Lateralization in C-11-Metomidate PET and outcome of adrenalectomy in primary aldosteronism

Introduction Subtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone C-11-metomidate positron emission tomography (C-11-MTO-PET) for subtype classification. Methods Postoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative C-11-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on C-11-MTO-PET alone and those with concordant or discordant lateralization in C-11-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure. Results Adrenalectomy side was based on C-11-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after C-11-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant C-11-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with C-11-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery. Conclusions Outcomes of adrenalectomy based on clinically significant lateralization in C-11-MTO-PET alone correspond to those based on C-11-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with C-11-MTO-PET in case of discordant lateralization studies.Peer reviewe

Type 1 tyrosinemia in Finland: a nationwide study

Background Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. Results Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. Conclusions Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.Peer reviewe

Type 1 tyrosinemia in Finland: a nationwide study

Background Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. Results Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. Conclusions Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.Peer reviewe

Lateralization in 11C-Metomidate PET and outcome of adrenalectomy in primary aldosteronism

IntroductionSubtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone 11C-metomidate positron emission tomography (11C-MTO-PET) for subtype classification.MethodsPostoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative 11C-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on 11C-MTO-PET alone and those with concordant or discordant lateralization in 11C-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure.ResultsAdrenalectomy side was based on 11C-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after 11C-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant 11C-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with 11C-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery.ConclusionsOutcomes of adrenalectomy based on clinically significant lateralization in 11C-MTO-PET alone correspond to those based on 11C-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with 11C-MTO-PET in case of discordant lateralization studies.</p

Various vascular malformations are prevalent in Finnish pseudoxanthoma elasticum (PXE) patients : a national registry study

BACKGROUND: Pseudoxanthoma elasticum (PXE, OMIM# 264800) is an inborn error of metabolism causing ectopic soft tissue calcification due to low plasma pyrophosphate concentration. We aimed to assess the prevalence of PXE in Finland and to characterize the Finnish PXE population. A nationwide registry search was performed to identify patients with ICD-10 code Q82.84. Information was gathered from available medical records which were requisitioned from hospitals and health centers. Misdiagnosed patients and patients with insufficient records were excluded. RESULTS: The prevalence of PXE in Finland was 1:260,000 with equal sex distribution. Patients with high conventional cardiovascular risk had more visual and vascular complications than patients with low risk. Four patients (19%) had at least one vascular malformation. A high proportion (33%) of ABCC6 genotypes were of the common homozygous c.3421C > T, p.Arg1141Ter variant. Nine other homozygous or compound heterozygous allelic variants were found. CONCLUSIONS: The prevalence of diagnosed PXE appears to be lower in Finland than in estimates from other countries. Decreased visual acuity is the most prevalent complication. We suggest that various vascular malformations may be an unrecognized feature of PXE.publishedVersionPeer reviewe

Ambulatory daytime blood pressure versus tonometric blood pressure measurements in the laboratory : effect of posture

Objective To compare blood pressure (BP) in tonometric radial artery recordings during passive head-up tilt with ambulatory recordings and evaluate possible laboratory cutoff values for hypertension. Methods Laboratory BP and ambulatory BP were recorded in normotensive (n=69), unmedicated hypertensive (n=190), and medicated hypertensive (n=151) subjects. Results Mean age was 50.2 years, BMI 27.7kg/m2, ambulatory daytime BP 139/87mmHg, and 276 were male (65%). As supine-to-upright changes in SBP ranged from -52 to +30mmHg, and in DBP from -21 to +32mmHg, the mean values of BP supine and upright measurements were compared with ambulatory BP. The mean(supine+upright) systolic laboratory BP was corresponding to ambulatory level (difference +1mmHg), while mean(supine+upright) DBP was 4mmHg lower (P<0.05) than ambulatory value. Correlograms indicated that laboratory 136/82mmHg corresponded to ambulatory 135/85mmHg. When compared with ambulatory 135/85mmHg, the sensitivity and specificity of laboratory 136/82mmHg to define hypertension were 71.5% and 77.3% for SBP, and 71.7% and 72.8%, for DBP, respectively. The laboratory cutoff 136/82mmHg classified 311/410 subjects similarly to ambulatory BP as normotensive or hypertensive, 68 were hypertensive only in ambulatory, while 31 were hypertensive only in laboratory measurements. Conclusion BP responses to upright posture were variable. When compared with ambulatory BP, mean(supine+upright) laboratory cutoff 136/82mmHg classified 76% of subjects similarly as normotensive or hypertensive. In the remaining 24% the discordant results may be attributed to white-coat or masked hypertension, or higher physical activity during out-of-office recordings.Peer reviewe

