Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males.

When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred, depending on the time interval for hormone replacement. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was generally associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. Thus an indirect effect of T via early stimulation of TSH may be at least partly responsible for the high incidence of irradiation-induced thyroid tumors in rats.

Hypothalamic prolactin stimulates the release of luteinizing hormone-releasing hormone from male rat hypothalamus.

Previous works from our laboratory and others have shown that there is a PRL-like immunoreactive protein with immunological, chromatographic, and biological characteristics identical to those of pituitary PRL, and this is widely distributed in the rat central nervous system. Since pituitary PRL is important in controlling hypothalamic LHRH release, we have hypothesized that hypothalamic PRL-like immunoreactive protein might serve a similar role, that of an endogenous neuromodulator influencing hypothalamic LHRH release. To this end, we have examined the effect of PRL antiserum and normal rabbit serum on the release of immunoreactive LHRH from rat hypothalamic fragments cultured in vitro. In the first experiment, LHRH release from hypothalami of intact rats, bathed in PRL antiserum (1:200 in Krebs-Ringer bicarbonate buffer), was significantly lower than that from hypothalami bathed in normal rabbit serum (1:200 in Krebs-Ringer bicarbonate buffer) for 90 min of incubation. It was, however, possible that the PRL, immunoneutralized in the first experiment, was material that represented contamination from pituitary PRL. Therefore, we repeated the experiment using hypothalami from animals that had been hypophysectomized 2 weeks before death. Again, PRL antibody significantly inhibited the release of LHRH compared with that by hypothalami incubated in normal rabbit serum. Since testosterone is important to LHRH synthesis, a third experiment was carried out using hypothalami from hypophysectomized male rats that had been implanted sc with testosterone-containing capsules 72 h before death. By 72 h serum testosterone levels had normalized. PRL antibody added to medium containing hypothalamic explants from these animals substantially inhibited in vitro LHRH release, a pattern essentially similar to that seen in intact and hypophysectomized animals without testosterone replacement. From these studies we have concluded that hypothalamic PRL is an important neuromodulator that promotes the release of LHRH from the hypothalamus. Testosterone, at least under the experimental conditions employed, appears not to be essential in this hypothalamic PRL-LHRH interaction.

Osteosclerosis in primary hyperparathyroidism.

Osteosclerosis in adults with primary hyperparathyoidism is rare; the usual skeletal manifestation, when presented, is diffuse osteropenia. We describe a patient with generalized osteosclerosis in association with primary hyperparathyroidism. The findings are documented by conventional and fine-detail radiography, absorptiometric bone mineral analysis, quantitative microradiography and histologic examination of bone. The unique features are contrasted with the manifestations recorded in a recently studied group of 87 hyperparathyroid patients. The data presented here support a causal relationship in this patient between parathyroid hormone excess and the development of densely sclerotic bones.

Lung transplantation for advanced bronchioloalveolar carcinoma confined to the lungs.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) is a well-differentiated lung adenocarcinoma that has a tendency to spread chiefly within the confines of the lung by aerogenous and lymphatic routes and may therefore be amenable to local therapy. However, a high rate of local recurrence after lung transplantation was recently reported. We describe two patients with unresectable and recurrent extensive BAC limited to the lung parenchyma who underwent lung transplantation with curative intent. METHODS: Patients were chosen to receive lung transplants for BAC if they met the following criteria: (1) recurrent or unresectable BAC limited to the lung parenchyma without nodal involvement and (2) suitable candidate for lung transplantation. RESULTS: The first patient relapsed in the lungs at 9 months after transplantation. The pattern of disease suggested contamination of the new lungs at the time of implantation. Repeat lung transplantation was performed, with cardiopulmonary bypass and irrigation of the remaining upper airway. This patient has had no evidence of local or systemic tumor recurrence at more than 4 years since the second transplantation. The second patient underwent transplantation using the modified technique and expired 16 months after transplantation of other causes. An autopsy showed no evidence of recurrent BAC in the lungs or of metastatic lesions at any site. CONCLUSIONS: Lung transplantation may be an option for unresectable or recurrent BAC confined to the lungs. Isolation of the diseased lungs and the use of cardiopulmonary bypass during surgery may be important in this disease and should be studied further.

Papillary clear cell carcinoma of the thyroid gland.

A case of an unusual papillary clear cell carcinoma of the thyroid gland is described. The patient expired 17 days after operative biopsy and thyroxine suppression. Special stains were helpful in differentiating renal cortical carcinoma and parathyroid malignant disease from primary papillary clear cell carcinoma of the thyroid. Ultrastructural features of this tumor may relate to the effects of thyroid stimulating hormone as well as the malignant nature of the tumor.

