title: A Cohort Historical Analysis of the Relationship between Thyroid Hormone Malady and Alpha-Human Herpesvirus Activation.
abstract: BACKGROUND
  A number of physiological factors have been suggested to participate in the alpha- Human Herpesvirus (αHHV) reactivation, such as hormonal aberration. Thyroid hormone (TH) was shown to play a suppressive role in Herpes Simplex Virus Type-1 (HSV-1) gene expression and replication in cell culture and animal models. We hypothesize that reactivation of αHHV in humans may be due to, at least in part, by TH status.
  
  
  METHODS
  Prior to implementing a full-scale population-based prospective inquiry into this hypothesis, a pilot study using a medical claims data base and a case-controlled, retrospective cohort investigation was conducted to develop a hypothetical link between TH complication and αHHV reactivation. Using diagnostic codes for treating thyroid disorders and αHHV infections as proxies for biologic/clinic outcomes, we queried a large, comprehensive hospital data base to construct two patient cohorts: Cohort 1 was comprised of patients receiving TH diagnoses over a twelve-year period, and Cohort 2 was composed of patients not receiving TH diagnoses during this period. Diagnoses of αHHV were recorded for each cohort and the difference in the frequency was examined for statistical significance. Demographic analyses such as age, gender, etc were also performed.
  
  
  RESULTS
  Using 2×2 contingency table analyses and Statistical Analysis Software (SAS), an Odds Ratio (OR) of 2.83 was observed for the total population of 21 years old and above with a chi-square of 61.55 and p < 0.001, confirming that a severe significant difference was found between these two cohorts. This result suggested that patients with αHHV diagnosis have higher chances to have TH disorders. Additional investigation revealed that female were at higher/significant probability to have both TH and αHHV diagnosis, indicating a link of αHHV reactivation to a complex hormonal profile difference between genders. Our observation indicated that female patients of 21 years of age and above exhibited a very high incidence (OR of 3.40, p < 0.001) compared to the male groups (OR of 1.91, p < 0.05), indicating the possibility that hormonal alteration in females maybe transient but robust and can lead to αHHV reactivation more often than the males.
  
  
  CONCLUSIONS
  These results indicated that TH dysfunction may have implication in αHHV pathogenesis and females exhibited much higher probability to suffer αHHV reactivation due to TH disruption. Although the results from this pilot study have limitations and require additional controlled clinical examination such as more detailed patient records, lab data, therapeutic outcome, etc, it provides a tool to assess the effects of hormone imbalance on virus reactivation by retrospective analyses using existing large scale data base.
authors.affiliation: Department of Pediatrics, Division of Pediatric Critical Care Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang-Gung University, Kweishan, Taiwan.
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Hsia
authors.affiliation: School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Hsia S
keywords: HSV-1; ICD-9 diagnostic codes; Medical claims; Odds ratio; Retrospective study; Risk ratio; Thyroid Hormone; Viral reactivation; αHHV
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