Response to letter on use of functional imaging by 11C-metomidate PET for primary aldosteronism subtyping

Non peer reviewe

Intraperitoneal Versus Subcutaneous Insulin Treatment in Diabetic Patients on Continuous Ambulatory Peritoneal Dialysis Therapy

Jopa 40% sokeritautipotilaista ajautuu munuaisten vajaatoimintaan ja joutuu dialyysihoitoon elämänsä aikana. Potilaat, joilla on sokeritaudin aiheuttama loppuvaiheen munuaistauti ovat suurin ja nopeimmin kasvava yksittäinen dialyysihoitoa vaativa potilasryhmä. Jatkuva peritoneaalidialyysihoito (CAPD) on yleisesti käytetty hoitomuoto sokeritautipotilailla. Valtimonkovettumataudin kehittyminen on merkittävä ongelma tässä potilasryhmässä. Heistä yli puolet kuolee valtimonkovettumataudin komplikaatioiden vuoksi. Insuliinin annostelun vatsaonteloon uskotaan olevan luonnollisin käytössä oleva tapa korvata puuttuva haiman insuliinin eritys. CAPD-hoitoa varten asetetaan vatsaonteloon johtava kanyyli, jonka kautta voidaan antaa myös insuliinia. Vatsaontelon sisäinen insuliinihoito onkin yleisesti käytetty sokeritautia sairastavilla CAPD-potilailla. Sokeritautipotilailla, joilla ei ole munuaistautia, on tutkittu paljon ihonalaisen ja vatsaontelonsisäisen insuliinipumppuhoidon aiheuttamia aineenvaihdunnan eroja. Sen sijaan munuaisen vajaatoimintaa sairastavilla sokeritautipotilailla vatsaonteloon annetun tai ihonalaisen insuliinihoidon eroja on tutkittu hyvin vähän CAPD-hoidon aikana. Tässä tutkimuksessa verrattiin ihonalaisen ja vatsaonteloon annetun insuliinin aiheuttamia aineenvaihdunnan muutoksia 26 diabetespotilaalla CAPD-hoidon aikana. Erityisen huomion kohteina olivat sokeritasapaino, insuliiniherkkyys, rasva-aineenvaihdunta ja maksan rasvoittuminen. Vatsaonteloon annostellun insuliinin aikana plasman keskimääräinen sokeripitoisuus, insuliiniherkkyys ja plasman insuliinipitoisuus olivat matalampia kuin ihonalaisen insuliinihoidon aikana. Väestöpohjaisissa tutkimuksissa vastaavat muutokset ovat vähentäneet sairastuvuutta ja kuolleisuutta. Vatsaonteloon annetun insuliinihoidon aikana LDL/HDL-kolesterolisuhde lisääntyi ja seerumin HDL-kolesterolipitoisuus väheni verrattuna ihonalaiseen annosteluun. Havaitut rasva-aineenvaihdunnan muutokset voivat osittain liittyä lisääntyneeseen sydän- ja verisuonisairastuvuuteen ja kuolleisuuteen. Siirryttäessä ihonalaisesta vatsaonteloon annettuun insuliinihoitoon havaittiin plasman leptiinipitoisuuden ja painon lasku, jotka ovat mahdollisesti edullisia muutoksia, sillä niillä ei näytä olevan yhteyttä huonoon ravitsemustilaan. Edellä mainittujen aineenvaihdunnan muutoksien syynä voi olla vatsaontelonsisäisen insuliinin tehokas, suora vaikutus maksaan ja toisaalta matalampi plasman insuliinipitoisuus verrattuna ihonalaiseen insuliiniin. Vatsaontelonsisäisen insuliinin aiheuttaman maksan kapselinalaisen rasvakertymän merkitys potilaan ennusteen kannalta on epäselvä. Tämän tutkimuksen perusteella sekä ihonalainen että vatsaontelonsisäinen insuliinihoito sopii käytettäväksi peritoneaalidialyysihoidon aikana. Vatsaontelonsisäinen insuliini vaikuttaa kuitenkin ihonalaista insuliinia paremmalta hoitomuodolta.Up to 40% of diabetic patients are faced with nephropathy and renal failure leading to dialysis treatment after decades of diabetes mellitus. Diabetic patients with end-stage renal disease are the largest and fastest growing patient group on dialysis therapy. Continuous ambulatory peritoneal dialysis (CAPD) is a commonly used renal replacement therapy option for diabetic patients. Atherosclerosis is a major concern in this patient group, since more than 50% die from atherosclerotic complications. Insulin administration to peritoneal cavity is theoretically considered to be the most physiologic available way of replacing the compromised pancreatic insulin production. CAPD treatment provides an intraperitoneal access to administer intraperitoneal insulin. Intraperitoneal insulin administration is commonly used in diabetic CAPD patients. Intraperitoneal compared to subcutaneous insulin treatment has been studied in many aspects in non-uraemic diabetic patients with implantable intraperitoneal versus subcutaneous insulin pumps, but studies on diabetic patients on CAPD treatment are scarce. In the present study the metabolic effects subcutaneous versus intraperitoneal insulin administration have been compared in 26 diabetic CAPD patients. Special attention was given to glycaemic control, insulin sensitivity, lipoprotein metabolism and hepatic steatosis. Intraperitoneal insulin treatment facilitates lower mean plasma glucose levels, plasma free insulin concentration, and less insulin resistance than subcutaneous insulin. These changes are associated with lower morbidity and mortality in epidemiologic studies. Switching from subcutaneous to intraperitoneal insulin increased the ratio of LDL/HDL-cholesterol and decreased serum HDL-cholesterol making plasma lipoprotein levels potentially more atherogenic. Weight reduction and decreased plasma leptin after transition from subcutaneous to intraperitoneal insulin are potentially positive changes since they do not seem to be associated with malnutrition. Both direct intense insulinisation of the liver and low peripheral insulin concentration are implicated as causes for the metabolic changes induced by intraperitoneal insulin treatment. Intraperitoneal insulin treatment induced hepatic subcapsular steatosis formation, the meaning of which on patient survival, is unclear. According to these results, both subcutaneous and intraperitoneal insulin therapy are acceptable from clinical standpoint. Intraperitoneal insulin treatment seems, however, preferable to subcutaneous insulin treatment

