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WS04.4 Prevalence of vitamin D deficiency and effectiveness of two different high dose (stoss) oral vitamin D supplementation protocols in a paediatric cystic fibrosis clinic in Australia
Workshop 4. Hormone and Vitamin D metabolism
Oral Presentations
WS04.1 Hypersecretion of glucagon-like peptide 1 (GLP1) in cystic fibrosis G.H. Jones1,2 , P. Dyce1 , N.M. Tidbury3 , J. Greenwood1 , M.J. Ledson1 , M.J. Walshaw1,2 . 1 Liverpool Heart and Chest Hospital, Adult CF Unit, Liverpool, United Kingdom; 2 University of Liverpool, Institute of Ageing and Chronic Disease, Liverpool, United Kingdom; 3 Liverpool Heart and Chest Hospital, Research Department, Liverpool, United Kingdom Objectives: GLP1, an incretin hormone important in post-prandial glucose regulation, is inactivated by enzymes which may be up-regulated in inflammatory conditions such as CF. We looked for evidence of incretin inactivation in individuals with and without CF-related diabetes (CFRD). Methods: GLP1 levels (total & active) were measured during stimulation (oral glucose tolerance test) in 10 individuals with CF (5 CFRD) whilst clinically stable and compared to a matched control group. Samples were processed with DPP4 inhibitor using an ELISA assay (Millipore, Germany). Results: Baseline circulating levels of both active and total GLP1 were similar in all groups. Total GLP1 responses were most pronounced in the CFRD group whose levels rose most sharply; peaked highest and then returned to baseline quicker than the remaining CF patients who in turn had a higher and more sustained rise than controls. Both CF groups therefore significantly hypersecreted total GLP1 (p < 0.05) to achieve the same modest rise in active GLP1 as the control group. GLP1 responses during OGTT
Baseline GLP1 levels
CFRD (n = 5)
Nondiabetics (n = 5)
Controls (n = 6)
12.9 (2.5)
11.4 (3.0)
10.0 (2.5)
Peak GLP1
27.0 (7.9)
22.8 (7.2)
13.1 (6.3)
Time to peak GLP1 (min)
30 (15)
45 (45)
30 (30)
% total secretion 0−30 min
78% (65%)
51% (47%)
61% (49%)
% total secretion 0−60 min
100% (92%)
91% (91%)
95% (97%)
Total incremental rise in GLP1
448.6 (203.0)
736.9 (272.4)
178.1 (167.1)
Values in parentheses are active levels.
Conclusion: Individuals with CF, irrespective of glycemic status, hypersecrete total GLP1 to achieve similar levels of active hormone seen in matched controls. This suggests that CF is associated with higher levels of incretin degradation even in stable non-diabetic patients. Delayed insulin release − common in CFRD − may contribute to the high peaks of GLP1 seen in this group, as normal physiological negative feedback will be lost.
