"Aging bull'.

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime. Associated with these abnormalities, however-and not seen in age-matched cows of comparable breeds-are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C cells' of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma-in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy. Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands-bilateral pheochromocytomas and pituitary acidophil adenomas.

Management of ectopic thyroid nodules.

BACKGROUND: Surgical dictum states that the so-called lateral aberrant thyroid represents metastatic thyroid cancer. METHODS AND RESULTS: We present sixteen cases of patients with benign ectopic thyroid tissue. Seven cases were discovered during evaluation and treatment of hyperparathyroidism. The remaining nine cases were discovered during the evaluation and treatment of thyroid disorders or cervical nodules. In fifteen cases there is benign histology on the nodules. One case has been followed for 4 years with scans revealing a normal thyroid gland with an unchanging ectopic thyroid nodule in the superior mediastinum. In eight of our cases there have been thyroid resections searching for occult carcinomas. Histologic examination on these eight thyroid glands revealed either normal thyroid or benign nodules. CONCLUSIONS: Not all lateral aberrant thyroid tissue is malignant. The histologic condition of the nodule combined with intraoperative examination of the ipsilateral thyroid lobe can reliably guide therapy. The old dictum concerning lateral aberrant thyroid representing metastatic cancer should be removed from or modified in review texts and surgical examinations.

Multiple endocrine adenopathy.

The syndromes of multiple endocrine adenopathy (MEA) have associated endocrine abnormalities that are similar to the clinical syndromes based in the same hyperfunctions of parathyroid, pancreatic islets, thyroid C-cell and chromaffin tissue seen in sporadic cases. The natural history, histopathology and management of these problems when they occur in the hereditary MEA syndromes differ in significant and instructive ways over the isolated disorders. These differences and similarities of MEA adenopathies were discussed at an international conference, with the suggestion that the MEA syndromes afford opportunity to investigate regulation and control of pathogenesis in surgical endocrinological syndromes.

Radiologic recommendation for breast biopsy on screening mammography reports.

Radiologic reports on screening mammography findings often obligate breast biopsy. Ready recommendation for biopsy of nonpalpable lesions imaged by x ray is a conservative radiologic policy but is unsettling for patients and creates an imperative bind for surgeons. Like the decision to send the patient with right lower quadrant abdominal pain home rather than to the operating room, the diagnosis that requires clinical confidence and precision is nonappendicitis. Noncancer of the breast is a similar diagnosis that can usually be made on clinical and mammographic findings rather than passing such patients through to invasive diagnosis. A series of 84 patients was referred for needle localization of nonpalpable mammographically detected lesions called suspicious on screening examination. Of these 84 patients, new radiographic reports reinterpreting the findings without biopsy were written on the original mammogram in 15 patients. This is a cancellation rate of 21 per cent. In 69 patients needle localization was carried out with the finding of cancer in 28 per cent, compared with the national average of 15 per cent. This higher than average yield caused concern whether any unbiopsied cancers had been followed, and a review of these patients was undertaken. In the log of patients referred for needle localization, the prereading by the mammographer performing the needle localization was recorded in advance of biopsy confirmation, and specificity proved to be 94 per cent and sensitivity 96 per cent. Of the cancers that were detected, 39 per cent were proven in patients older than 50 years.(ABSTRACT TRUNCATED AT 250 WORDS)

[Environment and genetics of endocrine polyoncoses. An aging bull model]. / Environnement et génétique des polyoncoses endocriniennes. Un modèle: "le taureau vieillissant".

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis--this stiffening up limite, rather than accentuates, the value and reproduction potential of a stud bull past prime. But associated with these abnormalities--and not seen in age-matched cows of comparable breeds--are fascinating endocrine neoplasms that might suggest a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies, that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C-cells" of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma--in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudogout as a clue and complication in primary hyperparathyroidism.

The pseudogout syndrome has been suggested to be a diagnostic clue of hyperparathyroidism or a complication after parathyroidectomy that abruptly relieves hypercalcemia. In this report of 20 patients who had pseudogout, eight had intermittent attacks of arthritis associated with chondrocalcinosis that led through the pseudogout syndrome to a confirmed diagnosis of primary hyperparathyroidism. In an additional 12 patients, the diagnosis of pseudogout was made in patients who suffered from acute arthritis after parathyroidectomy that relieved the primary hyperparathyroidism. The postoperative attacks were seen most commonly on or after the second day after surgery and were associated with the lowest point in serum calcium levels. Pseudogout occurred in one or more joints, often involving the knee. The diagnosis was proved by aspiration of joint synovial fluid in many of the patients and identification of calcium pyrophosphate dihydrate crystals. To estimate the incidence of pseudogout in the population of patients with primary hyperparathyroidism, these 20 patients were distinguished in 531 patients undergoing parathyroidectomy, for a 3.8% incidence of the pseudogout feature. No other markers of higher risk for this complication were apparent, including age, sex, biochemistry, or prior history. This collected experience suggests that (1) pseudogout is a biochemical entity associated with primary hyperparathyroidism and may offer a useful clue to the recognition of the disease in screening; (2) acute arthritis after parathyroidectomy is most likely pseudogout, and this complication occurs more frequently than has been recognized previously; (3) patients with hypercalcemia have a high incidence of calcium pyrophosphate dihydrate crystal deposition in articular cartilage (chondrocalcinosis); and (4) relative hypocalcemia after parathyroidectomy is a stimulus for crystal shedding into synovial fluid, which may precipitate acute attacks of pseudogout.

