Early Symptoms and Clinical Manifestations in Korean Patients with Multiple Endocrine Neoplasia

Ki-Ho Kim M.D.; Min-Young Koo M.D.; Sung-Mo Hur M.D.; Se-Kyung Lee M.D.; Jun-Ho Choe M.D.; Jeong Eon Lee M.D.; Jee Soo Kim M.D.; Jae-Hoon Chung M.D.; Seok Jin Nam M.D.; Jung-Hyun Yang M.D.; Jung-Han Kim M.D.

doi:10.16956/kjes.2010.10.4.266

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M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., and M.D.: Early Symptoms and Clinical Manifestations in Korean Patients with Multiple Endocrine Neoplasia

Review Article

Korean J Endocrine Surg 2010;10(4):266-275.

Published online: 18 December 2010

DOI: https://doi.org/10.16956/kjes.2010.10.4.266

Early Symptoms and Clinical Manifestations in Korean Patients with Multiple Endocrine Neoplasia

Ki-Ho Kim M.D., Min-Young Koo M.D., Sung-Mo Hur M.D., Se-Kyung Lee M.D., Jun-Ho Choe M.D., Jeong Eon Lee M.D., Jee Soo Kim M.D., Jae-Hoon Chung M.D., Seok Jin Nam M.D., Jung-Hyun Yang M.D., Jung-Han Kim M.D.

Department of Surgery, Metabology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

¹Division of Endocorin and Metabology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

Multiple endocrine neoplasia (MEN) syndrome is an inherited, autosomal dominant disease that presents as a combination of several endocrine tumors. Early diagnosis of this syndrome is difficult, because of the nonspecific symptoms and signs. This study analyzed early manifestations and clinical characteristics in patients with MEN syndrome.

Results:

The 35 patients had been diagnosed as MEN1 (n=14), MEN2A (n=19) and MEN2B (n=2). The early manifestations of the 14 MEN1 patients were related with hyperparathyroidism (n=5), pituitary tumor (n=3), and pancreatic endocrine tumor (n=2). There were tumors of the parathyroid gland in all 14 patients, anterior pituitary in eight patients, and pancreatic islet cells in seven patients. Four cases were incidentally detected during the screening examination. Six cases harbored a MEN1 gene mutation. The twenty-one patients diagnosed with MEN2 comprised medullary thyroid cancer (n=20), adrenal pheochromocytoma (n=15), and hyperparathyroidism (n=4). The MTC-related symptoms in the 21 MEN2 patients included neck mass or discomfort in 12 patients and pheochromocytoma-related symptoms in seven patients. Two cases were detected through familial genetic screening test. The RET gene mutationwas detected in 19 cases.

Conclusion:

Early manifestations of MEN syndrome were very different between the types of MEN and the types of its presenting tumor. The early diagnosis and proper management of MEN requires awareness of the clinical characteristics of each expressed tumor and is influenced by genetic screening methods. (Korean J Endocrine Surg 2010; 10:266-275)

Keywords: Multiple endocrine neoplasia (MEN), Early symptom, Clinical manifestation, Early diagnosis

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Table 1.

Clinical expression of multiple endocrine neoplasia type 1 (MEN1) patients

Pt	Age	Sex	HPT∗	Pancreas tumor	Pituitary tumor	Other	Family history
1	17	F	O	Insulinoma	Prolactinoma
2	28	F	O		Prolactinoma
3	28	F	O	Insulinoma	Prolactinoma		Insulinoma
4	39	F	O		Prolactinoma
5	41	M	O	Gastrrinoma			MEN1
6	47	M	O		NF		MEN1
7	58	M	O	NF^†	Ga	astric carcinoid
8	53	F	O		NF
9	61	F	O				MEN1
10	35	F	O	Gastrinemia	NF
11	46	F	O				MEN1
12	30	M	O	NF	Th	hymic cancer	MEN1
13	59	M	O
14	46	M	O	Glucagonoma	NF		MEN1
	Total		100%	50%	64.3%	14.3%	41.7%

^∗ HPT = hyperparathyroidism;

^† NF = nonfunctioning tumor.

Table 2.

