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  • 1
    In: Problems of Endocrinology, Endocrinology Research Centre, Vol. 65, No. 4 ( 2019-12-25), p. 227-235
    Abstract: BACKGROUND: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI). AIM: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI. METHODS: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured. RESULTS: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l). CONCLUSION: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.
    Type of Medium: Online Resource
    ISSN: 2308-1430 , 0375-9660
    URL: Issue
    Language: Unknown
    Publisher: Endocrinology Research Centre
    Publication Date: 2019
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  • 2
    In: Problems of Endocrinology, Endocrinology Research Centre, Vol. 65, No. 5 ( 2019-11-23), p. 330-340
    Abstract: BACKGROUND: The most of the current studies include patients who are different by the etiology of secondary adrenal insufficiency (SAI), or investigate SAI among other late effects of the radiation therapy. AIMS: To describe the features of SAI and to select the best method of screening SAI in adult patients followed complex treatment of nonpituitary brain tumors in childhood. MATERIALS AND METHODS: It was the retrospective cross-sectional study. 31 patients after the complex treatment of nonpituitary brain tumors in childhood and 20 healthy volunteers were examined. Age and sex ratio were comparable between the groups. Biochemical and clinical blood tests, levels of cortisol, ACTH, DHEA-C were evaluated. The insulin tolerance test (ITT) was performed for all patients and 11 volunteers. RESULTS: The prevalence of SAI by ITT was 45.2%. The levels of basal cortisol (BC) were significantly higher in patients without SAI in comparison with the SAI group and volunteers (505 [340; 650] vs 323 [233; 382] and 372 [263; 489] nmol / l; pSAI- without_SAI=0.001; pwihtout_SAI-healthy = 0.04). The SAI group had DHEA-C significantly lower than in other groups one (3.1 [1.8; 3.4] vs 5.1 [2.5; 6.4] and 6.8 [4.1; 8.9] ; рSAI- without_SAI = 0.036; pSAI-healthy = 0.001). ROC analysis showed that BC and DHEA-S can be used as high-quality screening tests for SAI (AUC = 89.3% and 88.3%). The maximum level of cortisol (656 [608-686] vs 634 [548-677] ; p = 1) and the time of its increase (45 and 60 min) did not differ during ITT in patients without SAI and volunteers. Side effects: delayed hypoglycemia occurred in 4/14 patients of the SAI group 4090 minutes late of injection 60-80 ml of 40% glucose solution for stopping hypoglycemia in the test. CONCLUSIONS: 45.2% of patients followed craniospinal irradiation had SAI that is characterized by a decrease in DHEA-C levels. A highly normal level of basal cortisol was observed in 45% of patients without SAI. DHEA-C and blood cortisol can be used for SAI screening.
    Type of Medium: Online Resource
    ISSN: 2308-1430 , 0375-9660
    URL: Issue
    Language: Unknown
    Publisher: Endocrinology Research Centre
    Publication Date: 2019
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  • 3
    Online Resource
    Online Resource
    Endocrinology Research Centre ; 2016
    In:  Problems of Endocrinology Vol. 62, No. 5 ( 2016-09-22), p. 74-75
    In: Problems of Endocrinology, Endocrinology Research Centre, Vol. 62, No. 5 ( 2016-09-22), p. 74-75
    Abstract: Background. The insulin tolerance test (ITT) is the “gold standard” of the secondary adrenal insufficiency (SAI) diagnosis but it is rather difficult to carry out, has some contraindications and requires patient’s hospitalization. The availability of a reliable screening method could reduce the necessity of using ITT.Aim: to compare different methods of screening with ITT and to work out an optimal diagnostic algorithm of SAI.Methods. 40 patients (20 women) after craniospinal (CSI) irradiation in a doze 35 Gy were examined. The average age at the time of the observation was 19,5±3 years, at the time of treatment 12,5±3,5 years. Patient’s blood samples were collected for basal cortisol (BC), DHEA-S. ITT was performed for all patients, glucagon stimulation test (GST) was for 27 persons. Patients were divided into groups: SAI and without SAI (W-SAI) after ITT. ROC- analysis was conducted to identify the thresholds for BC, DHEA-S and GST. Cut-off points for BC and DHEA-S levels corresponding to 100% sensitivity (Se) for SAI group and 100% specificity (Sp) for W-SAI patients were estimated to select a group of patients which do not require stimulative tests. Linear regression was used to construct a predictive model (PM) of SAI occurrence after CSI.Results. 22/40 subjects failed ITT, 13/27 passed GST. 3 patients failed ITT but passed GST. Their level of neutrophils and monocytes was higher than the other patients'. SAI-patients had BC and DHEA-S lower than W-SAI (321±102 vs 516± 183; p=0,003 and 2,6±1,4 vs 5,1±2,1, p=0,003). ROC-analysis showed area under curve (AUC) for GST=0,91 with optimal cut-off for cortisol=489 which corresponds to 100% Sp and 62% Se. AUC was 0,83 for BC and 0,84 for DHEA-S.In 70% patients' BC was in a “grey zone” (32% of them passed ITT), 8% had BC lower than 200 (which corresponds to 100% Se) and 22% more than 499 (100% Sp). 50% of patients were in a “grey zone” for DHEA-S (50% of them had SAI), 18% had DHEA-S level below 2,0 and 32% above 4,7. A combination of BC and DHEA-S in the PM of SAI (0,592+0,001*BC+0,11*DHEA-S) had AUC 94%. This PM didn’t give the prognosis of SAI for 32% (CI: 18-49%) of patients. The addition of maximal cortisol (MC) level during GST (0,53+0,01*BC+0,066*DHEA-S+0,001*MC) increased AUC to 99% and didn’t allow to predict SAI in 8% (3,2% - 24,9%) of patients only.Conclusions. When the screening methods were used separately, they showed comparable accuracy and it was not high. The PM may be used as optimal screening method for SAI and may allow to use ITT more rarely. But further studies are required to validate the PM proposed in this study.
