ orbitopathy is the extrathyroidal manifestation of Graves’ disease, which is the most common cause of exophthalmos. As eye symptoms usually coincide with the development of thyrotoxicosis, the diagnosis of the disease is rarely difficult. The aim of the authors was to summarize the differential diagnosis of Graves’ orbitopathy based on literature review and presentation of their own four problematic cases on this topic. They conclude that symptoms similar to endocrine orbitopathy are present in other disorders. Endocrinologists need to be aware of these other conditions to avoid treatment failures. Orv. Hetil., 2016, 157(8), 310–315.

The aim of this study was to investigate aortic stiffness and left ventricular (LV) systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxine (L-T4) therapy and after L-T4 withdrawal to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. Twenty-four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24 ± 0.11 mU/L), and 4 weeks after L-T4 withdrawal (sTSH 89.82 ± 29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrand factor activity (vWF) were measured. Twenty-two healthy volunteers matched for age and sex served as euthyroid controls. Aortic stiffness was increased both in hypothyroidism (6.04 ± 2.88 cm2/dyn/103, p

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