Ann M. Maguire

Other complications and associated conditions with diabetes in children and adolescents

aChildren’s Hospital auf der Bult, Hannover, Germany; bthe Children’s Hospital at Westmead, NSW, Australia; cUniversity of Helsinki, Finland; dMedical University Vienna, Austria; eUniversity of Genova, Italy; fUniversitat Ulm, Uni West, Germany; gUniversity of Sydney, Australia Corresponding author: Prof. Dr. med. Olga Kordonouri Diabetes Center for Children and Adolescents Children’s Hospital auf der Bult Hannover, Germany Tel: +49 511/8115-3340; fax: +49 511/8115-3334; e-mail: kordonouri@hka.de

Autonomic Nerve Testing Predicts the Development of Complications: A 12-year follow-up study

OBJECTIVE—Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS—From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0–16.8], duration of diabetes 6.3 years [4.0–9.6], and A1C 8.3% [7.5–9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS—At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32–14.42], P = 0.016) and retinopathy (4.83 [1.3–17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS—In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Sick day management in children and adolescents with diabetes

Departmentof Pediatrics, Uddevalla Hospital, Uddevalla, SwedenCorresponding author:Ragnar Hanas, MD, PhDDepartment of Pediatrics, Uddevalla HospitalS-451 80 UddevallaSweden.Tel: 146 522 92000;fax: 146 522 93149;e-mail: ragnar.hanas@vgregion.seEditors of the ISPAD Clinical Practice Consensus Guidelines2006–2007: Ragnar Hanas, Kim Donaghue, GeorgeannaKlingensmith, and Peter Swift.

Evaluation of adrenal function using the human corticotrophin-releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency

Background  The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin‐releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed.

Prolonged Hypocortisolemia in Hydrocortisone Replacement Regimens in Adrenocorticotrophic Hormone Deficiency

OBJECTIVES. Studies of adults have shown that thrice-daily hydrocortisone dosing results in more physiologic cortisol profiles than twice-daily dosing. There are no data on thrice-daily dosing and only limited data on twice-daily dosing in children despite the possible adverse effects of glucocorticoid underreplacement or overreplacement. METHODS. Using 24-hour cortisol and glucose profiles, along with computerized cognitive testing, our aim was to assess prescribed hydrocortisone regimens in children and adolescents with hypopituitarism. RESULTS. Twenty patients with adrenocorticotrophic hormone deficiency participated. The hydrocortisone dosing regimen was thrice daily in 9 patients and twice daily in 11 patients (mean total daily dose: 8.3 ± 2.6 and 7.6 ± 2.1 mg/m2 per day, respectively). Those on twice-daily dosing had more waking hours (between 8:00 am and 8:00 pm) below the reference range than those on thrice-daily dosing (5.5 vs 2.1) and more daytime prolonged hypocortisolemia, defined as plasma cortisol level of <50 nmol/L for ≥4 hours (64% vs 0%). Morning doses >4 mg/m2 caused larger postdose peaks than <4 mg/m2 (151 vs 47 nmol/L, above the 97.5th percentile). However, there was no difference in the length of time taken to reach nadir below the 2.5th percentile (5.2 vs 4.8 hours). This was true for evening doses of >2.5 mg/m2 and < 2.5 mg/m2. No hypoglycemia or hyperglycemia was detected in association with low or high cortisol levels. On predose and postdose cognitive testing (34 paired tests), no significant change in reaction speed was detected (453.3 vs 438.8 milliseconds) or in subgroup analysis of those who had symptoms of lethargy, predose cortisol levels of <50 nmol/L, or prolonged hypocortisolemia. CONCLUSIONS. Thrice-daily dosing resulted in less frequent and prolonged hypocortisolemia than twice-daily regimens, but we were unable to relate either regimen to acute clinical end points of glycemia, lethargy, or cognitive function.

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia

Objective: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia.

Cortisol response to general anaesthesia for medical imaging in children

Objective  The cortisol response to surgical stress has been frequently studied, and recommendations developed for steroid replacement in adrenally insufficient patients. There are currently no guidelines, however, for adrenal hormone replacement during anaesthesia alone. The objective of this study was to characterize the normal cortisol response to general anaesthesia in the absence of a surgical procedure in children.

