0021-972X/91/7203-0724$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1991 by The Endocrine Society
Vol. 72, No. 3 Printed in U.S.A.
Pneumocystis Carinii Infection of the Thyroid in a Hypothyroid Patient with AIDS: Diagnosis by Fine Needle Aspiration Biopsy* RUGGERO BATTAN*, PETER MARIUZt, MARIO C. RAVIGLIONE$, MARIA T. SABATINI, MICHAEL P. MULLEN, AND LEONID PORETSKY Departments of Medicine and Pathology (M.T.S.), Cabrini Medical Center, New York, New York 10003; and New York Medical College, Valhalla, New York 10595
ABSTRACT. A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver stain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A re-
P
peated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of Tiypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients. (J Clin Endocrinol Metab 72: 724-726, 1991)
ager. He had no previous history of thyroid disease and denied having heat or cold intolerance, palpitations, diarrhea or constipation, or any other symptoms suggestive of hyper- or hypothyroidism. There was no family history of thyroid disorder. During the last 2 yr he had been working and feeling well. He was receiving prophylactic aerosolized pentamidine (300 mg monthly) via Respigard II nebulizer and oral ketoconazole (200 mg daily). Zidovudine and acyclovir had been discontinued 2 months earlier because of anemia. Physical examination revealed a clinically euthyroid patient with a goiter. Both thyroid lobes were enlarged, with the left lobe approximately twice the size of the right lobe. The left lobe had a nodular surface and was firm and nontender. The right lobe appeared homogenous on palpation. The initial serum T4 level was 58 nmol/L (normal, 58-160 nmol/L), free T4 (hy RIA) was 9 pmol/L (normal, 11-28 pmol/ L), the thyroid hormone binding index was 0.24 (normal, 0.250.35), and the TSH level was 14.7 mU/L (normal, 0.4-6.0 mU/ L). Serum cholesterol was 3.46 mmol/L, and creatine kinase was 183 U/L (normal, 0-218). An 123I radionuclide thyroid scan revealed no uptake in the left lobe and homogeneous uptake in an enlarged right lobe (Fig. 1A); the 24-h 123I uptake was 7.5% (normal, 10-40%). A sonogram showed thyroid enlargement (left lobe measuring 5.7 x 3.5 x 5.4 cm; right lobe measuring 4.3 X 3.0 x 3.0 cm) with a heterogeneous echogenic pattern. Papanicolau stain smear of a specimen obtained from the left thyroid mass with fine needle aspiration biopsy (FNAB) showed scattered follicular cells on
NEUMOCYSTIS carinii (P. carinii) pneumonia is the most frequent life-threatening opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), occurring in up to 80% of them (1). While the overwhelming majority of infections with P. carinii involve the lungs, extrapulmonary pneumocystosis has been reported more frequently in recent years (2-6). We present a unique case of pneumocystosis of the thyroid with hypothyroidism in a patient with AIDS.
Case Report A 49-yr-old white homosexual man presented with a leftsided neck mass. His past medical history was significant for one episode of P. carinii pneumonia 2 yr earlier, oral thrush, amoebic dysentery, and posttraumatic splenectomy as a teenReceived July 19,1990. Address all correspondence and requests for reprints to: Dr. Leonid Poretsky, Division of Endocrinology, Cabrini Medical Center, 227 East 19th Street, New York, New York 10003. * This work was supported by NIH Grant HD-22738 and the Roberto Pope Research Fund at Cabrini Medical Center. t Current address: Division of Endocrinology and Diabetes, University of Massachusetts Medical Center, Worcester, Massachusetts 01655. $ Current address: Division of Infectious Diseases, State University of New York, Stony Brook, New York 11794. § Current address: Division of Infectious Diseases, Beth Israel Hospital, Boston, Massachusetts 02215.
724
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 23:04 For personal use only. No other uses without permission. . All rights reserved.
