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Biomedical subjects

F Maloof

Publications and source records attributed to F Maloof.

At least 19 recordsLinked to original sources
PubMed1992

Benign thyroid diseases and the risk of death from breast cancer.

A survey of the causes of death among women with benign thyroid disease was conducted to assess the risk of breast cancer mortality in thyroid patients. The study population was all women diagnosed with one of several types of thyroid disease at the Massachusetts General Hospital Thyroid Clinic from 1925 to 1974. A population-based comparison group was matched to the Clinic patients for age and socioeconomic status, resulting in a total of 9,520 matched pairs. A search of the Massachusetts mortality records located death certificates for 10.9% (1,039) of the Thyroid Clinic patients and 10.5% (995) of the comparison women. Cancer was the cause of death in 21% (218) of the Thyroid Clinic patients and 24% (239) of the comparison women. Fewer patients than comparison women died from cancers of the digestive organs (30.2 vs. 45.5%), but more patients died from thyroid cancer (3.7 vs. 0%), lymphatic and hematopoietic cancers (11.5 vs. 4.2%), and cancers of other sites (8.3 vs. 3.8%). Breast cancer deaths accounted for 21.6% of cancer deaths in the patients and 22.2% of cancer deaths in the comparison women. When specific thyroid diagnoses were considered, the percent of all deaths due to breast cancer ranged from 1.9 to 5.6%, compared to 5.3% in the comparison women. Of the diagnostic groups studied, patients with Hashimoto's thyroiditis had the lowest percent of deaths due to breast cancer, while those with nontoxic nodular goiter had the highest.

Adult↗
PubMed1990

Cancer mortality in women with thyroid disease.

A retrospective follow-up study of 7338 women with either nontoxic nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, or no thyroid disease was conducted. All women patients at the Massachusetts General Hospital Thyroid Clinic who were seen between 1925 and 1974 and who were treated for a minimum of 1 year were traced. A total of 2231 women (30.4%) were dead and 2012 women (27.4%) were alive as of December 31, 1978. Partial follow-up information was available for the remaining 3095 women (42.2%). The average length of follow-up was 15.2 years. When losses to follow-up were withdrawn at the time of their loss, the standardized mortality ratios (SMR) for all causes of death were 1.2 [95% confidence interval (CI), 1.1-1.3] for women with nontoxic nodular goiter, 1.2 (95% CI 1.0-1.3) for those with thyroid adenoma, 1.4 (95% CI 1.3-1.5) for women with hyperthyroidism, 1.5 (95% CI 1.3-1.7) for hypothyroid women, 1.2 (95% CI 0.9-1.5) for those with Hashimoto's thyroiditis, and 1.5 (95% CI 1.4-1.6) for those without thyroid disease. For deaths from all cancers, the standardized mortality ratios were 1.5 (95% CI 1.2-1.8) for women with nontoxic nodular goiter, 1.5 (95% CI 1.1-1.9) for those with thyroid adenoma, 1.2 (95% CI 1.0-1.4) for women with hyperthyroidism, 1.0 (95% CI 0.7-1.4) for the hypothyroid women, 1.2 (95% CI 0.7-2.1) for those with Hashimoto's thyroiditis, and 1.3 (95% CI 1.0-1.5) for those women without thyroid disease. When specific cancer sites were studied, excess numbers of deaths were observed from breast cancer in women with nontoxic nodular goiter (SMR = 1.6, 95% CI 1.0-2.6) and from lymphatic and hematopoietic cancer in women with nontoxic nodular goiter (SMR = 2.4, 95% CI 1.2-4.3) and thyroid adenoma (SMR = 2.7, 95% CI 1.1-5.2). An increase in thyroid cancer risk was observed in women with thyroid adenoma (SMR = 11.7, 95% CI 1.3-42.1) but was based on only two deaths. In hyperthyroid women, statistically significant increases in the number of deaths were observed from pancreatic cancer (SMR = 2.6, 95% CI 1.4-4.3) and respiratory cancer (SMR = 2.2, 95% CI 1.3-3.5), but not breast cancer (SMR = 1.3, 95% CI 0.8-1.8). When the data were stratified by the time between the onset of thyroid symptoms and death, a nonsignificant excess number of cancer deaths was observed in hyperthyroid women who died 20 or more years after their symptoms began.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1988

Radioactive iodine therapy and breast cancer. A follow-up study of hyperthyroid women.

