Rapid increase in volume of the remnant after hemithyroidectomy does not correlate with serum concentration of thyroid stimulating hormone.

OBJECTIVE: To study the effect of postoperative thyroxine on the volume of the thyroid remnant after lobectomy for benign nontoxic goitre. DESIGN: Prospective, randomised study. SETTING: University hospital, Sweden. SUBJECTS: 50 consecutive patients who underwent lobectomy for benign non-toxic goitre. INTERVENTIONS: Patients were randomised postoperatively to take thyroxine 0.1 mg or placebo daily. MAIN OUTCOME MEASURES: The median volume of the remaining thyroid lobe measured by ultrasound. Serum concentrations of thyroxine, triiodothyronine (T3) and thyroid stimulating hormone (TSH) were measured preoperatively and 1, 3, 6, 12 months postoperatively. RESULTS: The median volume of the remaining lobe had increased significantly compared with preoperatively by 1 month postoperatively by 30% in the thyroxine group and 25% in the placebo group (p < 0.01). The difference between the groups was not significant. After the first month the volume did not change significantly. In the thyroxine group, the TSH concentration was unchanged and the thyroxine concentration increased significantly throughout the study. In the placebo group there was a significant increase in TSH concentration and a significant decrease in that of thyroxine at all follow-up examinations. CONCLUSIONS: There is a significant increase in the volume of the remaining thyroid 1 month after lobectomy that persisted throughout the first year. Thyroxine given in a dose that kept the serum TSH concentration at the same level as preoperatively did not seem to influence volume changes; consequently we consider that these are caused by factors other than TSH.

Cytopathological variables in parathyroid lesions: a study based on 1,600 cases of hyperparathyroidism.

Fine-needle aspirates and tissue sections from 120 surgically treated parathyroid (PT) lesions and histologic archive material from PT lesions in 1,500 additional cases of hyperparathyroidism were reviewed to assess the importance of various features in distinguishing PT disease from other types of lesions by aspiration cytology. We conclude that the morphologic variation shown by PT lesions is so many-sided that this distinction cannot be based on the presence or absence of a single feature only. Instead the cytologic picture as a whole must be taken into account and evaluated with full knowledge of the anatomical conditions pertaining to the lesion examined. If still in doubt, the diagnosis can be substantiated by supplementary immunocytochemical examinations.

Cytologic features in fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia.

Fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia showed peculiar but nonspecific features. The overall picture seems more important than individual elements in recognizing this rare entity cytologically, since the predominant type of malignant cells has a deceptively bland appearance. The differential diagnoses include other primary thyroid malignancies, as well as metastatic growth and Hashimoto's thyroiditis.

Clue helping to distinguish hyalinizing trabecular adenoma from carcinoma of the thyroid in fine-needle aspirates.

Fine-needle aspirates from four hyalinizing trabecular thyroid adenomas stained with May-Grünwald-Giemsa showed a distinctive component of purplish red stromal deposits corresponding to accumulations of basement membrane material occurring in such tumors. Recognition of these deposits helps to prevent cytologic overdiagnosis of malignancy in this rare benign tumor, which has a number of traits in common with both papillary and medullary carcinoma of the thyroid.

Clinicopathological peculiarities in parathyroid disease with hypercalcaemic crisis.

