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Open access

Shweta Birla, Viveka P Jyotsna, Rajiv Singla, Madhavi Tripathi and Arundhati Sharma

Summary

Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein‘menin’ involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease.

Learning points

  • Identification of a novel pathogenic MEN1 deletion mutation.

  • MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology.

  • Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome.

Open access

Kirun Gunganah, Ashley Grossman and Maralyn Druce

Summary

A 22-year-old female student presented with a history of recurrent pancreatitis. The commonest causes of pancreatitis, including drugs, gallstones, corticosteroids, excess alcohol and hypertriglyceridaemia, were excluded. She was found to have an elevated serum calcium level that was considered to be the cause of her pancreatitis, with a detectable serum parathyroid hormone (PTH). An initial diagnosis of primary hyperparathyroidism was made. However, two neck explorations failed to reveal a parathyroid adenoma. She was referred to our unit three years later as her episodes of pancreatitis were becoming more frequent and her calcium level remained persistently elevated. Her investigations were as follows: elevated adjusted calcium level of 2.79 mmol/l (2.2–2.58), PTH level of 4.2 pmol/l (0.6–6.0), low 24 h urine calcium of 0.3 mmol/l and a urine calcium:creatinine ratio of <0.003. A clinical diagnosis of familial hypocalciuric hypercalcaemia (FHH) was made and confirmed on genetic testing that showed a c.1703 G>A mutation in the calcium-sensing receptor gene. Although the hypercalcaemia of FHH is usually without sequelae due to the generalised changes in calcium sensing, in the presence of this complication she was started on cinacalcet 30 mg daily. She had one further episode of pancreatitis with calcium levels ranging between 2.53 and 2.66 mmol/l. Her cinacalcet was gradually increased to 30 mg three times daily, maintaining her calcium levels in the range of 2.15–2.20 mmol/l. She has not had a further episode of pancreatitis for more than 2 years.

FHH is usually a benign condition with minimal complications from hypercalcaemia. Pancreatitis has been reported rarely, and no clear management strategy has been defined in these cases. Cinacalcet was successfully used in treating recurrent pancreatitis in a patient with FHH by maintaining calcium levels in the lower part of the reference range. Whether or not this is an effective long-term treatment remains yet to be seen.

Learning points

  • FHH is an important differential diagnosis for hypercalcaemia.

  • FHH can rarely cause pancreatitis.

  • No clear strategy is available to help in the management of patients with pancreatitis due to FHH.

  • Cinacalcet was effective in lowering serum calcium levels and reducing the frequency of pancreatitis in our patient with FHH.