Alpha human atrial natriuretic peptide and anterior pituitary hormones secretion in men.
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Biomedical subjects
Publications and source records attributed to B Busnardo.
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Serum levels of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and TSH were measured in euthyroid subjects after a single dose of 4 mg D-thyroxine (DT4) or of 0.25 mg L-thyroxine (LT4). The same parameters and TSH response to TRH were also evaluated in 7 dyslipidemic patients before and after one month of treatment with 6 mg DT4. T4 levels increased about 165% at h 4 after DT4 and only 47% after LT4; T3 levels remained unchanged until h 10 both after DT4 and after LT4; rT3 levels increased almost 179% after DT4 and only 32% after LT4. TSH levels decreased about 30% after both DT4 and LT4. In the long term study similar variations of the same parameters were observed: basal TSH levels decreased and TSH response to TRH was inhibited in all patients but one; T4 levels increased 62%, T3 levels increased 35%, while rT3 levels increased 545%. Our results show that: both acute and long-term treatment with DT4 suppress TSH secretion; DT4 both in acute and in long-term administration, is preferentially dealogenated in the alaninic ring with production of rDT3, instead of in the phenolic ring with production of DT3. This may contribute to explain its lower metabolic activity.
Calcitonin is a potent inhibitor of bone resorption and in both sexes, plasma levels progressively decrease with age: therefore, a relative deficiency of calcitonin may be involved in the pathogenesis of osteoporosis in the elderly. Calcitonin plasma levels of young hypogonadic men with osteoporosis are significantly lower than controls: the hypothesis that the decreased calcitonin plasma levels in the elderly are due to a reduced secretory capacity of the "C" cells of the thyroid gland, related to age, does not explain the low calcitonin plasma levels found in young hypogonadic osteoporotic men. Our hypothesis is that gonadal steroid deficiency may participate in the mechanisms regulating calcitonin secretion. Therefore, we studied ten males affected by hypogonadotropic hypogonadism and ten normal men, of comparable age, as controls: we measured plasma levels of testosterone, 17 beta estradiol, androstenedione and calcitonin, and the response of calcitonin to an i.v. bolus of pentagastrin, a well known "C" cells stimulatory drug. Testosterone and calcitonin plasma levels and the response of calcitonin to pentagastrin were also evaluated after 6 months of replacement therapy with testosterone. Basal levels of testosterone, 17 beta estradiol, androstenedione and calcitonin, and the response of calcitonin to pentagastrin, are significantly lower in our patients than in controls, demonstrating that hypogonadotropic hypogonadic subjects have a lower secretory reserve of calcitonin. After testosterone therapy the basal calcitonin plasma levels and its response to pentagastrin stimulus did not differ from controls, suggesting that gonadal steroids influence the calcitonin secretion and reserve. Our data cannot clarify whether osteoporosis of hypogonadotropic hypogonadic patients is related to androgen or estrogen deficiency; however, they suggest that the mechanisms by which gonadal steroid influence bone metabolism may involve calcitonin secretion.
In 3737 subjects without clinically thyroid disorders we evaluated the incidence of thyroid microsomal and thyroglobulin antibodies. These autoantibodies were found in 7% of a normal population, in 9% of patients with various non-autoimmune diseases, and in 11-16% of groups who either had or were at risk for autoimmune diseases: patients with IDDM, vitiligo, alopecia areata, idiopathic hypoparathyroidism, Addison's disease, and first-degree relatives of IDDM patients. Functional thyroid evaluation with TRH test was performed in 197 seropositive subjects and 144 seronegative controls. One-quarter (26%) of the subjects with thyroid autoantibodies showed functional abnormalities on TRH testing, whereas only 2.8% of the 144 seronegative controls showed subclinical hypothyroidism. After an observation period of 12-44 months, 102 persistently seropositive subjects were reassessed and 31% of them showed an impairment in TRH test response.
Serum thyroglobulin (Tg) levels were measured during thyroid-hormone suppressive therapy in 291 patients who had been treated for well-differentiated thyroid carcinoma. The findings were compared with those of a subsequent total body scan (TBS) and with Tg levels measured after thyroid-hormone withdrawal. Of the patients with low Tg levels during suppressive therapy, 91.6% were subsequently shown to be free of disease or to have only remnants in the thyroid bed, whereas 8.4% had metastases (false-negative). Of the patients with false-negative findings, 89.3% had nodal metastases; 60.8% of the patients with nodal metastases exhibiting radioiodine uptake and only 23% of those with nonfunctioning nodal metastases had low Tg levels during suppression therapy. After thyroid-hormone withdrawal, all but 1 of the patients with nodal metastases had high Tg levels. All but 2 of the patients with distant metastases had high Tg levels during suppression therapy; 1 of these 2 patients exhibited high Tg levels after T3 withdrawal. No differences between Tg levels in patients with functioning and non-functioning metastases were found. Our study indicates that Tg assays performed during suppressive therapy have a fairly good predictive value and can be used as a general guide in the follow-up of thyroid cancer. However, since most differentiated metastases produce Tg only when stimulated by thyroid-stimulating hormone, measurements of Tg levels after the discontinuation of suppressive therapy would also seem to be necessary.
