ADRENAL CRISIS IN FEMALE NEWBORN WITH UNRECOGNIZED CONGENITAL ADRENAL HYPERPLASIA – CASE REPORT

Sažetak. Kongenitalna adrenalna hiperplazija (KAH) zbog deficita 21-hidroksilaze je najčešći uzrok dvosmislenog spolovila u ženske novorođenčadi. Nedostatak ovog enzima dovodi do poremetnje biosinteze kortizola u kori nadbubrežne žlijezde i ekscesivne produkcije adrenalnih androgena s posljedičnom virilizacijom ženskih fetusa. U klasičnom obliku bolest se javlja pojavnošću od 1:10000–15000 živorođenih. Kod ¾ oboljelih postoji i poremećaj biosinteze aldosterona, uslijed kojeg se javljaju potencijalno letalne krize gubitka soli u prvim tjednima života. Prikazujemo slučaj neprepoznate virilizacije ženskog novorođenčeta koje je hospitalizirano u adrenalnoj krizi dvanaestog dana života. Nadoknada glu-kokortikoida (hidrokortizon), te mineralokortikoida (fludrokortizon) uz dodatak soli dovela je do brzog oporavka i zadovoljavajuće kontrole bolesti tijekom 40 dana hospitalizacije. Djevojčica je otpuštena kući s dobrom prognozom za budući rast i razvoj uz preporuku trajne nadoknadne terapije pod kontrolom endokrinologa.Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent cause of genital ambiguity in female newborns. Enzyme deficiency causes a disorder of cortisol synthesis by the adrenal cortex and leads to excessive androgen production resulting in subsequent genital virilization of female fetuses. The incidence of the classical form is 1:10000–15000 live births. About ¾ of affected infants also suffer from a disorder of aldosterone biosynthesis, which can lead to potentially lethal salt-losing crises within the first weeks of life. Here, we report of the case of an unrecognized virilization of a female newborn, who was hospitalized after an adrenal crisis at the twelfth day of life. Supplementary glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) treatment with the addition of salt led to a fast recovery and satisfactory control of disease during 40 days of hospitalization. The girl was released from the hospital with good prognosis for the future growth and develompent with the recommended ongoing supplementary treatment under the supervision of an endocrinologist

ADRENAL CRISIS IN FEMALE NEWBORN WITH UNRECOGNIZED CONGENITAL ADRENAL HYPERPLASIA – CASE REPORT

Sažetak. Kongenitalna adrenalna hiperplazija (KAH) zbog deficita 21-hidroksilaze je najčešći uzrok dvosmislenog spolovila u ženske novorođenčadi. Nedostatak ovog enzima dovodi do poremetnje biosinteze kortizola u kori nadbubrežne žlijezde i ekscesivne produkcije adrenalnih androgena s posljedičnom virilizacijom ženskih fetusa. U klasičnom obliku bolest se javlja pojavnošću od 1:10000–15000 živorođenih. Kod ¾ oboljelih postoji i poremećaj biosinteze aldosterona, uslijed kojeg se javljaju potencijalno letalne krize gubitka soli u prvim tjednima života. Prikazujemo slučaj neprepoznate virilizacije ženskog novorođenčeta koje je hospitalizirano u adrenalnoj krizi dvanaestog dana života. Nadoknada glu-kokortikoida (hidrokortizon), te mineralokortikoida (fludrokortizon) uz dodatak soli dovela je do brzog oporavka i zadovoljavajuće kontrole bolesti tijekom 40 dana hospitalizacije. Djevojčica je otpuštena kući s dobrom prognozom za budući rast i razvoj uz preporuku trajne nadoknadne terapije pod kontrolom endokrinologa.Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent cause of genital ambiguity in female newborns. Enzyme deficiency causes a disorder of cortisol synthesis by the adrenal cortex and leads to excessive androgen production resulting in subsequent genital virilization of female fetuses. The incidence of the classical form is 1:10000–15000 live births. About ¾ of affected infants also suffer from a disorder of aldosterone biosynthesis, which can lead to potentially lethal salt-losing crises within the first weeks of life. Here, we report of the case of an unrecognized virilization of a female newborn, who was hospitalized after an adrenal crisis at the twelfth day of life. Supplementary glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) treatment with the addition of salt led to a fast recovery and satisfactory control of disease during 40 days of hospitalization. The girl was released from the hospital with good prognosis for the future growth and develompent with the recommended ongoing supplementary treatment under the supervision of an endocrinologist

Učinak terapije hormonom rasta u djece s Prader-Willijevim sindromom - prva vlastita iskustva

