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Diazoxide-induced Pulmonary Hypertension in Hyperinsulinaemic Hypoglycaemia: Recommendations From a Multicentre Study in the United Kingdom

Diazoxide-induced Pulmonary Hypertension in Hyperinsulinaemic Hypoglycaemia: Recommendations From a Multicentre Study in the United Kingdom

Suet Ching Chen, Antonia Dastamani, Donatella Pintus, Daphne Yau, Sommayya Aftab, Louise Bath, Craig Swinburne, Lindsey Hunter, Alessandro Giardini, Georgi Christov, Senthil Senniappan, Indraneel Banerjee, etc.

Clin Endocrinol (Oxf). 2019 Dec;91(6):770-775.

PMID: 31520536

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP364987-A	Diazoxide		364-98-7	Price

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