Intraperitoneal Versus Subcutaneous Insulin Treatment in Diabetic Patients on Continuous Ambulatory Peritoneal Dialysis Therapy

Jopa 40% sokeritautipotilaista ajautuu munuaisten vajaatoimintaan ja joutuu dialyysihoitoon elämänsä aikana. Potilaat, joilla on sokeritaudin aiheuttama loppuvaiheen munuaistauti ovat suurin ja nopeimmin kasvava yksittäinen dialyysihoitoa vaativa potilasryhmä. Jatkuva peritoneaalidialyysihoito (CAPD) on yleisesti käytetty hoitomuoto sokeritautipotilailla. Valtimonkovettumataudin kehittyminen on merkittävä ongelma tässä potilasryhmässä. Heistä yli puolet kuolee valtimonkovettumataudin komplikaatioiden vuoksi. Insuliinin annostelun vatsaonteloon uskotaan olevan luonnollisin käytössä oleva tapa korvata puuttuva haiman insuliinin eritys. CAPD-hoitoa varten asetetaan vatsaonteloon johtava kanyyli, jonka kautta voidaan antaa myös insuliinia. Vatsaontelon sisäinen insuliinihoito onkin yleisesti käytetty sokeritautia sairastavilla CAPD-potilailla. Sokeritautipotilailla, joilla ei ole munuaistautia, on tutkittu paljon ihonalaisen ja vatsaontelonsisäisen insuliinipumppuhoidon aiheuttamia aineenvaihdunnan eroja. Sen sijaan munuaisen vajaatoimintaa sairastavilla sokeritautipotilailla vatsaonteloon annetun tai ihonalaisen insuliinihoidon eroja on tutkittu hyvin vähän CAPD-hoidon aikana. Tässä tutkimuksessa verrattiin ihonalaisen ja vatsaonteloon annetun insuliinin aiheuttamia aineenvaihdunnan muutoksia 26 diabetespotilaalla CAPD-hoidon aikana. Erityisen huomion kohteina olivat sokeritasapaino, insuliiniherkkyys, rasva-aineenvaihdunta ja maksan rasvoittuminen. Vatsaonteloon annostellun insuliinin aikana plasman keskimääräinen sokeripitoisuus, insuliiniherkkyys ja plasman insuliinipitoisuus olivat matalampia kuin ihonalaisen insuliinihoidon aikana. Väestöpohjaisissa tutkimuksissa vastaavat muutokset ovat vähentäneet sairastuvuutta ja kuolleisuutta. Vatsaonteloon annetun insuliinihoidon aikana LDL/HDL-kolesterolisuhde lisääntyi ja seerumin HDL-kolesterolipitoisuus väheni verrattuna ihonalaiseen annosteluun. Havaitut rasva-aineenvaihdunnan muutokset voivat osittain liittyä lisääntyneeseen sydän- ja verisuonisairastuvuuteen ja kuolleisuuteen. Siirryttäessä ihonalaisesta vatsaonteloon annettuun insuliinihoitoon havaittiin plasman leptiinipitoisuuden ja painon lasku, jotka ovat mahdollisesti edullisia muutoksia, sillä niillä ei näytä olevan yhteyttä huonoon ravitsemustilaan. Edellä mainittujen aineenvaihdunnan muutoksien syynä voi olla vatsaontelonsisäisen insuliinin tehokas, suora vaikutus maksaan ja toisaalta matalampi plasman insuliinipitoisuus verrattuna ihonalaiseen insuliiniin. Vatsaontelonsisäisen insuliinin aiheuttaman maksan kapselinalaisen rasvakertymän merkitys potilaan ennusteen kannalta on epäselvä. Tämän tutkimuksen perusteella sekä ihonalainen että vatsaontelonsisäinen insuliinihoito sopii käytettäväksi peritoneaalidialyysihoidon aikana. Vatsaontelonsisäinen insuliini vaikuttaa kuitenkin ihonalaista insuliinia paremmalta hoitomuodolta.Up to 40% of diabetic patients are faced with nephropathy and renal failure leading to dialysis treatment after decades of diabetes mellitus. Diabetic patients with end-stage renal disease are the largest and fastest growing patient group on dialysis therapy. Continuous ambulatory peritoneal dialysis (CAPD) is a commonly used renal