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Biomedical subjects

L Persani

Publications and source records attributed to L Persani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in the differential diagnosis of the syndromes of inappropriate secretion of TSH.

BACKGROUND AND OBJECTIVE: Serum TSH assay is a very sensitive and specific index of thyroid hormone (TH) action. Nevertheless, in particular clinical situations, such as those of inappropriate TSH secretion, the measurement of additional parameters evaluating peripheral TH action may be required in order to achieve a correct diagnosis and to assess the impact that thyroid hormone have on a given tissue. The availability of a specific RIA for serum carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) prompted us to study the usefulness of this specific marker of bone resorption in the differential diagnosis of thyroid disorders. DESIGN: Serum ICTP levels were measured in: (a) 10 patients with TSH-secreting pituitary adenoma (TSH-oma), (b) 40 with thyroid hormone resistance (RTH), as well as in (c) 28 patients with Graves' disease or toxic nodular goitre, (d) 31 with autoimmune primary hypothyroidism (PH) and in 8 of them during L-T4 replacement therapy, (e) 23 with central hypothyroidism (CH) during L-T4 therapy and 2 months after its withdrawal, and (f) 26 during TSH-suppressive treatment for goitre or non-metastatic differentiated thyroid cancer. Results were compared with those obtained in 2 groups of normal controls (Group A, n = 61, age range: 23-68 years; Group B, n = 32, age range: 6-15 years). METHODS: Serum TSH, free T4 (FT4) and free T3 (FT3) were measured by immunofluorometric assays. Serum ICTP was measured by a specific RIA with a sensitivity of 0.5 +/- 0.1 microgram/l, and intra- and interassay coefficients of variation lower than 6%. RESULTS: Mean values of serum ICTP levels in adult controls were 3.8 +/- 1.6 (+/-SD) microgram/l, while in pre- or peri-pubertal controls it was higher than in adults (14.4 +/- 3.1 micrograms/l). Patients with TSH-oma showed significantly increased ICTP levels (8.7 +/- 5.0 micrograms/l, P < 0.001 vs controls), in contrast to those with RTH (3.0 +/- 1.0 micrograms/l, P < 0.02 vs controls). In the differential diagnosis of inappropriate secretion of TSH, ICTP values above 5 micrograms/l strongly indicated the presence of a TSH-oma. Circulating ICTP concentrations were definitely high in thyrotoxic patients (9.4 +/- 4.7 micrograms/l, P < 0.001) and values overlapping the normal range were observed in 8 cases, thus giving to this test a sensitivity and specificity of 71% and 93%, respectively. In contrast, serum ICTP levels in both PH and CH untreated patients were in the normal range, although significantly lower than in controls (2.6 +/- 1.0 and 1.8 +/- 0.7 micrograms/l, P < 0.001). During replacement therapy, ICTP levels rose significantly in both hypothyroid groups (5.1 +/- 2.5 and 2.7 +/- 1.3 micrograms/l). In 2 CH patients, borderline high ICTP levels (7.0 and 7.1 micrograms/l), associated with FT3 concentrations in the upper limit of the normal range, suggested the presence of L-T4 overtreatment; L-T4 dose reduction was followed by the decrease of both indices in a more physiological range (ICTP: 4.2 and 4.7 micrograms/l; FT3: 8.5 and 6.0 pmol/l). In patients treated with TSH-suppressive therapy at the minimal effective dose, ICTP levels did not significantly differ from those observed in adult controls (4.3 +/- 2.0 micrograms/l). The overall correlations between serum ICTP and FT4 or FT3 levels were highly significant (P < 0.001). CONCLUSIONS: The present data indicate that serum type I collagen (ICTP) concentrations are modulated by circulating thyroid hormone concentrations. ICTP measurement is particularly useful in the differential diagnosis of the syndromes of inappropriate TSH secretion, in estimating thyroid hormone impact on bone in primary hyperthyroid states, and its longitudinal evaluation may reveal L-T4 overtreatment in patients on substitutive or TSH-suppressive therapy.

Adenoma↗
PubMed1997

Clinical and hormonal outcome after two years of triiodothyroacetic acid treatment in a child with thyroid hormone resistance.

