Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening. (30th January 2014)

• Record Type: Journal Article
• Authors: Maiorana, Arianna; Barbetti, Fabrizio; Boiani, Arianna; Rufini, Vittoria; Pizzoferro, Milena; Francalanci, Paola; Faletra, Flavio; Nichols, Colin G.; Grimaldi, Chiara; de Ville de Goyet, Jean; Rahier, Jacques; Henquin, Jean‐Claude; Dionisi‐Vici, Carlo
• Is Part Of: Clinical endocrinology. Volume 81:Number 5(2014:Nov.)
• Page Start: 679
• Page End: 688
• Publication Date: 2014-01-30
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12400
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12400-abs-0001"> <title>Summary</title> <sec id="cen12400-sec-0001" sec-type="section"> <title>Objective</title> <p>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<bold>.</bold> 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 <italic>vs</italic> 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.</p> </sec> <sec id="cen12400-sec-0002" sec-type="section"> <title>Patients, Methods and Results</title> <p>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 <italic>K</italic><sub>ATP</sub> channel genes, and <sup>18</sup>F‐DOPA PET‐CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia.</p> </sec> <sec id="cen12400-sec-0003" sec-type="section"> <title>Conclusions</title> <p>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 <italic>ABCC8</italic> or <italic>KCNJ11</italic> mutations should always be subjected to <sup>18</sup>F‐DOPA PET‐CT.</p> </sec> </abstract>