Ungewöhnliche Ursache einer Hyperkalzämie in der Schwangerschaft

Zusammenfassung

Hintergrund In der Schwangerschaft diagnostizierte neuroendokrine Tumoren (NET) sind eine absolute Rarität. Die vorliegende Kasuistik beschreibt Diagnostik und Therapie eines im 2. Trimenon symptomatisch gewordenen metastasierten NET des Pankreas.

Fallbeschreibung Eine 33-jährige Patientin stellte sich in der 19. Schwangerschaftswoche (SSW) mit persistierender Diarrhoe in der Notaufnahme vor. Laborchemisch fiel eine ausgeprägte Hyperkalzämie (3,53 mmol/l) auf. In der Bildgebung fand sich eine Raumforderung im Bereich des Pankreaskorpus/-schwanzes mit ausgedehnter Lebermetastasierung. Histologisch zeigte sich ein NET (G2, SSTR-positiv) mit einer paraneoplastischen Parathormon-related-Peptide-Sekretion als Ursache der Hyperkalzämie. Unter einer Therapie mit Octreotid normalisierte sich das Kalzium, die Diarrhoe sistierte. Nach Geburt eines gesunden Kindes (32. SSW per sectio) fand sich ein Progress; der Pankreastumor wurde komplett entfernt, die Leberfiliae so weit wie möglich. In einem postoperativen CT zeigten sich verbliebene metastasensuspekte Läsionen, eine palliative Therapie mit Lanreotid wurde eingeleitet. Darunter ist die Patientin seit einem Jahr symptomfrei, das Serumkalzium blieb normwertig. Das Kind entwickelte sich unauffällig.

Diskussion Dieser ungewöhnliche Fall zeigt, dass es auch bei ausgedehnt metastasierten symptomatischen NETs in der Schwangerschaft weitreichende diagnostische und therapeutische Optionen geben kann, die in enger interdisziplinärer Zusammenarbeit unter sorgfältiger Risiko-Nutzen-Abwägung für Mutter und Kind eine Fortführung der Schwangerschaft erlauben.

Abstract

Background Neuroendocrine tumors (NET) diagnosed during pregnancy are extremely rare. This case report describes diagnosis and treatment of a metastasized pancreas NET that became symptomatic in the second trimester.

Case description A 33-year-old patient presented to the emergency department in the 19^th week of pregnancy (WOP) with persistent diarrhea. Laboratory tests showed a pronounced hypercalcemia (3.53 mmol/l). Imaging revealed a mass in the pancreatic corpus/tail with extensive liver metastasis. Histologically, a NET (G2, SSTR-positive) with paraneoplastic parathormone-related-peptide secretion was found to be the cause of hypercalcemia. Under a treatment with octreotide, calcium values normalized and diarrhea stopped. After delivery of a healthy child (32.WOP via cesarean section) tumor progress was found. The pancreatic mass was resected completely, the liver metastases as far as possible. Postoperatively, in a CT scan, residual suspicious liver lesions could be found, and a palliative therapy with lanreotide was initiated. With this treatment, the patient has been asymptomatic for one year, and serum calcium remained normal. The child developed normally.

Discussion This unusual case shows that even in extensively metastasized symptomatic NETs during pregnancy, there may be sufficient diagnostic and therapeutic options that allow for a continuation of pregnancy in close interdisciplinary cooperation under careful risk-benefit assessment for mother and child.

Schlüsselwörter

Hyperkalzämie - Schwangerschaft - Pankreatischer neuroendokriner Tumor - Somatostatin-Analoga

Key words

hypercalcemia - pancreatic neuroendocrine tumor - pregnancy - somatostatine analogues

