Multiple endocrine neoplasia, the old and the new: a mini review

Multiple endocrine neoplasia syndromes have since been classified as types 1 and 2, each with specific phenotypic patterns. MEN1 is usually associated with pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC) more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and familial MTC (FMTC) have been defined based on the risk of pheochromocytoma, hyperparathyroidism, and the presence or absence of characteristic physical features). MEN2 occurs as a result of germline activating missense mutations of the RET (REarranged during Transfection) proto-oncogene. MEN2-associated mutations are almost always located in exons 10, 11, or 13 through 16. Strong genotype-phenotype correlations exist with respect to clinical subtype, age at onset, and aggressiveness of MTC in MEN2. These are used to determine the age at which prophylactic thyroidectomy should occur and whether screening for pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can also impact management in patients presenting with apparently sporadic MTC. Therefore, genetic testing should be performed before surgical intervention in all patients diagnosed with MTC. Recently, Pellegata et al. have reported that germline mutations in CDKN1B can predispose to the development of multiple endocrine tumours in both rats and humans and this new MEN syndrome is named MENX and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC, CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker. New insights on MEN syndrome pathogenesis and related inherited endocrine disorders are of particular interest for an adequate surgical and therapeutic approach.

Spontaneous Cirrhosis Regression in an IFN-beta-induced AIH-like Syndrome Following Drug Withdrawal: Art of Facts or Artifacts?

Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) administration for multiple sclerosis (MS). Based on liver autoimmune serology, histology and appropriate exclusion of other liver diseases, a diagnosis of AIH-related cirrhosis was established. Following discontinuation of IFNβ-1b, a complete resolution of biochemical activity indices was observed and the patient remained untreated on her own decision. However, 3 years later, after a course of intravenous methylprednisolone for MS, a new acute transaminase flare was recorded which subsided again spontaneously after 3 weeks. Liver biopsy and elastography showed significant fibrosis regression (F2 fibrosis). To our knowledge, this is the first report showing spontaneous cirrhosis regression in an IFNβ-1b-induced AIH-like syndrome following drug withdrawal, suggesting that cirrhosis might be reversible if the offending fibrogenic stimulus is withdrawn.