We report here a new family with thyroid hormone resistance (RTH), with phenotypic variability among subjects. Particular emphasis is given to the clinical and hormonal outcome after 2 years of triiodothyroacetic acid (TRIAC) treatment in an affected child with peripheral thyrotoxic features (pituitary RTH [PRTH]). The genetic defect was a substitution in position 1642 (C to A) within the exon 10 of thyroid hormone receptor beta1 (TRbeta1) gene, resulting in the codon change P453T. The mutant receptor had a significantly reduced triiodothyronine (T3) binding affinity. Within this family, the child and the mother suffered from hyperthyroidism and were clinically classified as PRTH, while the maternal grandmother was clinically euthyroid, indicating a generalized form of the disease (GRTH). Rapid normalization of heart rate was initially obtained by the association of the cardioselective beta-blocker atenolol with TRIAC. Nevertheless, long-term TRIAC therapy, through its lowering action of serum thyrotropin (TSH) and thyroid hormone levels, maintained a normal heart rate after atenolol discontinuation and normalized the neurological disturbances and the clinical signs in the child, without any apparent side effect. In fact, growth velocity remained unchanged and no alteration of several parameters of thyroid hormone action at the tissue level was observed, whereas soluble interleukin-2 receptor levels improved significantly, confirming the safety and efficacy of long-term TRIAC therapy for PRTH also during childhood. We thus recommend testing the efficacy of TRIAC therapy in all RTH patients presenting with clinical features of hyperthyroidism.

Biomarkers↗
PubMed1997

Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH.

Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH beta-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the Gs alpha gene of one family analyzed by GC-clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-Gs alpha cascade and genes participating in its regulation.

Adult↗
PubMed1997

Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH.

The TSH receptor is a G protein-coupled receptor that mediates the effects of TSH in thyroid development, growth, and synthetic function. We report here that a child with features of TSH resistance, including markedly increased serum TSH concentrations and low normal thyroid hormone levels, is a compound heterozygote for two novel mutations in the TSH receptor gene. One allele has a G to A transition corresponding to an arginine to glutamine change at codon 109 (R109Q) in the extracellular domain of the receptor. The other allele has a G to A transition corresponding to a premature termination codon at tryptophan 546 (W546X) in the fourth transmembrane segment. Each parent is heterozygous for one mutation, and both parents have normal thyroid function. Cells transiently transfected with the R109Q mutant exhibited reduced membrane binding of [125I]TSH and impaired signal transduction in response to TSH. In contrast, the W546X mutant was nonfunctional, with negligible membrane radioligand binding. Our findings indicate that a single normal TSH receptor allele is sufficient for normal thyroid function, but that the compound abnormality in the proband leads to TSH resistance.

Amino Acid Sequence↗
PubMed1997

Lack of effects of circulating thyroid hormone levels on serum leptin concentrations.

Leptin is the protein product of the ob gene, secreted by adipocytes. It has been suggested that it may play an important role in regulating appetite and energy expenditure. The aim of this study was to evaluate a possible interaction of thyroid hormones with the leptin system. We studied 114 adult patients (65 females and 49 males): 36 were affected with primary hypothyroidism (PH), 38 with central hypothyroidism (CH) and 40 with thyrotoxicosis (TT). Patients with CH were studied both before and after 6 months of L-thyroxine replacement therapy. Body mass index (BMI; kg/m2), thyroid function and fasting serum leptin were assessed in all patients. Since BMI has been proved to be the major influencing variable of circulating leptin levels, data were expressed as standard deviation score (SDS) calculated from 393 male and 561 female controls matched for age and BMI. No difference in SDS was recorded between males and females whatever the levels of circulating thyroid hormones. In males, no significant difference was recorded among the SDSs of PH (-0.36 +/- 1.2), TT (-0.35 +/- 1.2) and CH (0.01 +/- 1.4) patients. Females with PH had an SDSs significantly lower than TT females (-0.77 +/- 1.0 vs -0.06 +/- 1.2; P < 0.02), while no significant differences between CH (-0.34 +/- 0.7) and TT females or between CH and PH females were observed. SDS in CH patients after 6 months of L-thyroxine therapy significantly varied only in females (0.25 +/- 1.4). In conclusion, circulating thyroid hormones do not appear to play any relevant role in leptin synthesis and secretion. However, as females with either overt hypo- or hyper-thyroidism or central hypothyroidism after L-thyroxine therapy show differences in their SDSs, a subtle interaction between sex steroids and thyroid status in modulating leptin secretion, at least in women, may occur.

Adult↗
PubMed1997

Unique binding pattern to concanavalin A lectin of glycoprotein hormones alpha-subunit hypersecreted by non-functioning pituitary adenomas.

