Advertisement

Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis

  • L. Montefusco
    Affiliations
    U.O. di Malattie Endocrine e Diabetologia, Ospedale San Giuseppe Multimedica, Milan, Italy

    MultiMedica IRCCS, Milan, Italy
    Search for articles by this author
  • S. Harari
    Correspondence
    Corresponding author at: U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria - Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe-MultiMedica IRCCS, via San Vittore 12, CAP 20123 Milan, Italy.
    Affiliations
    MultiMedica IRCCS, Milan, Italy

    U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria - Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe Multimedica, Milan, Italy
    Search for articles by this author
  • D. Elia
    Affiliations
    MultiMedica IRCCS, Milan, Italy

    U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria - Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe Multimedica, Milan, Italy
    Search for articles by this author
  • A. Rossi
    Affiliations
    U.O. di Malattie Endocrine e Diabetologia, Ospedale San Giuseppe Multimedica, Milan, Italy

    MultiMedica IRCCS, Milan, Italy
    Search for articles by this author
  • C. Specchia
    Affiliations
    MultiMedica IRCCS, Milan, Italy

    Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Italy
    Search for articles by this author
  • O. Torre
    Affiliations
    MultiMedica IRCCS, Milan, Italy

    U.O. di Pneumologia e Terapia Semi-Intensiva Respiratoria - Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe Multimedica, Milan, Italy
    Search for articles by this author
  • G. Adda
    Affiliations
    U.O. di Malattie Endocrine e Diabetologia, Ospedale San Giuseppe Multimedica, Milan, Italy

    MultiMedica IRCCS, Milan, Italy
    Search for articles by this author
  • M. Arosio
    Affiliations
    U.O. di Endocrinologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy
    Search for articles by this author
Published:November 29, 2017DOI:https://doi.org/10.1016/j.ejim.2017.11.011

      Highlights

      • A population of adults affected by Langerhans cell histiocytosis is described.
      • Pituitary involvement is common, but mostly in presence of diabetes insipidus.
      • High prevalence of obesity and diabetes, independently from endocrine involvement
      • Occurrence of BRAV600E positive thyroid papillary carcinoma has been described.

      Abstract

      Context

      Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet.

      Objectives

      Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH.

      Methods

      Observational cross-sectional study on 18 adults (7 M/11 F, 42 ± 12 years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism.

      Results

      Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung+). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient.