WS04.2 Growth hormone deficiency (GHD) in adult patients (pts) with cystic fibrosis (CF) C. Pascucci1 , R.V. De Biase2 , D. Savi2 , G. Cimino2 , V. D’Al`u2 , E. Sbardella1 , A.M. Isidori1 , S. Quattrucci2 . 1 Sapienza University of Rome, Endocrinology and Experimental Medicine, Roma, Italy; 2 Sapienza University of Rome, Pediatrics and Pediatrics Neurology − Cystic Fibrosis Center, Roma, Italy Introduction: CF adult pts complain signs and symptoms that overlap with the GHD: loss of muscle mass, physical function, occurrence of bone fragility, cardiovascular complications and lower stress tolerance. Aim: To assess the prevalence of GHD in a cohort of CF adults. Methods: 41 pts (30M) with a mean age of 36.9±10.7 yrs were enrolled. Exclusion criteria: liver or lung transplantation, age <18 years, FEV1 <30% and oxygen therapy. All pts underwent an Arginine+GHRH test for GH and H-QLS questionnaire. BMI-adjusted criteria were used for the diagnosis of severe GHD and partial GHD. Results: Enrolled subjects had the following characteristics: BMI:21.7±2.8 kg/m2 , FEV1: 61.9±18.3%, FEF25−75 39±23.7%, CVF 78.7±19.5%. All pts with GHD have a severe genotype: have both alleles with mutations of the first 3 classes. Evaluation of the GH-IGF1 axis revealed 34.2% with a GHD: severe in 12.2% and partial in 22%. In severe GHD, mean GH peak was 9.2±1.3 ng/ml and mean IGF1 185.4±51.5 ng/ml, in partial GHD mean GH peak 13.2±1.5, mean IGF1 208±39.7, and in pts with normal GH response, mean GH peak was 51±38.6, mean IGF1 210.6±77.5. All pts with severe GHD showed a DF508 mutation (60% in homozygous). We found a significant difference in GHD pts than no GHD: in BMI (23.4±2.4 vs 20.9±2.7) and fasting glucose (115.9±29.1 vs 87.7±13.7) and that these variables are inversely correlated with the GH peak (BMI: R = −0.33, p = 0.04; fasting glucose: R = −0.31, p = 0.05). Discussion: To our knowledge there are no studies on the GHD in adults pts CF. You have to follow these pts over time to assess the impact of GHD on general health; should be increased cases in the study to see if this data is confirmed.
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WS04.3 Deficiency of dehydroepiandrosterone sulfate in pediatric and adult patients with cystic fibrosis G. Shmarina1,2 , D. Pukhalskaya1 , S. Semykin3 , L. Avakian3 , E. Amelina4 , S. Krasovskiy4 , M. Usacheva4 , V. Alioshkin2 , N. Kashirskaya1 . 1 Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moscow, Russian Federation; 2 G.N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russian Federation; 3 Federal State Budgetary Institution “Russian Pediatric Clinical Hospital”, Moscow, Russian Federation; 4 Federal Institution ‘Pulmonology Research Institute’, Federal Medical and Biological Agency of Russia, Moscow, Russian Federation Objectives: Dehydroepiandrosterone (DHEA) is the most abundant adrenal steroid, and the serum concentrations of its sulfate ester, DHEA-S, are 20-fold higher than those of any other circulating steroid hormone. Decreased levels of DHEA-S are associated with pulmonary hypertension and cardiovascular diseases, immune abnormalities, osteoporosis, glucose intolerance and diabetes, deterioration of lipid metabolism. The aim of the study was to evaluate DHEA-S concentrations in children and adults with cystic fibrosis (CF). Methods: 125 pediatric (6−17 years) and 38 adult patients (18−28 years) with CF were enrolled into the study. Plasma DHEA-S and ACTH levels were assayed with commercially available kits. Results: DHEA-S concentrations were significantly below the age-adjusted median values in 68% of children and 73% of adults with CF. The hormone deficiency was more pronounced in subjects with cirrhosis and in the group of young women where, respectively, 100% and 82% of participants had DHEA-S concentrations below the age-adjusted median values. Pediatric patients (6−11 years) with minimal DHEA-S levels demonstrated significantly lower Body Mass Indexes compared to those of CF children who had normal hormone concentrations (14.4 vs 16.3 kg/m2 , p < 0.01). At the same time adult subjects with minimal DHEA-S levels showed decreased ACTH concentrations (9.2 vs 14.4 pg/ml, p < 0.01). Conclusion: Our data indicate that most pediatric and adult CF patients suffer from DHEA-S deficiency. Since DHEA is a well-tolerated and inexpensive drug, its supplementation might prove useful for the clinical management of CF patients with low levels of the hormone.