The clinical utility of alternative, less invasive sampling techniques in the assessment of oral hydrocortisone therapy in children and adolescents with hypopituitarism

OBJECTIVE The aim of glucocorticoid replacement therapy in ACTH-deficient patients is to mimic the normal diurnal variation of cortisol. However, current hydrocortisone (HC) replacement results in prolonged episodes of hypocortisolaemia and supraphysiological peaks. Plasma cortisol profiles are an accurate yet labour-intensive method of assessing HC replacement. Salivary and bloodspot cortisol sampling methods are less invasive and may be useful tools for assessing glucocorticoid replacement, particularly in children. Therefore, we aimed to define normal salivary and bloodspot cortisol levels in children and their correlations with the gold standard (plasma cortisol). DESIGN Cross-sectional study in a paediatric teaching hospital. METHODS Plasma, saliva and bloodspot cortisol profiles were performed on 30 ACTH-deficient children and 22 healthy siblings. RESULTS In ACTH-deficient patients taking oral HC, the bloodspot-plasma correlation (p=0.90) was stronger than the salivary-plasma correlation (p=0.49). Using target ranges for salivary and bloodspot cortisol levels based on normal data from control subjects, the less invasive sampling methods had low rates of agreement with plasma cortisol target ranges (saliva 65% and bloodspot 75%). Using the plasma-bloodspot correlation regression equation to convert bloodspot to calculated plasma cortisol, there was a high concordance between calculated and actual measured plasma cortisol (88%). CONCLUSION Bloodspot cortisol sampling is a feasible and accurate method for monitoring oral HC replacement in paediatric patients without necessitating hospital admission, but salivary sampling is not useful.

Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age.

Objective. To examine patterns of hospitalisation for acute medical conditions in children with congenital adrenal hyperplasia (CAH). Design. A retrospective study of hospitalisation using administrative data. Setting. All hospitals in NSW, Australia. Patients. All patients admitted with CAH and a random sample of admissions in patients aged 0 to 18 years without adrenal insufficiency (AI). Main Outcome Measures. Admissions and comorbidities by age and sex. Results. Of 573 admissions for medical problems in CAH children, 286 (49.9%) were in males, and 236 (41.2%) had a principal diagnosis of CAH or had an adrenal crisis (AC). 37 (6.5%) ACs were recorded. An infection was found in 43.5% (n = 249) of the CAH patient admissions and 51.7% (n = 1613) of the non-AI group, p < 0.001. Children aged up to one year had the highest number of admissions (n = 149) and six ACs (four in males). There were 21 ACs recorded for children aged 1–5 years. Older CAH children had fewer admissions and fewer ACs. No in-hospital deaths were recorded. Conclusions. Admission for medical problems in CAH children declines with age. An AC was recorded in 6.5% of the admissions, with the majority of ACs occurring in the 1 to 5 years age group and there were no deaths.

Desmopressin administration in children with central diabetes insipidus: a retrospective review

Abstract Background: Central diabetes insipidus (DI) is a rare disorder in children caused by a deficiency of antidiuretic hormone arginine (vasopressin). Desmopressin is the first line agent in management of central DI. However, one of the side effects of desmopressin is water intoxication and hyponatraemia. This study reviews the patterns of desmopressin use and side effects in our institution. Methods: Retrospective chart review of all patients with central DI followed up in one tertiary centre between 1 January 2008 and 31 December 2010. Results: Forty-one patients (22 males and 19 females) were included. Twelve patients (29.3%) had congenital and 29 patients (70.7%) had acquired DI, mostly as a result of intracranial tumours. Thirty-six (87.8%) patients were on oral desmopressin and the remaining on nasal formulation. The median oral dose was 9.5 (4.2–17.0) μg/kg/day with median frequency of 2.5 (2–3). The median nasal dose was 0.7 (0.4–1.4) μg/kg/day with median frequency of 2.0 (2–3.5). Fourteen patients (34.1%) were switched from nasal to oral desmopressin with the median dose conversion factor of 20.1 (10.7–31.8). Forty percent of patients on nasal desmopressin experienced hypo/hypernatraemia compared to 18.1% on oral, however, there were no significance difference between standardized hypo/hypernatraemia episodes per treatment year. Conclusions: Oral desmopressin is used in the majority of our patients including infants and toddlers. There is wide inter-individual variation in dose requirement and dosing intervals. Management of central diabetes insipidus remains a challenge in adipsic patients and in young children during intercurrent illness regardless of the desmopressin formulation.