Subscribe to RSS
DOI: 10.1055/s-2002-20216
Unterschiede im Insulin-Sekretionsverhalten erleichtern die Differentialdiagnose von Insulinom und Hypoglycaemia factitia
Differences in insulin secretion facilitate the differential diagnosis of insulinoma and factitious hypoglycaemiaPublication History
Manuskript-Eingang: 17. April 2001
Annahme nach Revision: 11. Dezember 2002
Publication Date:
21 February 2002 (online)

Anamnese und klinischer Befund: Eine 33-jährige Krankenschwester (verheiratet; zwei Kinder; BMI 30,9 kg/m2) litt seit einigen Monaten unter rezidivierenden symptomatischen Hypoglykämien.
Untersuchungen: Zwei Hungerversuche wurden nach 26 Stunden aufgrund von Bewusstlosigkeit abgebrochen. Das verbesserte Insulin/Glukose-Verhältnis betrug ∞ und 6,1 [mU/l]/[mg/dl] (Normalwert < 0,5). In einem hyperinsulinämisch-hypoglykämischen »Clamp«-Versuch trat eine C-Peptid-Suppression auf minimal 0,26 bis 0,38 nmol/l (Normalwert 0,06 ± 0,01 nmol/l) auf. Weder im Hungerversuch noch im »Clamp«-Versuch zeigten sich spontane oder paradoxe Anstiege der Insulin-, bzw. C-Peptid-Konzentrationen. Eine Serumanalyse auf Sulfonylharnstoffe ergab den mehrfachen Nachweis von Glibenclamid in Konzentrationen über dem therapeutischen Bereich.
Therapie und Verlauf: Die Patientin verneinte jegliche Einnahme oraler Antidiabetika. In den Folgemonaten traten keine Hypoglykämien mehr auf.
Diagnose: Aufgrund des Sulfonylharnstoff-Nachweises im Serum wurde die Diagnose einer Hypoglycaemia factitia gestellt.
Folgerung: Hinsichtlich einer Insulin- oder C-Peptid-Suppression unterschieden sich die Ergebnisse von Hungerversuch und »Clamp«-Test bei Hypoglycaemia factitia nicht von denen bei einem Insulinom. Allerdings kommt es unter Sulfonylharnstoffen nicht zu dem insulinomtypischen Auftreten von Insulin- oder C-Peptid-»Bursts«. Der Suchtest auf Sulfonylharnstoffe im Serum bzw. im Urin ist im Zweifel die einzige sichere Möglichkeit, eine Hypoglycaemia factitia durch Sulfonylharnstoffeinnahme zu diagnostizieren.
Differences in insulin secretion facilitate the differential diagnosis of insulinoma and factitious hypoglycaemia
History: A 33-year-old female nurse (married; two children; BMI 30.9 kg/m²) had recurrent episodes of symptomatic hypoglycaemia over some months.
Investigations: Two fasting tests were terminated after 26 hours because the patient became unconscious. Improved insulin/glucose ratio was ∞ and 6.1 [mU/l]/[mg/dl] (normal value < 0.5). An hyperinsulinaemic-hypoglycaemic »clamp« test produced a C-peptide suppression to minimally 0.26 - 0.38 nmol/l (normal value 0.06 ± 0.01 nmol). There was no spontaneous or paradoxical burst in insulin or C-peptide concentration after either the fasting or the »clamp« test. Serum analysis of sulphonylurea on several occasions documented an increase of glibenclamide above therapeutic range.
Treatment and course: The patient denied any intake of oral antidiabetic preparations, but there were no further hypoglycaemia attacks in subsequent months.
Diagnosis: The demonstration of sulphonylurea in serum confirmed the diagnosis of factitious hypoglycaemia.
Conclusion: With regard to insulin or C-peptide suppression, the results of the fasting and clamp tests are the same in factitious hypoglycaemia and insulinoma. However, under the influence of sulphonylurea drugs there are no insulin or C-peptide bursts so typical of insulinoma. In case of doubt, detection of sulphonylurea preparations in serum or urine is the only reliable way of diagnosing factitious hypoglaema due to the ingestion of sulphonylurea.
Literatur
- 1
Asher R.
Münchhausen’s
syndrome.
Lancet.
1951;
I
339-41
MissingFormLabel
- 2
Berman N, Genter P, Chou H F, Cortez C, Bowsher R, Ipp E.
Erratic oscillatory
characteristics of plasma insulin content in patients with insulinoma:
mechanism for unpredictable hypoglycemia.
J Clin Endocrinol
Metab.
1997;
82
2899-2903
MissingFormLabel
- 3
Burge M R, Schmitz-Fiorentino K, Qualls C R, Schade D S.
A prospective
trial of risk factors for sulfonylurea-induced hypoglycemia in type
2 diabetes mellitus.
JAMA.
1998;
279
137-143
MissingFormLabel
- 4
Cimmino M, Agosto A, Minaire Y, Geloen A.
In situ regulation of
lipolysis by insulin and norepinephrine: a microdialysis study during
euglycemic-hyperinsulinemic clamp.
Metabolism.
1995;
44
1513-1518
MissingFormLabel
- 5
Creutzfeldt C, Track N S, Creutzfeldt W.
In
vitro studies of the rate of proinsulin and insulin turnover in
seven human insulinomas.
Eur J Clin Invest.
1973;
3
371-384
MissingFormLabel
- 6
Creutzfeldt W, Arnold R, Creutzfeldt C, Deuticke U, Frerichs H, Track N S.