OBJECTIVE: To draw attention to some hitherto unnoticed clinicopathological aspects of primary hyperparathyroidism in patients who develop hypercalcaemic crisis. DESIGN: Retrospective review of records and histopathological archive material. SETTING: University hospital. SUBJECTS: 54 patients treated for primary hyperparathyroidism with hypercalcaemic crisis between 1961 and 1988. MAIN OUTCOME MEASURES: Correlation of age, serum calcium concentration, histopathological appearance and size of tumours associated with hypercalcaemic crisis. RESULTS: 11/54 (20%) of the patients with hypercalcaemic crisis were younger than 40 years of age. Among 460 patients treated at the same hospital for primary hyperparathyroidism without hypercalcaemic crisis, 23 (5%) belonged to the same age category (p less than 0.001). There was no difference between the two groups of patients regarding histopathological characteristics, with the exception of mitotic activity which was remarkably high in some benign lesions causing hypercalcaemic crisis. The correlation between tumour size and degree of hypercalcaemia was poor, and one-third of the adenomas did not exceed 2 cm in diameter. CONCLUSIONS: Young age is a risk factor regarding the development of hypercalcaemic crisis in primary hyperparathyroidism; the proportions of the pathological entities causing hypercalcaemic crisis do not differ markedly from other cases of primary hyperparathyroidism; the correlation between adenoma size and degree of hypercalcaemia is poor; oxyphil adenomas are as likely to be associated with hypercalcaemic crisis as other types of parathyroid adenoma; and some benign parathyroid lesions associated with hypercalcaemic crisis (hyperplastic glands as well as adenomas) show high mitotic activity.

Primary hyperparathyroidism due to solitary adenoma. A comparative multicentre study of early and long-term results of different surgical regimens.

Surgical regimens for treatment of solitary parathyroid adenoma were compared in a multicentre study in five departments of surgery in the United States and Europe. Three hundred and twenty-five patients fulfilled the inclusion criteria. Eight years after the operation 272 patients (84%) were available for follow-up investigation. Severe postoperative hypocalcaemia (less than 2.00 mmol) was significantly more common after bilateral than unilateral exploration (p less than 0.001), and in women (p less than 0.01). Neither age nor preoperative serum calcium concentration was related to the severity of postoperative hypocalcaemia. At follow-up, 96% of the patients who had had unilateral, and 89% of those who had had Bilateral exploration had remained normocalcaemic without further treatment. Of the patients who had had incisional biopsies of normal glands 8% had hypercalcaemia and 8% had hypocalcaemia. Of patients operated on without a biopsy being taken or who had had one whole normal gland removed 1% were hypercalcaemic and 4% were hypocalcaemic. Early and late hypocalcaemia are reduced by atraumatic handling of the normal parathyroid gland without increasing the risk of persistent or recurrent hypercalcaemia.

Papillary carcinoma of the thyroid with mucoepidermoid features.

The significance and differential diagnoses of signet-ring cells found in the fine-needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are reported and discussed. The primary tumor occurred in a 35-year-old man, who had a history of neck irradiation during his childhood. Despite postoperative treatment with 60 Gy external radiation and 1,200 mCi 131I, the patient has at present--12 years after the initial operation--progressive disease with local recurrence in the neck as well as lung metastases.

Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management.

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.

Stricture and perforation of the esophagus: overlooked threats in the Zollinger-Ellison syndrome.

This study was undertaken to assess the frequency of significant esophageal involvement in the Zollinger-Ellison syndrome (ZES). In a consecutive series of 24 patients with this disease, 9 (37%) showed endoscopic evidence of acid-induced esophageal lesions ranging from erosive inflammation to ulceration with massive bleeding, severe stricture formation, and perforation. In 3 cases, pronounces esophagitis was known 1-5 years before the underlying disease was diagnosed. Severe esophageal complications developed despite treatment with antisecretory drugs. It is emphasized that the best way to limit such complications is by excision of the underlying gastrin-secreting tumor(s) when possible.

Oncocytic tumor of the pancreas. Report of a case with aspiration cytology.

The fine needle aspiration (FNA) cytologic findings in a case of pancreatic oncocytoma are reported, and the differential diagnoses are discussed. The FNA picture was consistent with an oncocytic, acinar or islet cell neoplasm; electron microscopy was required to make the definitive diagnosis. The partially cystic tumor measured 7 cm and occurred in the head of the pancreas in a 63-year-old man with symptoms related to compression of the common bile duct. The clinical findings in this and a few other known cases indicate that the malignant potential of pancreatic oncocytoma may be low. Thus, it is important to distinguish this type of tumor from the cytologically similar acinar carcinoma of the pancreas, which has a poor prognosis in general.

Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence?

Review of medical records in 600 consecutive cases of primary hyperparathyroidism revealed 10 patients with a documented history of iodine 131 (131I) treatment. In seven cases 131I had been given because of Graves' disease and in three cases for ablation of thyroid remnants after tumor operations. All but one of the patients were women. Their age at the time of 131I treatment ranged from 21 to 72 years, and the interval to detection of hypercalcemia was between 3 and 27 years. It is noteworthy that all patients treated for Graves' disease had absorbed radiation doses large enough to cause permanent hypothyroidism, and half of them showed complete absence of the thyroid gland at subsequent operation for hyperparathyroidism. Furthermore, parathyroid adenomas had developed at the sites of thyroid remnants in cases with 131I ablation after tumor operations. Our findings support other observations indicating that not only external radiation but also radiation from 131I is a risk factor for development of hyperparathyroidism, and it is emphasized that age at the time of radiation treatment may be of decisive importance in this context.

The surgical treatment of gastrinoma in MEN I syndrome patients.

The pancreatic component of the multiple endocrine neoplasia type I (MEN I) syndrome is a difficult and controversial problem because the entire endocrine pancreas is diffusely involved with varying degrees of islet-cell hyperplasia, microadenomatosis, and nesidioblastosis. In addition, in patients with functional syndromes, islet-cell tumors usually develop, and these may or may not be malignant. Because of the presumed inability to alleviate or cure the Zollinger-Ellison syndrome (ZES) in MEN patients, total gastrectomy was the treatment of choice before the introduction of H2 antagonists and omeprazole. At present, many physicians and surgeons consider H2 antagonists the best treatment and advise pancreatic exploration only when a gross pancreatic tumor is demonstrated on imaging studies. During the past 10 years we have studied all MEN I patients with ZES without hepatic metastases or gross pancreatic tumors using percutaneous transhepatic selective venous gastrin samplings. Two patterns of gastrin secretion were identified: (1) diffuse from multiple pancreatic sites and (2) localized regional secretion. Four patients from the latter group were selected for attempted surgical "cure" without gastrectomy or total pancreatectomy. Two additional patients are included who had resection of gastrinomas and have maintained basal serum gastrin levels within the normal range for extended periods. The follow-up on these patients ranges from 5 months to 12 years. All six patients have normal basal gastrin values, and those with remaining stomachs require no drug therapy.

Chromosome studies in thyroid neoplasia.

Cytogenetic studies in thyroid neoplasia were performed by G-banding of chromosome preparations obtained from the in vitro cultures of nine adenomas, one follicular carcinoma, five papillary carcinomas, and two medullary carcinomas. Complex structural chromosome aberrations were found in one adenoma. Two more adenomas, both composed of Hürthle cells, showed multiple numerical chromosome deviations with trisomy 4 and tetrasomy 7 in common. Six metastasizing carcinomas were characterized by normal stemlines, which indicates that malignancy in thyroid neoplasia cannot be excluded by cytogenetic techniques used currently. Comparisons between cytogenetic findings and cytophotometric DNA measurements in the material studied illustrate that euploid tumors represent a heterogenous group including cases with various gross structural chromosome aberrations of yet unknown clinical significance. Further studies of additional material with long-term follow-up are called for by our findings of structural and numerical chromosome aberrations in follicular neoplasms that are benign according to histologic criteria.

ABO blood group antigens in parathyroid adenoma and hyperplasia.

Immunohistochemical determination of ABO blood group antigens was performed on parathyroid tissue to see if the presence or absence of such antigens could be used as an aid to distinguish adenoma from hyperplasia in primary hyperparathyroidism. Material from nine cases of solitary adenoma and seven cases of hyperplasia fixed in formalin and embedded in paraffin was studied using monoclonal antibodies and avidin-biotin-peroxidase complex technique. The two categories of tissue did not show any consistent differences in the extent or intensity of immunoreactivity, and the method tested did not permit distinction between adenomatous and hyperplastic disease of the parathyroid glands.

