title: High rate of hypothyroidism in multidrug-resistant tuberculosis patients co-infected with HIV in Mumbai, India.
abstract: BACKGROUND
  Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients.
  
  
  METHODS
  This was a prospective, observational cohort study, using routine laboratory data in a Médecins Sans Frontières (MSF) clinic in collaboration with Sewri TB Hospital, Mumbai, India. Hypothyroidism was defined as a thyroid stimulating hormone (TSH) result >10 mIU/L at least once during treatment. Patients having a baseline result and one additional result after 3 months were eligible for enrolment.
  
  
  RESULTS
  Between October 2006 and March 2013, 116 patients were enrolled, 69 of whom were included. The median (IQR) age was 38 years (34-43) and 61% were male. By March 2013, 37/69 (54%) had hypothyroidism after at least 90 days of treatment. Age, gender, CD4 counts and stavudine-based ART were not associated with the occurrence of hypothyroidism in multivariate models. The co-administration of PAS and ethionamide was found to double the risk of hypothyroidism (RR: 1.93, 95% CI: 1.06-3.54).
  
  
  CONCLUSIONS
  High rate of hypothyroidism was recorded in a Mumbai cohort of MDR-TB/HIV co-infected patients on treatment. This is a treatable and reversible AE, however, it may go undiagnosed in the absence of regular monitoring. Care providers should not wait for clinical symptoms, as this risks compromising treatment adherence. Simple, affordable and reliable point-of-care tools for measuring TSH are needed, especially in high MDR-TB burden countries. Our findings suggest the need for TSH screening at baseline, three months, six months, and every six months thereafter for HIV-infected patients on MDR-TB treatment regimens containing PAS and/or ethionamide, until newer, safer and more efficacious MDR-TB regimens become available.
authors.affiliation: Médecins sans Frontières, Mumbai, India.
authors.forename: Aristomo
authors.initials: A
authors.lastname: Andries
authors.forename: Petros
authors.initials: P
authors.lastname: Isaakidis
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Das
authors.forename: Samsuddin
authors.initials: S
authors.lastname: Khan
authors.forename: Roma
authors.initials: R
authors.lastname: Paryani
authors.forename: Chitranjan
authors.initials: C
authors.lastname: Desai
authors.forename: Alpa
authors.initials: A
authors.lastname: Dalal
authors.forename: Homa
authors.initials: H
authors.lastname: Mansoor
authors.forename: Reena
authors.initials: R
authors.lastname: Verma
authors.forename: Dolorosa
authors.initials: D
authors.lastname: Fernandes
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Migliori
authors.forename: Peter
authors.initials: P
authors.lastname: Saranchuk
mesh_terms: D000328:Adult; D010131:Aminosalicylic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy; D005000:Ethionamide / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced* / Q000453:epidemiology*; D015994:Incidence; D007194:India / Q000453:epidemiology; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D018119:Stavudine / Q000009:adverse effects* / Q000627:therapeutic use; D013972:Thyrotropin / Q000097:blood; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D010131:Aminosalicylic Acid; D013972:Thyrotropin; D018119:Stavudine; D005000:Ethionamide