This study analyzed the structural differences of the carbohydrate chains of circulating free alpha-submit (alpha-SU) hypersecreted in various non-tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH-, GH- and pure alpha-secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free alpha-SU were investigated by means of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free alpha-SU in three different fractions (unbound = UB, weakly bound = WB and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of alpha-SU in serum and in Con-A fractions were measured by a sensitive and specific IRMA. Free alpha-SU hypersecreted from postmenopausal women, primary hypothyroids, and patients with chronic uremia showed similar binding patterns to Con-A, the percentage of UB fractions (UB: 44.5 +/- 1.9%, 39.5 +/- 3.8%, 48.2 +/- 5.6% respectively) being higher than both WB and FB fractions (WB: 33.2 +/- 1.4%, 30.7 +/- 4.6%, 28.5 +/- 2.1%; FB: 22.3 +/- 0.7%, 29.8 +/- 6.6%, 23.3 +/- 4.2% respectively). In normal fetuses the amount of UB fraction was very high (UB: 70.7 +/- 5.4%). Free alpha-SU from patients with TSH- and GH-secreting adenomas showed a binding pattern to Con-A significantly different from that observed in postmenopausal women taken as controls, the WB fractions being significantly higher (WB: 56.9 +/- 16.8% and 71 +/- 12.4% respectively, P < 0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature alpha-SU molecules eluted in the FB fraction, was found in patients with pure alpha-secreting adenomas. This chromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoids (FB: 41.8 +/- 5.0%, 22.3 +/- 0.7%, 16.8 +/- 6.6%, 10.6 +/- 2.0% respectively). Moreover, in these latter patients the pattern of free alpha-SU binding was exactly the opposite of that observed in pure alpha-secreting adenomas, with a prevalence of mature alpha-SU molecules (UB: 59.1 +/- 4.4 vs 18.3 +/- 7.2%). In conclusion, our data on Con-A affinity chromatography clearly demonstrate that carbohydrate branching of circulating free alpha-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral conditions. Moreover, the finding of a greater proportion of circulating free alpha-SU forms that firmly bind to Con-A in patients with pure alpha-secreting adenomas, seems to be pathognomonic of non-functioning pituitary adenomas.

Adenoma↗
PubMed1996

Thyrotropin-secreting pituitary adenomas.

Normal or elevated thyrotropin (TSH) levels in hyperthyroid patients are characteristic of rare TSH-secreting pituitary adenoma (TSH-oma), which is easily detectable by computed tomographic (CT) scan or magnetic resonance imaging (MRI). Other diagnostic aids are an absent/impaired TSH response to thyrotropin-releasing hormone (TRH), discrepant TSH and alpha-subunit responses to TRH, high sex hormone-binding globulin (SHBG) levels, high alpha-subunit levels, and a high alpha-subunit/TSH molar ratio. Familial studies help rule out thyroid hormone resistance (RTH). Surgical removal of TSH-oma leads to clinical and biochemical remission in most patients. In surgical failures, radiotherapy and octreotide treatment have a high success rate. Undetectable TSH 1 week postsurgery suggests a definitive cure, backed up by tests for cosecreted hormones from the adenoma and dynamic tests of TSH suppression.

Adenoma↗
PubMed1996

Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas.

The recorded number of patients with central hyperthyroidism due to TSH-secreting pituitary adenoma doubled in the last few years after the introduction of ultrasensitive TSH assays in the assessment of thyroid function; however, information about the results and the criteria for cure after pituitary surgery is scanty. Seventeen patients with a TSH-secreting adenoma, diagnosed on the basis of detectable TSH levels in the face of high free thyroid hormone concentrations and pituitary lesion at neuroimaging, underwent pituitary surgery. Hypersecretion of other pituitary hormones was diagnosed in 5 of 17 patients. Four patients were initially misdiagnosed and treated with thyroid surgery or radioiodine therapy. The majority (86%) of hyperthyroid patients normalized thyroid hormone concentrations and regained euthyroidism, although pituitary imaging, alpha-subunit, and alpha-subunit/TSH molar ratio normalized in only 47%, 54%, and 58% of patients, respectively. Moreover, TSH secretion was normally suppressed by T3 in 40% of the patients. Interestingly, the finding of undetectable TSH levels 7 days after surgery was highly predictive of successful outcome. During long term follow-up, there was one relapse of hyperthyroidism. Early diagnosis of TSH-secreting adenomas permits a high rate of remission of hyperthyroidism after surgery. However, normalization of thyroid function alone does not necessarily reflect complete removal of the tumor, and more comprehensive criteria of cure based on pituitary imaging, hormone measurement, and suppression of TSH during T3 administration should be used. Lastly, all patients need an accurate long term follow-up to monitor the possible recurrence of the adenoma.