Prader-Willi syndrome (PWS) is the most common cause of morbid obesity in childhood. It is the consequence of the lack of expression of genes on the paternally inherited 15q11.2-q13 region. Hyperphagia, obesity, short stature, psychomotor retardation and deterioration of behavior predominate in clinical presentation. Recombinant human growth hormone (rhGH) therapy, along with restriction of caloric intake, has become the mainstay in the management of PWS patients. Anthropometric parameters (height, body mass index (BMI)), therapy effect on carbohydrate and lipid metabolism, and occurrence of side effects were monitored in four children with PWS treated with rhGH for ³2 years at doses of up to 1 mg/m2/day. During the follow-up, the height standard deviation score (SDS) increased in comparison with baseline values, and after ³2 years of treatment with rhGH it was within the reference range for the general children population. BMI SDS decreased after the first year of treatment, but thereafter increased again; still, the level of BMI SDS was much better in comparison with most children with PWS of the same age and gender. RhGH therapy had no negative effect on glucose and lipid metabolism, nor caused any other adverse effect. Therapy including a customized diet for PWS, along with rhGH therapy, provided a satisfactory growth rate and prevented development of morbid obesity without side effects. This treatment approach would ensure transition of a greater number of PWS patients into adult care, where the multidisciplinary approach in care should be continued.Prader-Willijev sindrom (PWS) najčešći je uzrok teške debljine u dječjoj dobi. Posljedica je izostanka ekspresije očevih gena u regiji 15q11.2-q13. Kliničkom slikom dominira hiperfagija, debljina, nizak rast, psihomotoričko zaostajanje i poremećaji ponašanja. Terapija rekombinantnim humanim HR (rhHR) postala je, uz ograničenje energetskog unosa, imperativ u zbrinjavanju bolesnika s PWS-om. U 4 djece s PWS-om koja su ³2 godine liječena rhHR u dozi do 1 mg/m2/dan pratili smo antropometrijske parametre, tjelesnu visinu (TV) i indeks tjelesne mase (ITM) te učinak terapije na metabolizam ugljikohidrata, lipida i pojavu neželjenih učinaka. Uz primjenu rhHR je TV standard deviation score (SDS) bio u porastu u odnosu na početnu vrijednost i nakon ³2 godine liječenja bio je unutar referentnog raspona za opću dječju populaciju. ITM SDS snizio se nakon prve godine liječenja, potom je bio u porastu, ali je i nadalje razina bila bolja nego u većine djece u populaciji s PWS-om. Terapija rhHR-om nije nepovoljno utjecala na metabolizam glukoze i lipida te nije izazvala neželjenih učinaka. Terapija koja uključuje prehranu prilagođenu PWS-u i rhHR-om osigurala je zadovoljavajući rast djece i spriječila razvoj teške debljine bez neželjenih učinaka. Takav pristup liječenju osigurat će tranziciju većeg broja bolesnika u internističku skrb koja treba nastaviti s multidisciplinarnim pristupom u liječenju i skrbi za ovu skupinu bolesnika

Relationship between cardiorespiratory fitness, insulin resistance and metabolic health of obese children and adolescents: the role of physical activity

Pretilost je veliki javnozdravstveni problem, a njena incidencija u porastu je u dječjoj i adolescentnoj dobi te povećava kardiometabolički rizik i psihosocijalni komorbiditet u kasnijoj životnoj dobi. Postoje brojni čimbenici rizika za nastanak pretilosti; od genetskih, epigenetskih i okolišnih, a nastanak pretilosti u bliskoj je korelaciji i s inzulinskom rezistencijom, predijabetesom, šećernom bolesti tipa 2 te kardiorespiratornom sposobnosti. Redovita tjelesna aktivnost ima dokazane povoljne učinke na smanjenje i inzulinske rezistencije i povećanje kardiorespiratorne sposobnosti te je samim time važan čimbenik u prevenciji pretilosti, održavanju poželjne tjelesne mase te smanjenju metaboličkih komorbiditeta. Stoga bi uključivanje pretile djece i adolescenata u redovitu tjelesnu aktivnost trebao biti terapijski imperativ.Overweight and obesity is a global health concern, with rising incidence and prevalence among children and adolescents, attributing to cardiometabolic risk and psychosocial comorbidities later in life. Numerous factors influence development of obesity; genetics, epigenetics and environmental being among them. Moreover, obesity is closely related to insulin resistance, prediabetes and type 2 diabetes mellitus, and cardiorespiratory fitness. Regular physical activity has proven beneficial effects on reducing insulin resistance and improving cardiorespiratory fitness and as such is an important means of obesity prevention and attainment of desired weight as well as reduction of metabolic comorbidities. Therefore, inclusion of overweight and obese children and adolescents in regular physical activity should represent a therapeutic imperative