Sex hormone modulation of serum TSH levels.

This study was undertaken to determine the effects of estrogen and testosterone on baseline and thyrotropin-releasing hormone (TRH)-stimulated serum thyroid-stimulating hormone (TSH) levels in rats. Seven groups of 20 rats each were studied: intact males (group I), intact females (group II), castrated males (group III), castrated females (group IV), castrated males with testosterone replacement (group V), castrated females with testosterone supplement (group VI), and intact females with testosterone supplement (group VII). Two weeks after initiation of these hormone treatments, blood samples for TSH levels were obtained before and 10 minutes after TRH injection. Testosterone levels were also determined to verify hormone release. The results of these studies indicated that (1) testosterone has a primary, stimulatory role in the control of TSH concentration in that it causes elevation of both baseline and TRH-stimulated TSH levels, (2) endogenous estrogens have no such direct effect on TSH levels, and (3) in the presence of testosterone, endogenous estrogens partially inhibit the TSH-elevating effect of the androgen. As TSH stimulation is considered requisite for thyroid carcinogenesis, the different effects of testosterone and estrogen on TSH levels, demonstrated in this study, may in part explain differences in incidence and prognosis of thyroid carcinoma observed between the sexes in both rats and human beings.

Hyperparathyroidism unmasked by the treatment of hypothyroidism secondary to Hashimoto's thyroiditis.

Primary hyperparathyroidism masked by untreated hypothyroidism was first noted by Kissin and Bakst in 1947; since then there has been only a single case reported. As a result, it has been thought to be a rare complex of parathyroid disease. During the past 17 years we observed 17 patients who developed primary hyperparathyroidism after their treatment for hypothyroidism (secondary to Hashimoto's thyroiditis) with thyroxine had been well underway. The patients were all women whose ages ranged between 16 and 76 years. The clinical and biochemical manifestations of hyperparathyroidism were noted 2 months to 30 years after thyroxine therapy. All patients underwent standard subtotal parathyroidectomy. Fourteen patients had a single parathyroid adenoma and three had multiglandular adenomatous hyperplasia. It is of interest that all 17 patients were found to have Hashimoto's thyroiditis, based on antimicrosomal antibody titers or histopathologic criteria. Thus we present a series of patients who developed primary hyperparathyroidism in a background of Hashimoto's thyroiditis and hypothyroidism treated with thyroxine. We are intrigued by the association of hyperparathyroidism and Hashimoto's chronic thyroiditis. From this experience it seems appropriate to evaluate parathyroid function in patients with hypothyroidism secondary to Hashimoto's thyroiditis before the initiation of treatment with thyroxine and at intervals thereafter.

Radioiodine sensitivity of parafollicular C cells in aged Long-Evans rats.

An earlier study from our laboratory demonstrated that the incidence of thyroid C cell neoplasia in aging Long-Evans rats was high. When radioactive iodine was administered to 8-week-old Long-Evans rats, this incidence was reduced, although thyroid follicular cell neoplasia was increased. The aim of this study was to determine whether iodine-131 (131I) administered to an aged population of Long-Evans rats with established C cell hyperplasia would have a C cell ablative effect as pronounced as that observed in studies of young rats. For this study, 180 18-month-old Long-Evans rats (90 male and 90 female) were used. Baseline serum calcitonin levels were determined, and control and experimental groups containing equal numbers of animals were designated. 131I was administered by intraperitoneal injection to the experimental group, while equal volumes of saline solution were given to the control group. Blood samples for determination of serum calcitonin levels were obtained at 6-week intervals until the rats were 24 months old. Thyroid glands were then removed, and tissues were fixed, sectioned, and stained with hematoxylin and eosin and with peroxidase-antiperoxidase (PAP) using an anticalcitonin antibody. Examination of thyroid tissues showed that the incidence of C cell neoplasia was significantly reduced in irradiated animals as compared with nonirradiated controls (chi 2 analysis, p less than 0.05). PAP staining demonstrated diminished intracytoplasmic calcitonin in the radiation-treated group. Analysis of serum calcitonin levels over time showed significantly lower levels in the irradiated rat group than in the nonirradiated group (p less than 0.006).

Total thyroidectomy and parathyroid autotransplantation for radiation-associated thyroid cancer.