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The effects of thyrotoxicosis and of hypothyroidism on human muscle have been studied on single fiber preparations. In thyrotoxic muscle, the ratio between fibers showing the fast type of myofibrillar protein isoforms (fast fibers) and fibers showing the slow type (slow fibers) is increased, as is the percentage of fibers with incomplete segregation of fast and slow myosin (intermediate fibers). Furthermore, in fast fibers, the volume and, to a greater extent, the rate of Ca transport of sarcoplasmic reticulum (SR) are increased, without changes in the affinity for Ca2+ of the Ca-pump or in its sensitivity to the cyclic adenosine monophosphate (cAMP) dependent protein kinase system. These effects are completely reversed by the removal of thyroid hormones, as demonstrated by hypothyroid muscles. It is suggested that in human muscle cells thyroid hormones are critical for the expression of fast genes and for SR Ca transport.
UNLABELLED: Serum thyroglobulin (Tg) was measured in 429 patients with well-differentiated thyroid carcinoma, during thyroid hormone suppression therapy. 324 patients out of 429 were considered free of disease; 44 had only remnants in the thyroid bed; 61 had metastases, of them 40 were detected by TBS and 21 were nonfunctioning and were detected by other diagnostic procedures. Tg was measured by a RIA method in 257 patients and by an IRMA method in 277 patients. The correlation between the two methods was very good (r = 0.914) for values higher than 25 ng/ml with the RIA method. The cut-off limit to distinguish pathological from nonpathological values was considered the mean value found in the patients free of disease plus 2SD. The cut-off limit for the RIA method was 24.2 ng/ml and 3.0 ng/ml for the IRMA method. Of patients with high Tg levels 92% had metastases, either nodal or distant; only 8% had remnants in the thyroid bed. Tg levels were high in 80% of the patients with metastases, all but two of the patients with metastases and low Tg levels had nodal metastases. Moreover, Tg levels were high in 76% of the patients with metastases unable to take up radioiodine. IN CONCLUSION: patients with low levels of serum Tg during suppression therapy have a high probability of being free of disease, even though the presence of tumors cannot be excluded. On the other hand a value greater than the cut-off limit suggests the presence of metastases despite a negative scan.
The aim of this study was to ascertain whether there was an interrelationship between male osteoporosis, calcitonin and androgens. Ten young hypogonadal osteoporotic men were studied: testosterone and calcitonin plasma levels were measured before and after therapy with testosterone enanthate (200 mg im every three weeks for four months). In these patients testosterone and calcitonin plasma levels were significantly lower than controls, before therapy (p less than 0.001 and p less than 0.01 respectively). Testosterone treatment significantly increased (p less than 0.05) serum calcitonin. The conclusion was that androgen deficiency may cause osteoporosis also by decreasing calcitonin secretion.
Serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) were evaluated in a group of 41 patients with histologically proven medullary thyroid carcinoma (MCT) before and sequentially after treatment for a period up to 7 years. Before thyroidectomy, CT levels were high in all patients, and significantly more elevated when metastases were present. On the other hand, CEA levels were high in most but not all the patients, and they also were found more frequently to be elevated in patients with metastases. After treatment, most of the patients without metastases showed persistently normal basal and pentagastrin stimulated CT and CEA levels. In some patients either without or with local metastases, postoperative CT levels, although considerably reduced, remained persistently above normal limits, whereas CEA levels became completely normal. This pattern may be due to the persistence of minute occult foci of the tumor, not sufficient to produce measurable amounts of CEA, which is not synthesized by all tumor cells. Most of the patients with metastases at diagnosis, showed still elevated CT and CEA levels after treatment. In the nonprogressive cases both markers decreased after adjunctive treatment or remained unchanged. In patients with progressive disease, an increase of CEA levels in the absence of a parallel increase of CT levels, which even decreased, was often observed. In one patient with progressive disease high CEA levels were seen for the first time when liver metastases had occurred. These data seem to suggest that, even though CEA production is not recognizable in all patients with MCT, in the CEA positive cases CEA levels may follow a nonparallel pattern and may have a distinct diagnostic meaning with respect to CT levels. In some cases, particularly in advanced disease, CEA may be a more useful marker of poor prognosis.
Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.
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The rate of TSH suppression in patients with differentiated thyroid cancer, when therapy is re-started after total body scan, was investigated adopting an optimal saturation regimen, either with T4 or with T3. The first group of 6 patients received T4 as follows: from day 1 to 7 = 22, 11, 6, 4, 3.5, 3.2, 3.2 micrograms/day/kg body weight (b w) and continued with 3.2; the second group of 8 patients received T3 as follows: 2.4, 1.8, 1.4, 1.2, 1.1, 1.1 micrograms/day/kg BW and continued with 1.1. At time 0, TSH levels were high in all patients (range 80-180 microU/ml); T3 and T4 levels were below the limit of detectability. After the beginning of the therapy, the decrease of TSH levels and the inhibition of TSH response to TRH occurred faster in patients taking T3 than in patients taking T4. In the former, at day 7, mean basal TSH level was 1.9 +/- 0.5 microU/ml and 30 min after 200 micrograms TRH iv mean TSH level was 9.9 +/- 4.4 microU/ml; at day 10 they were 1.4 +/- 0.5 and 2.7 +/- 0.8 microU/ml respectively. In the latter, at day 7, mean basal TSH level was 4.6 +/- 3.9 microU/ml and 30 min after TRH mean TSH level was 42.2 +/- 34.2 microU/ml. Only at day 20 they were 0.8 +/- 0.2 and 1.2 +/- 0.9 microU/ml respectively. In patients taking T3 by saturation regimen, serum levels of T3 rose rapidly to supranormal values (at day 3, mean serum T3 level was 297 +/- 62 ng/100 ml), reached a peak at day 5 (340 +/- 62 ng/100 ml) and decreased thereafter, always remaining however above normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)
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