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Biomedical subjects

N W Thompson

Publications and source records attributed to N W Thompson.

At least 55 records · Page 3Linked to original sources

Health status improvement after surgical correction of primary hyperparathyroidism in patients with high and low preoperative calcium levels.

BACKGROUND: We conducted a prospective cohort study to determine whether there are differences in functional health status between patients with low (< 10.9 mg/dL) and high (> or = 10.9 mg/dL) serum calcium levels before surgical correction of primary hyperparathyroidism (HPT) and to compare changes in health status after correction of primary HPT. METHODS: The SF-36 Health Survey, which provides demographic and condition-specific information, was used to obtain information on patients with primary HPT seen in a university hospital endocrine surgery clinic over a 4-year period before operation and again 2 months and 6 months after operation. RESULTS: A total of 155 patients were studied; 86 had calcium levels < 10.9 mg/dL (normal < 10.5 mg/dL) and 69 had serum calcium levels > or = 10.9 mg/dL (range 10.9 to 13.4 mg/dL). One hundred four patients completed 6-month reports, 55 with low calcium levels and 49 with high calcium levels. Both high and low calcium groups showed marked and virtually identical impairment of functional health status. Both groups showed marked improvement in health status at 2 months and additional improvement at 6 months, returning to normal or near normal in 6 of 8 SF-36 domains. CONCLUSIONS: Patients with primary hyperparathyroidism have significant functional health status impairment independent of the level of serum calcium. Dramatic improvement is seen after surgical correction. Referral for surgical treatment of primary HPT should not be delayed until serum calcium is elevated, as recommended in the 1990 National Institutes of Health consensus statement.

Calcium↗

Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both.

The management of multiple endocrine neoplasia type 1 (MEN-1) pancreatic-duodenal disease, particularly when the Zollinger-Ellison syndrome (ZES) is the presenting manifestation, has remained controversial. The management of hypoglycaemia and other syndromes as well as large tumours detected by imaging is less controversial, although standardized surgical techniques have not been generally adapted. The rationale for an aggressive operative management plan for ZES and other syndromes is based on the facts that neuroendocrine tumours of both the pancreas and the duodenum have malignant potential and that the functional manifestations can be controlled with appropriate surgical procedures based on current concepts of the MEN-1 disease. Of the ten concepts presented, the one critical to the surgical treatment of ZES is that a duodenotomy is essential in detecting the source of hypergastrinaemia in most MEN-1 patients. The complete operation is multifaceted and includes peripancreatic lymph node dissection (ZES), enucleation of any head or uncinate tumours and a distal pancreatectomy. Our results in 40 MEN-1 patients with functional syndromes treated with these procedures are encouraging. Ten patients with hypoglycaemia (four with concomitant ZES) have been 'cured' with follow-up as long as 18 years. Sixty-eight per cent of 34 patients with ZES have remained eugastrinaemic during follow-up as long as 19 years. One patient developed a solitary liver metastasis that was excised a year ago without other evidence of recurrence. There has been no operative mortality and three subsequent deaths were due to unrelated disease.

Duodenal Neoplasms↗

Alterations of the MEN1 gene in sporadic parathyroid tumors.

Primary hyperparathyroidism is a common endocrine disease that also occurs in a number of inherited disorders, including multiple endocrine neoplasia type 1 (MEN1). Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 has been found in 30% of sporadic parathyroid tumors, making the recently cloned MEN1 gene a prime candidate for involvement in parathyroid tumorigenesis. Using LOH and single strand conformation analysis, we screened 45 sporadic tumors from 40 patients for alterations involving the MEN1 gene. Thirteen tumors showed LOH at 11q13, and in 6 of these cases, somatic mutation of the MEN1 gene was detected. In tumors without LOH, no mutations were detected. The mutations consisted of 3 small deletions, 1 insertion, and 2 missense mutations that had not been reported in MEN1 patients or parathyroid tumors previously. Using messenger ribonucleic acid in situ hybridization, the expression of the MEN1 gene was studied. There was no difference in expression between normal and tumor tissue. In conclusion, the findings of inactivating mutation in tumors with LOH at 11q13 confirm the role of the MEN1 tumor suppressor gene in a subset of sporadic parathyroid tumors.

