Metabolic maladaptation: individual and social consequences of medical intervention in correcting endemic hypothyroidism.

Endemic hypothyroidism has been studied in a Central African population in remote Congo (ex-Zaire) to investigate the prevalence, severity, causes, and potential control of this disorder, with questions as to why this disease is conserved, and whether it confers any adaptive advantage in this resource-constrained environment. Iodine deficiency, cassava goiterogens, and selenium deficiency were found to be the factors implicated in the severe hypothyroidism expressed in congenital cretinism and high goiter incidence in this isolated population, which continues to be under observation following medical intervention. Profound hypothyroidism was encountered in whole village populations as measured by serum thyrotropin determinations ranging from very high to over 1000 IU, and thyroxin levels ranging from low to undetectable; cretinism rates were as high as 11% and goiter incidence approached 100%. Assessment of endocrinologic status, caloric requirement, energy output, fertility, and ecologic factors was carried out before and during iodine repletion by depot injection. Hypothyroidism was corrected and cretinism eliminated in the treatment group, with goiters reduced in most instances (with regrowth exhibited in some who escaped control) and some symptomatic goiter patients were offered surgical treatment for respiratory obstruction. Individual patient benefits, including improved strength and increased energy output, were remarkable. The social and developmental consequences observed within the collective groups of treated patients were remarkable for an increase in caloric requirement and a dramatic increase in fertility that led to quantitative as well as qualitative increases in resource consumption. Micronutrient iodine repletion was not accompanied by any concomitant increase in macronutrient supply, and hunger and environmental degradation resulted. The highly prevalent disease of hypothyroidism is found in highest incidence in areas of greatest resource constraint. It may be that hypothyroidism is conserved in such areas because it may confer adaptive advantage in such marginal environments as an effect, as well as a cause, of underdevelopment. Hypothyroidism may limit energy requirements, fertility, and consumer population pressure in closed ecosystems that could otherwise be outstripped. Single factor intervention in a vertical health care program not sensitive to the fragile biologic balance and not part of a culture-sensitive development program might result in medical maladaptation.

"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)

Methods of arterial site skin preparation and dressing.

Before an arterial line is inserted, the skin at the site is prepped typically with the traditional iodophor-based preps. The arterial site is then covered with an occlusive dressing. When arterial lines are maintained for even a few days, it is not uncommon that some form of complication develops at the arterial site, such as redness, inflammation, positional problems, or even infection. Unfortunately, due to the nature of this traditional preparation and dressing method, the site is obscured constantly and complications are not always detected before a resulting infection occurs. This prospective study was designed to examine the efficiency and effectiveness of a new transparent prep, used with a transparent dressing at the arterial site. Sixty patients' arterial line sites were evaluated to determine the incidence of complications of the two arterial site prep and dressing methods. The effectiveness that the dressings may serve in securing the arterial lines in place was also evaluated. There were no complications in this study directly related to either skin preparation or dressing method, thus, there were no statistically significant differences. However, the transparent prep and transparent dressing method provided constant visual access to the arterial site and required fewer steps, clearly significant advantages not provided by the traditional method.

New approaches to serious infections in the surgical patient.

The primary treatment of serious surgical infections involves a surgical procedure--debridement, drainage, or diversion--coupled with the adjunctive use of antibiotic therapy. Antibiotics are administered as prophylaxis, as presumptive therapy, or as precise therapy. Prophylactic antibiotics must be nontoxic, inexpensive, and have a broad spectrum of activity. It is also important that they not interfere with the primary treatment or the host defense. Antibiotics for presumptive therapy must be active against a wide range of presumed pathogens, but they are chosen primarily for their efficacy and secondarily for their lack of toxic and immunosuppressive effects. Because surgical infections are polymicrobial, standard therapy has consisted of a combination of antibiotics; monotherapy with an agent that is less toxic but as effective as combination therapy is a promising new approach to treatment.

[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.