A follow-up study of 1,762 hyperthyroid women who were treated at the Massachusetts General Hospital Thyroid Unit between 1946 and 1964 was conducted. The average length of follow-up was 17.2 years. A 1978 mailing address or a death certificate was located for 92% of the women, and 88% of 1,058 living patients responded to a mail questionnaire. The standardized mortality ratio (SMR) for all causes of death was 1.3 (95% confidence interval (CI) 1.2-1.4). The standardized mortality ratios for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.7-1.1) and 1.3 (95% CI 0.8-1.9), respectively. More deaths than expected were observed from endocrine and metabolic diseases (SMR = 1.8, 95% CI 1.2-2.7), circulatory system diseases (SMR = 1.4, 95% CI 1.3-1.6), and respiratory system diseases (SMR = 1.9, 95% CI 1.3-2.6). The standardized incidence ratios (SIR) for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.8-1.1) and 1.2 (95% CI 0.9-1.5), respectively. A nonsignificant excess breast cancer risk was observed 10 years after the onset of thyroid symptoms and was present at the end of 30 years of observation. A statistically significant excess number of pancreatic cancer cases (SIR = 2.0, 95% CI 1.0-3.7) and a nonsignificant excess of brain cancer cases (SIR = 2.3, 95% CI 0.7-5.3) were observed. Eighty per cent of the women were treated with radioactive iodine. When age at treatment and year of treatment were controlled, women who were ever treated with radioactive iodine had a standardized rate ratio for breast cancer of 1.9 (95% CI 0.9-4.1), compared with those who were never treated with radioactive iodine. Women who developed hypothyroidism as a result of their treatment for hyperthyroidism did not have an increased risk of developing breast cancer (SIR = 1.1, 95% CI 0.8-1.6).

Adult↗
PubMed1979

The relationship between endogenous hyperprolactinaemia and plasma aldosterone.

It has been suggested that prolactin is a regulator of aldosterone secretion. In order to test this hypothesis, we measured prolactin, thyrotrophin and aldosterone by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in eight normal women before and after the intravenous injection of 200 microgram of thyrotrophin releasing hormone (TRH). Prolactin increased from 4.1 +/- 1.1 ng/ml (mean +/- SE) to a peak of 27.4 +/- 3.8 (P less than 0.005) at 15 min following TRH. Plasma renin activity was not different from control levels (1.0 +/- 0.2 ng/ml/h) during the first hour following the administration of TRH, nor did the plasma aldosterone concentration differ significantly from the control levels (39 +/- 7 pg/ml) during this period. However, with upright posture, an increase in aldosterone (from 31 +/- 3 pg/ml at 1 h to 68 +/- 9 at 2 h, P less than 0.005) and in plasma renin activity (from 0.9 +/- 0.2 ng/ml/h at 1 h to 2.0 +/- 0.5 at 2 h, P less than 0.05) was noted, demonstrating a normal capacity to secrete aldosterone in these subjects. Similarly, no change in aldosterone was seen in nine patients with primary hypothyroidism given TRH, despite the fact that the increase in prolactin was greater than normal. Chronic hyperprolactinaemia was not associated with hyperaldosteronism in six patients with pituitary tumour. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

Adrenal Cortex↗
PubMed1979

Augmentation of pituitary thyrotrophin response to thyrotrophin releasing hormone during subphysiological tri-iodothyroinine therapy in hypothyroidism.

Five hypothyroid patients are reported with increased pituitary TSH response to TRH during administration of T3. In one patient treated with intravenous T3, 50 micrograms daily for 10 days, the peak serum TSH and total pituitary TSH reserve after TRH increased coincident with increases in serum T3 and T4 levels and a decrease in the basal TSH concentration. In four patients treated with oral T3, the peak serum TSH and total pituitary TSH reserve after TRH increased during administration of subphysiological doses of T3. Peak serum T3 levels occurred 4 h after ingestion and increased progressively with increasing T3 doses. Serum TSH levels decreased modestly with the nadir at 4 h after T3 ingestion and then returned to basal levels at 24 h. Augmentation of TSH responses to TRH occurred simultaneously with decreases in serum cholesterol, as well as increases in the pituitary prolactin response to TRH, and increase in the GH and cortisol response to insulin induced hypoglycaemia where these responses could be studied. These data demonstrated a positive effect of subphysiological T3 therapy in these hypothyroid patients on the TSH response to TRH as well as increases in the responses of other pituitary hormones to stimulation.