Adult↗

Surgical correction of primary hyperparathyroidism improves quality of life.

BACKGROUND: The SF-36 health status assessment tool is well suited for measuring the morbidity associated with primary hyperparathyroidism (HPT). The purpose of this study was to test the hypothesis that surgical correction of primary HPT leads to measurable improvement in patient reported functional health status and well-being. METHODS: For the past 4 years patients with primary HPT have been asked to complete the SF-36 and to provide additional demographic and condition-specific information for study before operation. They then completed the SF-36 again by mail 2 months and 6 months after operation. RESULTS: One hundred forty patients entered the study through March 1998; 110 patients completed follow-up at 2 months and 82 at 6 months. Marked impairment compared to population norms occurred before operation in 7 of 8 domains of health status. Substantial improvement occurred in 5 of 8 domains of health status at 2 months and in 6 of 8 domains at 6 months. Statistically significant improvement was demonstrated in limitations caused by physical and emotional role function, social function, bodily pain, and vitality. CONCLUSIONS: Successful operation to correct primary HPT significantly improves patient reported functional health status and quality of life. Most improvement is seen within 2 months, but additional improvement in both physical and mental function is seen at 6 months.

Adult↗

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.

Adenoma↗

Diagnostic dilemma of small incidentally discovered adrenal masses: role for 131I-6beta-iodomethyl-norcholesterol scintigraphy.

Incidentally discovered adrenal masses are detected in 0.35% to 5. 00% of patients imaged with computed tomography (CT) for reasons other than suspected adrenal pathology. Most small adrenal masses are benign, although malignant tumors </= 3 cm in diameter are well described. In the setting of normal adrenal hormonal secretion, the preferential accumulation of 131I-6beta-iodomethyl-norcholesterol (NP59) by adrenocortical tissues allows the distinction of adenomas from other space-occupying or destructive lesions, with diagnostic images being obtained in 100% of lesions > 2 cm. Although some lesions </= 2 cm have yielded nondiagnostic images, the frequency of this phenomenon and thus the utility of NP59 scintigraphy for the evaluation of small adrenal lesions has remained incompletely characterized. Between January 1976 and December 1994 a total of 166 patients with nonhypersecretory unilateral adrenal masses </= 3 cm in maximal diameter, discovered incidentally during CT examinations of the abdomen or chest for reasons other than clinically suspected adrenal disease, were studied with NP59 scintigraphy. Nonhypersecretory masses </= 1 cm, > 1 to </= 2 cm, and > 2 to </= 3 cm yielded diagnostic images in 52%, 89%, and 100% of patients, respectively. Lesions other than adenomas, including malignancies, > 1 to </= 2 cm and > 2 to </= 3 cm were present in 9% and 10% of patients, respectively. These findings emphasize the need to determine the nature of small incidentally discovered adrenal masses whose management may alter patient care and confirm the utility of NP59 scintigraphy to evaluate nonhypersecretory adrenal masses regardless of size.

19-Iodocholesterol↗

Fas (APO-1, CD95)-mediated apoptosis in thyroid cells is regulated by a labile protein inhibitor.

To determine whether thyroid cell apoptosis observed in autoimmune thyroid disease could be related to activation of the Fas pathway, we examined the expression and function of Fas on thyroid follicular cells in vitro. Fas messenger RNA was found to be present using two different techniques and was expressed at equal levels in thyrocytes cultured either in the presence or absence of TSH. Fas antigen protein expression was demonstrated by Western blot of thyroid cell lysates and by immunohistochemical staining of thyrocytes, and the amount of Fas protein present did not appear to vary regardless of culture conditions. Despite expressing substantial amounts of Fas protein, thyrocytes treated with anti-Fas monoclonal antibody failed to undergo apoptosis. The addition of either interferon-gamma or interleukin-1beta to the anti-Fas-treated cell cultures also did not promote apoptotic signaling through this pathway. In contrast, the concomitant administration of cycloheximide allowed the induction of apoptosis through the activation of Fas in thyrocytes. These results suggest that Fas is constitutively expressed in thyrocytes, but that the induction of apoptosis through the Fas pathway is blocked by a labile protein inhibitor.

