title: Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?
abstract: BACKGROUND
  Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1.
  
  
  METHODS
  The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed "adenoma-like" kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence.
  
  
  CONCLUSIONS
  Despite well-defined diagnostic criteria and guidelines, diagnosis of MEN1 can still be challenging. When diagnosis is doubtful, appropriate management may be difficult to establish.
authors.affiliation: General Surgery Unit, Department of Surgical Sciences, San Giovanni di Dio Hospital, University of Cagliari, Cagliari, Italy. enricoerdas@medicina.unica.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Erdas
authors.forename: Nicola
authors.initials: N
authors.lastname: Aste
authors.forename: Luca
authors.initials: L
authors.lastname: Pilloni
authors.forename: Angelo
authors.initials: A
authors.lastname: Nicolosi
authors.forename: Sergio
authors.initials: S
authors.lastname: Licheri
authors.forename: Antonello
authors.initials: A
authors.lastname: Cappai
authors.forename: Marco
authors.initials: M
authors.lastname: Mastinu
authors.forename: Filomena
authors.initials: F
authors.lastname: Cetani
authors.forename: Elena
authors.initials: E
authors.lastname: Pardi
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
authors.forename: Mariano
authors.initials: M
authors.lastname: Pomata
mesh_terms: D018249:Adenoma, Oxyphilic / Q000150:complications / Q000503:physiopathology; D000368:Aged; D005260:Female; D005935:Glucagonoma / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000150:complications* / Q000503:physiopathology / Q000601:surgery; D018761:Multiple Endocrine Neoplasia Type 1; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000503:physiopathology; D013964:Thyroid Neoplasms / Q000150:complications* / Q000503:physiopathology