replacement therapy option for diabetic patients. Atherosclerosis is a major concern in this patient group, since more than 50% die from atherosclerotic complications. Insulin administration to peritoneal cavity is theoretically considered to be the most physiologic available way of replacing the compromised pancreatic insulin production. CAPD treatment provides an intraperitoneal access to administer intraperitoneal insulin. Intraperitoneal insulin administration is commonly used in diabetic CAPD patients. Intraperitoneal compared to subcutaneous insulin treatment has been studied in many aspects in non-uraemic diabetic patients with implantable intraperitoneal versus subcutaneous insulin pumps, but studies on diabetic patients on CAPD treatment are scarce. In the present study the metabolic effects subcutaneous versus intraperitoneal insulin administration have been compared in 26 diabetic CAPD patients. Special attention was given to glycaemic control, insulin sensitivity, lipoprotein metabolism and hepatic steatosis. Intraperitoneal insulin treatment facilitates lower mean plasma glucose levels, plasma free insulin concentration, and less insulin resistance than subcutaneous insulin. These changes are associated with lower morbidity and mortality in epidemiologic studies. Switching from subcutaneous to intraperitoneal insulin increased the ratio of LDL/HDL-cholesterol and decreased serum HDL-cholesterol making plasma lipoprotein levels potentially more atherogenic. Weight reduction and decreased plasma leptin after transition from subcutaneous to intraperitoneal insulin are potentially positive changes since they do not seem to be associated with malnutrition. Both direct intense insulinisation of the liver and low peripheral insulin concentration are implicated as causes for the metabolic changes induced by intraperitoneal insulin treatment. Intraperitoneal insulin treatment induced hepatic subcapsular steatosis formation, the meaning of which on patient survival, is unclear. According to these results, both subcutaneous and intraperitoneal insulin therapy are acceptable from clinical standpoint. Intraperitoneal insulin treatment seems, however, preferable to subcutaneous insulin treatment

Primaarin aldosteronismin diagnostiikka ja hoito

Vertaisarvioitu. Teema : verenpainetautiPrimaari aldosteronismi (PA) on yleisin hoidettava mutta alidiagnosoitu sekundaarisen hypertension syy. Essentiaaliseen verenpainetautiin verrattuna se aiheuttaa selvästi suurentuneen elinkomplikaatioiden ja kuoleman riskin. Seulonta aldosteroni-reniinisuhteen mittauksella tulisi kohdistaa erityisesti työikäisiin, vaikeahoitoista verenpainetautia sairastaviin potilaisiin, joilla verenpaineeseen yhdistyy taipumus hypokalemiaan. Seulonta- ja varmentavien kokeiden oikeaan suorittamiseen ja tulkintaan tulee kiinnittää huomioita ja negatiiviset kokeet uusia kliinisen epäilyn jatkuessa. Diagnoosin jälkeen kliininen tilanne, potilaan toiveet hoidosta ja aldosteronin erityksen puolieron tutkimukset ratkaisevat, valitaanko hoidoksi mineralokortikoidireseptorin antagonisti vai toispuoleinen adrenalektomia. Nämä täsmähoidot parantavat ennustetta, mutta leikkauksen jälkeen pienellä osalla PA uusii toisessa lisämunuaisessa, joten potilaat tarvitsevat seurantaa ja valtimotaudin kaikkien riskitekijöiden hyvää hoitoa.Peer reviewe