Sandostatin LAR for functional neuroendocrine tumor in MEN 1
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1 ase Report 1 Sandostatin LR for functional neuroendocrine tumor in MEN 1 uthors: ho-lun Tsai, 1 M.., Tsu-Yao heng, 2,3 M.., Hsiu-Po Wang, 3 M.. ffiliation: 1. epartment of Internal Medicine, itmanson Medical Foundation hia-yi hristian Hospital, No. 539 Zhongxiao East Rd., East district, hiayi 60002, Taiwan. 2. epartments of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University ollege of Medicine, No.7 hang Shan South Road, Taipei 100, Taiwan 3. epartment of Internal Medicine, National Taiwan University Hospital, National Taiwan University ollege of Medicine, No.7 hang Shan South Road, Taipei 10002, Taiwan SE ESRIPTION 50 year-old woman had past history of multi-nodular goiters and received right thyroidectomy in She started to have diplopia since March The symptom aggravated when she looked down. Other symptoms were fullness sensation over left orbital and paranasal area, and occasional headache. She denied vertigo, vomiting, tinnitus, hearing impairment, dysarthria, or chocking. rain T and MRI revealed 3.8 cm pituitary tumor at the para-sellar, and supra-sellar region. The tumor invaded to the left tentorium, left sphenoid sinus and cavernous sinuses. Trans-sphenoidal surgery with incomplete resection was performed and the pathology revealed pituitary adenoma. She received post-operative radiotherapy without hormone supplement. Three years later, multiple thyroid goiters with parathyroid lesions were noted incidentally at other hospital. esides, bilateral adrenal mass was also found (right: 5.4 cm, left: 2 cm and 1.4 cm) during an episode of abdominal pain. She was referred to our hospital for further management. For study of thyroid and parathyroid glands, ultrasound was arranged and it revealed multinodular goiter with cystic change in left thyroid and a hypoechoic lesion at left thyroid bed (Fig. 1). spiration cytology for the hypoechoic lesion revealed parathyroid hyperplasia or adenoma. The ipth level of the sono-guided fine needle aspirates was high ( pg/ml). ondition of pituitary gland was also surveyed. Skull X-ray revealed blurring of sella floor and dorsum sellae (Fig. 2). Head and neck MRI showed infiltrative lesion of isointensity on T2WI and hypointensity on T1WI and it showed moderately heterogenous enhancement (Fig. 3). Invasive Figure 1 Thyroid ultrasound finding. It reveals multinodular goiter with cystic change in left thyroid and a hypoechoic lesion at left thyroid bed. Figure 2 Skull X-ray finding. It reveals blurring of sella floor and dorsum sellae (arrow). 2
2 Figure 3 Head and neck MRI findings. (a) T2 axial view (b) T1W sagital view (c) T2W coronal view (d) T1W coronal view. There is Iinfiltrative lesion of isointensity on T2WI (a) and hypointensity on T1WI (b) and it shows moderately heterogenous enhancement (c, d) (arrows). Invasive pituitary adenoma was considered. pituitary adenoma was considered. Serum ipth was pg/ml (normal range: pg/ ml), serum calcium, 2.79 mmol/l (normal range: mmol/l) and prolactin, 47.7 ng/ml (normal range: ng/ml). ecause of the involvement of parathyroid and pituitary glands, multiple endocrine neoplasia (MEN)-type 1 was considered. She was referred for pancreatic survey. bdominal ultrasound revealed at least four cm hypoechoic tumors at the body and tail of the pancreas. bdominal T revealed multiple strongly enhancing pancreatic tumors Figure 4 bdominal T finding. There are multiple hypervascular tumors in pancreas (arrows). 3
3 Figure 5 EUS findings. There are multiple pancreatic hypervascular hypoechoic tumors from the body to tail, at least 10 in number, with size from 1.9 mm~9.9 mm (a,b,c). EUS-FN is performed (d). in body and tail (Fig.4). EUS showed multiple pancreatic hypervascular hypoechoic tumors from body to tail, at least 10 in number, with size from mm (Fig. 5). FN proved neuroendocrine tumors. Serum chromogranin (g) level was ng/ml. She received distal pancreatectomy, splenctomy, left thyroidectomy, left parathyroidectomy and implatation of parathyroid. Pathology of pancreatic tumors was grade 1 neuroendocrine tumors with positive synaptophysin and g immunostaining. fter the surgery, serum g level decreased to the level around 4,000-5,000 ng/ml. However, diarrhea, acid regurgitation and flushing developed and serum g increased to ng/ml. t the same time, follow-up MRI and EUS revealed a 3.5 cm cystic lesion with mural nodules at pancreatic section margin. Tumor recurrence was Figure 6 bdminal MRI findings. There is recurrent cystic tumor (a, b). Two months after Sandostatin LR treatment, it is disappeared (c, d). 4
4 /23/ OP /23/2013 7/23/2013 8/23/2013 9/23/ /23/ /23/ /23/2013 1/23/ LR 2/23/2014 3/23/2014 4/23/2014 5/23/ /23/2014 7/23/2014 8/23/2014 9/23/ Figure 7 The change of serum chromogranin levels during the course of the treatment. suspected (Fig 6a). Sandostatin LR was given (30 mg IM injection per every month). The g level dropped dramatically and all the carcinoid symptoms disappeared. The cystic pancreatic tumor disappeared in the following T (Fig.6b). She was followed up at our out-patient clinic now. Fig. 7 showed the change of serum g levels during the course of the treatment. MEN type I gene analysis of the patient revealed c263del. with frame shift mutation. MEN type IIa RET gene analysis revealed no causal variant (Fig. 8). (a) Normal (b) c263del.c Figure 8 MEN type I gene analysis of the patient reveals c263del. with frame shift mutation. 5
5 ISUSSION MEN 1 is an autosomal dominant disease caused by mutations in the MEN1 gene. It is diagnosed when the patients suffer from (1) two of the three tumors, the parathyroid glands, anterior pituitary gland, and entero-pancreatic endocrine tumors, (2) one of the three tumors with positive family history or (3) genetic mutations. 1 These patients usually showed up to our clinic with presentation of multiple endocrine tumors and functional appearance. 1 Some of these patients had been troubled by carcinoid syndrome and complications of hypercalcemia for many years before MEN 1 was diagnosed. We represented a MEN 1 case with invasive pituitary tumor, severe hyperparathyroidism and functional neuroendocrine tumor. Her g level was very high initially. Sandostatin LR was given after surgical intervention. The g level dropped gradually to the normal and carcinoid syndrome disappeared. She is doing great now and followed up at our clinic. In conclusion, The MEN 1 with pancreatic neuroendocrine tumors usually needed an effective teamwork with gastroenterologist, endocrinologist, oncologist and surgeon. The somatosatin analogue may play a role in neuroendocrine tumor management, controlling carcinoid syndrome and even have anti-tumor effects. 2 REFERENES 1. Thakker RV, Newey PJ, Walls GV, et al. linical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J clin Endocrinol Metab 2012;97: Nikou G, Lygidakis NJ, Toubanakis, et al. urrent diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-, somatostatin receptor scintigraphy and somatostatin analogues. Hepatogastroenterology 2005;52:
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