The developmental changes in plasma adrenal androgens during infancy and adrenarche are associated with changing activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase.

The plasma concentrations of dehydroepiandrosterone, androstenedione, and dehydroepiandrosterone sulfate decrease during the first year of life, remain low during childhood, and then increase during adrenarche. To determine whether alterations in adrenal enzyme activity might explain the changing secretory pattern of the adrenal androgens, we measured human adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase, 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase activities. 12 adrenals from individuals aged 3 mo to 60 yr were studied. The patients were divided into three groups based upon the age of the patient when the adrenal glands were obtained: group 1, infants aged 3--8 mo (n = 3); group 2, preadrenarchal or early adrenarchal children aged 2--9 yr (n = 4); and group 3, adults aged 20--60 yr (n = 5). The mean activity of the 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase fell by 50% and that of 3 beta-hydroxysteroid dehydrogenase-isomerase activity rose 80% from group 1 to 2. A fourfold increase in 17,20-desmolase (P less than 0.002) and 17-hydroxylase (P less than 0.001) activity and a doubling in 21-hydroxylase activity (P less than 0.005) occurred between groups 2 and 3. We conclude that the decline in plasma adrenal androgens after birth appears to be associated with a rise in 3 beta-hydroxysteroid dehydrogenase-isomerase and a fall in 17,20-desmolase and 17-hydroxylase activity. The subsequent increase in plasma adrenal androgen concentration during adrenarche is coincident with a rise in 17,20-desmolase and 17-hydroxylase activity.

Disseminated Trichosporon infection. Occurrence in an immunosuppressed patient with chronic active hepatitis.

A 62-year-old woman with chronic active hepatitis receiving immunosuppressive drugs was initially admitted with sepsis secondary to an intra-abdominal abscess caused by Klebsiella pneumoniae. She had a stormy course despite adequate antimicrobial therapy. Her postoperative course was further complicated by a fungal infection. Blood, urine, and sputum cultures were positive for Trichosporon. Antifungal therapy was given but her condition deteriorated and she died. At autopsy, a disseminated fungal infection was found. Diagnosis and management of such infections in the immunosuppressed host are difficult.

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.

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.

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.

Parathyroid adenolipoma: clinical and morphologic features.

Adenolipoma--or parathyroid hamartoma--has been described s a very rare lesion of the parathyroid gland, often unassociated with clinical hyperparathyroidism. A few reported cases in which the diagnosis was discovered pathologically following parathyroid resection for hyperparathyroidism have been called unique. In a 2-year period the diagnosis of parathyroid adenolipoma was made in three instances, with each clinical presentation consistent with primary hyperparathyroidism. In the first patient, a 64-year old man reporting to an emergency department for treatment of migraine headache, a prolonged history of unrecognized hypercalcemia was discovered, and he underwent cervical exploration. At operation, a 105 by 2.0 cm tumor weighing 17.5 gm was encountered. The other two patients were middle-aged women who had hypercalcemia (one requiring preoperative calcitonin treatment). The diagnosis of adenolipoma was made morphologically, although the clinical course was otherwise indistinguishable from other forms of primary hyperparathyroidism. Each of the three patients were cured following adenolipoma resection. This small series of patients in the experience of a single surgeon in a brief period might indicate that this diagnosis is by no means rare, and the functional nature of these tumors was the characteristic that brought them to diagnosis. The hypercalcemia was somewhat more severe in these cases--but the hyperparathyroidism was otherwise unremarkable. The morphologic features of these tumors include unusual size, proliferating fat content, and a fibrillar stroma. Adenolipoma of the parathyroid can cause primary hyperparathyroidism and should be considered in the differential diagnosis of the morphologic lesions of the parathyroid glands that can produce a hypercalcemic syndrome.

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.

Intraoperative imprints for the identification of parathyroid tissue.

Parathyroid exploration involves identification of all accessible parathyroid glands and the distinguishing of normal and pathologic parathyroid glands. Close collaboration of the surgeon and the surgical pathologist is characterized by courtesy and efficiency with special techniques by each that facilitate accuracy and speed, particularly at the conclusion of the surgical exploration when the biopsy specimens have been passed to the pathologist on a "parathyroid map" and the patient remains anesthetized. Parathyroid imprint by touch preparation technique allowed cytologic examination in less than 1 minute per specimen, with ready identification of the presence or absence of parathyroid tissue. Pathologic diagnoses were also possible on abnormal parathyroid glands when the parathyroid imprint was used as a screening procedure to select specimens for frozen section. Accuracy and speed were excellent as used in this series of parathyroid surgical pathology consultations. Intraoperative imprint confirmation of parathyroid tissue is suggested as an improvement in pathologic consultation during parathyroid exploration.

Management of the adrenal "incidentaloma".