In seventy patients with nodular thyroids and a history of radiation exposure, total thyroidectomy disclosed a 54% incidence of carcinoma; more than half of them had cervial node metastases; four had distant metastases. Fourteen patients required radical neck dissection. The carcinoma was multicentric (both lobes) in 45%. In four patients the carcinoma was found in the lobe contralateral to the one containing the palpable nodule. These findings support the advocates of total thyroidectomy for patients with a nodular thyroid and a history of radiation exposure, provided this operation can be performed with a low incidence of recurrent nerve palsy and hypoparathyroidism.

Thyroid carcinoma in Graves' disease.

The prevailing hypothesis of thyroid carcinogenesis is that thyroid-stimulating hormone (TSH) is a prime factor in the growth and possibly the genesis of thyroid carcinoma. On the other hand, Graves' disease is a hyperthyroid state caused presumably by human thyroid-stimulating immunoglobulin (HTSI), not TSH. However, the literature does contain scattered reports of an association between Graves' disease and thyroid carcinoma. With this background, we retrospectively reviewed our series of 117 consecutive patients operated on for Graves' disease from 1961 through 1984. The series contains 23 male and 94 female patients, with a mean age of 26.3 years at operation (median 26 years; range 8 to 58 years). Of these patients, six (two males and four females) were found to have carcinoma, four papillary and two follicular, for an incidence of 5.1%. Four of the 117 patients had a history of head and neck irradiation; two (50%) subsequently developed carcinoma. For the six patients with carcinoma, mean follow-up has been 8.1 years (median 8 years; range 1 to 14 years). To date there have been no recurrences of carcinoma, and all six are alive and well. Thus our series shows a carcinoma rate of 5.1% in patients with Graves' disease, which is markedly higher than the 0.1% to 0.2% incidence in random autopsy series of all patients. This raises the question of a possible carcinogenic role for HTSI, similar to that hypothesized for TSH, in patients with presumably suppressed TSH.

Testosterone enhancement of thyroid carcinoma in rats: the role of TSH.

Radiation treatment of Long-Evans male rats (40 mu Ci Na131I at the age of 2 months) led to a high incidence of thyroid follicular carcinomas at the age of 24 months; castration of males before irradiation caused a significant reduction in incidence of this tumor. In this study, replacement testosterone (T) was administered to castrated male rats by means of implanted, slow-release hormone-containing pellets (T-physiologic dose). Three testosterone doses (0.1T, 1.0T, and 30T) were used to treat groups of castrated irradiated and castrated nonirradiated rats from 2 to 18 months of age. The incidence of thyroid follicular carcinoma at 18 months in irradiated rats depended on the dose of replacement testosterone used. Tumor incidence was 8%, 14%, 41%, and 50% after treatment with 0T, 0.1T, 1.0T, and 30T, respectively. The incidence of thyroid follicular carcinoma in nonirradiated rats ranged from 0 to 7%. Mean serum thyroid-stimulating hormone (TSH) values in irradiated animal groups were elevated significantly above those for age-matched nonirradiated animals. The degree of TSH elevation in irradiated animals was related directly to the testosterone-replacement level. All rat groups showed age-dependent decreases in serum T4 levels, and T4 levels were also lowered by replacement testosterone in nonirradiated castrated animals. In aging irradiated animals, serum T4 levels were similarly decreased by testosterone, despite elevated TSH levels in these groups. In this study, testosterone appeared to act indirectly to promote development of irradiation-induced thyroid tumors by early and prolonged elevation of TSH levels.

The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters.

The incidence of carcinoma in patients with multinodular goiters has been reported to be considerably lower than in patients with a single cold nodule. However, the definition of a "single cold nodule" is highly subjective and has therefore been modified by qualifiers such as "clinically solitary" or "clinically dominant." In this retrospective study, we find no significant difference in the incidence of carcinoma in patients with multinodular goiters compared with patients with a solitary cold nodule confirmed by operation and histopathologic examination. In a consecutive series of thyroidectomies over a 22-year period, all patients with factors predisposing them to neoplasia, such as a history of radiation exposure and thyroiditis, were eliminated. Furthermore, all patients thought to have additional nodules documented by gross examination at operation or subsequently by histopathologic examination were also eliminated. The remaining 69 patients with clinically evident multinodular goiters were compared with the remaining 96 patients with a solitary cold nodule. The incidence of carcinoma in the 96 patients with a solitary cold nodule was 17%. In the 69 patients with clinically evident multinodular goiters, the incidence of carcinoma was 13%. The difference is not significant. It is of interest that male patients with multinodular goiters had the highest incidence of carcinoma at 29%, whereas, males with a solitary cold nodule had an incidence of only 13%. In conclusion, once known factors that predispose patients to neoplasia are eliminated, there does not seem to be a significant difference in the incidence of thyroid carcinoma between patients with operatively and histopathologically proved solitary cold nodules and those with multinodular goiters.

