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Biomedical subjects

A Pacchiarotti

Publications and source records attributed to A Pacchiarotti.

33 records · Page 2Linked to original sources
PubMed1988

Free thyroxine and free triiodothyronine measurement in dried blood spots on filter paper by column adsorption chromatography followed by radioimmunoassay.

Free thyroxine (FT4) and free triiodothyronine (FT3) were measured by column adsorption chromatography followed by radioimmunoassay in dried blood spots on filter paper in euthyroid subjects, hyperthyroid and hypothyroid patients, and in subjects with TBG excess. The sensitivity (B/T% = 95%) was 1.5 pg/ml (working range 1.5-46.4 pg/ml) for FT4 and 1.5 pg/ml (working range 1.5-32.0 pg/ml) for FT3. Intraassay coefficient of variations (CVs) ranged 4.4-8.8% for FT4, 8.7-10.1% for FT3; interassay CVs varied from 8.9-9.0% for FT4, 9.3-10.4% for FT3. FT4 and FT3 values found in dried blood spots were highly correlated with the corresponding values in serum (r = 0.97, P less than 0.001 for FT4; r = 0.96, P less than 0.001 for FT3). FT4 concentrations in dried blood spots ranged 8.1-20 pg/ml in euthyroid subjects, 19.4-60.0 pg/ml in hyperthyroid patients, less than 1.5-7.1 pg/ml in hypothyroid patients, 7.8-18.8 pg/ml in euthyroid subjects with TBG excess. FT3 values in dried blood spots ranged 2.5-5.8 pg/ml in euthyroid subjects, 7.1-30.0 pg/ml in hyperthyroid patients, less than 1.5-2.8 pg/ml in hypothyroid patients, 2.5-5.2 in euthyroid subjects with TBG excess. The results of the present study, while confirming previous data on FT4 determination in dried blood spots, represent the first report on FT3 measurement in the same system, thus allowing a more complete assessment of thyroid status made by mail at the expense of few drops of blood.

Adolescent↗
PubMed1987

Further studies on the role of glycosylation in thyroxine-binding globulin secretion by human hepatoma (HEP G2) cells.

To investigate the role of glycosylation of T4-binding globulin (TBG) in the secretion of the protein, human hepatoma (Hep G2) cells were continuously labeled with [35S] methionine or [3H]mannose or pulse-chase labeled with [35S] methionine in the absence or presence of 1 microgram/ml swainsonine, an inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidase. In the presence of this alkaloid, TBG was released into the medium at a faster rate than in control cells (50% being secreted after 35 min and 47 min, respectively), owing to accelerated intracellular transport of the newly synthesized protein. TBG secreted from swainsonine-treated cultures moved faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, probably because of the reduced sialylation of TBG consequent to the perturbed processing of the oligosaccharide units. Furthermore, secreted TBG was sensitive to endo-beta-N-acetylglucosaminidase H digestion as shown by the shift in the apparent molecular size in sodium dodecyl sulfate-polyacrylamide gel electro-phoresis from 50,000 to 45,000 daltons. Sensitivity to endo H indicated the presence of hybrid-type oligosaccharide chains with high mannose structures. This was also suggested by the higher incorporation of [3H]mannose in swainsonine-treated cultures. In conclusion, the results of the present study demonstrate that swainsonine accelerates the release of TBG from Hep G2 cells and that complete processing of oligosaccharide moieties is not required for TBG secretion.

Alkaloids↗
PubMed1987

Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients.