      Conclusions

      The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Girschikofsky M.
        • Aricò M.
        • Castillo D.
        • Chu A.
        • Doberauer C.
        • Fichter J.
        • et al.
        Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net.
        Orphanet J Rare Dis. 2013; 8: 72
        • Harari S.
        • Caminati A.
        Pulmonary Langerhans' cell histiocytosis.
        Eur Respir Mon. 2009; 46: 155-175
        • Emile J.F.
        • Abla O.
        • Fraitag S.
        • Horne A.
        • Haroche J.
        • Donadieu J.
        • et al.
        Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages.
        Blood. 2016; 127: 2672-2681
        • Tazi A.
        • Lorillon G.
        • Haroche J.
        • Neel A.
        • Dominique S.
        • Aouba A.
        • et al.
        Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study.
        Orphanet J Rare Dis. 2017; 12: 95
        • Watanabe R.
        • Tatsumi K.
        • Hashimoto S.
        • Tamakoshi A.
        • Kuriyama T.
        • Respiratory Failure Research Group of Japan
        Clinicoepidemiological features of pulmonary histiocytosis X.
        Intern Med. 2001; 40: 998-1003
        • Vassallo R.
        • Harari S.
        • Tazi A.
        Current understanding and management of pulmonary Langerhans cell histiocytosis.
        Thorax. 2017 Jul 8; ([Epub ahead of print])https://doi.org/10.1136/thoraxjnl-2017-210125
        • Elia D.
        • Torre O.
        • Cassandro R.
        • Caminati A.
        • Harari S.
        Pulmonary Langerhans cell histiocytosis: a comprehensive analysis of 40 patients and literature review.
        Eur J Intern Med. 2015; 26: 351-356
        • Senechal B.
        • Elain G.
        • Jeziorski E.
        • Grondin V.
        • Patey-Mariaud de Serre N.
        • Jaubert F.
        • et al.
        Expansion of regulatory T cells in patients with Langerhans cell histiocytosis.
        PLoS Med. 2007; 4e253
        • Badalian-Very G.
        • Vergilio J.A.
        • Degar B.A.
        • MacConaill L.E.
        • Brandner B.
        • Calicchio M.L.
        • et al.
        Recurrent BRAF mutations in Langerhans cell histiocytosis.
        Blood. 2010; 116: 1919-1923
        • Mourah S.
        • How-Kit A.
        • Meignin V.
        • Gossot D.
        • Lorillon G.
        • Bugnet E.
        • et al.
        Recurrent NRAS mutations in pulmonary Langerhans cell histiocytosis.
        Eur Respir J. 2016; 47: 1785-1796
        • Rizzo F.M.
        • Cives M.
        • Simone V.
        • Silvestris F.
        New insights into the molecular pathogesis of Langerhans cell histiocytosis.
        Oncologist. 2014; 19: 151-163
        • Broadbent V.
        • Dunger D.
        • Yeomans E.
        • Kendall B.
        Anterior pituitary function and computed tomography/magnetic resonance imaging in patients with Langerhans cell histiocytosis and diabetes insipidus.
        Med Pediatr Oncol. 1993; 21: 649-654
        • Grois N.
        • Favara B.
        • Mostbeck H.
        • Prayer D.
        Central nervous disease in Langerhans cell histiocytosis.
        Haematol Oncol Clin North Am. 1998; 12: 287-297
        • Aricò M.
        • Eceler R.
        Clinical aspects of Langerhans cell histiocytosis.
        Haematol Oncol Clin North Am. 1998; 12: 247-258
        • Haupt R.
        • Nanduri V.
        • Calevo M.G.
        • Bernstrand C.
        • Braier J.L.
        • Broadbent V.
        • et al.
        Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group.
        Pediatr Blood Cancer. 2004; 42: 438-444
        • Kaltsas G.A.
        • Powles T.B.
        • Evanson J.
        • Plowman P.N.
        • Drinkwater J.
        • Jenkins P.J.
        • et al.
        Hypothalamo-pituitary abnormalities in adult patients with Langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment.
        J Clin Endocrinol Metab. 2000; 85: 1370-1376
        • Makras P.
        • Samara C.
        • Antoniou M.
        • Zetos A.
        • Papadogias D.
        • Nikolakopoulou Z.
        • et al.
        Evolving radiological features of hypothalamo-pituitary lesions in adult patients with Langerhans cell histiocytosis (LCH).
        Neuroradiology. 2006; 48: 37-44
        • Malpas S.J.
        Langerhans cell histiocytosis in adults.
        Hematol Oncol Clin North Am. 1998; 12: 259-268
        • French Langerhans Cell Histiocytosis Group
        A multicentric retrospective survey of Langerhans' cell histiocytosis: 348 cases observed between 1983 and 1993.
        Arch Dis Child. 1996; 75: 17-24
        • Rigaud C.
        • Barkaoui M.A.
        • Thomas C.
        • Bertrand Y.
        • Lambilliotte A.
        • Miron J.
        • et al.
        Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age.
        British J Haematol. 2016; 174: 887-898
        • Amato M.C.
        • Elias L.L.
        • Elias J.
        • Santos A.C.
        • Bellucci A.D.
        • Moreira A.C.
        • et al.
        Endocrine disorders in pediatric-onset Langerhans cell histiocytosis.
        Horm Metab Res. 2006; 38: 746-751
        • Makras P.
        • Alexandraki K.I.
        • Chrousos G.P.
        • Grossman A.B.
        • Kaltsas G.A.
        Endocrine manifestation in Langerhans cell histiocytosis.
        Trends Endocrinol Metab. 2007; 18: 252-257
        • Makras P.
        • Papadogias D.
        • Kontogeorgos G.
        • Piaditis G.
        • Kaltsas G.A.
        Spontaneous gonadotrophin deficiency recovery in an adult patient with Langerhans cell histiocytosis (LCH).
        Pituitary. 2005; 8: 169-174
        • Kurtulmus N.
        • Mert M.
        • Tanakol R.
        • Yarman S.
        The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.
        Endocrine. 2015; 48: 949-956
        • Ben Ghorbel I.
        • Houman M.H.
        • B'chir S.
        • Chamakhi S.
        • Miled M.
        A disseminated form of Langerhans histiocytosis associated with diabetes insipidus and diabetes mellitus.
        Rev Med Interne. 2001; 22: 469-474
        • Rowntree L.G.
        • Poppiti R.J.
        Diabetes insipidus, diabetes mellitus and insulin resistance with histiocytosis.
        JAMA. 1954; 156: 310-312
        • Alexandraki K.I.
        • Makras P.
        • Protogerou A.D.
        • Dimitriou K.
        • Stathopoulou A.
        • Papadogias D.S.
        • et al.
        Cardiovascular risk factors in adult patients with multisystem Langerhans-cell histiocytosis: evidence of glucose metabolism abnormalities.
        QJM. 2008; 101: 31-40
        • Xia C.X.
        • Li R.
        • Wang Z.H.
        • Lv F.J.
        • Tang X.Q.
        • Li Q.F.
        • et al.
        A rare cause of goiter: Langerhans cell histiocytosis of the thyroid.
        Endocr J. 2012; 59: 47-54
        • Foulet-Roge A.
        • Josselin N.
        • Guyetant S.
        • Gardet J.J.
        • Besancon A.
        • Saint-André J.P.
        • et al.
        Incidental Langerhans cell histiocytosis of thyroid: case report and review of the literature.
        Endocr Pathol. 2002; 13: 227-233
        • Behrens R.J.
        • et al.
        Langerhans cell histiocytosis of the thyroid: a report of two cases and review of the literature.
        Thyroid. 2001; 11: 697-705
        • Lollar K.
        • Farrag T.Y.
        • Cao D.
        • Niparko J.
        • Tufano R.P.
        Langerhans cell histiocytosis of the thyroid gland.
        Am J Otolaryngol. 2008; 29: 201-204
        • Patten D.K.
        • Wani Z.
        • Tolley N.
        Solitary langerhans histiocytosis of the thyroid gland: a case report and literature review.
        Head Neck Pathol. 2012; 6: 279-289
        • Lassalle S.
        • Hofman V.
        • Santini J.
        • Sadoul J.L.
        • Hofman P.
        Isolated Langerhans cell histiocytosis of the thyroid and Graves' disease: an unreported association.
        Pathology. 2008; 40: 525-527
        • Ramadas P.T.
        • Kattoor J.
        • Mathews A.
        • Abraham E.K.
        Fine needle aspiration cytology of Langerhans cell thyroid histiocytosis and its draining lymph nodes.
        Acta Cytol. 2008; 52: 396-398
        • Wohlschlaeger J.
        • Ebert S.
        • Sheu S.Y.
        • Schmid K.W.
        • Totsch M.
        Immunocytochemical investigation of Langerin (CD207) is a valuable adjunct in the cytological diagnosis of Langerhans cell histiocytosis of the thyroid.
        Pathol Res Pract. 2009; 205: 433-436
        • Jamaati H.R.
        • Shadmehr M.B.
        • Saidi B.
        • Khosravi A.
        • Arab M.
        • Mohammadi F.
        Langerhans cell histiocytosis of the lung and thyroid, co-existing with papillary thyroid cancer.
        Endocr Pathol. 2009; 20: 133-136
        • Grossman A.B.
        The diagnosis and management of central hypoadrenalism.
        JCEM. 2010; 95: 4855-4863
        • Corneli G.
        • Di Somma C.
        • Baldelli R.
        • Rovere S.
        • Gasco V.
        • Croce C.G.
        • et al.
        The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index.
        Eur J Endocrinol. 2005; 153: 257-264
        • Buvat J.
        • Maggi M.
        • Guay A.
        • Torres L.O.
        Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment.
        J Sex Med. 2013; 10: 245-284
        • Melmed S.
        • Casanueva F.F.
        • Hoffman A.R.
        • Kleinberg D.L.
        • Montori V.M.
        • Schlechte J.A.
        • et al.
        Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline.
