Case history: 63 year man with two trans-temporal incomplete resections of a glomus jugulare tumour (HNPGL) in 1993 and 2000 with regular surveillance scans for residual disease. Eight years later, an MRI demonstrated an incidental pituitary macroadenoma with cavernous and sphenoid sinuses invasion. The patient was asymptomatic but, his biochemistry revealed a markedly raised prolactin of 43,000 mIU/l with no other pituitary hormone deficiency. Cabergoline was commenced and the macroprolactinoma demonstrated an excellent response, with normalization of serum prolactin within one year. Family history revealed that his brother was also diagnosed with a glomus vagale tumour and his cousin with pituitary tumour. The patient was referred to a clinical geneticist. Our patient was found to be positive for missense SDHC mutation as a variant of uncertain significance. Further genetic testing demonstrated that his brother and sister also had SDHC mutation. Interestingly his cousin with NFPA did not.
Result and treatment: Biochemical screening showed a raised plasma 3-methoxytyramine (3MT) 1014 pmol/l (0180) but normal metanephrine and normetanphrine. His whole body MRI scan showed stable residual HNPGL with no other lesion detected. We questioned if the isolated rise in 3MT could be a drug induced phenomenon as the patient was concurrently treated with dopamine agonist (cabergoline) and 3MT is a metabolite of the neurotransmitter dopamine. Carbergoline was temporarily stopped; his repeated 3MT was 1965 and 2185 pmol/l at 2 and 4 weeks of ceasing cabergoline respectively. Most HNPGLs are functionless but the isolated high 3MT level was suggestive of metastatic disease. Functional imaging with (123)I-MIBG and (68)Ga-DOTATATE PET/CT were performed to exclude multifocal disease. (68)Ga-DOTATATE PET/CT demonstrated avid uptake at his residual neck disease and another focus of uptake in his sacrum. Biopsy of the lesion was not possible given its size and location. He received fractionated radiotherapy for his skull base and sacral lesions. Follow-up in the next 3 year remains stable with Ga-68 PET/CT demonstrated reduced uptake in the sacrum with stable HNPGL and 3MT around 700 pmol/l.
Discussion: We are reporting a very interesting patient who harbors SDHC germ-line mutation with metastatic HNPGL and pituitary tumour. SDHC mutation is typically benign and non-functioning but a recent publication of metastatic disease has been reported. The relationship of pituitary tumour and SDHC remains un-defined, as loss of heterozygosity study is not available. The other interesting phenomenon is the rise in 3MT with dopamine agonist withdrawal.
08 - 10 Apr 2019
Society for Endocrinology