Successful adrenal autotransplantation in Cushing's disease.

Since Cushing's disease was delineated as a distinct entity, a wide array of therapeutic modalities has been employed to treat its symptoms, which are primarily the result of hypercortisolism. With the advent of pituitary polytomography and the concept of microadenomas, a wave of enthusiasm has developed in recent years in favor of transsphenoidal microdissection. In a recent national survey, however, one third of 30 endocrinologists reported cure rates below 60% and, according to several respondents, recurrence was a serious problem at 50% or greater incidence. We report on four patients treated by bilateral adrenalectomy and autotransplantation. They were weaned off all corticosteroid medication for up to 6 years. Two of the four patients have demonstrable iodocholesterol uptake at the site of autotransplantation. We also report on three additional patients who are taking reduced doses of cortisone. All seven patients have no demonstrable iodocholesterol uptake in the adrenal fossae or other possible ectopic sites. We believe that bilateral adrenalectomy with autotransplantation is a worthy alternative in the long-term treatment of Cushing's disease.

Parathyroid carcinoma: biochemical and pathologic response to DTIC.

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as peripheral necrosis of the tumor, which was thought to be the result of the cytotoxic effect of DTIC. From this experience and because of the grim prognosis in patients with recurring parathyroid carcinoma, it may be that aggressive use of chemotherapy with DTIC early in the course of treatment should be considered.

Resection of parathyroid tumor in the aorticopulmonary window without prior neck exploration.

Of 522 patients with hyperparathyroidism operated on from 1973 to 1987 at our institution, there were seven (1.3%), each with an ectopic, hyperfunctioning mediastinal parathyroid adenoma, who required median sternotomy. In three of these seven patients, the tumor was located in the aorticopulmonary window. A 61-year-old woman with primary hyperparathyroidism had a preoperative thallium-technetium subtraction scan that showed thallium uptake at the base of the heart without any uptake in the neck. After further workup and without prior neck exploration, a parathyroid adenoma was found in the aorticopulmonary window through a median sternotomy. Six months later, serum calcium, phosphorus, and parathyroid hormone values remain normal. Two other cases of parathyroid adenoma in the aorticopulmonary window are presented. Of these two patients, the thallium scan was a key element in the immediate mediastinal exploration of one, who was transferred from another hospital comatose and intubated, in acute hypercalcemic crisis. Since mediastinal parathyroid tumors that necessitate median sternotomy occur in less than 2% of patients with primary hyperparathyroidism, we do not advocate routine preoperative localization studies before an initial cervical operation; localization, however, may be justified in selected cases, such as in critically ill patients or in instances of acute hyperparathyroidism, when the first operation needs to be curative.

Altered TSH levels associated with increased serum 1,25-dihydroxyvitamin D3: a possible link between thyroid and parathyroid disease.

The physiologic relationship between the thyroid and parathyroid glands remains poorly understood. A high incidence of coexistent thyroid disease and primary hyperparathyroidism has been well documented. Elevation of serum 1,25-dihydroxyvitamin D3 (vitamin D) has been detected in some patients with primary hyperparathyroidism. A report of specific binding sites and uptake of vitamin D by the thyrotrophs of the anterior pituitary indicates that vitamin D may modulate production or secretion of thyroid-stimulating hormone (TSH). To test this concept, we investigated the influence of elevated serum levels of vitamin D on basal and stimulated TSH. Vitamin D was administered by subcutaneously implanted sustained-release pellets at four dosages. Thyrotropin releasing hormone (TRH) stimulation tests were performed at time zero, 72 hours, 1 week, 2 weeks, and 5 weeks. Animals administered vitamin D became significantly hypercalcemic and demonstrated elevations of vitamin D, which peaked at 72 hours and remained elevated for 2 weeks after pellet implantation. TRH-stimulated TSH levels were significantly elevated at 72 hours and at 1 week and returned to normal after 5 weeks. Parathyroid hormone levels were suppressed at 72 hours and at 1 week and displayed significant elevation at 2 weeks. These results provide in vivo evidence for an interaction and a possible regulatory role of 1,25 on pituitary TSH secretion and parathyroid function.

Thyroid carcinoma and hyperparathyroidism after radiation therapy for adolescent acne vulgaris.