Adult↗
PubMed1979

Metabolic clearance and production rates of prolactin in man.

Metabolic clearance rates (MCR) and production rates (PR) of prolactin (PRL) have been determined by the constant infusion to equilibrium technique in 11 normal subjects, 6 patients with hyperthyroidism, 4 patients with hypothyroidism, and 9 patients with hyperprolactinemia. PRL MCR was also determined tin four patients during dopamine infusion. Mean PRL MCR was 46 +/- 1 ml/min per m2 in women and 44 +/- 3 ml/min per m2 in men, and was significantly correlated with body mass (r = 0.84, P less than 0.001). In contrast with controls, PRL MCR was higher in hyperthyroidism (MCR = 52 +/- 8 ml/min per m2, P less than 0.05), was slightly lower in hypothyroidism (MCR = 38 +/- 10 ml/min per m2, P = NS), and was significantly correlated with serum thyroxine (r = 0.46, P less than 0.02). PRL MCR was lower than controls in hyperprolactinemia (MCR = 40 +/- 5 ml/min per m2, P less than 0.01) and was inversely correlated with serum PRL (r = -0.72, P less than 0.001). PRL MCR was not significantly changed by dopamine infusion. Mean PRL PR for women and men was 211 +/- 74 and 187 +/- 44 micrograms/d per m2, respectively (P = NS). In hyperthyroidism the PRL PR was elevated (PR = 335 +/- 68 micrograms/d per m2, P less than 0.02), but in hypothyroidism the increase (PR = 233 +/- 159 micrograms/d per m2) was not significant. In hyperprolactinemia the PRL PR was extremely high (PR = 31,000 +/- 29,000 micrograms/d per m2). Dopamine infusion decreased RPL PR from 270 to 66 micrograms/d per m2 indicating that its effect was on pituitary PRL secretion and not PRL metabolism. To evaluate possible circulating PRL heterogeneity that might arise during infusion, gel filtration of infusate and serum obtained during the MCR procedure was performed. Labeled monomeric PRL (peak III, Kav (partition coefficient) = 0.4) was partially converted to two larger forms (peaks I and II) in vivo. Peak I (Kav = 0) was 30--40% immunoprecipitable, although peak II (Kav = 0.2) was not immunoprecipitable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of peak I resulted in greater than or equal to 90% conversion to peak III and restoration of full immunoactivity. Thus, peak I is a noncovalently linked aggregate that is partially immunoactive, and therefore able to alter MCR determinations. These studies demonstrate the impact of hormone heterogeneity on MCR estimations and suggest that gel filtration of immunoprecipitable material be an integral part of future MCR measurements.

Adenoma↗
PubMed1979

Thiourea and cyanamide as inhibitors of thyroid peroxidase: the role of iodide.

Thiourea, methylmercaptoimidazole, propylthiouracil, and thiouracil are all potent inhibitors of thyroid peroxidase (TPO)-catalyzed iodination. Unlike the cyclic thioureylenes, thiourea at 5 mM has no effect on guaiacol oxidation. If iodide is added to guaiacol assays containing thiourea, enzyme activity is lost. The latter observation may be explained as follows. In the presence of iodide, the iodinating species [TPO.Ioxid], oxidizes thiourea to formamidine disulfide. This product decomposes to cyanamide at neutral pH. We have shown cyanamide to be an inhibitor of the peroxidative and iodinating functions of TPO. Studies in rats demonstrate that doses of thiourea which completely inhibit in vivo protein-bound iodine formation have no irreversible effect on TPO, as measured by guaiacol peroxidation after removal of the thyroids. The major in vivo action of cyanamide is similar to that of thiourea. The data suggest that the primary in vivo and in vitro mode of action of thiourea is the reversible Ioxid-trapping mechanism. The anomalous inhibition of guaiacol peroxidation seen in the presence of thiourea plus iodide derives from the formation of formamide disulfide, followed by its nonenzymic decomposition to cyanamide.