WS04.4 Prevalence of vitamin D deficiency and effectiveness of two different high dose (stoss) oral vitamin D supplementation protocols in a paediatric cystic fibrosis clinic in Australia N. VanderHaak1 , A. Day2 , J. Miller3 , A. Pena4,5 , A. Tai5,6 , J. Martin6 . 1 Women’s and Children’s Hospital, Nutrition Department, Adelaide, Australia; 2 Flinders University, Bachelor of Nutrition and Dietetics, Adelaide, Australia; 3 Flinders University School of Medicine, Nutrition and Dietetics, Adelaide, Australia; 4 Women’s and Children’s Hospital, Endocrine and Diabetes, Adelaide, Australia; 5 The University of Adelaide, Adelaide, Australia; 6 Women’s and Children’s Hospital, Department of Respiratory and Sleep Medicine, Adelaide, Australia Objectives: To determine the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in children with cystic fibrosis (CF) in South Australia and to evaluate the effectiveness of 2 stoss vitamin D supplementation protocols. Methods: A retrospective case-note review was conducted for 143 children with CF (0−18 years, 75 males) for the period Nov 2012-Sept 2014 where 25(OH)D levels were collected. In Nov 2012 a stoss protocol was adopted where children with inadequate 25(OH)D (defined as <75 nmol/L) were supplemented with a single dose of 200,000–500,000 IU vitamin D (depending on age and 25(OH)D level). In Oct 2013 the protocol was revised to include 1000IU vitamin D additional daily dose. Results: Vitamin D deficiency was observed in 69% of children (n = 98). 73 received stoss therapy. Serum 25(OH)D levels 2 months post stoss were available for 53 children. Both protocols increased mean±SD 25(OH)D levels significantly (71.2±25.3 vs 56.5±8.7 nmol/L, p < 0.001) with 49% (26/53) achieving adequate vitamin D status. There was no significant difference between protocol 1 and 2 in vitamin D levels post stoss (70.9±26.3 vs 71.7±24.1 nmol/L, p = 0.9) or the proportion of children no longer vitamin D deficient (50% vs 47%, p = 0.9). There was no significant difference in post stoss vitamin D levels between pancreatic sufficient and insufficient children (85.3±33.0 vs 68.3±22.8 nmol/L, p = 0.06). Conclusion: Vitamin D deficiency is highly prevalent in this population. Stoss therapy increases 25(OH)D levels however 51% of children did not achieve adequate vitamin D levels regardless of protocol used. Further investigation is required to improve the effectiveness of vitamin D supplementation.
Oral Presentations
WS04.1 Hypersecretion of glucagon-like peptide 1 (GLP1) in cystic fibrosis G.H. Jones1,2 , P. Dyce1 , N.M. Tidbury3 , J. Greenwood1 , M.J. Ledson1 , M.J. Walshaw1,2 . 1 Liverpool Heart and Chest Hospital, Adult CF Unit, Liverpool, United Kingdom; 2 University of Liverpool, Institute of Ageing and Chronic Disease, Liverpool, United Kingdom; 3 Liverpool Heart and Chest Hospital, Research Department, Liverpool, United Kingdom Objectives: GLP1, an incretin hormone important in post-prandial glucose regulation, is inactivated by enzymes which may be up-regulated in inflammatory conditions such as CF. We looked for evidence of incretin inactivation in individuals with and without CF-related diabetes (CFRD). Methods: GLP1 levels (total & active) were measured during stimulation (oral glucose tolerance test) in 10 individuals with CF (5 CFRD) whilst clinically stable and compared to a matched control group. Samples were processed with DPP4 inhibitor using an ELISA assay (Millipore, Germany). Results: Baseline circulating levels of both active and total GLP1 were similar in all groups. Total GLP1 responses were most pronounced in the CFRD group whose levels rose most sharply; peaked highest and then returned to baseline quicker than the remaining CF patients who in turn had a higher and more sustained rise than controls. Both CF groups therefore significantly hypersecreted total GLP1 (p < 0.05) to achieve the same modest rise in active GLP1 as the control group. GLP1 responses during OGTT
Baseline GLP1 levels
CFRD (n = 5)
Nondiabetics (n = 5)
Controls (n = 6)
12.9 (2.5)
11.4 (3.0)
10.0 (2.5)
Peak GLP1
27.0 (7.9)
22.8 (7.2)
13.1 (6.3)
Time to peak GLP1 (min)
30 (15)
45 (45)
30 (30)
% total secretion 0−30 min
78% (65%)
51% (47%)
61% (49%)
% total secretion 0−60 min
100% (92%)
91% (91%)
95% (97%)
Total incremental rise in GLP1
448.6 (203.0)
736.9 (272.4)
178.1 (167.1)
Values in parentheses are active levels.