Treatment of hyperparathyroidism

Pt	Approach	Identified glands	Excised glands	Multifocal	PTH(pg/ml)
Pt	Approach	Identified glands	Excised glands	Multifocal	Pre-op	Post-op
1	Bilateral	4	2	O	133	10
2	Minimally invasive	1	1		81	24
3	No operation	2		O	↑^†
4	Bilateral	4	3＋1/2	O	257	10
5	Bilateral	3	3∗	O	220	81
6	Bilateral	4	3＋1/2∗	O	270	121
7	Bilateral	4	3＋1/2∗	O	263	25
8	No operation	1			105
9	Bilateral	2	2	O	124	Normal^‡
10	No operation				↑^†
11	Bilateral	4	3＋1/2	O	234	40
12	Bilateral	4	3＋1/2	O	↑^†	Normal^‡
13	Bilateral	2	2	O	290	101
14	Bilateral	2	2	O	243	8

Parathyroid reoperation;

^† Elevated, but not specified; ‡Normal, but not specified.

Table 3.

Treatment of pancreas and pituitary tumor

Pt Pancreastumor	Pancreas resection	Pituitar tumor	ry r Pituitary tumor removal
1 Insulinoma	Distal	Prolactino	oma TSA∗
2		Prolactino	oma
3 Insulinoma	Distal＋	Prolactino	oma Gamma
	Enucleation		knife
4		Prolactino	oma
5 Malignant	Subtotal
gastrinoma
6		NF
7 NF	F/U
8		NF	TSA
10 Gastrinemia	F/U	NF	TSA
12 NF	F/U
14 Malignant	Total	NF
glucagonoma

^∗ TSA = transsphenoidal pituitary adenoma resection.

Table 4.

Clinical expression of multiple endocrine neoplasia type 2A (MEN2A) patients

Pt	Age	Sex	Medullary thyroid cancer	Pheochromocytoma	Hyperparathyroidi	sm Family history
1	19	F	O	O	O	MEN2A
2	32	M	O	O		MEN2A
3	33	F	O	O		MEN2A
4	14	F	O	O		MEN2A
5	20	F	O			MEN2A
6	32	M	O			MEN2A
7	19	F	O	O		MEN2A
8	34	F	O	O		MEN2A
9	32	M	O	O	O	MEN2A
10	27	F	O	O	O	MEN2A
11	53	F	O	O		MEN2A
12	28	M	O
13	29	F	O		O
14	35	F	O	O
15	53	F	O	O		Adrenal tumor
16	55	F	O	O		MEN2A
17	56	F	O	O
18	30	F	O	O
19	47	M	O	O
	Total		100%	78.9%	21.1%	68.4%

Table 5.

Treatment of medullary thyroid cancer

Pt	Onset (year)	Thyroidectomy	y Lymph node dissection T	Tumor size (cm)	Lymph node metastasis	Multifocal	Recurrence
1	19	Total		0.4		O
2	32	Total	CND∗		O	O	O
3	33	Total	CND			O
4	14	Total	Bilateral MRND	4.5		O	O
5	20	Total	Bilateral MRND	4		O
6	32	Total	CND	1.2	O	O
7	19	Total	Bilateral MRND^†	4.5	O	O
8	34	Total	Bilateral MRND	4		O
9	39	Total	Bilateral MRND	1	O	O
10	27	Total		2		O
11	53	Total	CND	1		O
12	28	Total	Bilateral MRND	2	O	O	O
13	29	Total	CND	0.5		O
14	35	Total		4		O
15	53	Total	Rt. MRND	1		O
16	55	Total	Bilateral MRND	2	O	O	O
17	56	Total		3.4
19	47	Total	Bilateral MRND	3.5	O	O

^∗ CND = central neck node dissection; †MRND = modified radical neck node dissection.

Table 6.

Treatment of phechromocytoma

Pt	Location	Occurrence	Contralateral	Recurrence	Adrenalectomy
1	Bilateral	Metachronous	Left	O	Bilateral, open
2	Bilateral	Metachronous	Left	O	Right, open
3	Bilateral	Synchronous			Bilateral, open
4	Bilateral	Metachronous	Right		Lap∗, subtotal^†
7	Bilateral	Metachronous	Right		Lap, subtotal
8	Bilateral	Metachronous	Right		Left, lap
9	Left
10	Bilateral	Synchronous		O	Open, subtotal
11	Bilateral	Metachronous	Left		Bilateral, open
13	Bilateral	Synchronous			Open, subtotal
15	Bilateral	Synchronous			Lap, subtotal
16	Bilateral	Synchronous			Bilateral, open
17	Bilateral	Synchronous			Bilateral, open
18	Bilateral	Metachronous	Right		Open & lap, subtotal
19	Left				Left, lap

^∗ Lap = laparoscopic;

^† Subtotal = unilateral adrenalectomy＋contralateral partial adrenalectomy.

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