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Multiple endocrine neoplasia type 4 & primary hyperparathyroidism: What the surgeon needs to know

  • Akie Watanabe
    Affiliations
    Department of Surgery, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6, Canada
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  • Sam M. Wiseman
    Correspondence
    Corresponding author. Department of Surgery, St. Paul's Hospital. C303-1081 Burrard Street, Vancouver, British Columbia, Canada.
    Affiliations
    Department of Surgery, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6, Canada
    Search for articles by this author
      Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia with increasing incidence and prevalence.
      • Wilhelm S.M.
      • Wang T.S.
      • Ruan D.T.
      • et al.
      The American association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism.
      Approximately 2–5% of PHPT cases are caused by familial multiple endocrine neoplasia (MEN) syndromes.
      • Cristina E.-V.
      • Alberto F.
      Management of familial hyperparathyroidism syndromes: MEN1, MEN2, MEN4, HPT-Jaw tumour, Familial isolated hyperparathyroidism, FHH, and neonatal severe hyperparathyroidism.
      MEN encompasses a group of autosomal dominant genetic disorders with a variety of clinical presentations primarily affecting endocrine organs.
      • McDonnell J.E.
      • Gild M.L.
      • Clifton‐Bligh R.J.
      • Robinson B.G.
      Multiple endocrine neoplasia: an update.
      Familial PHPT is diagnosed in 95% of MEN1 patients (mutation in menin gene) and 20% of MEN2a patients (mutation in RET gene).
      • Medina J.E.
      • Randolph G.W.
      • Angelos P.
      • et al.
      Primary hyperparathyroidism: disease of diverse genetic, symptomatic, and biochemical phenotypes.
      Surgery is the mainstay for definitive treatment of PHPT,
      • Wilhelm S.M.
      • Wang T.S.
      • Ruan D.T.
      • et al.
      The American association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism.
      of which both syndromes have well-established guidelines.
      • Cristina E.-V.
      • Alberto F.
      Management of familial hyperparathyroidism syndromes: MEN1, MEN2, MEN4, HPT-Jaw tumour, Familial isolated hyperparathyroidism, FHH, and neonatal severe hyperparathyroidism.
      ,
      • McDonnell J.E.
      • Gild M.L.
      • Clifton‐Bligh R.J.
      • Robinson B.G.
      Multiple endocrine neoplasia: an update.
      In recent years, a new MEN syndrome, MEN4, has been characterized, where >80% of patients present with PHPT.
      • Medina J.E.
      • Randolph G.W.
      • Angelos P.
      • et al.
      Primary hyperparathyroidism: disease of diverse genetic, symptomatic, and biochemical phenotypes.
      ,
      • Frederiksen A.
      • Rossing M.
      • Hermann P.
      • Ejersted C.
      • Thakker R.V.
      • Frost M.
      Clinical features of multiple endocrine neoplasia type 4: novel pathogenic variant and review of published cases.
      Its overall incidence, however, is rare, and concrete management guidelines are not established. A recent case of MEN4 diagnosed in a patient with persistent PHPT following a focused parathyroidectomy at our institution has prompted a review of current literature, with the aim to increase surgeon awareness and to help guide management of this uncommon familial PHPT associated syndrome.
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      References

        • Wilhelm S.M.
        • Wang T.S.
        • Ruan D.T.
        • et al.
        The American association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism.
        JAMA Surg. 2016; 151: 959https://doi.org/10.1001/jamasurg.2016.2310
        • Cristina E.-V.
        • Alberto F.
        Management of familial hyperparathyroidism syndromes: MEN1, MEN2, MEN4, HPT-Jaw tumour, Familial isolated hyperparathyroidism, FHH, and neonatal severe hyperparathyroidism.
        Best Pract Res Clin Endocrinol Metabol. 2018; 32: 861-875https://doi.org/10.1016/j.beem.2018.09.010
        • McDonnell J.E.
        • Gild M.L.
        • Clifton‐Bligh R.J.
        • Robinson B.G.
        Multiple endocrine neoplasia: an update.
        Intern Med J. 2019; 49: 954-961https://doi.org/10.1111/imj.14394
        • Medina J.E.
        • Randolph G.W.
        • Angelos P.
        • et al.
        Primary hyperparathyroidism: disease of diverse genetic, symptomatic, and biochemical phenotypes.
        Head Neck. 2021; 43: 3996-4009https://doi.org/10.1002/hed.26861
        • Frederiksen A.
        • Rossing M.
        • Hermann P.
        • Ejersted C.
        • Thakker R.V.
        • Frost M.
        Clinical features of multiple endocrine neoplasia type 4: novel pathogenic variant and review of published cases.
        J Clin Endocrinol Metab. 2019; 104: 3637-3646https://doi.org/10.1210/jc.2019-00082
        • Alrezk R.
        • Hannah-Shmouni F.
        • Stratakis C.A.
        MEN4 and CDKN1B mutations: the latest of the MEN syndromes.
        Endocr Relat Cancer. 2017; 24: T195-T208https://doi.org/10.1530/ERC-17-0243
        • Buzzola R.
        • Kurukulasuriya L.R.
        • Touza M.
        • Litofsky N.S.
        • Brietzke S.
        • Sowers J.R.
        A possible new multiple endocrine neoplasia mutation in a patient with a prototypic multiple endocrine neoplasia presentation.
        Cardiorenal Med. 2016; 6: 129-134https://doi.org/10.1159/000440985
        • Manoharan J.
        • Albers M.B.
        • Bollmann C.
        • et al.
        Single gland excision for MEN1-associated primary hyperparathyroidism.
        Clin Endocrinol. 2020; 92: 63-70https://doi.org/10.1111/cen.14112
        • Tonelli F.
        • Giudici F.
        • Giusti F.
        • et al.
        A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.
        Eur J Endocrinol. 2014; 171: K7-K17https://doi.org/10.1530/EJE-14-0080