Nama : Karina Wulan Mei

Nama Legiun : Oncology

GLUCAGONOMA

Glucagonoma is an extremely rare neuroendocrine tumor arising from

pancreatic islet cells. Although patients with glucagonoma manifest multiple
typical symptoms, early diagnosis remains difficult due to the scarcity of this
disease. According to the World Health Organization classification, glucagonoma
is a type of functional pancreatic neuroendocrine neoplasm (pNEN); as such, it
should be diagnosed as a clinical syndrome. This pNEN causes a combination of
symptoms named the glucagonoma syndrome.
Glucagonoma syndrome is a rare paraneoplastic phenomenon defined as
necrolytic migratory erythema (NME), glucagonoma, glucose intolerance, anemia,
weight loss, glossitis, and cheilitis. Because of its rarity, the correct diagnosis is
often made too late, leading to poor prognosis. It has been attributed to
hypoaminoacidemia and zinc or essential fatty acid deficiency (6); however,
details of NME pathogenesis are still unclear. Recent genome-wide analysis
identified death-domain associated protein (DAXX) and alpha thalassemia/mental
retardation syndrome X-linked (ATRX) as candidate pathogenetic genes for
PanNET (7, 8), but the genetics of glucagonoma remain unknown.
Oversecretion of glucagon by islet α-cells in tumors contributes to the
paraneoplastic phenomenon, namely glucagonoma syndrome. Glucagon exhibits
its physiological functions by increasing the hepatic glucose output and
maintaining the blood glucose level. Glucagon also exerts a catabolic role by
attenuating protein synthesis. The elevated glucagon secreted by glucagonoma
results in amino acid catabolism and serum glucose elevation, which are
considered to be responsible for skin lesions and DM. Glucagonoma syndrome
consists of a triad comprising glucagon-secreting tumors, DM and NME.

DM is a further clinical hallmark of glucagonoma. Elevated glucagon

levels promote the glucose output and antagonize the effect of insulin. Although
only 40% of glucagonoma patients presented DM at the onset of symptoms, ~90%
went on to develop it. The severity of the diabetes remains controversial in the
literature, and NME usually occurs prior to the emergence of the diabetes. In the
present case, the patient exhibited intermittent glucose elevation one and a half
years after the initiation of the skin rash, and the diabetes resulted in the rapid
damage of her lens.

NME is a cutaneous manifestation generally associated with glucagonoma

syndrome. This cutaneous finding is not unique to glucagonoma and can occur in
other pathologic setting that may or may not be accompanied by an increased
level of serum glucagon. NME is a bullous dermatosis that develops in 2 weeks.
Lesions first manifest as itching or painful vesicles and bullae and then develop as
scaly patches and plaques with irregular and advancing borders. The appearance
of this cutaneous finding has sometimes an eczematous state similar to psoriasis
that gradually improves and disappears and new lesions appear over time.

References

1. Wei Jishu, Song Xujun, Liu Xinchun, and others. Glucagonoma and
Glucagonoma Syndrome: One Center's Experience of Six Cases. J
Pancreat Cancer. 2018; 4(1): 11–16.
2. S Fang, S Lie, T Cai. Glucagonoma syndrome: a case report with focus on
skin disorders. Onco Targets and Therapy . 13 Mei 2014; 2014(07): 1449-
1453.
3. Tamura Ai, Ogasawara,Tatsuki Fujii Yoichi, and others. Glucagonoma
With Necrolytic Migratory Erythema: Metabolic Profile and Detection of
Biallelic Inactivation of DAXX Gene. The Journal of Clinical
Endocrinology & Metabolism. 2018;103(7): 2417–2423
4. Wei Jishu, Lin Shibo, Wang Cong, and other. Glucagonoma syndrome: A
case report. Oncology Letters. 2015; 10: 1113-1116.
5. Saniee Sara, Saniee Yalda, Zare AG, Davarnia Ghazaleh. Necrolytic
Migratory Erythema Associated With Glucagonoma Syndrome. Crescent
Journal of Medical and Biological Sciences. 2018; 5(2): 160-162.