UNLABELLED: Factors affecting TSH suppression by L-T4 administration were retrospectively evaluated in 452 patients: 180 who were athyreotic after total thyroidectomy and remnant radioiodine ablation for differentiated thyroid carcinoma and 272 with nontoxic diffuse or nodular goiter. All patients were considered clinically euthyroid. TSH secretion was assessed by iv TRH stimulation testing. The T4 dose associated with an undetectable basal serum TSH level and no increase in serum TSH after TRH administration (suppressive dose) averaged 2.7 +/- 0.4 (SD) micrograms/kg body weight (BW)/day in athyreotic patients and 2.1 +/- 0.3 micrograms/kg BW/day in goitrous patients (P less than 0.001). The 25th-75th percentile intervals were 2.5-2.9 micrograms/kg BW/day for athyreotic patients and 1.9-2.3 micrograms/kg BW/day for goitrous patients. The suppressive dose of T4 was dependent in both groups on patient age, younger patients needing higher doses than older patients. The duration of treatment also proved to be an important parameter, since in both groups the percentage of patients with suppressed TSH secretion increased if TRH testing was carried out after at least 6 months after the initiation of therapy. Serum total T4, total T3, free T3 (FT3), free T4 (FT4) index, and FT3 index values did not differ in the two groups and were significantly higher (P less than 0.001) than in normal subjects. Mean serum FT4 was significantly higher in athyreotic patients than in goitrous patients with suppressed TSH secretion. Among athyreotic patients with suppressed TSH secretion, 24% had elevated serum FT4 and FT3, and 47% had elevated serum FT4 alone. Of goitrous patients with suppressed TSH secretion, 20% had elevated serum FT4 and FT3, and 27% had elevated serum FT4 alone. On the other hand, 35% of athyreotic patients and 14% of goitrous patients whose TSH secretion was not suppressed had elevated serum FT4. Serum sex hormone-binding globulin concentrations were measured in 3 groups of goitrous women. Values above normal limits were found in 13/26 patients (50%) with high serum FT4 and FT3, in 4/30 patients (13%) with elevated serum FT4 alone, and in 1/25 patients (4%) with normal FT4 and FT3. IN CONCLUSION: TSH suppression requires daily doses of T4 between 2.5 and 2.9 micrograms/kg BW in athyreotic patients and between 1.9 and 2.3 micrograms/kg BW in goitrous patients, with appropriate adjustments in relation to the age of the patient; Assessment of the adequacy of treatment should not be carried out before 6 months after the institution of therapy.

Adolescent↗
PubMed1987

Evaluation of the nocturnal serum thyrotropin (TSH) surge, as assessed by TSH ultrasensitive assay, in patients receiving long term L-thyroxine suppression therapy and in patients with various thyroid disorders.

Circadian variations of serum TSH concentrations have been reported, with higher values occurring in the late evening or early morning. In patients receiving long term L-T4 suppression therapy, it may be important to achieve suppression of TSH secretion throughout the day. To investigate whether undetectable serum TSH values in the morning are associated with undetectable serum TSH levels at night, serum TSH concentrations were measured by an ultrasensitive immunoradiometric assay in 16 normal subjects, 20 hyperthyroid patients, 10 patients with primary hypothyroidism (either untreated or inadequately treated with L-T4), 1 patient with central hypothyroidism, 10 patients with nontoxic nodular goiter, 5 patients with functioning thyroid adenoma, 20 patients receiving L-T4 replacement therapy, and 30 patients receiving L-T4 suppression. In 6 subjects blood was drawn at hourly intervals for 24 h; in 2 normal subjects a major TSH surge occurred between 2300-0100 h, with other minor peaks, and the same pattern was found in two patients receiving L-T4 replacement, whereas in 2 patients receiving L-T4 suppression, serum TSH was constantly below the limit of detection of the assay (i.e. less than 0.07 mU/L). In the remaining patients blood was drawn at hourly intervals between 2300-0200 h and on the next morning before (0830-0900 h) and 30 min after iv TRH administration. In normal subjects, in patients receiving L-T4 replacement therapy, and in hypothyroid patients, serum TSH values at night were higher than in the morning, with normal responses to TRH in the first 2 groups and exaggerated responses in the latter. The patient with central hypothyroidism had no nocturnal TSH surge and no TSH response to TRH. In all hyperthyroid patients, serum TSH was undetectable both at night and during the day, and none had a serum TSH response to TRH. Among patients with nontoxic goiter, 7 had detectable serum TSH in the morning, with higher values at night, and a normal response to TRH; the remainder had undetectable serum TSH both at night and in the morning, and subnormal or absent TSH responses to TRH. All 5 patients with a functioning thyroid adenoma had undetectable serum TSH levels in the morning and during the night, and subnormal or absent TSH responses to TRH. Of the 30 patients receiving long term (greater than 6 months) L-T4 suppression therapy, 28 had undetectable serum TSH both during the night and in the morning and unresponsiveness to TRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1986

Serum free thyroid hormones in subclinical hypothyroidism.

Serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in a group of 52 patients with subclinical hypothyroidism (SH) and in an equal group of age and sex-matched normal controls. SH was defined by normal total T4 (TT4) and total T3 (TT3) concentrations, normal FT4 and FT3 indices, raised TSH levels, in the absence of signs and symptoms of hypothyroidism. Serum FT4 levels averaged 6.1 +/- 1.6 pg/ml (mean +/- SD, p less than 0.001 vs controls), with values below lower normal limits in 33/52 patients; mean FT3 concentrations averaged 3.1 +/- 0.7 pg/ml (p less than 0.001 vs controls), with values below lower normal limits in 8/52 patients. The analysis of results by the Galen and Gambino predictive value model demonstrated a higher sensitivity, but a lower specificity of FT4 as compared to FT3 in the diagnosis of SH. These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.

Adult↗
PubMed1986

Serum thyrotropin by ultrasensitive immunoradiometric assay and serum free thyroid hormones in pregnancy.

Variations of serum TSH, measured by an ultrasensitive immunoradiometric assay, of serum total and free thyroid hormones and of thyroxine-binding globulin (TBG) and sex hormone-binding globulin (SHBG) were investigated in a group of 18 normal women before and during pregnancy. A gradual increase of total thyroid hormones, TBG and SHBG was observed, while mean serum free thyroxine and free triiodothyronine progressively decreased. Serum TSH concentrations were comprised within the normal range throughout pregnancy, although a small but significant increase was found in the 2nd and 3rd trimester. These changes may represent a compensatory mechanism to meet the increased demand for thyroid hormones in pregnancy and must be taken into account for a correct evaluation of thyroid function during gestation.

Adult↗
PubMed1986

Effect of the antileukemic agent L-asparaginase on thyroxine-binding globulin and albumin synthesis in cultured human hepatoma (HEP G2) cells.

L-Asparaginase (ASNase), a drug widely used in the treatment of acute lymphoblastic leukemia, has been reported to decrease serum T4-binding globulin (TBG) levels, while results of serum albumin determinations were conflicting. This effect in vivo has been attributed to depressed liver protein synthesis, but this hypothesis has not been proved. To investigate this problem, human hepatoma (Hep G2) cells were continuously labeled for 4 h with 100 microCi/ml [35S]methionine in the absence or presence of graded amounts of ASNase (from 0.1 nM to 0.1 mM). Media and cell lysates were collected, immunoprecipitated with antialbumin or anti-TBG serum and protein A, and submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were sliced, and the radioactivity was counted in a beta-counter. A dose-dependent inhibition of TBG and albumin biosynthesis (as well as of total protein synthesis) was demonstrable, but TBG appeared to be more sensitive to the action of the drug. In fact, TBG biosynthesis was reduced by 8% with 0.1 nM ASNase, while an effect on albumin was observed only at 1 nM ASNase; 50% inhibition was obtained with 30 nM ASNase in the case of TBG and with 800 nM in the case of albumin. At the highest concentration (0.1 mM), TBG biosynthesis was reduced by 94%, and albumin biosynthesis by 75%. ASNase also proved to have a time-dependent effect, as assessed by the measurement of radioimmunoassayable TBG in the media from Hep G2 cells grown in the presence of 10 nM ASNase for 1-4 days. The TBG concentration was progressively reduced, by 40% after 1 day to 85% after 4 days. In pulse-chase experiments, a reduction of total (intracellular plus secreted) immunoprecipitable TBG and, to a lesser extent, albumin was observed, suggesting that the drug also affected the catabolism of newly synthesized proteins. These results provide the first in vitro evidence that ASNase actually inhibits TBG biosynthesis. This effect is not specific for TBG, but this protein appears to be more susceptible than albumin to ASNase action. This can explain why in patients treated with ASNase for leukemia, a decrease in serum TBG concentrations has not always been associated with a reduction in serum albumin levels.

Asparaginase↗
PubMed1985

Serum free thyroxine in patients with T3-toxicosis.