Conclusion: Individuals with CF, irrespective of glycemic status, hypersecrete total GLP1 to achieve similar levels of active hormone seen in matched controls. This suggests that CF is associated with higher levels of incretin degradation even in stable non-diabetic patients. Delayed insulin release − common in CFRD − may contribute to the high peaks of GLP1 seen in this group, as normal physiological negative feedback will be lost.
WS04.2 Growth hormone deficiency (GHD) in adult patients (pts) with cystic fibrosis (CF) C. Pascucci1 , R.V. De Biase2 , D. Savi2 , G. Cimino2 , V. D’Al`u2 , E. Sbardella1 , A.M. Isidori1 , S. Quattrucci2 . 1 Sapienza University of Rome, Endocrinology and Experimental Medicine, Roma, Italy; 2 Sapienza University of Rome, Pediatrics and Pediatrics Neurology − Cystic Fibrosis Center, Roma, Italy Introduction: CF adult pts complain signs and symptoms that overlap with the GHD: loss of muscle mass, physical function, occurrence of bone fragility, cardiovascular complications and lower stress tolerance. Aim: To assess the prevalence of GHD in a cohort of CF adults. Methods: 41 pts (30M) with a mean age of 36.9±10.7 yrs were enrolled. Exclusion criteria: liver or lung transplantation, age <18 years, FEV1 <30% and oxygen therapy. All pts underwent an Arginine+GHRH test for GH and H-QLS questionnaire. BMI-adjusted criteria were used for the diagnosis of severe GHD and partial GHD. Results: Enrolled subjects had the following characteristics: BMI:21.7±2.8 kg/m2 , FEV1: 61.9±18.3%, FEF25−75 39±23.7%, CVF 78.7±19.5%. All pts with GHD have a severe genotype: have both alleles with mutations of the first 3 classes. Evaluation of the GH-IGF1 axis revealed 34.2% with a GHD: severe in 12.2% and partial in 22%. In severe GHD, mean GH peak was 9.2±1.3 ng/ml and mean IGF1 185.4±51.5 ng/ml, in partial GHD mean GH peak 13.2±1.5, mean IGF1 208±39.7, and in pts with normal GH response, mean GH peak was 51±38.6, mean IGF1 210.6±77.5. All pts with severe GHD showed a DF508 mutation (60% in homozygous). We found a significant difference in GHD pts than no GHD: in BMI (23.4±2.4 vs 20.9±2.7) and fasting glucose (115.9±29.1 vs 87.7±13.7) and that these variables are inversely correlated with the GH peak (BMI: R = −0.33, p = 0.04; fasting glucose: R = −0.31, p = 0.05). Discussion: To our knowledge there are no studies on the GHD in adults pts CF. You have to follow these pts over time to assess the impact of GHD on general health; should be increased cases in the study to see if this data is confirmed.