    Type of Medium: Online Resource
    ISSN: 2308-1430 , 0375-9660
    URL: Issue
    Language: Unknown
    Publisher: Endocrinology Research Centre
    Publication Date: 2016
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  • 4
    In: Problems of Endocrinology, Endocrinology Research Centre, Vol. 62, No. 2 ( 2016-02-16), p. 12-24
    Abstract: Endocrine disorders are common in patients after treatment for brain tumors in childhood. Growth hormone (GH) deficiency is the most common consequence of cranial irradiation. Objective — to evaluate the prevalence of GH deficieny and metabolic disorders in patients after treatment for malignant tumors of the posterior cranial fossa (MT PCF) in childhood. Material and methods. In this study 40 patients (21 men, 19 women) who had undergone treatment for MT PCF were assessed. Patients underwent surgery, chemotherapy and craniospinal irradiation (CSI) in a dose of 34.9±1.6 Gy with a boost to the PCF 51.3±9.2 Gy. Age at the time of the survey — 19.8±3.05 years; age at the time of treatment — 10.9±3.4 years; follow-up — 7.2±4.2 years. Patient’s anthropometric and laboratory parameters were measured, GH failure was diagnosed by two tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). Results. According to ITT GH deficiency was observed in 82.1% and according to GST in 60.0% of patients. When comparing two tests GST showed 100% specificity, but lower sensitivity (72.2%). Manifestation of GH deficiency depends on the age at the time of treatment (p=0.002). There is significant correlation between age at the time of treatment and SDS of final height (r=0.632; p 〈 0.001). We found a significant correlation between age at the time of treatment and BMI (r=–0,327; p=0.04). Dyslipidemia occurred in 50% of cases. Insulin resistance was recorded in 16.7% of patients. We found significant correlation between the HOMA-IR and BMI (r=0.336; p=0.034). Conclusions. In patients after treatment for MT PCF in childhood GH deficiency and metabolic disorders is highly prevalent. This group of patients should be monitored by endocrinologist for timely detection and treatment of GH deficiency and metabolic complications.
    Type of Medium: Online Resource
    ISSN: 2308-1430 , 0375-9660
    URL: Issue
    Language: Unknown
    Publisher: Endocrinology Research Centre
    Publication Date: 2016
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  • 5
    In: Problems of Endocrinology, Endocrinology Research Centre, Vol. 62, No. 5 ( 2016-09-22), p. 62-63
    Abstract: Background. Endocrine consequences such as growth hormone deficiency (GHD), growth disturbances and metabolic disorders are common in childhood cancer survivors.Aim: to evaluate and compare the prevalence of growth disturbances and metabolic disorders in childhood posterior cranial fossa tumors (cPCFT) and acute lymphoblastic leukemia (cALL) survivors.Materials and methods. 40 subjects (21 men, 19 women) who had undergone treatment for cPCFT (group 1) and 25 subjects (9 men, 16 women) after treatment for cALL (group 2) were assessed. Group 1 underwent surgery, chemotherapy (CT) and craniospinal irradiation in a dose of 34.9 ± 1.6 Gy with a boost to the PCF 51.3 ± 9.2 Gy. Group 2 underwent CT (23 subjects were treated with ALL-BFM-90 protocol; 2 subjects were treated with ALL-MB-2002 protocol). All subjects of the group 2 received cranial irradiation in a dose 12,7±2 Gy. Age at the time of the survey in a group 1 and 2 – 19.8 ± 3.05 and 21.2±3.9 years; age at the time of treatment – 10.9 ± 3.4 and 6.9±3.4 years; follow-up – 7.2 ± 4.2 and 13.8±4.9 years, respectively. 16 age and sex matched healthy controls were included. Patient’s anthropometric and laboratory parameters were measured, GHD was diagnosed in group 1 by 2 tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). In group 2 these tests didn't perform. At the time of the survey no one in both groups received GH replacement therapy. Only 5 subjects (3 boys and 2 girls) in group 1 were treated with recombinant human GH during childhood.Results.Final height SDS in the group 1 was significantly less than in the group 2 (p=0.001) and in healthy controls (p 〈 0.001). In the group 1 and 2 there were significantly less patients reached target height compared to healthy controls (p 〈 0.001). Subjects of group 1 rarely reached their target height in comparison to the group 2 (p=0.006). IGF-1 SDS was significantly less in the group 1 (-1.37±1.24) than in the group 2 (0.5±1.24, p 〈 0.001). In group 1 GHD according to GST was diagnosed in 60% of subjects, according to ITT in 82.1% of subjects. Waist circumference was significantly bigger in group 2 compared to the group 1 (p=0.046) and to healthy controls (p=0.001). Overweight was registered in 10% of patients in group 1 and in 16% - in group 2. Dyslipidemia was diagnosed in 50% in group 1, in 19% in group 2 (p=0.226). In group 1 16.7% and in group 2 66.7% of subjects were insulin resistant.Conclusions. After treatment for cPCFT growth disturbances occurred more often than after cALL therapy. Metabolic disorders were diagnosed with different frequency in both cPCFT and cALL survivors. These patients need endocrinologist’ observation.
    Type of Medium: Online Resource
    ISSN: 2308-1430 , 0375-9660
    URL: Issue
    Language: Unknown
    Publisher: Endocrinology Research Centre
    Publication Date: 2016
    Location Call Number Limitation Availability
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