P. CARINII INFECTION OF THE THYROID
725
FIG. 1. 123I scan of the thyroid before (A) and after (B) treatment with trimethoprim-sulfamethoxazole.
t'
a background of diffuse foamy exudate. Gomori's methenamine silver stain subsequently revealed P. carinii organisms (Fig. 2). The patient was treated with oral levothyroxine (100 ng daily) and a 2-week course of iv trimethoprim (320 mg)-sulfamethoxazole (1600 mg) every 6 h, followed by oral trimethoprim (160 mg)-sulfamethoxazole (800 mg) every 12 h. The goiter
decreased in size, and a TSH level measured after 3 weeks of hormone replacement therapy was 7.2 mU/L (normal, 0.4-6.0 mU/L). Assays for antimicrosomal and antithyroglobulin antibodies were negative. A second thyroid FNAB performed 50 days after presentation showed an absence of P. carinii organisms on the left side. The specimen from the right thyroid lobe revealed foamy exudate with rare P. carinii organisms. Oral trimethoprimsulfamethoxazole was increased to 240/1200 mg every 6 h. After a month of this therapy a third FNAB did not reveal any P. carinii organisms. Levothyroxine was discontinued so that thyroid function could be reevaluated. Four weeks later, thyroid function tests showed a T4 level of 38 nmol/L, a thyroid hormone binding index of 0.23, and a TSH level of 73 mU/L. A second 123I thyroid scan showed a 24-h uptake of 18%, with reappearance of the isotope in the left lobe (Fig. IB). Replacement therapy with 150 Mg levothyroxine daily was resumed, and trimethoprim (160 mg)-sulfamethoxazole (800 mg) was continued orally twice a day. Two weeks after reinstitution of oral levothyroxine, TSH was found to be normal (2.1 mU/L).
Discussion
FIG. 2. Microphotograph of FNAB from the left thyroid lobe. Gomori's methenamine silver stain. A, P. carinii organisms within foamy exudate. Note the absence of inflammatory reaction. Original magnification, X480. B, A single typical P. carinii cyst surrounded by foamy exudate. Original magnification, X1200.
To date this is the third report of isolated P. carinii infection of the thyroid observed in a patient infected with human immunodeficiency virus (4, 6). Six more cases of thyroid involvement with this organism were also reported at autopsy in patients with AIDS (3, 7-10) and one in a patient with thymic alymphoplasia (11). However, in these seven individuals thyroid infestation with P. carinii was found after their death, and the thyroid was only one of many organs infested. Gallant et al. (6) described a euthyroid patient with AIDS presenting with a thyroid mass which failed to accumulate the iodine isotope. That patient was found to have P. carinii infection of the thyroid. Our patient presented in a similar way, but was found to be hypothyroid. Coincidental idiopathic hypothyroidism is difficult to
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 23:04 For personal use only. No other uses without permission. . All rights reserved.
726
BATTON ET AL.
exclude entirely. However, the return of 123I uptake in the left thyroid lobe, indicating partial recovery of thyroid function after treatment with trimethoprim-sulfamethoxazole, suggests that P. carinii infection was indeed responsible for this patient's hypothyroid state. This notion is further supported by the fact that the infection was multifocal (FNAB identified the organism in both thyroid lobes). The organism seems to have been eradicated from the thyroid with trimethoprim-sulfamethoxazole treatment, and a euthyroid state was restored with oral T4 replacement. At the present time, however, we cannot predict whether this patient's thyroid abnormalities will regress completely. All attempts to discontinue thyroid hormone replacement so far resulted in the elevation of TSH, proving that the patient is still hypothyroid even though
no P. carinii organisms were found on FNAB at this time. We chose to maintain the patient on long term trimethoprim-sulfamethoxazole therapy because aerosolized pentamidine proved ineffective in preventing extrapulmonary pneumocystosis. In an extensive review of thyroid infections from 1900 to 1983 (12), de novo hypothyroidism was documented in only a minority of patients with bacterial thyroiditis. We were unable to find any information regarding thyroid function in patients with parasitic or fungal infections. Our patient, however, appears to have developed hypothyroidism due to infection with an opportunistic organism. Based on this case, we think that P. carinii and other opportunistic infections should be considered in the differential diagnosis of human immunodeficiency virus-
JCE & M • 1991 Vol 72 • No 3
infected individuals presenting with cold thyroid nodules. FNAB is a valuable tool in assessing these patients; specific stains for opportunistic pathogens should be used when evaluating thyroid aspirates from patients with AIDS.
