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Diabetologie und Stoffwechsel 2016; 11(05): 31-49
DOI: 10.1055/s-0042-114885
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© Georg Thieme Verlag KG Stuttgart · New York

Hyperinsulinismus im Kindesalter

S. Kummer
,
T. Meissner
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Publication Date:
28 October 2016 (online)

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Zusammenfassung

Der kongenitale Hyperinsulinismus ist eine seltene Erkrankung, aber dennoch die häufigste Ursache einer persistierenden Hypoglykämie-Neigung im frühen Kindesalter. Rezidivierende Hypoglykämien können die kindliche Hirnentwicklung nachhaltig schädigen, sodass eine schnellstmögliche und konsequente Therapie jeder Hypoglykämie notwendig ist. Eine präzise Ursachenklärung ist die Basis zur Entwicklung eines therapeutischen Konzepts bei persistierender Hypoglykämie-Neigung. Rezidivierende hypoketotische Hypoglykämien mit inadäquat hohem Insulinspiegel sowie einem meist hohen Glukosebedarf sind die typischen Kennzeichen der Erkrankung. Die wichtige Unterscheidung zwischen diffuser und fokaler Form des Hyperinsulinismus ergibt sich häufig aus der genetischen Diagnostik und/oder funktionellen Bildgebung mittels 18F-DOPA-PET-CT.

In der Akuttherapie ist neben der Glukosezufuhr insbesondere Glukagon höchst effektiv und sicher. Die konservative Dauertherapie des Hyperinsulinismus beginnt mit einem Therapieversuch mit Diazoxid, auf welches die Patienten abhängig vom zugrundeliegenden genetischen Defekt oft nicht ausreichend ansprechen. Weitere Optionen sind die zulassungsüberschreitende Anwendung von Somatostatin-Analoga sowie eine begleitende Ernährungstherapie. Eine Pankreasteilresektion ist zumeist kurativ bei fokalem Hyperinsulinismus. Bei diffusem Hyperinsulinismus kann eine subtotale Pankreasresektion zwar stabilisierend wirken, ist aber meist nicht kurativ und langfristig mit der Entwicklung eines Diabetes mellitus und einer exokrinen Pankreasinsuffizienz assoziiert.

In letzter Zeit wachsen die Kenntnisse über viele dieser Aspekte rasch und ermöglichen zunehmend gezielte und individualisierte therapeutische Konzepte. Dies verbessert die Prognose für die Patienten und trägt dazu bei, Folgeschäden rezidivierender Hypoglykämien sowie Notwendigkeit und Ausmaß nebenwirkungsreicher Therapien auf ein geringstmögliches Maß zu limitieren. Dennoch stellt der kongenitale Hyperinsulinismus weiterhin eine hohe Belastung für die betroffenen Patienten und Familien dar und macht die Behandlung schwer betroffener Säuglinge selbst für spezialisierte Einrichtungen immer noch zu einer Herausforderung.

Abstract

Congenital hyperinsulinism (CHI) is a rare disease, but still the most frequent cause of persisting hypoglycemia in infancy and childhood, which may have devastating consequences on brain development of affected children. Therefore, timely diagnosis and thorough treatment are crucial. CHI is characterized by recurrent episodes of hypoketotic hypoglycemia with inappropriately high plasma insulin levels and high glucose requirements to maintain euglycemia. Differentiation between diffuse and focal disease is often derived from/achieved by precise genetic analyses and/or functional imaging using 18F-Dopa-PET-CT.

Therapeutically, besides glucose administration, glucagon is exceptionally effective and safe for blood glucose stabilization. Longterm treatment starts with diazoxide, which is often not sufficient to stabilize glucose concentration depending on the underlying genetic defect. Other common options are the off-label use of somatostatin analogues and/or concomitant nutritional therapy. Surgical treatment is usually curative in focal hyperinsulinism, whereas a subtotal pancreatectomy for diffuse disease is often stabilizing but not curative in most patients, and it is associated with the development of serious longterm complications such as diabetes mellitus.

Recently, rapidly increasing knowledge about many of these aspects enables a differentiated and individualized treatment of patients with CHI. However, longterm course is still characterized by multiple burdens for affected patients and their families, and the treatment of severely affected infants still represents an exceptional challenge even for experienced teams.

 

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