The suprarenal fossa has been a clinically silent area of the body where nonfunctional lesions of soccer ball size could go undetected until they disturbed functions of adjacent organs. Unless an adrenal tumor was suspected by biochemical or clinical screening information, early diagnosis was an exception, and localization usually required invasive techniques. With the advent of noninvasive computer-assisted radiologic and sonographic techniques, surgeons now have the reverse problem of early diagnosis of asymptomatic adrenal mass: do we need to know about nonfunctioning "incidentalomas" and what further action is compelled by their discovery? Sophisticated adrenal imaging techniques, even if noninvasive, should be be utilized as a localizing technique after the biochemical determination of adrenal disease is established. Localization should not precede the biochemical confirmation of endocrine active adrenal disease. For adrenal masses discovered in asymptomatic patients, predictability of curative adrenal surgery is only as good as the strength of the causal link between the clinical evidence of adrenal disease and the localizing information; thus the indication for operation does not rely solely upon the resolving power of adrenal imaging to demonstrate adrenal masses. This causal link is not strengthened by one radiographic test that confirms the results of another in the absence of evidence that adds functional significance to the radiographic findings. For the "incidentaloma" of the adrenal that might represent neoplasm, techniques similar to those employed for thyroid masses should be used for diagnosis rather than the routine prescription of operation based on the mere presence of a space-occupying lesion. Direct correlation of imaging studies applied to prior patient findings is necessary before operation is indicated for adrenal "incidentalomas."

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.

Long-term follow-up of patients with hyperparathyroidism treated by transcatheter staining with contrast agent.

Primary hyperparathyroidism is generally treated by primary neck exploration. Particularly in patients with hyperparathyroidism caused by adenoma, cervical exploration is generally curative, and extensive preoperative localization studies are unnecessary. If, after thorough primary cervical exploration, no adenoma is identified or at least four parathyroid glands are not confirmed and the patient's hypercalcemia persists, radiologic localization studies are indicated prior to a repeat operation. Persistent hypercalcemia in defined as the failure of calcium levels to return to normal soon after parathyroid exploration; recurrent hyperparathyroidism is defined as hypercalcemia that follows 6 months of low or normal serum calcium levels. Persistent or recurrent hypercalcemia not controlled by a primary cervical exploration may be due to an ectopic parathyroid adenoma, either outside the usual anatomic sites in the neck or in the mediastinum. Techniques used for localization of these ectopic adenomas include sonography, computed tomography scanning, venous sampling, digital angiography, and selective arteriography. Of these techniques, selective arteriography not only has been precise but also offers the possibility of therapy. A small group of patients who underwent embolization of ectopic parathyroid adenomas through the angiographic catheter was reviewed 6 years ago with the cautious suggestion that this technique, under highly specialized indications, might offer a percutaneous treatment of hyperparathyroidism in selected patients. Since the time of the preliminary report, radiologic techniques have been modified, indications for patient selection have been refined, and experience with this method of managing persistent hyperparathyroidism has increased. It is the purpose of this report to summarize this experience with long-term follow-up of those patients treated by transcatheter staining.

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.

Solitary parathyroid microadenoma.

In our experience with operations for primary hyperparathyroidism, a recurring problem centers on patients whose solitary adenomas are too small to be appreciated at the initial exploration. We have seen four patients with parathyroid microadenomas, which we define as lesions less than 6 mm in diameter in externally undeformed parathyroid glands. Two such patients were fortuitously cured at the initial exploration even though the operative findings were inconclusive. One, a 25-year-old man, underwent excision of an externally normal gland that contained a 3 by 2 by 2 mm microadenoma. He is eucalcemic since the operation. The other patient, a 70-year-old woman with hypercalcemia, responded to prednisone. She then underwent a neck exploration at which the diagnosis of sarcoidosis was confirmed by lymph node biopsy examination. A 4 by 2 by 2 mm parathyroid microadenoma was incidentally removed. The patient is normocalcemic receiving low-dose steroid treatment since the operation. In a third patient, a 34-year-old practical nurse, three explorations were needed to find a parathyroid gland, which was negative for adenoma on frozen-section microscopy. The solitary adenoma, 6 by 3 by 3 mm, was appreciated only on permanent sections. The majority of oxyphil microadenomas should be suspected to be nonfunctioning, as in a 59-year-old woman in whom the lesion coexisted with primary chief cell parathyroid hyperplasia. The hyperparathyroidism responded well to three and a half-gland resection. The 2 by 2 by 2 mm oxyphil adenoma was also removed. Solitary parathyroid adenomas can be subtle and small. Appraisal of parathyroid disease at the operating table is not always straightforward. As more patients with early hyperparathyroidism appear on routine calcium screening, we may expect to see increasing numbers of challenging solitary parathyroid microadenomas.

Nesidioblastosis in adults. A surgical dilemma.

Nesidioblastosis is the leading cause of hyperinsulinemia in newborns and infants. To our knowledge, it has not been previously reported in adults unless associated with other diseases. Three males and three females, aged 11 to 57 years, are described. Pancreatic resections ranged from 50% to 100%. Postoperatively, three patients were normoglycemic, two were insulin-dependent diabetics, and one had recurrent hypoglycemia controlled by drugs. The histologic findings in adults were very similar to those in infants with nesidioblastosis. It appears that a minimum resection of 75% to 80% of the pancreas will benefit the majority of patients, alleviating hypoglycemia and preventing the development of diabetes.

