A study of neuroendocrine dysfunction in patients of tuberculous meningitis


      • Tuberculous meningitis is a disease of high morbidity and mortality.
      • Endocrine dysfunction is quite common in tuberculous meningitis.
      • The endocrine dysfunction in TBM adversely affects the clinical outcome.



      Endocrine dysfunction is known to occur in various infectious diseases of the brain. The neuroendocrine dysfunction is not well studied in patients of Tuberculous meningitis (TBM). In this study, we aimed at knowing pattern of endocrine dysfunction in newly diagnosed patients of tuberculous meningitis, structural changes occurring in hypothalamic-pituitary region, assessing its predictors and correlative factors related to outcome.

      Materials and methods

      This was a prospective observational study. All newly diagnosed patients of tuberculous meningitis were subjected to clinical, laboratory, and hormonal evaluation along with neuroimaging of hypothalamic-pituitary region. All the patients were treated with antituberculous drugs along with corticosteroids as per WHO guidelines. The clinical outcomes of the patients were assessed at the end of 3 months.


      Out of 115 patients enrolled in the study, endocrine dysfunction was seen in 62 (53.9%) patients. Out of these 62 patients, single axis involvement was seen in 35 (30.4%) patients, while multiple axis dysfunction was observed in 27 (23.5%) patients. Most common hormonal axis involved was gonadotropic axis (33.9%) followed by hyperprolactinemia (22.6%), thyrotropic axis (17.4%), corticotropic axis (13%), SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) (9.6%) and somatotropic axis (7.8%). None had diabetes insipidus. The presence of multiple cranial nerve palsies, hypotension, stage II and III of TBM, baseline MBI ≤12 and basal exudates were significantly higher in endocrine dysfunction group, while the presence of basal exudates independently predicted the occurrence of endocrine dysfunction on multivariate analysis. Though the poor outcome was significantly higher in endocrine dysfunction group at the end of 3 months, on multivariate analysis factors independently associated with poor outcome were the presence of altered sensorium and stage III of TBM.


      Endocrine dysfunction occurs in a significant proportion of patients with tuberculous meningitis. The presence of basal exudates is significantly associated with the occurrence of endocrine dysfunction. Patients with endocrine dysfunction had a poorer outcome although it was not an independent predictor of the same nor associated with increased mortality.


      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 to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Tuberculosis (TB) [Internet]. World Health Organization. 2016 [cited 9 December 2016]. Available from:

