Thyrotoxicosis Secondary to Involvement of the Thyroid with Malignant Lymphoma KATSUTARO SHIMAOKA, ANDRE J. VANHERLE, AND AYDIN DINDOGRU The Division of Medicine, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York, and the Department of Medicine, University of California, U.C.L.A. Center for the Health Sciences, Los Angeles, California patient was treated with propylthiouracil, local radiotherapy, and nitrogen mustard and prednisone. The patient became euthyroid with the disappearance of goiter. Circulating levels of thyroglobulin and thyroid hormones returned to the normal range. (J Clin Endocrinol Metab 43: 64, 1976)
ABSTRACT. A patient with malignant lymphoma devel oped goiter and thy rotoxicosis during the course of her disease. A thyroid biopsy revealed involvement of the thyroid gland with a malignant lymphoma. This was associated with the high levels of circulating thyroglobulin and thyroid hormones. The
M
ALIGNANT lymphoma is a progressive disease which, during its course, may involve almost any organ in the body. In our previous study, we found that 11% of patients with malignant lymphoma had involvement of the thyroid gland at the time of autopsy (1). Non-Hodgkin's lymphomas involved the thyroid more often than Hodgkin's disease, but there was no significant difference in thyroid involvement between histiocytic and lymphocytic lymphomas (1). Although rare, malignant lymphomas may originate in the thyroid gland and may mimic primary thyroid tumor (2-17). Some of these cases were initially thought to be thyroid carcinoma, but careful histological examinations and the clinical courses usually revealed malignant lymphoma instead. This type of initial presentation of malignant lymphoma is more frequently seen in histiocytic lymphoma than in other types. A case of nodular well-differentiated lymphocytic lymphoma is presented in this report. About 3 years after the onset of the disease, the thyroid was involved and thyrotoxicosis developed. In spite of the many cases of malignant lymphoma of the thyroid gland reported in the literature, associated thyroidal dysfunction is extremely rare, and
we are not aware of previous documentation of associated thy rotoxicosis. The evaluation of thyroid function, such as the thyroid hormone level and radioiodine study had only rarely been carried out. Materials and Methods Case report A 37-year-old white female developed enlarged cervical lymph nodes in the spring of 1971. A few months later she complained of left flank pain and was admitted to a local hospital, where generalized lymphadenopathy and splenomegaly were found. Biopsy of the cervical lymph node showed a nodular, well differentiated, malignant lymphoma of the lymphocytic type (giant follicular lymphoma). She was then referred to Roswell Park Memorial Institute in November 1971. On initial evaluation, the bone marrow aspiration showed 90% lymphocytes, some of which were atypical in morphology; the patient was staged as Stage IVA. She responded well to induction chemotherapy with nitrogen mustard (HN2) and prednisone, which was then followed by daily oral cyclophosphamide (CTX) as the maintenance therapy. This regimen was continued until February 1974, at which time her spleen was found to be slightly enlarged, and she was suspected to be relapsing. The size of the spleen markedly increased during the subsequent 2 months, and she developed pancytopenia. In June 1972, her thyroid gland was easily palpable although not enlarged. The serum T4-I(C) at that time was 6.0 /ug/100 ml (normal,
Received May 14, 1975. Reprint requests to: Katsutaro Shimaoka, M.D., Department of Medicine B, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, New York 14263.
64
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 20:38 For personal use only. No other uses without permission. . All rights reserved.