Clinical effects of membrane lung support for acute respiratory failure.

Extrapulmonary support in respiratory failure has become possible for prolonged periods with clinical application of the membrane lung oxygenator. The membrane lung may be perfused in a venovenous circuit, in which case it functions by prepulmonary venous oxygenation, or it may be pumped in venoarterial perfusion as partial or total cardiopulmonary bypass. Four patients were placed on venovenous membrane lung (GE-Peirce) perfusion for periods ranging from 6 to 112 hours. In oxygenating blood flows of less than 50% of the cardiac output, a viable PaO2 (mean, 52 mm Hg) was obtained in 2 patients with 60% FIO2, including 1 survivor who was weaned from the membrane lung. The remaining 2 patients had heart failure and insufficient venovenous membrane lung flows to improve systemic oxygenation (mean PaO2, 45 mm Hg on 100% FIO2). Four other patients were placed on venoarterial membrane lung (GE-DuaLung) bypass for 18 to 110 hours. With 40 to 85% of the cardiac output bypassed through the membrane oxygenator, immediate improvement was seen in systemic oxygenation (mean PaO2, 75 mm Hg), effective compliance (mean increase of 75%), and reduction in pulmonary hypertension (mean decrease, 15 mm Hg). These changes during bypass allowed the lungs to be put at rest with a decrease in FIO2 and positive end-expiratory pressures. This clinical experience indicates that venoarterial membrane lung bypass may be both supportive and therapeutic, decompressing the pulmonary circuit and maintaining systemic oxygenation. Membrane lung supported by either mode of perfusion has been shown to be clinically effective in patients suffering acute respiratory failure.

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.

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.

Extensive cerebral nocardiosis cured with antibiotic therapy alone. Case report.

A 34-year-old renal transplant recipient developed multiple soft tissue and extensive cerebral nocardiosis. The number and locations of the cerebral abscesses and probable areas of cerebritis precluded surgical drainage procedures. Gradual resolution of all the cerebral lesions occurred over a period of 6 months with antibiotic therapy alone. A review of the literature revealed only one previous case of a patient with pulmonary nocardiosis who had a probable secondary brain abscess and who survived without surgical drainage. Thus, if surgical drainage is not possible, antibiotic therapy alone may offer a hope of survival in what otherwise has been considered a uniformly fatal disease.

Colonic pseudo-obstruction in surgical patients.

Colonic pseudo-obstruction (Ogilvie's syndrome) may occur in surgical patients, particularly those who have had orthopedic or blunt trauma, have uremia or diabetes, have complex metabolic or cardiac failure, have metastatic cancer involving the lymph nodes and neural tissue, or are addicted to narcotics. Although a single true cause has not been identified by fulfilling Koch's postulates, the clinical pattern has been recognized in a variety of surgical patients, and this pattern must be distinguished from true obstruction of the colon. Tumor or internal hernia may constitute an obstruction, but the important differential diagnosis of cecal volvulus must be excluded. Ischemic colitis may be confused with Ogilvie's syndrome or may follow it. Gangrene, infarction, and perforation may ensue as colon diameter increases and particularly if cecal distention reaches above 14 cm. This arbitrary number for cecal dilatation should not be awaited before treatment is instituted if signs of devitalization of the gut or peritoneal signs have developed in the patient. Treatment has changed recently with the widespread application of colonoscopy. Endoscopy is helpful in relieving distention but may also be dangerous in the patient with a massively distended colon, particularly at the level of the thin-walled cecum. Colonoscopy also appears to be associated with a high rate of treatment failure and recurrence. Surgical decompression may take the form of cecostomy or may require exteriorization or resection of the colon if infarction has occurred. A series of 12 patients has been presented. The patients were all referred to a single surgeon in a university medical center over a 4 1/2 year period with clinical patterns not suggestive of a common cause but a similar clinical evolution of Ogilvie's syndrome. The prognosis for such patients in whom the complication is recognized early and in whom decompression is performed endoscopically or surgically is encouraging. If recognition is late and particularly if perforation and gangrene result, mortality is nearly 50 percent.

Management of intravenous extensions of endocrine tumors and prognosis after surgical treatment.

The capacity of endocrine neoplasms to give rise to intravenous tumor extensions is a feature that is recognized preoperatively by the use of venography employed primarily for tumor localization. A series of adrenocortical tumors, a pheochromocytoma and an extraadrenal chromaffin tumor are reported in which the intravenous tumor component was recognized and the surgical approach was modified to include extirpation of the intravascular tumor. Although intravenous tumor propagation has implied a grave prognosis because of the possibility of blood-borne metastases from the intravascular tumor or physiologic disruption from clot or tumor embolus, resection designed for cure, including distal venous control and tumor thrombectomy, was carried out in each patient. Wider application of preoperative venography enables recognition of these intravenous neoplastic extensions from endocrine tumors; the results of surgical management suggest that this invasive feature should not be a grave prognostic indicator that inhibits attempt at operative eradication of the primary tumor and its intravenous extension.