Biomedical subjects
Publications and source records attributed to D S Ross.
It is becoming increasingly common to discover adrenal masses incidentally on radiologic imaging studies. Adrenal masses are also occasionally found unexpectedly during operation. Herein, we review 10 cases of incidentally discovered adrenal masses which illustrate the experience with the treatment of these lesions in the past 8 years. A management plan based on this experience and a review of previously published data are discussed.
Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status.
A new commercially available chemiluminescent TSH assay demonstrates an 8- to 10-fold increase in sensitivity over a sensitive immunoradiometric assay, allowing increased ability to distinguish partial from more complete thyrotroph suppression. Sera were analyzed from 145 patients who had TSH concentrations below 0.08 mU/L in the immunoradiometric assay. Most patients with overt hyperthyroidism had undetectable TSH concentrations in the chemiluminescent assay. Three groups of patients were identified, in which a large subgroup had undetectable values in the immunoradiometric assay and detectable values in the chemiluminescent assay (12 of 17 patients under treatment for hyperthyroidism who had recently normalized their serum thyroid hormone levels, 33 of 68 patients taking L-T4, and 4 of 8 patients with endogenous subclinical hyperthyroidism). In addition, several patients with undetectable basal and detectable TRH-stimulated TSH values in the immunoradiometric assay had detectable basal TSH values in the chemiluminescent assay. The utility of first generation TSH immunometric assays was their ability to distinguish hyperthyroidism from euthyroidism. The clinical utility of increasingly sensitive TSH assays will be to distinguish degrees of thyrotroph suppression in subclinical hyperthyroidism.
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The use of screening mammography has increased dramatically, leading to the discovery of suspicious, nonpalpable mammary lesions. Mammographic wire localization (MWL) is currently being used to facilitate the biopsy of these lesions. We reviewed 104 patients undergoing 106 biopsies after MWL during a 14 month period to determine the usefulness of MWL. The average age of the patients was 58 +/- 14 years, with a range of 38 to 83 years. Abnormal mammographic findings consisted of microcalcifications (48 per cent) or mass and density (43 per cent), or both (9 per cent). Lesions of the right side (55 per cent) and upper and outer quadrant (49 per cent) were predominant. An average of 1.4 (range of one to four) specimens taken at biopsy per patient were required to remove the lesion. The mean duration of the biopsy was 34 minutes, with a range of ten to 75 minutes, and the mean total time in the operating room was 63 (range 31 to 115) minutes. The average cost of the procedure did not differ significantly between local and general anesthesia ($1,030 versus $1,142, respectively). Pathologic findings included fibrocystic disease (77 per cent), carcinoma (12 per cent) and fibroadenoma (7 per cent). Normal mammary tissue was found in 4 per cent of the biopsies. Five of the 13 carcinomas were in situ and seven were either in situ (five) or microinvasive only (two); only six lesions were frankly invasive. Ten patients were treated with modified radical mastectomy while three had segmental resection. All patients had in situ or Stage I carcinoma. MWL effectively localized nonpalpable mammary lesions and allowed accurate diagnosis and treatment of early stage carcinoma of the breast.
The effect of piroxicam, a nonsteroidal anti-inflammatory drug, on a transplantable adenocarcinoma in Fischer rats was studied. Forty male Fischer rats were injected with 1 X 10(6) DMH-F317 adenocarcinoma cells, and after 2 weeks were assigned to be treated with piroxicam or carrier solution. The groups were as follows: Group 1, control; Group 2, 4.0 mg/kg piroxicam; Group 3, 6.0 mg/kg piroxicam; and Group 4, 8.0 mg/kg piroxicam. Thirty-nine of forty rats developed measurable tumors during this study. At the conclusion, 60% (6/10) of the rats in Group 2 were tumor free compared to 0/10 controls, 0/10 Group 3 rats, and 1/8 Group 4 rats. (P less than 0.005, chi 2). Mean tumor volumes (mm3) were calculated for each group and converted to log10. At Week 6, the mean log10 tumor volume (+/- SEM) for Group 2 was 1.5 +/- 0.6 vs 4.1 +/- 0.1 for Group 1 (P less than 0.05). The mean log10 volume for Group 3 was 3.8 +/- 0.1 (P less than 0.05 vs Group 2). The mean log10 volume for Group 4 was 3.4 +/- 0.05 and was not significantly different from that for Group 2 (P greater than 0.05). Plasma PGE2 levels for each treatment group were determined at the conclusion of the study and no statistical difference between treatment groups was found. It is concluded that piroxicam inhibits tumor growth in this model, and may have a role as a biological response modifier in cancer therapy.
Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.
Milk and blood samples were obtained from three Icelandic dairy herds. The herds were monitored regularly for mastitis incidence. Cell counts, adenosine triphosphate (ATP) and antitrypsin levels of the milk samples were recorded. In addition, red cell and BoLA typing were performed on the blood. Although cell counts and ATP levels showed significant associations with mastitis, antitrypsin levels did not. Red blood cell antigens N'2 and S1 and the lymphocyte antigen detected by the monoclonal antibody M7 were associated with low cell counts, whilst BoLA w6 and w6.1 were associated with high cell counts. BoLA w6.2 and w11 showed significant association with high antitrypsin levels. Only ED116 showed a significant association with mastitis.
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The incidence of metachronous colorectal cancer has been reported to be 1 to 5 percent, with most of the cases being discovered within ten years of the initial cancer. A retrospective review of all colorectal cancer patients was conducted at the Southern Illinois University Affiliated Hospitals to determine the incidence of metachronous colorectal cancer at the authors' institution. In this study, a metachronous cancer was defined as a second colorectal primary occurring at least three years following discovery of the initial lesion. Between 1978 and 1984, there were 24 patients with metachronous colorectal cancer identified in an operative series of 707 patients for a frequency of 3.4 percent. These metachronous cancers were discovered at intervals ranging from 3 to 35 years. Sixteen (67%) metachronous lesions occurred 11 years of more after the original cancer. Synchronous or interval adenomatous colorectal polyps were noted in 17 (71 percent) of the patients. Thirteen of the metachronous cancers appeared in the right colon, while six were distributed throughout the transverse and descending colon, and five were in the rectosigmoid region. The incidence of late-appearing metachronous colorectal cancers and the propensity to occur in the right colon underscores the need for evaluation of the entire colon as part of lifelong follow-up of the colorectal cancer patient.
Spontaneous hyperthyroidism and that due to excessive administration of thyroid hormone result in osteopenia. Bone density was measured in 28 white premenopausal female patients who were taking commonly prescribed suppressive doses of L-thyroxine (mean dose 0.171 +/- 0.035 g) for five or more years. The thyroxine level was 13.5 +/- 2.6 micrograms/dl (normal 8.0 +/- 2.4 micrograms/dl), the free thyroxine index was 4.4 +/- 1.0 (normal 2.4 +/- 0.8), and the triiodothyronine value was 154 +/- 26 ng/dl (normal 132 +/- 32 ng/dl). Basal thyrotropin was undetectable (less than 0.08 microIU/ml) in 23 patients, and thyrotropin measured 20 minutes after thyrotropin-releasing hormone administration was not demonstrable in 13 patients and subnormal in 10 patients. Women who had taken L-thyroxine for 10 or more years (n = 12, age 37 +/- 4 years) had a 9 percent reduction in bone density (0.667 +/- 0.044 g/cm2, p less than 0.01) compared with normal premenopausal age-matched control subjects (n = 56, age 35 +/- 6 years, bone density 0.733 +/- 0.055 g/cm2). It is concluded that prolonged suppressive L-thyroxine treatment may result in mild subclinical hyperthyroidism with adverse effects on bone. Patients requiring suppression of the pituitary-thyroid axis should be given the smallest dose of L-thyroxine necessary to achieve a satisfactory clinical response.