Effects of epidermal growth factor on thyroglobulin and adenosine 3',5'-monophosphate production by cultured human thyrocytes.

While several workers have identified epidermal growth factor (EGF) receptors on human thyroid membranes, very few reports have described EGF effects on intact human thyroid cells in primary culture, and these were short term studies indicating that EGF effects were primarily inhibitory [reduced iodide uptake and thyroglobulin (Tg), T4, and T3 release]. Paradoxically, in vivo EGF stimulates thyroid growth and increases colloid stores. In this study we examined the effects of EGF on cultured thyroid cells in regard to thymidine incorporation, Tg secretion, and cAMP production during a 12-day period. Addition of EGF (0-30 ng/mL) to medium for 6 or 12 days stimulated thymidine incorporation and enhanced Tg synthesis by thyroid cells. However, the profile of Tg release into medium was biphasic. Tg release was inhibited by EGF (0.1-10 ng/mL) during the first 3 days of culture, but the inhibitory effect disappeared by the sixth day, and EGF stimulated Tg release by day 12 and thereafter. EGF enhanced endogenous cAMP levels in thyroid cells, but did not augment TSH-stimulated increases in cAMP production. Our observations of EGF-stimulated growth and inhibited Tg secretion during short term culture are consistent with the findings of earlier studies with nonhuman thyrocytes. However, the later phase of enhanced cAMP levels with stimulation of Tg secretion indicates that EGF may have trophic effects on thyrocytes previously unrecognized because of the short term nature of the studies. These observations suggest an important role for EGF in maintenance of normal thyroid physiology.

Tracheomalacia from compressing goiter: management after thyroidectomy.

Tracheomalacia may result from prolonged compression by expanding goiter, particularly within the confines of the thoracic inlet. Constriction of the upper airway by the growing goiter may be indication for operation, but the residual problem of tracheomalacia after thyroidectomy is a life-threatening postoperative complication. Examples of postoperative tracheomalacia in patients with neglected goiters endemic in the third world or recurrent goiter with airway compromise in a western medical center referral practice are described for development of management methods. Two patients with lethal postthyroidectomy tracheomalacia led me to anticipate this complication in certain identifiable high-risk patients in my own practice, and the cases of five patients are described for whom several techniques of tracheal support were attempted. One patient, for whom staged tracheoplasty was planned, opted for tracheostomy, whereas four patients have had adequate tracheal airways restored by extrinsic support. One was treated by subtotal thyroidectomy with tracheal suspension; one by staged thyroid reductions; two were treated by creation of extrinsic tracheal neo-rings constructed of surgical wire and vascular prostheses. The patient with the most dramatic airway impairment from the most extensive tracheomalacia experienced very satisfactory airway security. A second patient was also supported by the prosthetic rings but extruded one of them, possibly because of tracheostomy contamination. Until tracheal replacement or better tolerated prosthetic or biologic supports are devised, tracheomalacia will remain a vexing problem complicating thyroidectomy for long-standing or recurrent airway-compressing goiter.

Intraoperative cytologic evaluation of lipid in the diagnosis of parathyroid adenoma.

Analysis of intraoperative air-dried imprints or smears of 20 cases of parathyroid adenoma revealed that the cells of the parathyroid adenomas did not contain extra- or intracellular lipid, but the cytologic material from accompanying normal or atrophic parathyroid glands had large amounts of intracellular lipid and variable amounts of extracellular lipid. Thus, rapid intraoperative cytologic preparation is not only effective in determining whether the specimen is parathyroid or not, but also in specifying the nature of the individual parathyroid glands. These observations again confirm that intraoperative cytologic evaluation of parathyroid tissue is an effective and important pathologic consultation method during parathyroid exploration.

Mucinous colon carcinoma in a black family.

Carcinoma of the large bowel developed in an autosomal dominant pattern in 13 members of a black-American family. Seven members were affected prior to initial ascertainment of the family in 1976. Thereafter, the remaining six were affected while 0.2 cases were expected (p less than 0.001). Median age at diagnosis of colon cancer was 39 years (range, 22-62 years) in this family, compared with 65 years among black-Americans, in general. Histologic review of surgical specimens from six patients and medical record data for a seventh patient showed mucinous adenocarcinoma of the colon, an uncommon histologic variant. Studies of several family members a decade ago had revealed no biologic markers of cancer susceptibility.

Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia.

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.