Biochemical
and morphological investigations of 30 human insulinomas.
Diabetologia.
1973;
9
217-231
MissingFormLabel
- 7
Gromada J, Dissing S, Kofod H, Frokjaer-Jensen J.
Effects of the
hypoglycaemic drugs repaglinide and glibenclamide on ATP-sensitive
potassium channels and cytosolic calcium levels in β TC3
cells and rat pancreatic beta-cells.
Diabetologia.
1995;
38
1025-1032
MissingFormLabel
- 8
Guiausseau P J, Mosse A, Lubetzki J.
C-peptide
in factitious hypoglycemia from sulfonylurea.
Diabetes
Care.
1983;
6
14-15
MissingFormLabel
- 9
Hosker J P, Burnett M A, Davies E G, Harris E A, Turner R C.
Sulfonylurea
therapy doubles B-cell response to glucose in Type 2 diabetic patients.
Diabetologia.
1985;
28
809-814
MissingFormLabel
- 10
Jönsson A, Rydberg T, Ekberg G, Hallengreen B, Melander A.
Slow elimination
of glyburide in NIDDM subjects.
Diabetes Care.
1994;
17
14214-5
MissingFormLabel
- 11
Jordan R M, Kammer H, Riddle M R.
Sulfonylurea-induced
factitious hypoglycaemia. A growing problem.
Arch Int
Med.
1977;
137
390-393
MissingFormLabel
- 12
Meier J J, Starke A AR, Post J, Berger M, Nauck M A.
Criteria
for autonomous insulin secretion from prolonged fasts in insulinoma
patients and control subjects.
Diabetologia.
2000;
43
A194
(Suppl 1))
MissingFormLabel
- 13 Nauck M, Creutzfeldt W. Boca Raton,
FD: CRC Press In: Dayal Y, Dayal Ys. Endocrine
pathology of the gut and pancreas 1991: 195-225
MissingFormLabel
- 14
Nauck M, Stöckmann F, Creutzfeldt W.
Evaluation of a
euglycaemic clamp procedure as a diagnostic test in insulinoma patients.
Eur
J Clin Invest.
1990;
20
15-28
MissingFormLabel
- 15
Nauck M A, Baum F, Seidensticker F, Røder M, Dinesen B, Creutzfeldt W.
A hyperinsulinaemic,
sequentially eu- and hypoglycaemic clamp test to characterize autonomous
insulin secrtetion in patients with insulinoma.
Eur J
Clin Invest.
1997;
27
109-115
MissingFormLabel
- 16
Nauck M A, Starke A AR, Post J, Berger M, Schmiegel W.
Secretory bursts
in insulinoma patients (abstract).
Exp Clin Endocrinol
Diab.
1998;
106
S
30
(Suppl 1))
MissingFormLabel
- 17
Panten U, Schwanstecher M, Schwanstecher C.
Sulfonylurea
receptors and mechanisms of sulfonylurea action.
Exp Clin
Endocrinol Diabetes.
1996;
104
1-9
MissingFormLabel
- 18
Petrides A S, Stanley T, Matthews D E, Vogt C, Bush A J, Lambeth H.
Insulin resistance in
cirrhosis: prolonged reduction of hyperinsulinemia normalizes insulin
sensitivity.
Hepatology.
1998;
28
141-149
MissingFormLabel
- 19
Porksen N K, Munn S R, Steers J L, Schmitz O, Veldhuis J D, Butler P C.
Mechanisms
of sulfonylurea¿s stimulation of insulin secretion in vivo:
selective amplification of insulin secretory burst mass.
Diabetes.
1996;
45
1792-1797
MissingFormLabel
- 20
Schatz H, Nierle C, Pfeiffer E F.
(Pro-)
insulin biosynthesis and release of newly synthesized (pro-) insulin
from isolated islets of rat pancreas in the presence of amino acids
and sulphonylureas.
Eur J Clin Invest.
1975;
21
477-485
MissingFormLabel
- 21
Service F J.
Hypoglycemic
disorders.
N Engl J Med.
1995;
332
1144-1152
MissingFormLabel
- 22
Shapiro E T, Van Cauter E, Tillil H. et al .
Glyburide enhances the responsiveness of
the beta-cell to glucose but does not correct the abnormal patterns
of insulin secretion in non-insulin-dependent diabetes mellitus.
J
Clin Endocrinol Metab.
1989;
69
571-576
MissingFormLabel
- 23
Siegel E G, Mayer G, Nauck M, Creutzfeldt W.
Hypoglycaemia
factitia durch Sulfonylharnstoff-Einnahme.
Dtsch Med Wochenschr.
1987;
112
1575-1579
MissingFormLabel
- 24
Turner R C, Oakley N W, Nabarro J DN.
Control
of basal insulin secretion, with special reference to the diagnosis
of insulinomas.
Brit Med J.
1971;
2
132-135
MissingFormLabel
- 25
UK Prospective Diabetes Study
(UKPDS) Group .
Intensive blood glucose control with
sulfonylureas or insulin compared with conventional treatment and
risk of complications in patients with type 2 diabetes.
Lancet.
1998;
352
837-853
MissingFormLabel
Korrespondenz
Prof. Dr. med. Michael Nauck
Diabetes-Zentrum Bad Lauterberg
Kirchberg 21
37431 Bad Lauterberg
Phone: 05524/81218
Fax: 05524/81398
Email: M.Nauck@diabeteszentrum.de