Antibodies, Monoclonal↗

Operative experience of U.S. general surgery residents with diseases of the adrenal glands, endocrine pancreas, and other less common endocrine organs.

The aim of this study was to determine if the experience of general surgery residents is adequate and effective. The Resident Statistic Summaries (Report C) of the Residence Review Committee (Surgery) for eight academic years from 1986 to 1994 were analyzed. The main outcome measurements were total number of residents and programs, average number of operations performed, maximum number of operations performed, standard deviation, and the most common number of operations performed. For adrenalectomy, the average per resident was 0.98. The maximum range was from 7 to 15. The standard deviations ranged from 1.12 to 2.00. For pancreatic endocrine operations the average per resident was 0.15 with maximums of 3 to 10. For other endocrine procedures (nonthyroid and nonparathyroid) the average per resident was 0.14, with the maximums ranging from 7 to 19. The most common number of any of these procedures performed by U.S. graduates was 0. The number of adrenal, endocrine pancreas, and other less common endocrine procedures available for graduates of U.S. residency training programs is limited. As a consequence, most U.S. resident graduates have little or no experience with any of these procedures. Our findings suggest a strong need for fellowship training for any surgeon hoping to develop expertise in the management of these unusual and infrequent endocrine surgical diseases.

Adrenal Gland Diseases↗

Riedel's thyroiditis: treatment with tamoxifen.

BACKGROUND: Riedel's thyroiditis is an often disabling disease with clinical and histologic similarity to several other fibrous inflammatory disorders. Surgical treatment alone is often unsatisfactory in permanently alleviating airway compression, dysphagia, neck immobility, pain, or chronic fatigue syndrome. Investigation of drugs shown to be of benefit in the treatment of related fibrous disorders in which hormonal factors or inflammatory deregulation appear to be important is indicated. Tamoxifen has not been previously used in the treatment of Riedel's thyroiditis. METHODS: Four patients with clinical and histologic diagnoses of Riedel's thyroiditis were evaluated before and after treatment with tamoxifen. Each had progressive symptomatic disease of 3 to 16 years' duration despite one or more surgical procedures and steroid therapy. Subjective improvement was noted in all cases, and objective changes were confirmed by periodic physical and computed tomographic examinations. RESULTS: Patients have been monitored for 1 to 4 years with subjective improvement in 100% and objective disease regression ranging from 50% to 100% in all patients. One patient had complete regression within 6 months, and another had more than 50% regression within 3 months. All have returned to predisease activity levels. There were no significant side effects of the therapy. CONCLUSIONS: Tamoxifen has proved to be the most effective drug therapy available for managing Riedel's thyroiditis. Our studies suggest that this is unrelated to antiestrogen activity. Tamoxifen's effectiveness may be caused by a mechanism by which it stimulates the release of transforming growth factor-beta, which may inhibit the fibroblastic proliferation characteristic of Riedel's thyroiditis.

Adult↗

Thyroid tumors in children.

Thyroid tumors in children continue to generate tremendous interest and controversy. Despite a frequent presentation with metastatic disease, these differentiated tumors have an excellent prognosis. Because most pediatric patients have prolonged survival, long-term follow-up is mandatory. The extent of surgery for this disease continues to be controversial. Genetic testing is changing dramatically the management of patients with multiple endocrine neoplasia and will lead to further understanding of this intriguing syndrome. Over the next decade, classification of differentiated thyroid cancers by means of more clinically useful biologic markers may affect the clinical management of children with thyroid cancer.

Adolescent↗

Simultaneous scintigraphic depiction of aldosteronoma and adrenal infarction.

