Endocrine Abstracts

Background: Familial paraganglioma type 1 syndrome is a hereditary form of paraganglioma due to an autosomal dominant, paternally inherited, germinal mutation in the SDHD subunit. Intestinal pseudo-obstruction is a rare complication of secretory PGL. We present a case of a patient with a malignant PGL syndrome type 1 who developed intestinal pseudo-obstruction.

Clinical case: The patient was a Dutch male, aged 39 years, carrier of a germinal mutation in exon 3 of the SDHD gene, with multiple malignant and functioning PGLs, with bone, liver and abdominal metastases. In 2007 he was diagnosed with a palpable right cervical paraganglioma that was surgically removed. Noradrenaline was the main secretion product. As disease progressed, multimodality treatment was required: alfa end beta adrenergic receptor blockers, alfa-methyl-p-tirosine, surgically excision of an abdominal PGL, hepatic metastases resection and chemoembolization, radiotherapy for several bone metastases, three Lu177 treatments (total activity =530 mCi), decompressive surgery for an orbital bone metastasis, bisphosphonate therapy, and six cycles of cyclophosphamide, vincristine and dacarbazine chemotherapy. Disease progression was evident clinically and biochemically with serum chromogranin A (normal range <100 ng/ml) and urinary metanephrines (normal range <1 ng/ml) reaching 78870 ng/ml and 77 mg/24 h, respectively). By the end of 2017, he developed recurrent vomiting, food intolerance, severe constipation and abdominal bloating. The abdominal CT scan showed massive right colon dilatation without evidence of structural obstruction. Medical therapy with enemas, laxatives, intravenous fluids, erythromycin and neostigmine was started, and phenoxybenzamine dose was increased. However, his condition worsened and a right hemicolectomy with ileostomy was performed, which proved to be ineffective as well. Intravenous phentolamine perfusion and labetalol were then initiated. Unfortunately, due to limited availability of phentolamine and the high dose of continuous intravenous administration that was required, this treatment was unsustainable. Finally, the patient developed gastrointestinal bleeding, dying a few days later.

Conclusion: Intestinal pseudo-obstruction is a severe, rare and often unrecognized consequence of excessive catecholamine production by paraganglioma/pheochromocytoma. Catecholamines activate alfa-1, alfa-2 and beta-2 adrenoreceptors of the intestinal smooth muscle cells, reducing gastrointestinal motility and increasing vasoconstriction. This was a rare case of malignant and secretory PGL with a fatal intestinal pseudo-obstruction complication. Early use of alfa-blockers, in particular intravenous phentolamine, and eventually methyltyrosine, may be useful in relieving this complication which can have a poor outcome.