References 1. Masur H, Lane CH, Kovacs JA, Allegra CJ, Edman JC. Pneumocystis pneumonia: from bench to clinic. Ann Intern Med. 1989;lll:8l3-26. 2. Hardy WD, Northfeld DW, Drake TA. Fatal disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine. Am J Med. 1989;87:329-31. 3. Raviglione MC. Extrapulmonary pneumocystosis. The first 50 cases. Rev Infect Dis. 1990;12:1127-38. 4. Spouge AR, Wilson SR, Gopinath N, Sherman M, Blendis LM. "Sparkling" echogenicity. A distinctive sonographic appearance of extrapulmonary Pneumocystis carinii. J Clin Endocrinol Metab. In Press. 5. Poretsky L, Maran A, Zumoff B. Endocrinological and metabolic manifestations of AIDS. Mt Sinai J Med. 1990;57:236-41. 6. Gallant JE, Enriquez RE, Cohen KL, Hammers LW. Pneumocystis carinii thyroiditis. Am J Med. 1988;84:303-6. 7. Macher AM, Bardenstein DS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection [Letter]. N Engl J Med. 1987;316:1092. 8. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic and electron microscopy study of Pneumocystis carinii choroiditis. Am J Ophthalmol. 1989;107:218-28. 9. Davey Jr RT, Margolis D, Kleiner D, Deyton L, Travis W. Digital necrosis and disseminated Pneumocystis carinii infection after aerosolized pentamidine prophylaxis. Ann Intern Med. 1989;lll:681-2. 10. Ravalli S, Garcia RL, Vincent RA, Shein R. Disseminated Pneumocystis carinii in the acquired immunodeficiency syndrome. NY State J Med. 1990;90:155-7. 11. Rahimi SA. Disseminated Pneumocystis carinii in thymic alymphoplasia. Arch Pathol. 1974;97:162-5. 12. Berger SA, Zonszein J, Villamena P, Mittman N. Infectious diseases of the thyroid gland. Rev Infect Dis. 1983;5:108-22.
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Vol. 72, No. 3 Printed in U.S.A.
Pneumocystis Carinii Infection of the Thyroid in a Hypothyroid Patient with AIDS: Diagnosis by Fine Needle Aspiration Biopsy* RUGGERO BATTAN*, PETER MARIUZt, MARIO C. RAVIGLIONE$, MARIA T. SABATINI, MICHAEL P. MULLEN, AND LEONID PORETSKY Departments of Medicine and Pathology (M.T.S.), Cabrini Medical Center, New York, New York 10003; and New York Medical College, Valhalla, New York 10595
ABSTRACT. A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver stain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A re-
P
peated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of Tiypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients. (J Clin Endocrinol Metab 72: 724-726, 1991)
ager. He had no previous history of thyroid disease and denied having heat or cold intolerance, palpitations, diarrhea or constipation, or any other symptoms suggestive of hyper- or hypothyroidism. There was no family history of thyroid disorder. During the last 2 yr he had been working and feeling well. He was receiving prophylactic aerosolized pentamidine (300 mg monthly) via Respigard II nebulizer and oral ketoconazole (200 mg daily). Zidovudine and acyclovir had been discontinued 2 months earlier because of anemia. Physical examination revealed a clinically euthyroid patient with a goiter. Both thyroid lobes were enlarged, with the left lobe approximately twice the size of the right lobe. The left lobe had a nodular surface and was firm and nontender. The right lobe appeared homogenous on palpation. The initial serum T4 level was 58 nmol/L (normal, 58-160 nmol/L), free T4 (hy RIA) was 9 pmol/L (normal, 11-28 pmol/ L), the thyroid hormone binding index was 0.24 (normal, 0.250.35), and the TSH level was 14.7 mU/L (normal, 0.4-6.0 mU/ L). Serum cholesterol was 3.46 mmol/L, and creatine kinase was 183 U/L (normal, 0-218). An 123I radionuclide thyroid scan revealed no uptake in the left lobe and homogeneous uptake in an enlarged right lobe (Fig. 1A); the 24-h 123I uptake was 7.5% (normal, 10-40%). A sonogram showed thyroid enlargement (left lobe measuring 5.7 x 3.5 x 5.4 cm; right lobe measuring 4.3 X 3.0 x 3.0 cm) with a heterogeneous echogenic pattern. Papanicolau stain smear of a specimen obtained from the left thyroid mass with fine needle aspiration biopsy (FNAB) showed scattered follicular cells on
NEUMOCYSTIS carinii (P. carinii) pneumonia is the most frequent life-threatening opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), occurring in up to 80% of them (1). While the overwhelming majority of infections with P. carinii involve the lungs, extrapulmonary pneumocystosis has been reported more frequently in recent years (2-6). We present a unique case of pneumocystosis of the thyroid with hypothyroidism in a patient with AIDS.