        • Garg R.K.
        Tuberculosis of the central nervous system.
        Postgrad. Med. J. 1999 Mar; 75: 133-140
        • Garg R.K.
        Tuberculous meningitis.
        Acta Neurol. Scand. 2010 Aug; 122: 75-90
        • Vani K.R.
        • Shankar S.K.
        • Das S.
        • Asha T.
        • Rao T.V.
        Involvement of hypothalamus in tuberculous meningitis, pathological changes at autopsy.
        Indian J. Tuberc. 1991; 38: 149-153
        • Beatrice A.M.
        • Selvan C.
        • Mukhopadhyay S.
        Pituitary dysfunction in infective brain diseases.
        Indian J. Endocr. Metab. 2013; 17: 608-611
        • Marais S.
        • Thwaites G.
        • Schoeman J.F.
        • Török M.E.
        • Misra U.K.
        • Prasad K.
        • Donald P.R.
        • Wilkinson R.J.
        • Marais B.J.
        Tuberculous meningitis: a uniform case definition for use in clinical research.
        Lancet Infect. Dis. 2010 Nov; 10: 803-812
        • Thwaites G.E.
        • Nguyen D.B.
        • Nguyen H.D.
        • Hoang T.Q.
        • Do T.T.
        • Nguyen T.C.
        • Nguyen Q.H.
        • Nguyen T.T.
        • Nguyen N.H.
        • Nguyen T.N.
        • Nguyen N.L.
        • Nguyen H.D.
        • Vu N.T.
        • Cao H.H.
        • Tran T.H.
        • Pham P.M.
        • Nguyen T.D.
        • Stepniewska K.
        • White N.J.
        • Tran T.H.
        • Farrar J.J.
        Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.
        N. Engl. J. Med. 2004 Oct 21; 351: 1741-1751
        • World Health Organization
        Treatment of Tuberculosis: Guidelines.
        4th ed. 2010 (WHO/HTM/TB/2009.420) World Health Organization (Accessed 9 Dec 2016)
        • Dhanwal D.
        • Vyas A.
        • Sharma A.
        • Saxena A.
        Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis.
        Pituitary. 2010; 13: 304-310
        • Behari S.
        • Shinghal U.
        • Jain M.
        • Jaiswal A.K.
        • Wadwekar V.
        • Das K.B.
        • Jha S.
        Clinicoradiological presentation, management options and a review of sellar and suprasellar tuberculomas.
        J. Clin. Neurosci. 2009 Dec; 16: 1560-1566
        • Bonifacio-Delgadillo D.
        • Aburto-Murrieta Y.
        • Salinas-Lara C.
        • Sotelo J.
        • Montes-Mojarro I.
        • Garcia-Marquez A.
        Clinical presentation and magnetic resonance findings in sellar tuberculomas.
        Case Rep. Med. 2014; 2014: 961913
        • Bommakanti K.
        • Panigrahi M.
        • Yarlagadda R.
        • Sundaram C.
        • Uppin M.S.
        • Purohit A.K.
        Optic chiasmatic-hypothalamic gliomas: is tissue diagnosis essential?.
        Neurol. India. 2010 Nov-Dec; 58: 833-840
        • Daoud E.
        • Mezghani S.
        • Fourati H.
        • Ketata H.
        • Guermazi Y.
        • Ayadi K.
        • Dabbeche C.
        • Mnif J.
        • Ben Mahfoudh K.
        • Mnif Z.
        MR imaging features of tuberculosis of the sellar region.
        J. Radiol. 2011 Jul-Aug; 92: 714-721
        • Nayil K.
        • Singh S.
        • Makhdoomi R.
        • Ramzan A.
        • Wani A.
        Sellar-suprasellar tuberculomas in children: 2 cases and literature review.
        Pediatr. Neurol. 2011 Jun; 44: 463-466
        • Mageshkumar S.
        • Patil D.V.
        • Philo A.J.
        • Madhavan K.
        Hypopituitarism as unusual sequelae to central nervous system tuberculosis.
        Indian J Endocrinol. Metab. 2011 Sep; 15: S259-S262
        • Ranjan R.
        • Agarwal P.
        • Ranjan S.
        Primary pituitary tubercular abscess mimicking as pituitary adenoma.
        Indian J Endocrinol. Metab. 2011 Sep; 15: S263-S266
        • Verma R.
        • Patil T.B.
        • Lalla R.
        Pituitary apoplexy syndrome as the manifestation of intracranial tuberculoma.
        BMJ Case Rep. 2014; 2014 (bcr2013201272)
        • Tanimoto K.
        • Imbe A.
        • Shishikura K.
        • Imbe H.
        • Hiraiwa T.
        • Miyata T.
        • Ikeda N.
        • Kuroiwa T.
        • Terasaki J.
        • Hanafusa T.
        Reversible hypopituitarism with pituitary tuberculoma.
        Intern. Med. 2015; 54: 1247-1251
        • Djoubairou B.O.
        • Gazzaz M.
        • Hammi S.
        • Bouya S.M.
        • Salami M.
        • El Mostarchid B.
        Panhypopituitarism revealing sellar tuberculoma.
        Ann. Endocrinol. (Paris). 2015 Jul; 76: 286-288
        • Joshi V.P.
        • Agrawal A.
        • Mudkanna A.
        • Rudrakshi S.S.
        • Kelkar G.P.
        Supra-sellar tubercular abscess.
        Asian J. Neurosurg. 2016 Apr-Jun; 11: 175-176
        • Srisukh S.
        • Tanpaibule T.
        • Kiertiburanakul S.
        • Boongird A.
        • Wattanatranon D.
        • Panyaping T.
        • Sriphrapradang C.
        Pituitary tuberculoma: a consideration in the differential diagnosis in a patient manifesting with pituitary apoplexy-likesyndrome.
        IDCases. 2016 Jul 29; 5: 63-66
        • Arunkumar M.J.
        • Rajshekhar V.
        Intrasellar tuberculoma presenting as pituitary apoplexy.
        Neurol. India. 2001 Dec; 49: 407-410
        • Deogaonkar M.
        • De R.
        • Sil K.
        • Das S.
        Pituitary tuberculosis presenting as pituitary apoplexy.
        Int. J. Infect. Dis. 2006 Jul; 10: 338-339
        • Asherson R.A.
        • Jackson W.P.
        • Lewis B.
        Abnormalities of development associated with hypothalamic calcification after tuberculous meningitis.
        Br. Med. J. 1965; 2: 839-843
        • Lam K.S.
        • Sham M.M.
        • Tam S.C.
        • Ng M.M.
        • Ma H.T.
        Hypopituitarism after tuberculous meningitis in childhood.
        Ann. Intern. Med. 1993 May 1; 118: 701-706
        • Haslam R.H.A.
        • Winternitz W.W.
        • Howieson J.
        Selective hypopituitarism following tuberculous meningitis.
        Am. J. Dis. Child. 1969; 118: 903-908
        • Oelkers W.
        Adrenal insufficiency.
        N. Engl. J. Med. 1996 Oct 17; 335: 1206-1212
        • Arlt W.
        The approach to the adult with newly diagnosed adrenal insufficiency.
        J. Clin. Endocrinol. Metab. 2009 Apr; 94: 1059-1067
        • Marik P.E.
        • Zaloga G.P.
        Adrenal insufficiency in the critically ill: a new look at an old problem.
        Chest. 2002 Nov; 122: 1784-1796
        • Gonzalez H.
        • Nardi O.
        • Annane D.
        Relative adrenal failure in the ICU: an identifiable problem requiring treatment.
        Crit. Care Clin. 2006 Jan; 22 (vii): 105-118
        • Marik P.E.
        • Kiminyo K.
        • Zaloga G.P.
        Adrenal insufficiency in critically ill patients with human immunodeficiency virus.
        Crit. Care Med. 2002 Jun; 30: 1267-1273