Publication History

Received: 31 October 2020

Accepted: 15 December 2020

Article published online:
08 February 2021

• Literatur

• 1 Heeg S, Brass V. Therapie gastroenteropankreatischer neuroendokriner Neoplasien. Onkologie heute 2015; 2: 20-22
• 2 Oberg K, Couvelard A, Delle Fave G. et al. ENETS Consensus Guidelines for Standard of care in Neuroendocrine Tumors: Biochemical Markers. Neuroendocrinology 2017; 105: 201-211
• 3 Taupenot L, Harper KL, O’Connor DT. et al. The chromogranin-secretogranin family. The New England Journal of Medicine 2003; 348: 1134-1149
• 4 Baudin E, Gigliotti A, Ducreux M. et al. Neuron-specific enolase and chromogranin A as markers of endocrine tumors. British Journal of Cancer 1998; 78: 1102-1107
• 5 Ludvigson F, Marschall HU, Hagström H. et al. Pregnancy outcome in women undergoing liver biopsy during pregnancy: A nationwide population-based cohort study. Hepatology 2018; 68: 625-633
• 6 Rinke A, Müller HH, Schade-Brittinger C. et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octeotride LAR in the control of tumor growths in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009; 27: 4656-4663
• 7 Rinke A, Wittenberg M, Schade-Brittinger C. et al. Placebo-controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octeotride LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term-Survival. Neuroendocrinology 2017; 104: 26-32
• 8 Costa F, Gumz B. Octreotide – A Review of its Use in Treating Neuroendocrine Tumours. EUR Endocrinol 2014; 10: 70-74
• 9 Rinke A, Wiedenmann B. et al. S2k-Leitlinie Neuroendokrine Tumore. Z Gastroenterol 2018; 56: 583-681
• 10 Norman J, Politz D, Politz L. et al. Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention. Clin Endocrinol (Oxf) 2009; 71: 104-109
• 11 Kamp K, Feelders RA, van Adrichem RCS. Parathyroid Hormone-Related Peptide (PTHrP) Secretion by Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): Clinical Features, Diagnosis, Management, and Follow-Up. J Clin Endocrinol Metab 2014; 99: 3060-3069
• 12 Schulze W, Schmitz V, Weidemann H. et al. Schwangerschaft bei hepatisch metastasiertem neuroendokrinen Karzinom des Duodenums. Z Geburtshilfe Neonatol 2013; DOI: 10.1055/s-0033-1361359.
• 13 Meoni G, Giommoni E, Petreni P. et al. Somatostatin analogs in pregnant patients with neuroendocrine tumor. Anticancer dr ugs 2020; DOI: 10.1097/CAD.0000000000000967.
• 14 Caron P, Broussaud S, Bertherat J. Acromegaly and Pregnancy: A Retrospective Multicenter Study of 59 Pregnancies in 46 Women. J Clin Endocrinol Metab 2010; 95 (10) 0000-0000
• 15 Maffei P, Tamagno G, Nardelli GB. et al. Effects of octreotide exposure during pregnancy in acromegaly. Clinical Endocrinology 2010; DOI: 10.1111/j.1365-2265.2009.03706.
• 16 Caplin ME, Pavel M, Ćwikła JB. et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371: 224-233
• 17 Caplin ME, Pavel M, Ćwikła JB. et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label-extension study. Endocr Relat Cancer 2016; 23: 191-199
• 18 Lesurtel M, Nagorney DM, Mazzafero V. et al. When should a liver resection be performed in patients with liver metastases from neuroendocrine tumors? A systematic review with practice recommendations. HPB (Oxford) 2015; 17: 17-22
• 19 Yuan CH, Wang J, Xiu DR. et al. Meta-analysis of Liver Resection Versus Nonchirurgical Treatments for Pancreatic Neuroendocrine Tumors with Liver Metastases. Ann Surg Oncol 2016; 23: 244-24
• 20 Norlen O, Stalberg P, Zedenius J. et al. Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumors. Br J Surg 2013; 100: 1505-1514
• 21 Osborne DA, Zervos EE, Strosberg J. et al. Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid neuroendocrine tumors. Ann Surg Oncol 2006; 134: 572-581
• 22 Bacchetti S, Pasqual EM, Bertozzi S. et al. Curative versus palliative surgical resection of liver metastases in patients with neuroendocrine tumors: a meta-analysis of observational studies. Gland Surg 2014; 3: 243-251