Animals↗
PubMed1979

Alkaline phosphatase isoenzyme patterns in hyperthyroidism.

Fifteen of 36 hyperthyroid patients had elevation in serum alkaline phosphatase activity. There was no difference in mean thyroxine (T4), triiodothyronine (T3), age, or duration of illness between the groups with high alkaline phosphatase and normal alkaline phosphatase levels. After treatment, serum alkaline phosphatase levels rose as T4 levels declined; at 3 months, the mean serum alkaline phosphatase value rose from 7.1 Bodansky units to 10.3 Bodansky units (P less than 0.005), while the mean T4 value fell from 18 microgram/dl to 7.2 microgram/dl (P less than 0.005). In some patients, serum alkaline phosphatase values have remained elevated for more than 1 year, despite continued normality in thyroid variables. Before therapy, isoenzyme patterns analyzed by polyacrylamide gel electrophoresis were qualitatively normal. As therapy was instituted, the isoenzyme patterns changed markedly, with increased amounts of bone alkaline phosphatase appearing in the serum as T4 levels were declining and total alkaline phosphatase was rising. Thyroid tissue homogenates from patients with Graves' disease were found to have very low levels of alkaline phosphatase activity and an isoenzyme pattern quite distinct from that found in the serum.

Adolescent↗
PubMed1978

Serum thyrotropin releasing hormone (TRH)-degrading activity: a sensitive and rapid radiochemical assay procedure.

A rapid and sensitive method has been developed to assay thyrotropin releasing hormone (TRH)-degrading activity in serum. In this assay, the formation of proline, a major serum degradation product of TRH (pGlu-His-Pro-NH2), is measured. The procedure is based on the finding that proline can be readily separated from TRH with Dowex 50 by a batchwise procedure in a test tube.

Animals↗
PubMed1978

Myocardial function in hypothyroidism. Relation to disease severity and response to treatment.

Systolic time intervals (ST) were used to evaluate myocardial function prospectively in 29 hypothyroid patients. The patients were divided into three categories of disease severity: (1) severe hypothyroidism, (2) mild hypothyroidism, and (3) decreased thyroid reserve or "prehypothyroidism." Groups 1 and 2 showed decreased myocardial contractility with a prolonged preejection period (PEP), shortened left ventricular ejection time (LVET), and increase PEP/LVET, compared with normal controls. The STI were more abnormal (P less than .05) in group 1 than in group 2, suggesting that the severity of myocardial dysfunction correlates with the severity of the hypothyroidism. Group 3 had normal STI. Ten patients were restudied when euthyroid and showed complete normalization of their STI, supporting the thesis that hypothyroidism was the sole cause of the initial myocardial dysfunction.

Female↗
PubMed1978

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate of formation of proline, a major TRH degradation product in serum, was one-quarter to one-third that in euthyroid adult sera. The differences were highly significant (P less than 0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera. The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.

Adult↗
PubMed1978

Decreased thyroid function and high plasma prolactin levels in rats of the Buffalo strain.

Rats of the inbred Buffalo strain have previously been reported to be susceptible to thyroiditis, as defined by histology. We have studied the endocrinology of the pituitary-thyroid axis of this strain by making direct measurements of the plasma concentrations of TSH and T4 in untreated, adult Buffalo rats of both sexes. Plasma PRL levels were also measured. All hormone determinations were by RIA. In addition, relative thyroid weights were noted and, in many cases, preliminary assessment of thyroid histology was made. Our principle findings were as follows. 1) Decreased thyroid function, in addition to the previously reported histological abnormalities, was found to occur spontaneously among the rats studied. Indications of decreased function included elevations of plasma TSH and thyroid weight and depressions of plasma T4. We estimated the incidence of unequivocal thyroid disease as approximately 3% in each sex. 2) Basal plasma PRL concentrations of Buffalo rats averaged three to four times higher than those of outbred CD rats. Our findings strongly suggest that rats of the Buffalo strain will provide a good model for the study of thyroid failure of varying degrees and concomitant changes in the circulating levels of pituitary hormones.

Animals↗