SAT-315 SDHC Germline Mutation Carrier with Primary Paraganglioma of the Thyroid Gland

Background Thyroid paragangliomas(PGLs) are less than 0.1% of all thyroid neoplasms. They represent a subset of inferior laryngeal PGL and can be located adjacent to or inside the gland. About 30% of paragangliomas are genetically determined, and 40% of those are succinate dehydrogenase (SDH) related. SDHD and SDHB are more frequently detected than SDHC and SDHA [1]. To date, thyroid paraganglioma has been reported in SDHA and B germline mutation carriers, but there is no case reported with thyroid paraganglioma related to SDHC and D mutations[2]. Clinical case A 50 year old female self-detected a nodularity on her neck. Fine needle aspiration biopsy of the nodule was suspicious for thyroid cancer. She had total thyroidectomy followed by radioactive iodine treatment. Five years after treatment, surgical specimen of thyroid slides were reviewed again upon relocation. Surprisingly, distinct pathologic changes of nodule with characteristic nesting pattern (zellaballen) was noted. On immunohistochemistry study, the cells of the lesion were positive for synaptophysin, chromogranin and S-100, and negative for keratin, CEA, thyroglobulin, TTF-1, calcitonin, EMA and Congo red stain. Based on the histologic feature and immunohistochemistry finding, right lobe paraganglioma was diagnosed retrospectively. When she was 67 years old, she developed symptoms of intermittent flushing, diarrhea, dizziness, and nausea. Her chromogranin A increased from 210 ng/mL to 3413 ng/mL in 6 months. Further pertinent laboratory work-up results included but not all: cortisol 15 mcg/dL, ACTH 35.7pg/mL(7.2-63.3 pg/mL), 24 hour urine free cortisol 17mcg (ref. range <= 176 mcg/24hr), dopamine 133pg/mL (0-20pg/mL), norepinephrine 725 pg/mL (80-520 pg/mL), epinephrine 48 pg/mL (10-200 pg/mL), normetanephrine 0.82 nmol/L (0.00-0.89 nmol/L). This was suggestive of functioning paraganglioma. The patient was evaluated by medical genetics, and a heterozygous germline pathologic variant, NM_003001.3(SDHC):c.43C>T (p.Arg15Ter) was identified. Galium-68-Dotatate scan showed a glomus tumor jugulare. Due to the location of the tumor, the patient was referred for radiation therapy (not yet completed). She was started on monthly octreotide injection and symptoms improved. Her chromogranin A decreased to 70 ng/mL ( 0-95 ng/mL) and dopamine reduced to 76 pg/mL( 0-20pg/mL). Conclusion This is the first case report of a primary paraganglioma of the thyroid gland in an SDHC mutation carrier. The Endocrine Society Clinical Guidelines Subcommittee recommends all patients with PPGLs to be engaged in shared decision making for germline genetic testing. This information can be important for future cancer screening for the patient and family cascade testing and counseling. Reference 1.Hereditary paraganlioma-Pheochromocytoma syndrome, GeneReviews, L Fishbein et al.2.Endocr Relat Cancer. 2015 Apr;22(2):191-204