Difficult decisions in the management of thyroid carcinoma.
Five unusual case studies are presented. Each case is followed by solutions proposed by three authorities and a concluding commentary by the editor.
Adenocarcinoma↗
Biomedical subjects
E Paloyan
Publications and source records attributed to E Paloyan.
Parathyroid autotransplantation in forty-four patients with primary hyperparathyroidism: the role of thallium scanning.
Forty-four patients with primary hyperparathyroidism were followed for 18 to 126 months after subtotal or total parathyroidectomy and parathyroid autotransplantation. Indications for autotransplantation included the devascularization of parathyroid glands during concomitant thyroid lobectomy or total thyroidectomy and the excision of the only remaining parathyroid tissue in patients with persistent hyperparathyroidism after previous unsuccessful parathyroidectomies. Before implantation, all parathyroid tissue was histologically evaluated by frozen-section light microscopy with hematoxylin and eosin stain. Fifteen patients had histologically normal implants; to date none of these patients have developed recurrent hyperparathyroidism. Twenty-nine patients had either adenomatous or hyperplastic parathyroid tissue used for implants; two of these patients developed graft-dependent recurrent hyperparathyroidism 4 and 7 years later. In both patients the grafts were preoperatively localized by thallium scanning and their resection restored eucalcemia. One hundred thirty-one patients from 11 series in the current literature had a cumulative incidence of 17.5% for presumed graft-dependent recurrence and a 9.2% incidence of graft excision followed by eucalcemia. In comparison, in the present series the incidence of graft-dependent recurrent hyperparathyroidism in patients with either adenomatous or hyperplastic implants stands at 6.9%. In contrast, in 15 patients with normal parathyroid tissue implants, the incidence was zero.
Adenoma↗
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.
Adenocarcinoma↗
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.
Carcinoma↗
Total thyroidectomy in irradiated patients. A twenty-year experience in 206 patients.
During a period of 20 years (1965-1985), 206 consecutive patients were operated on for radiation-associated nodular thyroids. The ages ranged between 8 and 76 years (mean 38.7). there were 136 women and 70 men. The average duration between radiation exposure and operation was 27 years. The operations performed were total thyroidectomy (192) or, in patients who had undergone a previous lobectomy in another institution, another lobectomy (14). In addition, 25 patients required a neck dissection for nodal metastases and 27 underwent simultaneous subtotal parathyroidectomy for coexistent hyperparathyroidism. The pathologic findings were: 87 (42.2%) carcinoma (73 papillary, 13 follicular, 1 undifferentiated); 92 (44.7%) follicular adenomas; and 27 (13.1%) thyroiditis. To date, with an average follow-up of 6 years (0.5-31 years), only two patients have expired from recurrent disease. A third died of unrelated cause. A comparison of the first 100 patients (12 years) with the last 106 patients (8 years) demonstrated that the incidence of carcinoma has dropped from 48 to 37%, the incidence of lymph node metastases has decreased from 35 to 26%, and the incidence of bilaterality has fallen from 75 to 54%. On the basis of this series, it was concluded that total thyroidectomy is still indicated for radiation-associated nodular thyroids. However, if the trend of decreasing incidence, bilaterality, and metastatic disease persists, this approach may have to be reevaluated in the near future.
Acne Vulgaris↗
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.
Adenocarcinoma↗
Localization of ectopic parathyroid adenomas by the technetium-thallium subtraction scan.
Among numerous methods utilized for preoperative localization of hyperfunctioning ectopic parathyroid tissue, the technetium-thallium scan appears to be a major advance. Eight patients are presented where this method located ectopic parathyroid tissue in the neck, in the mediastinum, within the pericardium, and within the thyroid gland. To date, these findings have been confirmed operatively in five of the eight patients. On the basis of our limited experience, the authors believe that this is a valuable method in the preoperative localization of ectopic parathyroid tissue, especially in patients with persistent or recurrent hyperparathyroidism following a thorough neck exploration.
Adenoma↗
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.
Adenocarcinoma↗
Parathyroid carcinoma. A report of five cases.
Parathyroid carcinoma, although rare, represents 0.5-4.0 per cent of the cases of hyperparathyroidism. The authors have encountered five cases of parathyroid carcinoma in their experience treating 445 patients with primary hyperparathyroidism (1.1%) since 1965. All five patients were women, ranging in age fro 29 to 60 years, and had marked hypercalcemia at the time of presentation, with values up to 26 mg/dl in one case. All the tumors were locally adherent to surrounding structures at the time of parathyroidectomy. Pathologically they were characteristic with a dense sclerotic reaction and fibrous bands criss-crossing islands of parathyroid cells. Three patients with local as well as distant metastases have died as a result of recurrent parathyroid carcinoma (follow-up: 2, 3, and 6 years). The remaining two patients became normocalcemic following resection, and have been asymptomatic for 1 and 7 years, respectively. The overall survival and clinical course, in our limited experience with five parathyroid carcinoma cases demonstrates that the morbidity and mortality in these patients is mainly due to local recurrence with the resultant metabolic disturbances, as has been previously noted in the literature.
Adult↗
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.
Adult↗
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.
Adenoma↗
Adult nesidiodysplasia.