LYMPHOMA OF THYROID WITH THYROTOXICOSIS 3.0-6.6). In April 1973, the T4-I(C) was 6.8 /ng/100 ml, and in September 1973, this value had increased to 8.2 /zg/100 ml. In April 1974, she was admitted with progressive lyinphoma, heat intolerance, persistent resting tachycardia of 145 per minute, and nervousness. These symptoms gradually developed several weeks prior to admission. There was no preceding URI or neck tenderness. Her thyroid gland was visibly and diffusely enlarged, nontender, and firm in consistency. She was hyperkinetic, but no fine finger tremor could be demonstrated. No eye signs of Graves' disease were present. Laboratory values on this admission were: T4-I(C), 15.6 /xg/100 ml; the effective thyroxine ratio (ETR), 1.57 (normal, 0.86-1.13) (18); and a 6-hour radioiodine _uptake 2.4% and a 24-hour uptake 0.6% (normal, 8-35). A thyroid scan was unsatisfactory because of low uptake. Long-acting thyroid stimulator was not detectable,1 and serum TSH was 5.0 ^iU/ml (normal
ABSTRACT. A patient with malignant lymphoma devel oped goiter and thy rotoxicosis during the course of her disease. A thyroid biopsy revealed involvement of the thyroid gland with a malignant lymphoma. This was associated with the high levels of circulating thyroglobulin and thyroid hormones. The
M
ALIGNANT lymphoma is a progressive disease which, during its course, may involve almost any organ in the body. In our previous study, we found that 11% of patients with malignant lymphoma had involvement of the thyroid gland at the time of autopsy (1). Non-Hodgkin's lymphomas involved the thyroid more often than Hodgkin's disease, but there was no significant difference in thyroid involvement between histiocytic and lymphocytic lymphomas (1). Although rare, malignant lymphomas may originate in the thyroid gland and may mimic primary thyroid tumor (2-17). Some of these cases were initially thought to be thyroid carcinoma, but careful histological examinations and the clinical courses usually revealed malignant lymphoma instead. This type of initial presentation of malignant lymphoma is more frequently seen in histiocytic lymphoma than in other types. A case of nodular well-differentiated lymphocytic lymphoma is presented in this report. About 3 years after the onset of the disease, the thyroid was involved and thyrotoxicosis developed. In spite of the many cases of malignant lymphoma of the thyroid gland reported in the literature, associated thyroidal dysfunction is extremely rare, and
we are not aware of previous documentation of associated thy rotoxicosis. The evaluation of thyroid function, such as the thyroid hormone level and radioiodine study had only rarely been carried out. Materials and Methods Case report A 37-year-old white female developed enlarged cervical lymph nodes in the spring of 1971. A few months later she complained of left flank pain and was admitted to a local hospital, where generalized lymphadenopathy and splenomegaly were found. Biopsy of the cervical lymph node showed a nodular, well differentiated, malignant lymphoma of the lymphocytic type (giant follicular lymphoma). She was then referred to Roswell Park Memorial Institute in November 1971. On initial evaluation, the bone marrow aspiration showed 90% lymphocytes, some of which were atypical in morphology; the patient was staged as Stage IVA. She responded well to induction chemotherapy with nitrogen mustard (HN2) and prednisone, which was then followed by daily oral cyclophosphamide (CTX) as the maintenance therapy. This regimen was continued until February 1974, at which time her spleen was found to be slightly enlarged, and she was suspected to be relapsing. The size of the spleen markedly increased during the subsequent 2 months, and she developed pancytopenia. In June 1972, her thyroid gland was easily palpable although not enlarged. The serum T4-I(C) at that time was 6.0 /ug/100 ml (normal,
Received May 14, 1975. Reprint requests to: Katsutaro Shimaoka, M.D., Department of Medicine B, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, New York 14263.
64
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 16 November 2015. at 20:38 For personal use only. No other uses without permission. . All rights reserved.
LYMPHOMA OF THYROID WITH THYROTOXICOSIS 3.0-6.6). In April 1973, the T4-I(C) was 6.8 /ng/100 ml, and in September 1973, this value had increased to 8.2 /zg/100 ml. In April 1974, she was admitted with progressive lyinphoma, heat intolerance, persistent resting tachycardia of 145 per minute, and nervousness. These symptoms gradually developed several weeks prior to admission. There was no preceding URI or neck tenderness. Her thyroid gland was visibly and diffusely enlarged, nontender, and firm in consistency. She was hyperkinetic, but no fine finger tremor could be demonstrated. No eye signs of Graves' disease were present. Laboratory values on this admission were: T4-I(C), 15.6 /xg/100 ml; the effective thyroxine ratio (ETR), 1.57 (normal, 0.86-1.13) (18); and a 6-hour radioiodine _uptake 2.4% and a 24-hour uptake 0.6% (normal, 8-35). A thyroid scan was unsatisfactory because of low uptake. Long-acting thyroid stimulator was not detectable,1 and serum TSH was 5.0 ^iU/ml (normal
