High Frequency of Thyroid Disorders in Patients Presenting With Neutropenia to an Outpatient Hematology Clinic STROBE-Compliant Article

Abstract

Granulopoiesis abnormalities have been described in association with thyroid disorders (TD). However, data regarding systematic evaluation of adult neutropenia and concurrent or prior TD are scarce. To investigate the frequency of TD among patients presenting with neutropenia, and the immunophenotypic and immunologic profile of neutropenic patients with concomitant thyroidopathy. Two hundred eighteen consecutive neutropenic patients were prospectively evaluated in our outpatient Hematology Clinic, with a detailed laboratory screen, including thyroid function tests, antineutrophil antibodies, blood lymphocytes immunophenotyping, and detection of T-cell clonality by PCR. Among 218 patients with neutropenia, 95 (43.6%) had TD, 65 chronic immunologic neutropenia, 20 clonal proliferation of T-large granular lymphocytes (T-LGL), 5 autoimmune disorders, and 33 other diagnoses. TD-patients had an increased frequency of recurrent infections compared with other patients (P = 0.045). The following correlations were found: negative correlation between FT3 and absolute neutrophil count (ANC) (r² = -0.274, P = 0.007), negative correlation between TPO-Abs/TG-Abs and C4 (r² = -0.16, P = 0.045; r² = -0.266, P = 0.001), and CD4⁺ counts were inversely correlated to T4 and positively to TSH (r² = -0.274, P = 0.024; r² = 0.16, P = 0.045). In addition, TD-patients had significantly higher percentages of CD4⁺ lymphocytes (P = 0.003). Among TD-patients, 23.4% had Hashimoto thyroiditis (HT), 4.1%, Graves disease (GD), 8.2% nontoxic multinodular goiter (NTMG), 5% subclinical hypothyroidism, and 2.8% had undergone total thyroidectomy associated with nodules (TTM). Thirteen TD-patients displayed T-LGL. Patients with autoimmune thyroidopathy had an increased frequency of concomitant autoimmune manifestations (P = 0.03). Significant differences between the different thyroidopathies included: HT-patients had higher percentages of B-lymphocytes, while the opposite was evident for the TTM-subgroup (P = 0.009, 0.02); GD-patients showed an increase of the proportion of NK cells and a decrease in the percentage of TCRγδ+ lymphocytes (P = 0.001, 0.045); and NTMG-patients had significantly higher ANC (P = 0.004) compared to other thyroidopathies. Antineutrophil antibodies were found in 37.2% of TD-patients tested. Anti-TPO titers were significantly higher in patients with positive antineutrophil antibodies (P = 0.04). The frequency of TD among neutropenic patients may be higher than previously reported. The existence of antineutrophil antibodies, as well as the different distribution of lymphocyte subsets among patients with different TD, suggests both humoral and cellular mechanisms in the pathophysiology of thyroid disease-associated neutropenia.

FIGURE 1

(A) Negative correlation between FT3 levels and absolute neutrophil counts (r² = −0.274, P = 0.007). (B) Positive correlation between TSH levels and absolute CD4⁺ counts (×10⁹/L), (r² = −0.16, P = 0.045). (C) Negative correlation between T4 levels and absolute CD4⁺ counts (×10⁹/L), (r² = −0.274, P = 0.024). FT3 = free triiodothyronine, T4 = thyroxine (total), TSH = thyroid-stimulating hormone, PMN = polymorphonuclear/neutrophil cells (absolute counts), CD4⁺ = subsets of T lymphocytes (absolute counts).

FIGURE 2

Anti-TPO Abs titers were significantly higher in patients, who had positive Anti-PMN Abs, compared with patients with negative Anti-PMN Abs tests (P = 0.04). Anti-PMN Abs = antineutrophil (antipolymorphonuclear) antibodies, Anti-TPO = antithyroid peroxidase antibodies, IQR = interquartile range.