Previous Article | Next Article 
Journal of Clinical Microbiology, October 2000, p. 3890-3891, Vol. 38, No. 10
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Histoplasmosis of the Thyroid
Luciano Z.
Goldani,1,*
Clóvis
Klock,2
Ada
Diehl,2
Ane C.
Monteiro,3 and
Ana
Luiza
Maia3
Infectious Diseases
Unit,1 Section of
Pathology,2 and Division of
Endocrinology,3 Hospital das Clínicas 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
 |
ABSTRACT |
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 Hashimoto's disease and non-Hodgkin's 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.
 |
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 Hashimoto's disease and
non-Hodgkin's 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 µg/dl
(normal, 4.5 to 11.0 µg/dl); and antimicrosomal antibody titer of
1:102,400. A fine-needle aspirate of the thyroid revealed innumerable
lymphocytes compatible with Hashimoto's disease, and the patient was
started on suppressive levothyroxine therapy (25 µg/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 37.5°C. 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 µg/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 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 patient's 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-Hodgkin's
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.

View larger version (116K):
[in this window]
[in a new window]
|
FIG. 1.
Thyroid aspirate with macrophage containing numerous
blastoconidia of H. capsulatum. Giemsa stain was used.
Original magnification, ×1,000.
|
|
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 (8-10). 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).
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.
 |
ACKNOWLEDGMENTS |
This work was supported in part by FIPE/HCPA, Brazil.
 |
FOOTNOTES |
*
Corresponding author. Mailing address: Serviço de
Medicina Interna, Ramiro Barcelos 2350, 90035-003, Porto Alegre, RS,
Brazil. Fax: 55-51-3168676. E-mail:
Lgoldani{at}vortex.ufrgs.br.
 |
REFERENCES |
| 1.
|
Basgoz, N., and M. N. Swartz.
1996.
Infections of the thyroid gland, p. 1049-1056.
In
L. E. Braverman, and R. D. Utiger (ed.), Werner and Ingbar's the thyroid, 7th ed. Lippincott-Raven, Philadelphia, Pa.
|
| 2.
|
Berger, A. S.,
J. Zonszein,
P. Vilamena, and N. Mittman.
1983.
Infectious diseases of the thyroid gland.
Rev. Infect. Dis.
5:108-115[Medline].
|
| 3.
|
Chan, K. S.,
M. Looi, and S. P. Chan.
1993.
Disseminated histoplasmosis mimicking miliary tuberculosis: a case report.
Malays. J. Pathol.
15:155-158[Medline].
|
| 4.
|
Goodwin, R. A.,
J. L. Shapiro,
G. H. Thurman,
S. S. Thurman, and R. M. De Prez.
1980.
Disseminated histoplasmosis: clinical and pathologic correlations.
Medicine
59:1-33[Medline].
|
| 5.
|
Halazun, J. F.,
C. S. Anast, and J. N. Lukens.
1972.
Thyrotoxicosis associated with Aspergillus thyroiditis in chronic granulomatous disease.
J. Pediatr.
80:106-108[CrossRef][Medline].
|
| 6.
|
Hazard, J.
1995.
Thyroiditis: a review.
Am. J. Clin. Pathol.
25:289-298.
|
| 7.
|
Klatt, E. C.,
M. Cosgrove, and P. R. Meyer.
1986.
Rapid diagnosis of disseminated histoplasmosis in tissues.
Arch. Pathol. Lab. Med.
11:1173-1175.
|
| 8.
|
Robinson, M. F.,
W. R. Forgan-Smith, and P. W. Craswell.
1975.
Candida thyroiditis treated with 5'fluorocytosine.
Aust. N.Z. J. Med.
5:472-474[Medline].
|
| 9.
|
Rosen, F.,
J. H. Deck, and N. B. Rewcastle.
1965.
Allescheria boydii unique systemic dissemination to thyroid and brain.
Can. Med. Assoc. J.
93:1125-1127.
|
| 10.
|
Smilack, J. D., and R. Argueta.
1998.
Coccidioidal infection of the thyroid.
Arch. Intern. Med.
158:89-92[Abstract/Free Full Text].
|
| 11.
|
Tomer, Y., and T. F. Davies.
1993.
Infection, thyroid disease, and autoimmunity.
Endocr. Rev.
14:107-120[Abstract/Free Full Text].
|
| 12.
|
Wheat, J.,
G. Sarosi,
D. McKinsey,
R. Hamill,
R. Bradsher,
P. Johnson,
J. Loyd, and C. Kauffman.
2000.
Practice guidelines for the management of patients with histoplasmosis.
Clin. Infect. Dis.
30:688-695[CrossRef][Medline].
|
Journal of Clinical Microbiology, October 2000, p. 3890-3891, Vol. 38, No. 10
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Lionakis, M. S., Samonis, G., Kontoyiannis, D. P.
(2008). Endocrine and Metabolic Manifestations of Invasive Fungal Infections and Systemic Antifungal Treatment. Mayo Clin Proc.
83: 1046-1060
[Abstract]
[Full Text]
-
Saikia, U. N., Jain, D., Joshi, K., Lal, A., Sakhuja, V.
(2007). Disseminated zygomycosis presenting as thyroid abscess in a renal allograft recipient. Nephrol Dial Transplant
22: 641-644
[Full Text]
-
Kauffman, C. A.
(2007). Histoplasmosis: a Clinical and Laboratory Update. Clin. Microbiol. Rev.
20: 115-132
[Abstract]
[Full Text]