Dexamethasone, like T3, inhibits the production of TSH. T3 inhibits TSH synthesis by reducing transcription of the genes encoding TSH-beta and alpha-subunits. Little information is available concerning the effects of dexamethasone on the individual subunits, or the combined effects of dexamethasone with T3. In a preliminary study, hypothyroid mice bearing the thyrotropic tumor TtT 97 were treated with 25, 250, or 500 micrograms dexamethasone ip daily for ten days. Plasma levels of TSH and its subunits were unchanged after 25 micrograms of dexamethasone and maximally suppressed after 250 micrograms. Plasma TSH was reduced to 51% (P less than .02), free TSH-beta to 54% (P less than .01), and alpha-subunit to 62% (P less than .001) of control values. In two similar experiments hypothyroid mice bearing TtT 97 were treated with dexamethasone (250 micrograms), T3 (0.5 or 1 microgram), or both dexamethasone with T3 for 10 days. Total alpha-subunit and TSH-beta were calculated by adding 1/2 TSH + free subunit concentrations. In the experiment using 1 microgram of T3, total plasma alpha-subunit was reduced by dexamethasone to 72%, by T3 to 45% (P less than .02), and by combined treatment to 23% (P less than .01) of control values. In the experiment using 0.5 microgram of T3, total plasma alpha-subunit was reduced by dexamethasone to 66% (P less than .05), by T3 to 67% (P less than .05), and by combined treatment to 46% (P less than .02) of control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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Lymphocyte antigens controlled by alleles at the BoLA-A locus were used to indicate which of two bulls could be eliminated as the sire in 18 cases of disputed parentage. The use of bovine lymphocyte antigens (BoLA) significantly increased the exclusion probability over that of the standard red cell and electrophoretic techniques.
We have abruptly discontinued T3 administration to hypothyroid mice bearing thyrotropic tumors and measured increases in tumor steady state TSH subunit mRNA levels with time. Hypothyroid mice bearing the thyrotropic tumor TtT97 were injected daily with T3 (10 micrograms/100 g BW, ip, daily) for 10 days. Groups of mice (n = 3) were killed on the day of the last T3 injection (day 0) and 1, 2, 3, or 5 days after stopping T3 treatment. Plasma T3 concentrations fell to subnormal values between days 1 and 2 after stopping T3 treatment. Plasma TSH and total TSH subunit concentrations were 3% of untreated hypothyroid control concentrations on day 0, and rose 4-fold between days 1 and 2 and 20-fold by day 5 (P less than 0.01). Plasma total alpha-subunit concentrations were 28% of untreated hypothyroid control concentrations on day 0, rose to 158% of baseline values by day 2, and rose 3-fold by day 5 (P less than 0.001). Tumor TSH beta and alpha-subunit mRNA levels were 5% and 52% (P less than 0.01) of hypothyroid control levels on day 0. TSH beta mRNA levels rose nearly 9-fold between days 1 and 2 (P less than 0.01). alpha-Subunit mRNA levels rose to 135% of initial values by day 2 and to 144% of initial values by day 3 (P less than 0.05). Changes in tumor TSH subunit mRNA levels paralleled changes in plasma subunit glycoprotein concentrations. Increases in tumor subunit mRNA levels after abruptly stopping T3 treatment occurred rapidly, predominantly between 24-48 h after stopping T3, and TSH beta mRNA was considerably more responsive than alpha-subunit mRNA.
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We have recently described a mouse pituitary tumor line which produces only the alpha-subunit of the glycoprotein hormones. This tumor line may be a useful animal model to study autonomous pituitary tumors which secrete only alpha-subunit. Our pure alpha-subunit producing tumor was derived from a thyrotropic tumor which secreted intact TSH as well as free alpha-subunit. Our current studies compare the regulation of alpha-subunit biosynthesis in a conventional thyrotropic tumor and the alpha-subunit producing tumor. Thyroxine or triiodothyronine administration to mice bearing the alpha-subunit producing tumor resulted in no change in plasma alpha-subunit concentration, and a 10-19% reduction in tumor alpha-subunit mRNA concentration that was not statistically significant. In contrast, thyroxine administration to mice bearing the thyrotropic tumor resulted in an 81% reduction in plasma alpha-subunit concentration, and a 75% reduction in tumor alpha-subunit mRNA concentration (P less than 0.01). Other studies using a cDNA specific for thyrotropin-beta (TSH beta) failed to detect TSH beta mRNA in the alpha-subunit producing tumor, while TSH beta mRNA was easily detected in the conventional thyrotropic tumor. We conclude that during the development of the alpha-subunit producing tumor from a thyrotropic tumor, loss of TSH beta mRNA was also associated with an impaired capacity for thyroid hormone to decrease concentrations of alpha-subunit mRNA.