S7
WS04.3 Deficiency of dehydroepiandrosterone sulfate in pediatric and adult patients with cystic fibrosis G. Shmarina1,2 , D. Pukhalskaya1 , S. Semykin3 , L. Avakian3 , E. Amelina4 , S. Krasovskiy4 , M. Usacheva4 , V. Alioshkin2 , N. Kashirskaya1 . 1 Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moscow, Russian Federation; 2 G.N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russian Federation; 3 Federal State Budgetary Institution “Russian Pediatric Clinical Hospital”, Moscow, Russian Federation; 4 Federal Institution ‘Pulmonology Research Institute’, Federal Medical and Biological Agency of Russia, Moscow, Russian Federation Objectives: Dehydroepiandrosterone (DHEA) is the most abundant adrenal steroid, and the serum concentrations of its sulfate ester, DHEA-S, are 20-fold higher than those of any other circulating steroid hormone. Decreased levels of DHEA-S are associated with pulmonary hypertension and cardiovascular diseases, immune abnormalities, osteoporosis, glucose intolerance and diabetes, deterioration of lipid metabolism. The aim of the study was to evaluate DHEA-S concentrations in children and adults with cystic fibrosis (CF). Methods: 125 pediatric (6−17 years) and 38 adult patients (18−28 years) with CF were enrolled into the study. Plasma DHEA-S and ACTH levels were assayed with commercially available kits. Results: DHEA-S concentrations were significantly below the age-adjusted median values in 68% of children and 73% of adults with CF. The hormone deficiency was more pronounced in subjects with cirrhosis and in the group of young women where, respectively, 100% and 82% of participants had DHEA-S concentrations below the age-adjusted median values. Pediatric patients (6−11 years) with minimal DHEA-S levels demonstrated significantly lower Body Mass Indexes compared to those of CF children who had normal hormone concentrations (14.4 vs 16.3 kg/m2 , p < 0.01). At the same time adult subjects with minimal DHEA-S levels showed decreased ACTH concentrations (9.2 vs 14.4 pg/ml, p < 0.01). Conclusion: Our data indicate that most pediatric and adult CF patients suffer from DHEA-S deficiency. Since DHEA is a well-tolerated and inexpensive drug, its supplementation might prove useful for the clinical management of CF patients with low levels of the hormone.
WS04.4 Prevalence of vitamin D deficiency and effectiveness of two different high dose (stoss) oral vitamin D supplementation protocols in a paediatric cystic fibrosis clinic in Australia N. VanderHaak1 , A. Day2 , J. Miller3 , A. Pena4,5 , A. Tai5,6 , J. Martin6 . 1 Women’s and Children’s Hospital, Nutrition Department, Adelaide, Australia; 2 Flinders University, Bachelor of Nutrition and Dietetics, Adelaide, Australia; 3 Flinders University School of Medicine, Nutrition and Dietetics, Adelaide, Australia; 4 Women’s and Children’s Hospital, Endocrine and Diabetes, Adelaide, Australia; 5 The University of Adelaide, Adelaide, Australia; 6 Women’s and Children’s Hospital, Department of Respiratory and Sleep Medicine, Adelaide, Australia Objectives: To determine the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in children with cystic fibrosis (CF) in South Australia and to evaluate the effectiveness of 2 stoss vitamin D supplementation protocols. Methods: A retrospective case-note review was conducted for 143 children with CF (0−18 years, 75 males) for the period Nov 2012-Sept 2014 where 25(OH)D levels were collected. In Nov 2012 a stoss protocol was adopted where children with inadequate 25(OH)D (defined as <75 nmol/L) were supplemented with a single dose of 200,000–500,000 IU vitamin D (depending on age and 25(OH)D level). In Oct 2013 the protocol was revised to include 1000IU vitamin D additional daily dose. Results: Vitamin D deficiency was observed in 69% of children (n = 98). 73 received stoss therapy. Serum 25(OH)D levels 2 months post stoss were available for 53 children. Both protocols increased mean±SD 25(OH)D levels significantly (71.2±25.3 vs 56.5±8.7 nmol/L, p < 0.001) with 49% (26/53) achieving adequate vitamin D status. There was no significant difference between protocol 1 and 2 in vitamin D levels post stoss (70.9±26.3 vs 71.7±24.1 nmol/L, p = 0.9) or the proportion of children no longer vitamin D deficient (50% vs 47%, p = 0.9). There was no significant difference in post stoss vitamin D levels between pancreatic sufficient and insufficient children (85.3±33.0 vs 68.3±22.8 nmol/L, p = 0.06). Conclusion: Vitamin D deficiency is highly prevalent in this population. Stoss therapy increases 25(OH)D levels however 51% of children did not achieve adequate vitamin D levels regardless of protocol used. Further investigation is required to improve the effectiveness of vitamin D supplementation.