Pulmonary hypertension and reopening of the ductus arteriosus in an infant treated with diazoxide.
ABSTRACT Diazoxide is the main therapeutic agent for persistent hyperinsulinemic hypoglycemia. Generally, it is tolerated well, but rarely it can cause severe life-threatening complications. We report a neonate who was treated with diazoxide for hyperinsulinemic hypoglycemia. On the 6th day of the treatment we observed sepsis-mimicking symptoms, mild pulmonary hypertension, and re-opening of the ductus arteriosus. All these findings resolved dramatically shortly after discontinuation of treatment. To our knowledge, this is the first reported case of re-opening of the ductus arteriosus due to diazoxide toxicity.
SourceAvailable from: Tohru Yorifuji[Show abstract] [Hide abstract]
ABSTRACT: The diagnosis and treatment of congenital hyperinsulinism (CHI) have made a remarkable progress over the past 20 years and, currently, it is relatively rare to see patients who are left with severe psychomotor delay. The improvement was made possible by the recent developments in the understanding of the molecular and pathological basis of CHI. Known etiologies include inactivating mutations of the KATP channel genes (ABCC8 and KCNJ11) and HNF4A, HNF1A, HADH, and UCP2 or activating mutations of GLUD1, GCK, and SLC16A1. The understanding of the focal form of KATP channel CHI and its detection by (18)F-fluoro-L-DOPA positron emission tomography have revolutionized the management of CHI, and many patients can be cured without postoperative diabetes mellitus. The incidence of the focal form appears to be higher in Asian countries; therefore, the establishment of treatment systems is even more important in this population. In addition to diazoxide or long-term subcutaneous infusion of octreotide or glucagon, long-acting octreotide or lanreotide have also been used successfully until spontaneous remission. Because of these medications, near-total pancreatectomy is less often performed even for the diazoxide-unresponsive diffuse form of CHI. Other promising medications include pasireotide, small-molecule correctors such as sulfonylurea or carbamazepine, GLP1 receptor antagonists, or mammalian target of rapamycin inhibitors. Unsolved questions in this field include the identification of the remaining genes responsible for CHI, the mechanisms leading to transient CHI, and the mechanisms responsible for the spontaneous remission of CHI. This article reviews recent developments and hypothesis regarding these questions.06/2014; 19(2):57-68. DOI:10.6065/apem.2014.19.2.57
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ABSTRACT: Background: Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing. Objectives: To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan. Methods: Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011. Results: One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications. Conclusions: Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported. © 2014 S. Karger AG, Basel.Neonatology 01/2014; 105(3):166-171. DOI:10.1159/000356772 · 2.37 Impact Factor
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ABSTRACT: Stress-related hyperinsulinism (HI) may lead to recalcitrant hypoglycemia for weeks or months following perinatal stress, often in premature newborn infants. Diazoxide is an effective and usually safe medication to treat this type and other types of neonatal HI. We report a male infant born at 35-week gestation with severe respiratory distress who developed prolonged hypoglycemia requiring high glucose infusion rates. He also had abnormal liver function tests, including hypoalbuminemia. Laboratory tests were consistent with HI, which responded to diazoxide treatment (10 mg/kg/day started at 10 days of age). The patient developed cardiorespiratory failure, hepatomegaly, worsening liver function tests, and hyperglycemia 7 weeks after the initiation of therapy. Diazoxide was discontinued with rapid resolution of the cardiorespiratory failure and without recurrence of hypoglycemia. Conclusion: We hypothesize that low albumin level may increase the toxicity of diazoxide, possibly by increasing the free diazoxide concentration, as this compound is typically >90 % bound to plasma proteins. What is Known: • Diazoxide binds to plasma proteins >90 % and excreted in urine. • Dose adjustment is recommended in patients with impaired kidney functions. What is New: • Literature is not available regarding diazoxide dose adjustment in patients with liver injury. • Diazoxide toxicity is not dose-dependent.European Journal of Pediatrics 01/2015; 174(3). DOI:10.1007/s00431-015-2488-6 · 1.98 Impact Factor