Relationship between cardiorespiratory fitness, insulin resistance and metabolic health of obese children and adolescents: the role of physical activity

Pretilost je veliki javnozdravstveni problem, a njena incidencija u porastu je u dječjoj i adolescentnoj dobi te povećava kardiometabolički rizik i psihosocijalni komorbiditet u kasnijoj životnoj dobi. Postoje brojni čimbenici rizika za nastanak pretilosti; od genetskih, epigenetskih i okolišnih, a nastanak pretilosti u bliskoj je korelaciji i s inzulinskom rezistencijom, predijabetesom, šećernom bolesti tipa 2 te kardiorespiratornom sposobnosti. Redovita tjelesna aktivnost ima dokazane povoljne učinke na smanjenje i inzulinske rezistencije i povećanje kardiorespiratorne sposobnosti te je samim time važan čimbenik u prevenciji pretilosti, održavanju poželjne tjelesne mase te smanjenju metaboličkih komorbiditeta. Stoga bi uključivanje pretile djece i adolescenata u redovitu tjelesnu aktivnost trebao biti terapijski imperativ.Overweight and obesity is a global health concern, with rising incidence and prevalence among children and adolescents, attributing to cardiometabolic risk and psychosocial comorbidities later in life. Numerous factors influence development of obesity; genetics, epigenetics and environmental being among them. Moreover, obesity is closely related to insulin resistance, prediabetes and type 2 diabetes mellitus, and cardiorespiratory fitness. Regular physical activity has proven beneficial effects on reducing insulin resistance and improving cardiorespiratory fitness and as such is an important means of obesity prevention and attainment of desired weight as well as reduction of metabolic comorbidities. Therefore, inclusion of overweight and obese children and adolescents in regular physical activity should represent a therapeutic imperative

Kontinuirano mjerenje glukoze i kontrola šećerne bolesti tip 1 u populaciji djece, adolescenata i mladih odraslih - razlozi za primjenu i učinak

Sensors for continuous glucose monitoring (CGM) in intercellular fluid are used as a contemporary method to achieve better control in type 1 diabetes mellitus (DM), which is best shown through lower glycated hemoglobin (HbA1c) levels.The aim of this study was to assess how many of our patients used CGM (parents were solely financing all the cost of the device) and what was the effect of CGM on the control of DM. Data were retrospectively collected from medical records of patients actively treated at the Division of Endocrinology, Diabetology, Pulmonology and Allergology, Department of Pediatrics, Sestre milosrdnice University Hospital Center. The t-test was used for independent samples to compare the mean levels of HbA1c before and after the inclusion of CGM. CGM was used by 81 (32.1%) of our patients with type 1 DM, of which 43 met the inclusion criteria. The mean HbA1c level 6 months before the introduction of CGM was 8.2%±1.9 and after 12 months of CGM use it was 7.4%±1.2, which was a statistically significant improvement (p=0.026). Furthermore, our results demonstrated that the greatest improvement in HbA1c level was recorded in the groups of young adults (18-25 years) and youngest children (<12 years). We confirmed the efficacy of CGM in achieving better control of type 1 DM by significantly improving HbA1c levels in a population of highly motivated patients.Senzori za kontinuirano mjerenje glukoze (continuous glucose monitoring, CGM) u međustaničnoj tekućini danas se rabe za postizanje bolje kontrole šećerne bolesti tip 1 (ŠB tip 1), što je najbolje vidljivo smanjivanjem vrijednosti glikiranog hemoglobina (HbA1c). Cilj ovog istraživanja provedenog u razdoblju kada su roditelji sami snosili troškove CGM-a bio je utvrditi koliko naših bolesnika primjenjuje navedenu metodu te kakav je učinak CGM-a na kontrolu bolesti. Restrospektivno su prikupljeni podaci iz medicinske dokumentacije bolesnika koji se aktivno liječe na Zavodu za endokrinologiju, dijabetologiju, pulmologiju i alergologiju Klinike za pedijatriju KBC Sestre milosrdnice. Za usporedbu srednjih vrijednosti HbA1c prije i poslije uvođenja CGM-a primijenjen je t-test za nezavisne uzorke. CGM je rabio 81 (32,1%) oboljeli od ŠB tip 1, od kojih su 43 bolesnika ispunili kriterije za uključivanje u ispitivanje. Prosječni HbA1c šest mjeseci prije uvođenja CGM-a bio je 8,2%±1,9, a nakon 12 mjeseci primjene CGM-a bio je 7,4%±1,2, što je statistički značajno poboljšanje (p=0,026). Nadalje, iz rezultata je vidljivo da je najveće poboljšanje u vrijednosti HbA1c imala skupina mladih odraslih (18-25 godina) te skupina najmlađe djece (<12 godina). Ovim ispitivanjem potvrdili smo učinkovitost CGM-a u postizanju bolje kontrole ŠB tip 1 kroz značajno poboljšanje razine HbA1c u populaciji visoko motiviranih bolesnika