        J Clin Endocrinol Metab. 2011; 96: 273-288
        • Leroy C.
        • Karrouz W.
        • Douillard C.
        • Do Cao C.
        • Cortet C.
        • Wémeau J.L.
        • et al.
        Diabetes insipidus.
        Ann Endocrinol (Paris). 2013; 74: 496-507
        • Bergman R.N.
        • Prager R.
        • Volund A.
        • Olefsky J.M.
        Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp.
        J Clin Invest. 1987; 79: 790-800
        • Katz A.
        • Nambi S.S.
        • Mather K.
        • Baron A.D.
        • Follmann D.A.
        • Sullivan G.
        • et al.
        Quantitative insulin sensitivity check index a simple, accurate method for assessing insulin sensitivity in humans.
        J Clin Endocrinol Metab. 2000; 85: 2402-2410
        • National Cholesterol Education program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Chamberlain J.J.
        • Rhinehart A.S.
        • Shaefer Jr., C.F.
        • Neuman A.
        Diagnosis and management of siabetes: synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes.
        Ann Intern Med. 2016; 164: 542-552
        • Mancia G.
        • et al.
        ESH/ESC guidelines for the management of arterial hypertension: the Task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
        Eur Heart J. 2013; 34: 2159-2219
        • Stone N.J.
        • et al.
        2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        Circulation. 2014; 129: S1-45
        • ISTAT
        Indagine multiscopo annuale sulle famiglie “Aspetti della vita quotidiana” Anno 2009; no. 5.
        2010
        • Dunstan D.W.
        • Zimmet P.Z.
        • Welborn T.A.
        • De Courten M.P.
        • Cameron A.J.
        • Sicree R.A.
        • et al.
        The rising prevalence of diabetes and impaired glucose tolerance.
        Diabetes Care. 2002; 25: 829-834
        • Aricò M.
        • Girschikofsky M.
        • Généreauc T.
        • Klersyd C.
        • McClaine K.
        • Grois N.
        • et al.
        Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society.
        Eur J Cancer. 2003; 39: 2341-2348
        • Grois N.
        • Pötschger U.
        • Prosch H.
        • Minkov M.
        • Arico M.
        • Braier J.
        • et al.
        DALHX- and LCH I and II Study Committee. Risk factors for diabetes insipidus in Langerhans cell histiocytosis.
        Pediatr Blood Cancer. 2006; 46: 228-233
        • Fleseriu M.
        • Hashim I.A.
        • Karavitaki N.
        • Melmed S.
        • Murad M.H.
        • Salvatori R.
        • et al.
        Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2016; 101: 3888-3921
        • Baumgartner I.
        • von Hochstetter A.
        • Baumert B.
        • Luetolf U.
        • Follath F.
        Langerhans-cell histiocytosis in adults.
        Med Pediatr Oncol. 1997; 28: 9-14
        • Darzy K.H.
        • Aimaretti G.
        • Wieringa G.
        • Gattamaneni H.R.
        • Ghigo E.
        • Shalet S.M.
        The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the postirradiation time interval.
        J Clin Endocrinol Metab. 2003; 88: 95-102
        • Obert J.
        • Vercellino L.
        • Van Der Gucht A.
        • de Margerie-Mellon C.
        • Bugnet E.
        • Chevret S.
        • et al.
        18F-fluorodeoxyglucose positron emission tomography-computed tomography in the management of adult multisystem Langerhans cell histiocytosis.
        Eur J Nucl Med Mol Imaging. 2017; 44: 598-610
        • Vergez S.
        • Rouquette I.
        • Ancey M.
        • Serrano E.
        • Caron P.
        Langerhans cell histiocytosis of the thyroid is a rare entity, but an association with a papillary thyroid carcinoma is often described.
        Endocr Pathol. 2010; 21: 274-276
        • Guarino S.
        • Giusti D.M.
        • Rubini A.
        • Favoriti P.
        • Fioravanti C.
        • Di Matteo F.M.
        • et al.
        Association between pituitary Langerhans cell histiocytosis and papillary thyroid carcinoma.
        Clin Med Insights Case Rep. 2013; 6: 197-200
        • Badalian-Very G.
        • Vergelio J.A.
        • Fleming M.
        • Rollins B.J.
        Pathogenesis of Langerhans cell histiocytosis.
        Annu Rev Pathol. 2013; 24: 1-20
        • Steele C.A.
        • Cuthbertson D.J.
        • MacFarlane I.A.
        • Javadpour M.
        • Das K.S.
        • Gilkes C.
        • et al.
        Hypothalamic obesity: prevalence, associations and longitudinal trends in weight in a specialist adult neuroendocrine clinic.
        Eur J Endocrinol. 2013; 168: 501-507
        • Lee M.
        • Korner J.
        Review of physiology, clinical manifestations, and management of hypothalamic obesity in humans.
        Pituitary. 2009; 12: 87-95