Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

BACKGROUND: Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. AIM: Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. MATERIALS AND METHODS: We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. RESULTS: The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients [41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71% [45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р<0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.>< 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

[Steroid profiling characteristics in pediatrc adrenal diseases].

BACKGROUND: Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the differential diagnosis of adrenal diseases. Steroid profiling by tandem mass spectrometry is one of the main diagnostic methods in steroidogenesis characterization. Currently plasma and urinary steroid profiling is of particular interest in differential diagnosis and subtyping patients with adrenocortical adenomas. AIM: Steroid profiling of pediatric patients with adrenal diseases (incidentalomas, ACTH-secreting pituitary adenoma, ACTH-independent Cushing syndrome, premature adrenarche). MATERIALS AND METHODS: We conducted a retrospective analysis of steroid profile of 41 pediatric patients with adrenal diseases who were observed between 2005 and 2020 at the Endocrinology Research Centre. RESULTS: All patients were divided into groups due to diagnosis: with ACTH-secreting pituitary adenoma [n=7], ACTH-independent Cushing syndrome (autonomous cortisol secretion by an adrenal adenoma) [n=4], with incidentaloma [n=7] and premature adrenarche [n=23]. In group of patients with ACTH-independent Cushing syndrome identified statistically significant higher levels of 11-deoxycortisol (р=0, 0035) and significant lower levels of 17-hydroxypregnenolone (р=0, 0026) and DHEA (р=0, 0047) compared to other groups. Statistically significant differences in steroid profiles between other groups were not identified. CONCLUSION: Results of our study steroid profiling can be used as additional differential diagnosis method in patients with adrenocortical adenomas with or without hormonal hyperproduction (ACTH-independent Cushing syndrome and incidentaloma). Further studies are needed to identify steroid markers for subtyping pediatric adrenal diseases.

[Genetic basis of Cushing's disease in children and targeted therapeutic future perspectives].

Cushing's disease (CD) is a multisystem disorder of a cortisol excess caused by ACTH -secreting pituitary tumor (corticotropinoma). CD in children is due to somatic or germline mutations with the late onset causing multiple endocrine tumors. If not treated, hypercortisolism leads to severe decrease in quality of life and life-threating conditions. The first-line treatment for CD is pituitary surgery, which might be followed by complications and relapse with necessity of additional surgery or initiations of second-line treatment. Recent studies of molecular basis of corticotropinoma development made it possible to employ medical therapy in CD. Understanding of corticotropinoma etiology and pathogenesis is an important part of education for pediatric endocrinologists since we need to keep in mind possibility of multisystem disorder in case of CD in children and because medical therapy might gain more important role for CD treatment in future.The most actual genetic aspects of corticotroph adenomas growth and the medical treatment opportunities are present in this review.