TRANSIENT NEONATAL DIABETES CAUSED BY ACTIVATING NOVEL KCNJ11 GENE MUTATION AND SUCCESSFULL TRANSFER TO SULPHONYLUREA THERAPY

Neonatalni diabetes mellitus (NDM) rijetka je monogenska forma dijabetesa koja se klinički prezentira uglavnom do 6. mjeseca života. Javlja se u obliku trajnog i prolaznog NDM-a. Dok je u trajnom NDM-u liječenje nužno cijeli život, u prolaznom NDM-u nakon nekoliko tjedana ili mjeseci liječenja dolazi do remisije, a samo oko 50% oboljelih doživi ­relaps bolesti tijekom adolescencije ili u ranoj odrasloj dobi. Mutacije ABCC8 ili rjeđe KCNJ11-genâ koji kodiraju pod­jedinice kalijeva kanala (KATP-kanal) ovisnog o adenozin trifosfatu uzrok su bolesti u manje od 30% oboljelih. Prikazujemo svoju bolesnicu s prolaznim NDM-om uzrokovanim novom aktivirajućom mutacijom KCNJ11-gena s učinkom na Kir6.2-podjedinicu KATP-kanala i uspješno prevođenje s inzulinske terapije na terapiju sulfonilurejom. Genetička analiza učinjena je u 22. godini života, 12 godina nakon relapsa bolesti te nakon 10 godina inzulinske terapije. Nakon 3 mjeseca terapije peroralnim preparatom sulfonilureje normalizirala se razina HbA1c, a potom i razina inzulina te C-peptida. Zaključak: Potvrdom monogenskog oblika dijabetesa genetička analiza može promijeniti terapijski pristup s pozitivnim učinkom na kontrolu i tijek bolesti, kvalitetu života te otvara mogućnost genetičkog savjetovanja.Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes that usually presents within the first six months of life. It occurs in the form of transient and permanent NDM. Permanent NDM requires life-long treatment while TNDM resolves few weeks or months after treatment initiation, with relapse occuring only in around 50% of patients ­during their adolescence or young adult life. Mutations in ABCC8, or less often in KCNJ11 gene (coding subunit of the ATP-sensitive potassium channel (KATP channel)) cause the disease in less than 30% of all patients. We present our female patient with transient NDM caused by a novel activating KCNJ11 mutation in the Kir6.2 subunit of the K-ATP channel and her successfull transfer from insulin to sulphonylurea therapy. Genetic testing was done at the age of 22 years, 12 years after disease relapse and ten years of insulin treatment. Three months after transfer to sulphonylurea therapy HbA1c levels normalised, followed by normalisation of C-peptide and insulin values as well. Conclusion: Using genetic analysis to confirm monogenic form of diabetes changes the therapeutical approach with positive effect on disease control and course and opens the possibility of genetic counseling

TRANSIENT NEONATAL DIABETES CAUSED BY ACTIVATING NOVEL KCNJ11 GENE MUTATION AND SUCCESSFULL TRANSFER TO SULPHONYLUREA THERAPY

