Association between plasma free metanephrines and the SDHB phenotype in pheochromocytoma and paraganglioma

doi:10.3969/j.issn.1004-583X.2026.06.009

Abstract

Abstract:

Objective To investigate the association between plasma free metanephrines (MNs) and the succinate dehydrogenase subunit B (SDHB) phenotype in pheochromocytoma and paraganglioma (PPGL). Methods A total of 190 patients with PPGL treated at our hospital from March 2021 to March 2025 were enrolled as the study group. In addition, 100 healthy individuals who underwent physical examination at the same hospital during the same period and had normal results were selected as the control group. Baseline data were collected for both groups. Plasma metanephrine (MN) and normetanephrine (NMN) levels were measured using high-performance liquid chromatography-tandem mass spectrometry. SDHB protein expression in the study group was detected by immunohistochemical EnVision two-step method. The correlation between MN/NMN levels and the SDHB phenotype (loss/positive) was analyzed, along with their associations with clinicopathological characteristics. Results Plasma MN and NMN levels were significantly higher in the study group than in the control group (P<0.05). Among the 190 patients with PPGL, SDHB loss was observed in 68 cases (35.79%), of which paraganglioma (PGL) accounted for 83.82% (57/68), significantly higher than pheochromocytoma (PCC) (16.18%, 11/68) (P<0.05). The plasma NMN level in the SDHB-loss group was significantly higher than that in the SDHB-positive group ([7.53±1.95] nmol/L vs [5.19±1.26] nmol/L, P<0.05), whereas no statistically significant difference in MN level was found between the two groups (P>0.05). SDHB loss was associated with age, hypertension, tumor location, tumor type, vascular invasion, Ki-67 proliferation index, metastasis, and plasma NMN level (P<0.05). Conclusion Plasma NMN level is closely associated with the SDHB phenotype in PPGL. SDHB loss is more common in PGL, and patients with SDHB loss often have elevated NMN levels. SDHB loss is also significantly associated with adverse clinicopathological features, including age, hypertension, tumor location, tumor type, vascular invasion, Ki-67 proliferation index, and metastasis.

Key words: pheochromocytoma, paraganglioma, free metanephrines, SDHB phenotype, correlation

CLC Number:

Wang Liyang, Xiang Dandan, Ding Ran. Association between plasma free metanephrines and the SDHB phenotype in pheochromocytoma and paraganglioma[J]. Clinical Focus, 2026, 41(6): 534-538.

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URL: https://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2026.06.009

https://www.lchc.cn/EN/Y2026/V41/I6/534

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References 19

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组别	例数	NMN	MN
研究组	190	6.03±1.90	0.57±0.22
对照组	100	0.53±0.15	0.18±0.09
t值		28.877	16.984
P值		<0.01	<0.01

组别	例数	NMN	MN
研究组	190	6.03±1.90	0.57±0.22
对照组	100	0.53±0.15	0.18±0.09
t值		28.877	16.984
P值		<0.01	<0.01

组别	例数			年龄(岁)[例(%)]					性别[例(%)]				高血压[例(%)]					肿瘤大小(cm)[例(%)]					肿瘤部位[例(%)]
组别	例数			≤55		>55			男		女		是			否		<3			≥3		肾上腺内			肾上腺外
SDHB缺失	68			45(66.18)		23(33.82)			41(60.29)		27(39.71)		40(58.82)			28(41.18)		26(38.24)			42(61.76)		15(22.06)			53(77.94)
SDHB阳性	122			52(42.62)		70(57.38)			66(54.10)		56(45.90)		47(38.52)			75(61.48)		53(43.44)			69(56.56)		65(53.28)			57(46.72)
χ²/t值				9.694					0.681				7.248					0.487					17.458
P值				0.002					0.409				0.007					0.485					<0.01
组别		肿瘤数目[例(%)]						肿瘤类型[例(%)]				肿瘤细胞形态[例(%)]					血管浸润[例(%)]					包膜浸润[例(%)]
组别		单发			多发			PGL		PCC		规则			异型		是			否		是			否
SDHB缺失		35(51.47)			33(48.53)			57(83.82)		11(16.18)		46(67.65)			22(32.35)		38(55.88)			30(44.12)		32(47.06)			36(52.94)
SDHB阳性		78(63.93)			44(36.07)			74(60.66)		48(39.34)		88(72.13)			34(27.87)		31(25.41)			91(74.59)		28(22.95)			94(77.05)
χ²/t值		2.814						10.946				0.422					17.531					11.745
P值		0.093						0.001				0.516					<0.01					0.001
组别			Ki-67增殖指数[例(%)]								转移情况[例(%)]								NMN(nmol/L)					MN(nmol/L)
组别			<3%				≥3%				是			否					NMN(nmol/L)					MN(nmol/L)
SDHB缺失			20(29.41)				48(70.59)				16(23.53)			52(76.47)					7.53±1.95					0.61±0.23
SDHB阳性			85(69.67)				37(30.33)				9(7.38)			113(92.62)					5.19±1.26					0.56±0.20
χ²/t值			28.627								9.969								10.029					1.565
P值			<0.01								0.002								<0.01					0.119

