PMID- 26492543
OWN - NLM
STAT- MEDLINE
DCOM- 20160729
LR  - 20210204
IS  - 1530-891X (Print)
IS  - 1530-891X (Linking)
VI  - 22
IP  - 2
DP  - 2016 Feb
TI  - AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2alpha 
      SIGNALING.
PG  - 190-5
LID - 10.4158/EP15889.OR [doi]
AB  - OBJECTIVE: To describe a patient with a germline succinate dehydrogenase (SDHC) 
      gene mutation presenting with primary hyperparathyroidism and a large 
      catecholamine-producing temporal bone paraganglioma (PGL). METHODS: Evaluation of 
      a SDHC mutation-positive PGL tumor biology using staining for tyrosine 
      hydroxylase (TH), hypoxia-inducible factors 1alpha (HIF-1alpha) and 2alpha (HIF-2alpha). RESULTS: 
      A 66-year-old man was noted to have a lytic skull base mass during work-up for 
      his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine 
      catecholamines and metanephrines revealed marked elevation of norepinephrine and 
      normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial 
      excision of skull base tumor was performed, which upon further examination 
      revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy 
      expression of TH and HIF-2alpha but reduced expression of HIF-1alpha. The remaining skull 
      base PGL was treated with adjuvant radiation therapy. The patient's 
      normetanephrine levels significantly decreased after surgery and radiation. 
      CONCLUSION: Here, we report an unusual case of a patient presenting with a 
      germline SDHC mutation-related functional PGL along with concomitant primary 
      hyperparathyroidism. The present case illustrates that overexpression of HIF-2alpha 
      but not of HIF-1alpha is linked to the pathogenesis of SDHC mutation-related PGL, and 
      it may be responsible for the aggressive clinical behavior of a usually indolent 
      course of SDHC-related PGLs.
FAU - Isaacson, Brandon
AU  - Isaacson B
FAU - Bullova, Petra
AU  - Bullova P
FAU - Frone, Megan
AU  - Frone M
FAU - Click, Arielle
AU  - Click A
FAU - Hamplova, Barbora
AU  - Hamplova B
FAU - Rabaglia, Jennifer
AU  - Rabaglia J
FAU - Woodruff, Stacey
AU  - Woodruff S
FAU - Nwariaku, Fiemu
AU  - Nwariaku F
FAU - Kathuria, Amita
AU  - Kathuria A
FAU - Pacak, Karel
AU  - Pacak K
FAU - Ghayee, Hans K
AU  - Ghayee HK
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151022
PL  - United States
TA  - Endocr Pract
JT  - Endocrine practice : official journal of the American College of Endocrinology 
      and the American Association of Clinical Endocrinologists
JID - 9607439
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Membrane Proteins)
RN  - 0 (SDHC protein, human)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
SB  - IM
MH  - Aged
MH  - Basic Helix-Loop-Helix Transcription Factors/*metabolism
MH  - Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Neoplasm Invasiveness
MH  - Paraganglioma/diagnostic imaging/genetics/metabolism/*pathology
MH  - Radionuclide Imaging
MH  - Signal Transduction
MH  - Skull Neoplasms/diagnostic imaging/genetics/metabolism/*pathology
MH  - Temporal Bone/*pathology
MH  - Up-Regulation
EDAT- 2015/10/23 06:00
MHDA- 2016/07/30 06:00
CRDT- 2015/10/23 06:00
PHST- 2015/10/23 06:00 [entrez]
PHST- 2015/10/23 06:00 [pubmed]
PHST- 2016/07/30 06:00 [medline]
AID - S1530-891X(20)39290-9 [pii]
AID - 10.4158/EP15889.OR [doi]
PST - ppublish
SO  - Endocr Pract. 2016 Feb;22(2):190-5. doi: 10.4158/EP15889.OR. Epub 2015 Oct 22.