Neonatalni diabetes mellitus (NDM) rijetka je monogenska forma dijabetesa koja se klinički prezentira uglavnom do 6. mjeseca života. Javlja se u obliku trajnog i prolaznog NDM-a. Dok je u trajnom NDM-u liječenje nužno cijeli život, u prolaznom NDM-u nakon nekoliko tjedana ili mjeseci liječenja dolazi do remisije, a samo oko 50% oboljelih doživi ­relaps bolesti tijekom adolescencije ili u ranoj odrasloj dobi. Mutacije ABCC8 ili rjeđe KCNJ11-genâ koji kodiraju pod­jedinice kalijeva kanala (KATP-kanal) ovisnog o adenozin trifosfatu uzrok su bolesti u manje od 30% oboljelih. Prikazujemo svoju bolesnicu s prolaznim NDM-om uzrokovanim novom aktivirajućom mutacijom KCNJ11-gena s učinkom na Kir6.2-podjedinicu KATP-kanala i uspješno prevođenje s inzulinske terapije na terapiju sulfonilurejom. Genetička analiza učinjena je u 22. godini života, 12 godina nakon relapsa bolesti te nakon 10 godina inzulinske terapije. Nakon 3 mjeseca terapije peroralnim preparatom sulfonilureje normalizirala se razina HbA1c, a potom i razina inzulina te C-peptida. Zaključak: Potvrdom monogenskog oblika dijabetesa genetička analiza može promijeniti terapijski pristup s pozitivnim učinkom na kontrolu i tijek bolesti, kvalitetu života te otvara mogućnost genetičkog savjetovanja.Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes that usually presents within the first six months of life. It occurs in the form of transient and permanent NDM. Permanent NDM requires life-long treatment while TNDM resolves few weeks or months after treatment initiation, with relapse occuring only in around 50% of patients ­during their adolescence or young adult life. Mutations in ABCC8, or less often in KCNJ11 gene (coding subunit of the ATP-sensitive potassium channel (KATP channel)) cause the disease in less than 30% of all patients. We present our female patient with transient NDM caused by a novel activating KCNJ11 mutation in the Kir6.2 subunit of the K-ATP channel and her successfull transfer from insulin to sulphonylurea therapy. Genetic testing was done at the age of 22 years, 12 years after disease relapse and ten years of insulin treatment. Three months after transfer to sulphonylurea therapy HbA1c levels normalised, followed by normalisation of C-peptide and insulin values as well. Conclusion: Using genetic analysis to confirm monogenic form of diabetes changes the therapeutical approach with positive effect on disease control and course and opens the possibility of genetic counseling

Kirurško liječenje bolesti štitnjače u pedijatrijskoj populaciji

Bolesti štitnjače jedne su od najčešćih endokrinih poremećaja u djece, ali pojavljuju se rjeđe u toj dobi nego u odraslih osoba. Poremećaji hormona štitnjače poput hipotireoze i hipertireoze u dječjoj dobi mogu uzrokovati zastoj u rastu i razvoju. S druge strane, tumori štitnjače u djece su, u usporedbi s odraslim osobama, u većem postotku maligni i imaju veću sklonost lokoregionalnom širenju i recidiviranju. Pristup djeci s bolestima štitnjače je multidisciplinarni, pedijatri endokrinolozi skrbe o bolesnicima dijagnostički i konzervativno ih liječe, a otorinolaringolozi provode kirurško liječenje. Kirurško liječenje primjenjuje se kod medikamentozno nekontrolirane hipertireoze, uvećane štitnjače koja uzrokuje kompresiju okolnih organa, te tumora štitnjače. Prikazana su tri oboljela djeteta kod kojih je primijenjena totalna tireoidektomija u svrhu liječenja bolesti štitnjače. Prva, osmogodišnja djevojčica koja je prije operativnog zahvata dvije godine medikamentozno liječena zbog hipertireoze uslijed Gravesove bolesti, druga, šesnaestogodišnjakinja kojoj je tijekom ultrazvučne obrade vratne limfadenopatije potvrđen papilarni karcinom štitnjače i treći, osmogodišnji dječak, nositelj mutacije na protoonkogenu RET, koja se klinički manifestira sindromom multiple endokrine neoplazije (MEN 2A). U redovitom praćenju pedijatra kod djeteta je primijećen porast kalcitonina u krvi, te je učinjena totalna tireoidektomij

Establishing paediatric reference intervals for thyroid function tests in Croatian population on the Abbott Architect i2000

Evaluation of thyroid function is often requested and therefore defining paediatric reference intervals (RIs) is of vital importance. Currently, there is a distinct lack of paediatric RIs for thyroid function tests in Croatia. Thus, we established RIs for thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) in the Croatian paediatric population. Reference intervals were calculated from 397 apparently healthy children, aged from 2 days to 0.3. All thyroid function tests required age partitioning, confirmed by SDR above 0.3. There was no need for sex partitioning, confirmed by SDR below 0.3. Still, FT3 was partitioned due to visually noticeable sex related difference for the oldest group (12 years to < 19 years). This is the first study to establish RIs for thyroid function tests in the Croatian paediatric population. We propose RIs for widely used Abbott platform, thus giving laboratories method- and population-specific paediatric RIs for thyroid function tests that should improve clinical test interpretation