Primary aldosteronism is a potentially curable cause of hypertension, especially when caused by an adrenal adenoma. Aldosteronomas because of their small size often elude techniques to locate them. This case illustrates the advantages, disadvantages and complications of noninvasive techniques used for their diagnosis. A patient with hypertension and hypokalemia underwent an adrenal venous effluent sampling for measurement of aldosterone concentrations. This procedure was complicated by an injury to the right adrenal gland. Subsequently, it was difficult to control the patient's hypertension and hypokalemia with medical therapy alone. A re-assessment years after his initial diagnosis included a CT scan, which now visualized a left adrenal tumor. The functional status of this tumor and lack of function of the previously injured right adrenal gland were demonstrated by NP-59 scintigraphy. This information modified the surgical intervention (adenectomy rather than total adrenalectomy) and the residual left sided adrenal tissue prevented adrenocortical insufficiency. A year later the patient remains euadrenal.

Adosterol↗

Subtotal parathyroidectomy in dialysis-dependent and post-renal transplant patients. A 25-year single-center experience.

OBJECTIVE: To determine long-term results and durability of parathyroidectomy in patients with chronic renal failure and renal transplant recipients. DESIGN: Retrospective chart review and structured telephone interviews. SETTING: Tertiary-care academic medical center. PATIENTS: Ninety-one consecutive patients (80 undergoing long-term dialysis, 11 with posttransplant hyperparathyroidism). Mean follow-up was 8 years (minimum follow-up, 2 years; longest follow-up, 25 years). The most common indications for operation were bone pain (70% [56/80]) and weakness (46% [37/80]) in patients with renal failure and hypercalcemia (91% [10/11]) in renal transplant recipients. INTERVENTION: Subtotal parathyroidectomy without remnant gland implantation. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality, relief and recurrence of symptoms. RESULTS: Symptoms were successfully ameliorated in 95% (86/91) of patients. Clinically significant complications occurred in 5% (5/91) of patients (one patient each with wound hematoma, wound infection, and permanent recurrent laryngeal nerve paralysis and two patients with permanent hypoparathyroidism). Recurrence occurred in five (5%) of 91 patients. Two of these patients required four operations each to eradicate all hyperfunctioning accessory glands. The other three recurrences were caused by hyperplasia of the remnant gland left in the neck. These were easily treated by simple excision, with no morbidity. The actuarial rate of recurrent hyperparathyroidism was 4.1% at 1 year and 11.7% at 20 years. Overall hospital mortality was 3% (3/91). None of the deaths was directly attributable to parathyroidectomy. CONCLUSIONS: We recommend subtotal parathyroidectomy without remnant implantation as a safe and durable intervention for hyperparathyroidism associated with renal failure and following renal transplantation. This intervention is associated with an acceptably low recurrence rate over extremely long periods of follow-up.

Adult↗

Scintigraphy of incidentally discovered bilateral adrenal masses.

The purpose of this study was to determine the patterns of iodine-131 6 beta-iodomethylnorcholesterol (NP-59) imaging and the correlation with computed tomography (CT)-guided adrenal biopsy and follow-up in patients with bilateral adrenal masses. To this end we investigated a consecutive sample of 29 euadrenal patients with bilateral adrenal masses discovered on CT for reasons other than suspected adrenal disease. Adrenal scintigraphy was performed using 1 mCi of NP-59 injected intravenously, with gamma camera imaging 5-7 days later. In 13 of the 29 patients bilateral adrenal masses were the result of metastatic involvement from lung carcinoma (5), lymphoma (3), adrenocarcinoma of the colon (3), squamous cell carcinoma of the larynx (1), and anaplastic carcinoma of unknown primary (1). Among these cases the NP-59 scan demonstrated either bilaterally absent tracer accumulation (in eight, all with bilateral metastases proven by CT-guided biopsy or progression on follow-up CT) or marked asymmetry of adrenocortical NP-59 uptake (in five). Biopsy of the adrenal demonstrating the least NP-59 uptake documented malignant involvement of that gland in five of five patients. In two patients an adenoma was found simultaneously in one adrenal with a contralateral malignant adrenal mass. In each of these cases, the adenoma demonstrated the greatest NP-59 uptake. In 16 patients diagnosis of adenoma was made on the basis of (a) CT-guided adrenal biopsy of the gland with the greatest NP-59 uptake of the pair (n = 4), or (b) adrenalectomy (n = 2), or (c) absence of change in the size of the adrenal mass on follow-up CT scanning performed 6 months to 3 years later (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adosterol↗