The serum free thyroxine concentration was measured by direct radioimmunoassay in 38 untreated T3-thyrotoxic patients with elevated serum total and free triiodothyronine, normal serum thyroxine and free thyroxine index, no TSH response to TRH, and with clinical evidence of hyperthyroidism. An elevation of circulating free thyroxine values was observed in 58% of the patients, whereas total serum thyroxine concentration was within the normal range. It is suggested, therefore, that T3-thyrotoxicosis should be reserved for patients with elevated serum total T3 and free T3 concentrations and normal serum total T4 and free T4 concentrations. Serum thyroxine-binding globulin concentrations were significantly lower (P less than 0.025) in patients with an elevated serum free thyroxine (18.7 +/- 3.6 micrograms/ml: mean +/- SD) as compared with those in patients with a normal free thyroxine concentration (23.4 +/- 2.6 micrograms/ml). In addition, no daily fluctuations in total and free thyroxine concentration were observed in 6 patients over a 4-8 day period.

Adult↗
PubMed1984

Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy.

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Adult↗
PubMedDate not supplied

Free thyroxine values in dried blood spots on filter paper in newborns are related to both gestational age and birth body weight.

The results of free thyroxine (FT4) measurements in dried blood spots on filter paper in 744 euthyroid newborns (616 at term, 128 preterm), 10 newborns with congenital hypothyroidism and 4 euthyroid newborns with congenital TBG deficiency are reported. FT4 was measured by column adsorption chromatography of free hormone followed by radioimmunoassay in the eluate. FT4 values averaged 24 +/- 0.2 pmol/L (mean +/- SE) in euthyroid newborns, 23.0 +/- 0.9 pmol/L in euthyroid newborns with TBG deficiency (p = NS), and 5.7 +/- 0.4 pmol/L in hypothyroid newborns (p less than 0.001 vs both groups). Total T4 (TT4) values in newborns with TBG deficiency were not different from those in hypothyroid newborns, but were significantly lower than those in euthyroid newborns without TBG abnormalities. FT4 values were higher in full-term newborns than in preterm newborns (25.2 +/- 0.3 vs 21.2 +/- 0.5 pmol/L, p less than 0.001). In both full-term and preterm newborns FT4 values in dried blood spots increased with birth body weight (bbw), virtually plateauing when bbw was greater than 2,500 g. The cut-off values established on the basis of the bbw (8.0 and 13.1 pmol/L for a bbw of less than or equal to 2,500 g and greater than 2,500 g, respectively) showed higher specificity and predictive value of positive results than the cut-off values based on the gestational age. In any case, the sensitivity, specificity and predictive values of FT4 determinations proved to be higher than those of TT4 and TSH measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMedDate not supplied

Effects of the antileukemic drug L-asparaginase on sex hormone-binding globulin: studies in vivo and in vitro.

L-asparaginase, an antineoplastic drug used in the treatment of acute lymphoblastic leukemia (ALL), has been previously shown to inhibit the hepatic synthesis of thyroxine-binding globulin (TBG). In two children treated by this drug for ALL, a dramatic decrease in serum sex hormone-binding globulin (SHBG) concentrations was also observed. Serum SHBG levels were still below normal 10 days after L-asparaginase withdrawal. To ascertain whether this reduction was due to the inhibition of SHBG synthesis, SHBG was measured by an immunoradiometric assay (IRMA) in the medium from human hepatoblastoma-derived cells, Hep G2 cells, grown in the absence or presence of graded amounts of the drug from 0.1 nM to 0.1 mM. The results showed a dose-dependent inhibition of SHBG synthesis, with a 50% reduction of SHBG in the medium, assayed by IRMA, using 250 nM L-asparaginase. Furthermore, a time-dependent inhibition was observed using a fixed concentration of the drug (50 nM) added for variable time intervals (1-4 days). These data suggest that the changes observed in vivo are likely due to the inhibitory effect exerted by the drug on SHBG synthesis. This action is not specific, but is part of a general effect at the hepatic level.

Antineoplastic Agents↗
PubMedDate not supplied

Relapsing bilateral uveitis and papilledema in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non-hereditary histiocytic proliferative disorder affecting young people, with extranodal manifestations in 28-43% of cases. Eye involvement is infrequent. Lymphoproliferation in the soft tissues of the orbit and in the lids has been reported in 12% of cases but intraocular involvement is rare. We describe the case of a 12-year-old boy affected by Rosai-Dorfman disease with bilateral relapsing uveitis and papilledema that appeared four years before the onset of lymphadenopathy.

Child↗