TY - JOUR
T1 - Focal congenital hyperinsulinism managed by medical treatment
T2 - A diagnostic algorithm based on molecular genetic screening
AU - Maiorana, Arianna
AU - Barbetti, Fabrizio
AU - Boiani, Arianna
AU - Rufini, Vittoria
AU - Pizzoferro, Milena
AU - Francalanci, Paola
AU - Faletra, Flavio
AU - Nichols, Colin G.
AU - Grimaldi, Chiara
AU - De Ville De Goyet, Jean
AU - Rahier, Jacques
AU - Henquin, Jean Claude
AU - Dionisi-Vici, Carlo
N1 - Publisher Copyright:
© 2014 John Wiley & Sons Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Objective Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions.Patients, Methods and Results Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and 18F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia.Conclusions Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to 18F-DOPA PET-CT.
AB - Objective Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions.Patients, Methods and Results Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and 18F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia.Conclusions Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to 18F-DOPA PET-CT.
UR - http://www.scopus.com/inward/record.url?scp=84912116073&partnerID=8YFLogxK
U2 - 10.1111/cen.12400
DO - 10.1111/cen.12400
M3 - Article
C2 - 24383515
AN - SCOPUS:84912116073
SN - 0300-0664
VL - 81
SP - 679
EP - 688
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 5
ER -