Common subclinical hypothyroidism during Whipple's disease

Abstract

Background: Classic Whipple's disease is caused by T. whipplei and likely involves genetic predispositions, such as the HLA alleles DRB1*13 and DQB1*06, that are more frequently observed in patients. T. whipplei carriage occurs in 2-4% of the general population in France. Subclinical hypothyroidism, characterized by high levels of TSH and normal free tetra-iodothyronine (fT4) dosage, has been rarely associated with specific HLA factors.

Methods: We retrospectively tested TSHus in 80 patients and 42 carriers. In cases of dysthyroidism, we tested the levels of free-T4 and anti-thyroid antibodies, and the HLA genotypes were also determined for seven to eight patients.

Results: In this study, 72-74% of patients and carriers were male, and among the 80 patients, 14 (17%) individuals had a high level of TSH, whereas none of the carriers did (p<0. 01). In the 14 patients with no clinical manifestations, the T4 levels were normal, and no specific antibodies were present. Four patients treated with antibiotics, without thyroxine supplementation, showed normal levels of TSHus after one or two years. One patient displayed a second episode of subclinical hypothyroidism during a Whipple's disease relapse five years later, but the subclinical hypothyroidism regressed after antibiotic treatment. HLA typing revealed nine alleles that appeared more frequently in patients than in the control cohort, but none of these differences reached significance due to the small size of the patient group.

Conclusion: Regardless of the substratum, classic Whipple's disease could lead to subclinical hypothyroidism. We recommend systematically testing the TSH levels in patients with Whipple's disease.

Figure 1

Time evolution of the TSH levels in four patients with CWD treated with antibiotics, without thyroxin supplementation.

Figure 2

TSH levels in the CWD and asymptomatic carrier groups. The difference between the two groups is significant (P < 0.001).

Figure 3

Histological assessment of a duodenal biopsy with positive periodic acid-Schiff staining (A) and positive immunohistochemical staining with polyclonal rabbit anti-T. whipplei antibody and Mayer’s haemalum counterstain (B).