Suet Ching Chen1, Antonia Dastamani2, Donatella Pintus3, Daphne Yau4, Sommayya Aftab2, Louise Bath5, Craig Swinburne6, Lindsey Hunter6, Alessandro Giardini7, Georgi Christov7, Senthil Senniappan3, Indraneel Banerjee4, Mohamad Guftar Shaikh1, Pratik Shah2,8. 1. Paediatric Endocrinology, Royal Hospital for Children, NHS Greater Glasgow and Clyde, Glasgow, UK. 2. Paediatric Endocrinology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK. 3. Paediatric Endocrinology, Alder Hey Children's Hospital, Liverpool, UK. 4. Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK. 5. Paediatric Endocrinology, Royal Hospital for Sick Children, Edinburgh, UK. 6. Paediatric Cardiology, Royal Hospital for Children, NHS Greater Glasgow and Clyde Glasgow, Glasgow, UK. 7. Paediatric Cardiology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK. 8. Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health, London, UK.
Abstract
OBJECTIVE: Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. DESIGN AND PATIENTS: Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide. MEASUREMENTS: The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association. RESULTS: Thirteen (6 men) of 177 HH diazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months. Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). CONCLUSION: Pulmonary hypertension can occur in 7% of diazoxide-treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload. Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops.
OBJECTIVE:Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. DESIGN AND PATIENTS: Retrospective cohort study involving four UK regional HH centres; review of case notes of HHpatients on diazoxide. MEASUREMENTS: The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association. RESULTS: Thirteen (6 men) of 177 HHdiazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months. Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). CONCLUSION:Pulmonary hypertension can occur in 7% of diazoxide-treated HHpatients. Risk factors include the presence of congenital heart disease and fluid overload. Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops.
Authors: Simone M Gelinas; Clare E Benson; Mohammed A Khan; Rolf M F Berger; Richard C Trembath; Rajiv D Machado; Laura Southgate Journal: Genes (Basel) Date: 2020-11-11 Impact factor: 4.096
Authors: Maria Gϋemes; Sofia Asim Rahman; Ritika R Kapoor; Sarah Flanagan; Jayne A L Houghton; Shivani Misra; Nick Oliver; Mehul Tulsidas Dattani; Pratik Shah Journal: Rev Endocr Metab Disord Date: 2020-12 Impact factor: 6.514