Histoplasmosis of the Thyroid

Luciano Z. Goldani, Clvis Klock, Ada Diehl, Ane C.

Monteiro and Ana Luiza Maia
J. Clin. Microbiol. 2000, 38(10):3890.

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JOURNAL OF CLINICAL MICROBIOLOGY, Oct. 2000, p. 38903891

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Copyright 2000, American Society for Microbiology. All Rights Reserved.

Vol. 38, No. 10

Histoplasmosis of the Thyroid

VIS KLOCK,2 ADA DIEHL,2 ANE C. MONTEIRO,3
LUCIANO Z. GOLDANI,1* CLO
3
AND ANA LUIZA MAIA
Infectious Diseases Unit,1 Section of Pathology,2 and Division of Endocrinology,3 Hospital das Clnicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Received 19 May 2000/Returned for modification 10 June 2000/Accepted 1 July 2000

macrophages containing numerous yeast cells consistent with

H. capsulatum (Fig. 1). Immunoperoxidase staining was performed as described previously (7) and identified H. capsulatum in cytological smears. Serologic testing of the patients
serum sample demonstrated immunoglobulin G-type immunodiffusion of H. capsulatum antibody to the M antigen and an H.
capsulatum complement fixation antibody titer of 1:64. An
open biopsy with histopathological examination and immunoperoxidase staining of the cervical lymph node established the
diagnosis of intermediate-grade B-cell non-Hodgkins lymphoma. Cytology of bone marrow aspirate was negative for
malignant cells. Cultures of bone marrow aspirate for bacterial
and fungal organisms were unrevealing. Staging of the lymphoma did not show any involvement outside the cervical
lymph node chain. Oral itraconazole (400 mg/day) and six
cycles of chemotherapy (predisone, cyclophosphamide, vincristine, and doxorubicin) were begun. At a 6-month follow-up
examination, the patient was doing well on suppressive itraconazole therapy (200 mg/day), with no symptoms and with
regression of the thyroid nodule and cervical adenopathy.

CASE REPORT
Infection of the thyroid gland with Histoplasma capsulatum
is rarely reported, even in geographic areas in which histoplasmosis is endemic (1). In fact, there has been only one case
report of disseminated histoplasmosis in which involvement of
the thyroid gland was recognized at autopsy (3).
The present report describes a patient with Hashimotos
disease and non-Hodgkins lymphoma in which H. capsulatum
infection of the thyroid was the first recognized manifestation
of fungal disease.
A 52-year-old, previously healthy woman was seen for evaluation of a thyroid nodule with an elevated thyroid-stimulating
hormone (TSH) level of 8.5 mU/ml (normal, 0.4 to 4.5 mU/
liter), thyroxine (T4), 9.3 g/dl (normal, 4.5 to 11.0 g/dl); and
antimicrosomal antibody titer of 1:102,400. A fine-needle aspirate of the thyroid revealed innumerable lymphocytes compatible with Hashimotos disease, and the patient was started
on suppressive levothyroxine therapy (25 g/day). Approximately 12 months later, the patient started experiencing enlargement of the thyroid gland, a 5-kg weight loss, and generalized weakness. Physical examination revealed she was well
developed. Her temperature was 37.5C. There were multiple
increased cervical lymph nodes with firm consistency. The thyroid gland was soft, nontender, and diffusely enlarged (100 g),
with a large nodule at the right lobe, measuring approximately
8 cm by sonography. The remaining findings of the physical
examination were unremarkable. A complete blood count
showed the following values: hemoglobin, 10.9 g/liter; leukocyte count, 12.4 109/liter; platelet count, 384 109/liter.
Other routine laboratory tests were within normal limits. The
thyroxine (T4) level was 12.4 g/dl, and the TSH level was 7.09
mU/ml. Three sets of blood cultures were negative by the
BACTEC 9240 system (Becton Dickinson, Sparks, Md.) after
6 weeks of incubation, and serology for antibodies to human
immunodeficiency virus was negative. A chest X ray and computed tomography were normal. A fine-needle nodule aspirate
of the thyroid nodule revealed innumerable lymphocytes and

