Rezidivierende Hypoglykämien und ein großer intraabdominaler Tumor bei einer 61-jährigen Patientin

 

 Buy Article Permissions and Reprints

Zusammenfassung

Anamnese und klinischer Befund: Eine 61-jährige Patientin wurde zu Hause von ihrem Ehemann bewusstlos vorgefunden. Der alarmierte Notarzt stellte eine Hypoglykämie von 1,7 mmol/l fest. Ein Diabetes mellitus war bei der Patientin in der Anamnese nicht bekannt. Die klinische Untersuchung und die Labordiagnostik ergaben keinen weiteren pathologischen Befund.

Untersuchungen: Der standardisierte Hungertest musste kurz nach Beginn wegen neuroglukopenischer Symptomatik abgebrochen werden (Plasmaglukose 2,1 mmol/l, Insulin < 0,2 mE/l, C-Peptid 0,02 nmol/l). Die Befunde schlossen einen organischen Hyperinsulinismus aus. In der Computertomografie des Abdomens zeigte sich eine mesenteriale Raumforderung mit einer Größe von ca. 9 cm, die sich in der histologischen Untersuchung als follikuläres Lymphom Grad 1 darstellte. Nach Ausschluss weiterer Ursachen der Hypoglykämien diagnostizierten wir eine sekundäre paraneoplastische Hypoglykämie bei neudiagnostiziertem follikulärem Lymphom (Nicht-Inselzell-Tumor-Hypoglykämie, NICTH).

Therapie und Verlauf: Eine Therapie mit dem CD20-Antikörper Rituximab (375 mg/m² 1× wöchentlich, 4 Gaben) wurde initiiert. Die klinische Symptomatik sistierte und die Patientin ist ein Jahr nach Beendigung der Therapie beschwerdefrei.

Folgerung: Beim Vorliegen einer Hypoglykämie muss nach Ausschluss endokrinologischer und weiterer Ursachen an das Vorliegen eines paraneoplastischen Syndroms im Sinne einer Nicht-Inselzell-Tumor-Hypoglykämie gedacht werden. Dies ist eine sehr seltene Differenzialdiagnose, bei der ein malignes Lymphom wiederum lediglich ca. 1 % ausmachen. Die Therapie der Grunderkrankung stellt auch die spezifische Therapie der Nicht-Inselzell-Tumor-Hypoglykämie dar.

Abstract

History and admission findings: A 61-year-old woman was found unconscious by her husband. The emergency doctor detected hypoglycemia (blood glucose 1.7 mmol/l). This was the first such event, the patient had not been known to have diabetes mellitus. At admission the physical examination and the laboratory findings revealed no abnormalities.

Investigations: A fasting test was aborted shortly after the start because of the onset of neurological symptoms. An insulinoma was excluded by detecting suppressed levels of insulin and C-peptide. Computed tomography of the abdomen revealed a mesenteric tumour of 9 cm in diameter, which was identified immunhistologically as a grade 1 follicular lymphoma (FL).  After exclusion of endocrinological causes the recurrent hypoglycaemia was diagnozed as part of a paraneoplastic syndrome associated with a non-islet cell tumour hypoglycaemia (NICTH) with a newly diagnosed FL.

Treatment and course: Specific medication with the CD20 antibody rituximab (375 mg/m², once per week for a total of four cycles) was initiated. There were no further episodes of hypoglycaemia. After one year the patient remains free of any symptoms.

Conclusions: After exclusion of any endocrinological reasons for hypoglycemia, differential diagnosis should include NICTH as paraneoplastic syndrome. In rare cases a hematological malignancy may be the underlying disease. The specific treatment of this disease likewise represents the causal treatment of NICTH.

• Literatur

• 1 Brabant G, Schöfl C, von zur Mühlen A. Hypoglycämie beim Erwachsenen. Dtsch Ärztebl 1998; 95: A-1022-1026
  PubMedGoogle Scholar
• 2 Buske C, Hoster E, Dreyling M et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma. Results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG) Leukemia 2009; 23: 153-161
  CrossrefPubMedGoogle Scholar
• 3 Buske C, Hoster E, Dreyling M et al. The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood 2006; 108: 1504-1508
  CrossrefPubMedGoogle Scholar
• 4 de Groot JW, Rikhof B, van Doorn J et al. Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases. Endocr Relat Cancer 2007; 14: 979-993
  CrossrefPubMedGoogle Scholar
• 5 Dreyling M. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21: v181-183
  CrossrefPubMedGoogle Scholar
• 6 Forstpointner R, Unterhalt M, Dreyling M et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas. Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG) Blood 2006; 108: 4003-4008
  CrossrefPubMedGoogle Scholar
• 7 Frystyk J, Skjaerbaek C, Zapf J et al. Increased levels of circulating free insulin-like growth factors in patients with non-islet cell tumour hypoglycaemia. Diabetologia 1998; 41: 589-594
  CrossrefPubMedGoogle Scholar
• 8 Fukuda I, Hizuka N, Ishikawa Y et al. Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. Growth Horm IGF Res 2006; 16: 211-216
  CrossrefPubMedGoogle Scholar
• 9 Ghielmini M. Follicular lymphoma. Ann Oncol 2010; 21: vii151-153
  CrossrefPubMedGoogle Scholar
• 10 Harris NL, Jaffe ES, Diebold J et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835-3849
  PubMedGoogle Scholar
• 11 Harris NL, Swerdlow SH, Jaffe ES et al. Mature B-cell neoplasms – Follicular Lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer (IARC); 2008: 220-226
  Google Scholar
• 12 Herold M, Haas A, Srock S et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma. An East German Study Group Hematology and Oncology Study J Clin Oncol 2007; 25: 1986-1992
  CrossrefPubMedGoogle Scholar
• 13 Martinelli G, Schmitz SF, Utiger U et al. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol 2010; 28: 4480-4484
  CrossrefPubMedGoogle Scholar
• 14 Nadler WA, Wolfer JH. Hepatogenic hypoglycemia associated with primary liver cell carcinoma. Arch Intern Med 1929; 44: 700-705
  CrossrefPubMedGoogle Scholar
• 15 Solal-Celigny P, Roy P, Colombat P et al. Follicular lymphoma international prognostic index. Blood 2004; 104: 1258-1265
  CrossrefPubMedGoogle Scholar