组别	例数			年龄(岁)[例(%)]					性别[例(%)]				高血压[例(%)]					肿瘤大小(cm)[例(%)]					肿瘤部位[例(%)]
组别	例数			≤55		>55			男		女		是			否		<3			≥3		肾上腺内			肾上腺外
SDHB缺失	68			45(66.18)		23(33.82)			41(60.29)		27(39.71)		40(58.82)			28(41.18)		26(38.24)			42(61.76)		15(22.06)			53(77.94)
SDHB阳性	122			52(42.62)		70(57.38)			66(54.10)		56(45.90)		47(38.52)			75(61.48)		53(43.44)			69(56.56)		65(53.28)			57(46.72)
χ²/t值				9.694					0.681				7.248					0.487					17.458
P值				0.002					0.409				0.007					0.485					<0.01
组别		肿瘤数目[例(%)]						肿瘤类型[例(%)]				肿瘤细胞形态[例(%)]					血管浸润[例(%)]					包膜浸润[例(%)]
组别		单发			多发			PGL		PCC		规则			异型		是			否		是			否
SDHB缺失		35(51.47)			33(48.53)			57(83.82)		11(16.18)		46(67.65)			22(32.35)		38(55.88)			30(44.12)		32(47.06)			36(52.94)
SDHB阳性		78(63.93)			44(36.07)			74(60.66)		48(39.34)		88(72.13)			34(27.87)		31(25.41)			91(74.59)		28(22.95)			94(77.05)
χ²/t值		2.814						10.946				0.422					17.531					11.745
P值		0.093						0.001				0.516					<0.01					0.001
组别			Ki-67增殖指数[例(%)]								转移情况[例(%)]								NMN(nmol/L)					MN(nmol/L)
组别			<3%				≥3%				是			否					NMN(nmol/L)					MN(nmol/L)
SDHB缺失			20(29.41)				48(70.59)				16(23.53)			52(76.47)					7.53±1.95					0.61±0.23
SDHB阳性			85(69.67)				37(30.33)				9(7.38)			113(92.62)					5.19±1.26					0.56±0.20
χ²/t值			28.627								9.969								10.029					1.565
P值			<0.01								0.002								<0.01					0.119

指标	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
指标	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
年龄	1.285	0.553	5.398	0.020	3.616	1.223	10.694
高血压	1.095	0.527	4.314	0.038	2.988	1.064	8.394
肿瘤部位	1.341	0.546	6.025	0.014	3.824	1.310	11.158
肿瘤类型	1.543	0.598	6.650	0.010	4.680	1.448	15.123
血管浸润	1.076	0.508	4.490	0.034	2.933	1.084	7.935
包膜浸润	0.349	0.530	0.433	0.510	1.418	0.501	4.009
Ki-67增殖指数	1.839	0.532	11.952	0.001	6.292	2.218	17.850
转移情况	2.722	0.801	11.548	0.001	15.216	3.165	73.151
NMN	1.050	0.200	27.556	<0.01	2.858	1.931	4.230
常量	-12.162	1.873	42.158	<0.01	<0.001	-	-