Nuclear DNA content and behavior of oxyphil thyroid tumors.

Microspectrophotometric measurement of nuclear DNA content was made on archival smears of fine-needle aspirates from 23 oxyphil thyroid neoplasms. Fourteen tumors were considered benign as judged from the histologic picture as well as follow-up for 7 to 18 years after the operation. Nine tumors were malignant; five of these showed capsular penetration and/or blood vessel invasion as the only signs of malignancy, whereas the remaining four in addition had histologically verified metastases and were the cause of death. The DNA patterns found--diploid, polyploid or aneuploid--appeared to have a limited diagnostic value, since malignancy could not be excluded on this basis. A practically useful finding was, however, that aneuploidy appeared to be associated with a high probability of invasive growth. As regards prognostic information, it was found that euploid patterns occurred in tumors from patients with long survival after surgical treatment, while tumors with aneuploid patterns showed a variable clinical course.

Fat staining in parathyroid disease--diagnostic value and impact on surgical strategy: clinicopathologic analysis of 191 cases.

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Surgical strategy in nonfamilial primary parathyroid hyperplasia: long-term follow-up of thirty-nine cases.

The extent and result of surgery in 39 cases of nonfamilial primary parathyroid hyperplasia followed from 2 to 20 years are reported. Thirteen patients had been subjected to subtotal parathyroidectomy leaving no gland intact, while 26 had undergone less extensive surgery leaving at least one grossly normal or near-normal gland intact without biopsy. In the former group two patients (15%) developed permanent hypoparathyroidism requiring vitamin D treatment. In the latter group there were two patients (8%) with persistent hypercalcemia, which might have been avoided with a subtotal parathyroidectomy. Judging from these results, we believe that an individualized surgical approach is justifiable in nonfamilial primary parathyroid hyperplasia. Subtotal parathyroidectomy, leaving no gland intact, is advocated as the method of choice only when all four glands are enlarged. If one or more glands are grossly normal or near normal, factors such as degree of hypercalcemia, symptoms, age, general condition, and life expectancy should be taken into consideration when the extent of the operation is decided. A more conservative operation leaving at least one grossly normal gland intact without biopsy appears to be sufficient for cure in most of these cases and minimizes the risk for development of permanent hypoparathyroidism.

Surgical strategy in hyperparathyroidism due to solitary adenoma.

Based on the postulate that parathyroid adenoma is practically always a solitary lesion, unilateral parathyroidectomy including the homolateral normal parathyroid was applied as a principle in the treatment of this form of primary hyperparathyroidism. The exploration was confined to the adenoma side if this was the first to be explored. Intraoperative oil-red-O staining of frozen sections was used to exclude the possibility of a multiglandular involvement. This principle was applied in a consecutive series of 102 patients operated for hyperparathyroidism from 1977 to 1981 and diagnosed as parathyroid adenoma. In 43 patients where the abnormal gland was found on the side explored first, unilateral parathyroidectomy was performed on that side, avoiding exploration of the contralateral side. In 45 patients where normal glands were found on the side first explored, unilateral parathyroidectomy was performed on the contralateral side. In 14 patients other types of operations were performed as the above-mentioned principle could not be achieved. At follow-up 1 to 5 years after surgery, no cases of hypocalcemia were recorded. The results of the different operations were compared as to early and late hypocalcemia. Early hypercalcemia was more pronounced after a bilateral exploration. Two of the patients who had an atypical operation had a permanent need for vitamin D in order to maintain an adequate serum calcium level. Surgical principles for various possible exploratory findings are outlined. These are based upon the idea of performing a unilateral parathyroidectomy whenever intraoperative oil-red-O staining excludes multiglandular involvement as a cause for the hyperparathyroidism.