Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome

Table 1 Serum glucagon levels

Time	Serum glucagon (pmol/L) (normal range: 0-50 pmol/L)
Pre-surgery
2 mo	66
Post-surgery
1 mo	7
5 mo	28
6 mo	6
17 mo	15
20 mo	29
31 mo	10

Table 2 Islet size and number of glucagon positive cells in the current case compared to 5 normal pancreata

	Average1islet size (μm)	Average1 number glucagon positive cells
		Count 1	Count 2
Patient	192	29.2	28.8
Control 1	256	59.8	61.8
Control 2	186	25.6	25.2
Control 3	255	32.2	31.6
Control 4	260	52.4	53.4
Control 5	190	44.6	42.6

¹Average of 5 pancreatic islets.

Table 3 Hyperglucagonemia without the glucagonoma syndrome-review of the literature

	Martignoni et al[4]	Henopp et al[1] (patient 2)	Yu et al[3], Zhou et al[6]	Present case
Patient	54, M	43, F	60, F	36, F
Origin	-	-	Persian	Caucasian
Clinical symptoms	Abdominal pain Diarrhea1	Abdominal pain	Abdominal pain Constipation	Abdominal pain
Serum Glucagon (pmol/L)	Elevated	Elevated (25-fold)2	170113	66
Imaging	Negative	Positive	Positive	Negative (positive on EUS)
OctreoScan®	Negative	-	Negative	Negative
Localization	No focal abnormality	Tail	Uncinate	Tail
Pancreatic pathology	α-cell hyperplasia nesidioblastosis	α-cell hyperplasia, large cystic tumor and small solid tumors, multiple microadenomas	α-cell hyperplasia non-functioning pancreatic NET microglucagonoma microadenoma	Normal pancreatic morphology on standard H and E staining
GCGR	-	-	Homozygous gDNA point mutation	Heterozygous gDNA deletion 5 point mutations
Other Genes	-	Negative for MEN1/VHL gDNA mutations	-	Negative for MEN1/VHL gDNA mutations
Relatives GCGR	-	-	Brother Negative	Daughter Negative

¹Mild diabetes was initially suspected but then found to be unlikely;

²The glucagon levels were only measured postoperatively;

³Glucagon levels converted to pmol/L from pg/mL. M: Male; F: Female; EUS: Endoscopic ultrasound; GCGR: Glucagon receptor.