Case Report A 49-yr-old white homosexual man presented with a leftsided neck mass. His past medical history was significant for one episode of P. carinii pneumonia 2 yr earlier, oral thrush, amoebic dysentery, and posttraumatic splenectomy as a teenReceived July 19,1990. Address all correspondence and requests for reprints to: Dr. Leonid Poretsky, Division of Endocrinology, Cabrini Medical Center, 227 East 19th Street, New York, New York 10003. * This work was supported by NIH Grant HD-22738 and the Roberto Pope Research Fund at Cabrini Medical Center. t Current address: Division of Endocrinology and Diabetes, University of Massachusetts Medical Center, Worcester, Massachusetts 01655. $ Current address: Division of Infectious Diseases, State University of New York, Stony Brook, New York 11794. § Current address: Division of Infectious Diseases, Beth Israel Hospital, Boston, Massachusetts 02215.
724
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 23:04 For personal use only. No other uses without permission. . All rights reserved.
P. CARINII INFECTION OF THE THYROID
725
FIG. 1. 123I scan of the thyroid before (A) and after (B) treatment with trimethoprim-sulfamethoxazole.
t'
a background of diffuse foamy exudate. Gomori's methenamine silver stain subsequently revealed P. carinii organisms (Fig. 2). The patient was treated with oral levothyroxine (100 ng daily) and a 2-week course of iv trimethoprim (320 mg)-sulfamethoxazole (1600 mg) every 6 h, followed by oral trimethoprim (160 mg)-sulfamethoxazole (800 mg) every 12 h. The goiter
decreased in size, and a TSH level measured after 3 weeks of hormone replacement therapy was 7.2 mU/L (normal, 0.4-6.0 mU/L). Assays for antimicrosomal and antithyroglobulin antibodies were negative. A second thyroid FNAB performed 50 days after presentation showed an absence of P. carinii organisms on the left side. The specimen from the right thyroid lobe revealed foamy exudate with rare P. carinii organisms. Oral trimethoprimsulfamethoxazole was increased to 240/1200 mg every 6 h. After a month of this therapy a third FNAB did not reveal any P. carinii organisms. Levothyroxine was discontinued so that thyroid function could be reevaluated. Four weeks later, thyroid function tests showed a T4 level of 38 nmol/L, a thyroid hormone binding index of 0.23, and a TSH level of 73 mU/L. A second 123I thyroid scan showed a 24-h uptake of 18%, with reappearance of the isotope in the left lobe (Fig. IB). Replacement therapy with 150 Mg levothyroxine daily was resumed, and trimethoprim (160 mg)-sulfamethoxazole (800 mg) was continued orally twice a day. Two weeks after reinstitution of oral levothyroxine, TSH was found to be normal (2.1 mU/L).
Discussion
FIG. 2. Microphotograph of FNAB from the left thyroid lobe. Gomori's methenamine silver stain. A, P. carinii organisms within foamy exudate. Note the absence of inflammatory reaction. Original magnification, X480. B, A single typical P. carinii cyst surrounded by foamy exudate. Original magnification, X1200.
To date this is the third report of isolated P. carinii infection of the thyroid observed in a patient infected with human immunodeficiency virus (4, 6). Six more cases of thyroid involvement with this organism were also reported at autopsy in patients with AIDS (3, 7-10) and one in a patient with thymic alymphoplasia (11). However, in these seven individuals thyroid infestation with P. carinii was found after their death, and the thyroid was only one of many organs infested. Gallant et al. (6) described a euthyroid patient with AIDS presenting with a thyroid mass which failed to accumulate the iodine isotope. That patient was found to have P. carinii infection of the thyroid. Our patient presented in a similar way, but was found to be hypothyroid. Coincidental idiopathic hypothyroidism is difficult to
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 23:04 For personal use only. No other uses without permission. . All rights reserved.