Discussion. Combined bacterial and fungal infection is an

uncommon cause of thyroiditis (1). Most reported cases have
involved Aspergillus species, presumably as part of disseminated disease (5). Isolated reports of thyroid involvement have
been described in the setting of disseminated candidiasis, coccidioidomycosis, and pseudallescheriasis (810). Although H.
capsulatum is mentioned as a rare cause of thyroid involvement
as part of disseminated histoplasmosis (1, 3), there is no reported case of Histoplasma involvement of the thyroid as the
only apparent locus of infection in the English-language literature.
Infection of the thyroid with H. capsulatum in this case was
diagnosed in a patient with a previous goitrous autoimmune
thyroiditis. The most common predisposing condition for thyroid infection appears to be preexisting thyroid disease (1, 11).
Predisposing conditions include simple goiter, nodular goiter,
adenoma, autoimmune thyroiditis, and carcinoma. A predisposing condition is noted in over two-thirds of women and
one-half of men with infections of the thyroid gland (2).

* Corresponding author. Mailing address: Servico de Medicina Interna, Ramiro Barcelos 2350, 90035-003, Porto Alegre, RS, Brazil.
Fax: 55-51-3168676. E-mail: Lgoldani@vortex.ufrgs.br.
3890

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Fungal infection of the thyroid is rare. Most reported cases have involved Aspergillus, Coccidioides, and
Candida species in the setting of disseminated disease. Infection of the thyroid with Histoplasma capsulatum is
rarely reported as part of disseminated disease, even in geographic areas where histoplasmosis is endemic. We
report a 52-year-old woman with a previous Hashimotos disease and non-Hodgkins lymphoma in which a
diffuse enlarged thyroid gland with a large nodule was the only apparent locus of histoplasmosis. Fine-needle
aspiration of the thyroid was an important diagnostic tool in establishing the diagnosis of histoplasmosis of the
thyroid. The patient was initially treated with itraconazole (400 mg/day) for the fungal infection and six cycles
of chemotherapy for the lymphoma. At a 6-month follow-up examination, the patient was doing well on
suppressive therapy of itraconazole (200 mg/day), with no symptoms and with regression of the thyroid nodule
and cervical adenopathy.

VOL. 38, 2000

CASE REPORTS

3891

Fungal infection of the thyroid usually presents with many

characteristics of subacute thyroiditis (6). Histoplasmosis of
the thyroid in this patient did not manifest with the characteristic of subacute thyroiditis. Gradual weight loss and increased
fatigability were constitutional symptoms that could be related
to either Histoplasma infection or lymphoma. Diffuse thyromegaly with a large nodule was the only clinical manifestation
of histoplasmosis in this patient. The diagnosis of histoplasmosis was made unexpectedly by a routine fine-needle aspiration
for evaluation of a thyroid nodule. The Histoplasma was isolated to the thyroid, and there was no symptomatic or clinical
evidence of histoplasmosis in other organs. The present case
appears to represent a chronic progressive disseminated form
of histoplasmosis in which the course of the disease is protracted over months to years with long asymptomatic periods
and terminated by reactivation of endogenous focus of latent
infection and patent expression of disease in mucosa, skin,
adrenals, gastrointestinal tract, meninges, and heart valves (4).
People who are immunocompromised and reside or lived in
regions of endemicity, such as the southern region of Brazil,
are susceptible to this clinical form of histoplasmosis.
Oral itraconazole is effective for mild or moderately severe
clinical forms of histoplasmosis (12). The introduction of azole
agents such as itraconazole has moved the treatment of histoplasmosis from an inpatient to an outpatient setting. However, in severe histoplasmosis, amphotericin B is the preferred
agent. Chronic suppressive therapy with itraconazole should be
considered for those patients who might remain on immunosuppressive therapy.
In summary, we report the first case of histoplasmosis in an
immunocompromised patient with a previous autoimmune

thyroiditis in which the thyroid gland was the only apparent

locus of infection. Fine-needle aspiration of the thyroid was an
important diagnostic tool in establishing the diagnosis of histoplasmosis of the thyroid.
This work was supported in part by FIPE/HCPA, Brazil.
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FIG. 1. Thyroid aspirate with macrophage containing numerous blastoconidia of H. capsulatum. Giemsa stain was used. Original magnification, 1,000.