Subtotal pancreatectomy specimens from two adults with hyperinsulinemic hypoglycemia and one adult with watery diarrhea syndrome were investigated. All three specimens were originally diagnosed as "nesidioblastosis"; none had a neoplasm, and all patients were cured of their endocrine dysfunction by the surgical procedure. Tissue samples were studied by light microscopy and light microscopic immunohistochemistry for serotonin, ACTH, bombesin, calcitonin, gastrin, glucagon, insulin, HPP, somatostatin, and VIP. The results were compared with those obtained from the parallel study of ten adult pancreata obtained at autopsy from patients without pancreatic disease or endocrine dysfunction. The total endocrine cell mass was not notably greater in the pancreata from patients with endocrine dysfunction than in the controls. Both groups had an estimated 95% of the endocrine cell population organized in islets while the remaining 5% was irregularly dispersed amidst the exocrine ducts and acini. Findings more conspicuous in patients with endocrine dysfunction but not absent in the controls included: large islets, islets with irregular contours and ragged edges, and large individual islet cells with abundant cytoplasm and bizarre nuclei. Immunoreactivity for insulin, glucagon, and somatostatin was demonstrated in all cases; the ratio among these hormones in the patients with endocrine dysfunction and in the controls was similar. In the patients with hyperinsulinemic hypoglycemia, step sections sequentially stained for insulin and somatostatin showed a close topographic relationship between these cell types. In the patient with the watery diarrhea syndrome, VIP immunoreactive cells were easily identified admixed with exocrine components; they were only rarely seen within islets. We suggest that the hyperinsulinemic hypoglycemia in these adults was not due to simple quantitative abnormalities in total endocrine cell mass nor to its maldistribution nor to lack of topographic proximity between insulin and somatostatin cells. We speculate that the syndrome may be based on still unknown derangements of insulin secretion, release, and/or its degradation. In the case of the watery diarrhea syndrome, the readily identifiable VIP immunoreactive cells represent the emergence of a functional expression regarded as ectopic for the endocrine cells of the pancreas. We conclude that nesidioblastosis per se cannot be viewed as the structural basis of these endocrine dysfunctions since many of its features were present in control pancreata lacking any such association.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
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.
19-Iodocholesterol↗
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.
Adult↗
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.
Adenoma↗
Subtotal parathyroidectomy for primary hyperparathyroidism. Long-term results in 292 patients.
Subtotal parathyroidectomy was performed in a consecutive series of 292 patients with primary hyperparathyroidism. We evaluated the long-term postoperative results during a period of 16 years. Patients ranged in age from 14 to 83 years and included 176 women and 116 men. Of these, 16% had a history of exposure to radiation in childhood or adolescence, while thyroid disease requiring some form of thyroidectomy coexisted in 91 (31%) of the patients. Histologic information on three or more parathyroid glands was obtained in 73% of the cases. We considered 285 patients (97.6%) cured after their first operation. The remaining seven patients (2.4%) had persistent hyperparathyroidism. However, five were cured after a sternum-splitting mediastinal exploration and one after a second neck exploration. The seventh remains hypercalcemic despite a subsequent mediastinal exploration. Temporary postoperative hypoparathyroidism occurred in 10% of our cases and permanent hypoparathyroidism in 1%. There have been no instances of recurrent hyperparathyroidism.
Adenocarcinoma↗
Fine needle aspiration biopsy of thyroid nodules.
The clinical value of the fine needle aspiration of thyroid nodules was evaluated by comparing preoperative cytology to subsequent pathology in 109 patients undergoing thyroidectomy. Preoperative cytology was reported as insufficient cellular material (31 patients), benign goiter (27 patients), follicular neoplasm (22 patients), thyroiditis (12 patients), suspicious for papillary carcinoma (nine patients), Hurthle cell neoplasm (five patients), medullary carcinoma (one patient), lymphoma (one patient), and metastatic adenocarcinoma (one patient). Operative findings demonstrated that the overall sensitivity of fine needle aspiration in diagnosing thyroid neoplasia (carcinoma or adenoma) was 88% and its specificity was 80%. Operation verified the cytologic diagnosis of medullary carcinoma, lymphoma, metastatic adenocarcinoma, and seven of nine papillary carcinomas. Of the five patients with an aspiration biopsy diagnosis of Hurthle cell neoplasm, three patients had carcinoma and one had an adenoma. Four carcinomas and 12 follicular adenomas were found in patients with a cytologic diagnosis of follicular neoplasm. Thyroiditis was confirmed at operation in all 12 patients with this diagnosis on fine needle aspiration. One carcinoma was found in the 27 patients with benign goiter diagnosed on cytology. Fine needle aspiration is a valuable tool that can lead to earlier diagnosis and treatment of thyroid cancer. However, a negative aspiration does not supplant good clinical judgement in determining the need for thyroidectomy.
Adenocarcinoma↗
Parathyroid cysts: a report of eleven cases including two associated with hyperparathyroid crisis.
Eleven parathyroid cysts were found in 325 patients who underwent parathyroid operations. Ten cysts were located in the neck and one was located in the mediastinum. The cysts ranged in size from 1.6 to 10 cm with a mean of 3.9 cm. The patients who had cysts included six women and five men, and their ages ranged from 28 to 72 years with a mean of 51 years. In contrast to other reports that have suggested that most parathyroid cysts are nonfunctional, all but one of our patients had hyperparathyroidism, as evidenced by hypercalcemia, hypophosphatemia, and elevated parathyroid hormone level, which was corrected by cyst removal. The nonfunctional cyst first appeared to be an asymptomatic neck mass. Two patients had acute hyperparathyroid crises, which required emergency operations. It is postulated that the crises may have been the result of spontaneous necrosis of preexisting parathyroid adenomas. This is supported by the pathologic findings of degeneration and early organization as well as by the presence within the cyst of sanguineous fluid that contained a parathormone concentration greater than 100 times normal serum levels.
Acute Disease↗