Thyroid and parathyroid disease after head and neck irradiation in infancy and childhood is well known. Patients irradiated for facial acne were older and received a comparatively lower dose of radiation. These mitigating factors suggest a decreased incidence of thyroid and parathyroid disease in these patients. Over the past 28 years (1961 through 1989), 347 consecutive patients were operated on for radiation-associated thyroid and/or parathyroid disease. One hundred and ten patients in this group were irradiated for treatment for adolescent facial acne vulgaris. The interval between radiation exposure and thyroidectomy ranged from 7 to 57 years (mean, 30 years). The overall incidence of thyroid carcinoma was 31% (34 of 110 patients). Regional metastases in 10 patients (29%) were treated with modified radical neck dissection. Hyperparathyroidism, detected in 31% (34 of 110 patients) of this population, was treated with sub-total parathyroidectomy in all cases. The association of thyroid carcinoma and hyperparathyroidism after adolescent radiation exposure for acne vulgaris appears to be more than coincidental. The incidence of thyroid and parathyroid disease may be independent of the timing and dosage of radiation treatment. These thyroid and parathyroid tumors may develop decades after the initial radiation exposure.

The incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and solitary cold nodules.

The reported incidence of thyroid carcinoma in Hashimoto's thyroiditis varies widely. For this reason the specific subpopulation of patients with Hashimoto's thyroiditis and a solitary cold nodule was analyzed. Between 1972 and 1984 we operated on 146 consecutive patients with solitary cold nodules and Hashimoto's thyroiditis. There were 47 carcinomas, for an incidence of 32%. The mean age of the 146 patients was 43 1/2 years (median 44 years), with 126 females and 20 males. There was a history of prior head and neck radiation exposure in 54 patients, with a 33% incidence of thyroid carcinoma. The 92 patients without a history of radiation exposure had a 31.5% incidence of carcinoma. The frequency of multicentricity (bilateralism) was 33% in the group that underwent radiation and 24% in the group that did not. To date, with a mean follow-up of 4.7 years, there have been no deaths and no evidence of recurrence. In conclusion, we report a 32% incidence of thyroid carcinoma in patients with Hashimoto's thyroiditis and a solitary cold nodule, with no apparent difference between the patients with or without a history of radiation exposure, although there was a higher incidence of bilateralism (33% versus 24%) in the carcinomas of the patients with a history of head and neck irradiation. We suggest that the operative management of these patients is total thyroidectomy for those with a history of head and neck radiation and thyroid lobectomy for patients with no history of radiation, followed by contralateral lobectomy if a carcinoma is demonstrated.

Spectrum of catecholamine-secreting tumors of the organ of Zuckerkandl.

In a series of 24 pheochromocytomas, four were tumors in the organ of Zuckerkandl. Their presenting symptoms of headache, palpitation, diaphoresis, and anxiety were similar to symptoms of adrenal pheochromocytomas. Two patients had paroxysmal and two patients sustained hypertension. All four had elevated urinary vanillylmandelic acid, metanephrine or catecholamine levels. Two of the tumors were localized with angiography before the availability of computerized tomography. Two patients underwent initial computerized tomography, which was nondiagnostic. Later scans looking specifically for organ of Zuckerkandl tumors were positive. Organ of Zuckerkandl tumors, like other ectopic pheochromocytomas, have a higher rate of malignancy. Two of the four were malignant tumors. One patient died 4 years after operation, but the other patient remains stable despite metastatic disease 8 years after operation. The two patients with benign tumors remain well 2 and 3 years after resection and treatment with alpha-blockade.

Hürthle cell tumors of the thyroid gland.

The recent controversy concerning the prognosis of Hürthle cell tumors instigated the review of our experience with 34 patients treated between 1972 and 1984. On the basis of strict histopathologic criteria, 14 patients with Hürthle cell hyperplasia, 10 with Hürthle cell adenoma, and 10 with Hürthle cell carcinoma were identified. There was a 40% incidence of bilateralism in Hürthle cell carcinoma, whereas we documented bilateral disease in only one of 10 patients with Hürthle cell adenoma. Lobectomies were performed in patients with tumors considered histopathologically benign and total thyroidectomy in patients with histologically malignant lesions as well as in most patients with a history of radiation exposure. Follow-up ranges from 4 months to 12 years (mean 3.1 years). To the present time there has been no evidence of recurrence and no deaths from Hürthle cell tumors. Consequently, in our experience, Hürthle cell tumors seem to behave in a rather benign manner. Therefore it seems that the appropriate treatment for Hürthle cell adenoma and nodular hyperplasia is a lobectomy. Total thyroidectomy is reserved for patients with Hürthle cell carcinoma primarily because of the high incidence of bilateralism.