726
BATTON ET AL.
exclude entirely. However, the return of 123I uptake in the left thyroid lobe, indicating partial recovery of thyroid function after treatment with trimethoprim-sulfamethoxazole, suggests that P. carinii infection was indeed responsible for this patient's hypothyroid state. This notion is further supported by the fact that the infection was multifocal (FNAB identified the organism in both thyroid lobes). The organism seems to have been eradicated from the thyroid with trimethoprim-sulfamethoxazole treatment, and a euthyroid state was restored with oral T4 replacement. At the present time, however, we cannot predict whether this patient's thyroid abnormalities will regress completely. All attempts to discontinue thyroid hormone replacement so far resulted in the elevation of TSH, proving that the patient is still hypothyroid even though
no P. carinii organisms were found on FNAB at this time. We chose to maintain the patient on long term trimethoprim-sulfamethoxazole therapy because aerosolized pentamidine proved ineffective in preventing extrapulmonary pneumocystosis. In an extensive review of thyroid infections from 1900 to 1983 (12), de novo hypothyroidism was documented in only a minority of patients with bacterial thyroiditis. We were unable to find any information regarding thyroid function in patients with parasitic or fungal infections. Our patient, however, appears to have developed hypothyroidism due to infection with an opportunistic organism. Based on this case, we think that P. carinii and other opportunistic infections should be considered in the differential diagnosis of human immunodeficiency virus-
JCE & M • 1991 Vol 72 • No 3
infected individuals presenting with cold thyroid nodules. FNAB is a valuable tool in assessing these patients; specific stains for opportunistic pathogens should be used when evaluating thyroid aspirates from patients with AIDS.
References 1. Masur H, Lane CH, Kovacs JA, Allegra CJ, Edman JC. Pneumocystis pneumonia: from bench to clinic. Ann Intern Med. 1989;lll:8l3-26. 2. Hardy WD, Northfeld DW, Drake TA. Fatal disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine. Am J Med. 1989;87:329-31. 3. Raviglione MC. Extrapulmonary pneumocystosis. The first 50 cases. Rev Infect Dis. 1990;12:1127-38. 4. Spouge AR, Wilson SR, Gopinath N, Sherman M, Blendis LM. "Sparkling" echogenicity. A distinctive sonographic appearance of extrapulmonary Pneumocystis carinii. J Clin Endocrinol Metab. In Press. 5. Poretsky L, Maran A, Zumoff B. Endocrinological and metabolic manifestations of AIDS. Mt Sinai J Med. 1990;57:236-41. 6. Gallant JE, Enriquez RE, Cohen KL, Hammers LW. Pneumocystis carinii thyroiditis. Am J Med. 1988;84:303-6. 7. Macher AM, Bardenstein DS, Zimmerman LE, et al. Pneumocystis carinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection [Letter]. N Engl J Med. 1987;316:1092. 8. Rao NA, Zimmerman PL, Boyer D, et al. A clinical, histopathologic and electron microscopy study of Pneumocystis carinii choroiditis. Am J Ophthalmol. 1989;107:218-28. 9. Davey Jr RT, Margolis D, Kleiner D, Deyton L, Travis W. Digital necrosis and disseminated Pneumocystis carinii infection after aerosolized pentamidine prophylaxis. Ann Intern Med. 1989;lll:681-2. 10. Ravalli S, Garcia RL, Vincent RA, Shein R. Disseminated Pneumocystis carinii in the acquired immunodeficiency syndrome. NY State J Med. 1990;90:155-7. 11. Rahimi SA. Disseminated Pneumocystis carinii in thymic alymphoplasia. Arch Pathol. 1974;97:162-5. 12. Berger SA, Zonszein J, Villamena P, Mittman N. Infectious diseases of the thyroid gland. Rev Infect Dis. 1983;5:108-22.
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