Adenoma↗
PubMed1996

Thyrotropin-secreting pituitary tumors in hyper- and hypothyroidism.

Thyrotropin (TSH)-secreting pituitary tumors may be found in two opposite clinical situations: the hyperthyroidism secondary to thyrotroph adenomas, also called central hyperthyroidism, and the long-standing primary hypothyroidism which can be accompanied by a compensatory pituitary enlargement. TSH-secreting pituitary adenomas belong to the syndromes of "inappropriate secretion of TSH" (IST). The adjective "inappropriate" indicates the lack of the expected suppression of TSH secretion when free thyroid hormone levels are actually elevated, as in the other forms of thyrotoxicosis. Moreover, TSH-omas have to be differentiated from the non-neoplastic form of IST which is due to resistance to thyroid hormone. Differently, pituitary hyperplasia, which is reversible on thyroid hormone replacement, is the more frequent cause of a pituitary mass occurring in the context of untreated primary hypothyroidism. Failure or delay in the recognition of the above clinical situations may cause dramatic consequences, such as unnecessary pituitary surgery in hypothyroid patients or improper thyroid ablation in those with central hyperthyroidism. In contrast, early diagnosis and proper treatment of TSH-secreting pituitary tumors prevents the appearance of signs and symptoms of mechanical compression of the adjacent structures by the expanding tumor mass (visual field defects, headache and hypopituitarism).

Adenoma↗
PubMed1995

Circulating levels of growth hormone, insulin-like growth factor-I and prolactin in normal, growth retarded and anencephalic human fetuses.

We measured growth hormone (GH), insulin-like growth factor-I (IGF-I), and both total and glycosylated prolactin (PRL) levels in 131 blood samples obtained by cordocentesis in normal and abnormal fetuses from 19 to 40 weeks of gestation. In normal fetuses, IGF-I and PRL levels showed a positive correlation and GH a negative correlation with gestational age. A negative relation between GH and IGF-I levels was observed, while PRL did not show any correlation with both GH and IGF-I concentrations. IGF-I increased from 5.6 +/- 3 (at 19-22 weeks) to 10.7 +/- 5 nmol/l at term; GH decreased from 31 +/- 10 to 7.7 +/- 4 micrograms/l and PRL increased from 16 +/- 18 to 139 +/- 76 micrograms/l. Glycosylated PRL accounted for about 15% of total PRL, a value similar to that found in normal adults. In 27 fetuses of 27-37 weeks with intra-uterine growth retardation, GH and PRL levels were higher and IGF-I levels lower than in normal fetuses matched for week of gestation. In 8 anencephalic fetuses of 19-26 weeks of gestation, both GH and IGF-I levels were lower, and PRL levels were higher than in matched controls. Altogether these data support the views that a) both GH and PRL secretion are under the hypothalamic control during fetal development, b) the serum GH decrease from midgestation to the end of pregnancy is mediated by the negative feed-back mechanism of increasing IGF-I levels and c) IGF-I production is mainly regulated by fuel supply and only partially by GH.

Anencephaly↗
PubMed1995

Thyrotropin with decreased biological activity, a delayed consequence of cranial irradiation for nasopharyngeal carcinoma.

Patients with TSH of decreased bioactivity have had previous surgery or no known cause (idiopathic). We describe eight patients with nasopharyngeal carcinoma treated with irradiation alone more than 5 yr ago. All had hypothalamic hypothyroidism with low FT4 and normal TSH. Iv TRH gave an exaggerated TSH response, with 60 min greater than 20 min values, without any FT4 or TT3 response at 24 h to the hypersecreted TSH. Radioiodine uptake in 2 patients before and after 3 days of bovine TSH increased from 13 to 31%, and 11 to 28%, respectively. Oral TRH given for 20 days to 5 patients showed a distinctive pattern in serum TSH, FT4 and TT3. Serum TSH rose markedly in the initial few days, dropped to moderate levels for a few days and finally dropped further towards normal values. In contrast, the FT4 and TT3 remained unchanged at hypothyroid levels in the first few days, despite the very elevated TSH; but increased to euthyroid levels and remained higher even while the serum TSH declined further. Direct measurement of TSH bioactivity in FRTL-5 cells in 3 patients showed low values of bioactivity to immunoactivity ratios: 0.4, < 0.2, and 0.35 (NR 0.6-2.1) which increased in 2 patients to 0.9 and 0.8 after 20 days TRH. Serum free alpha-subunit levels were low and unchanged (0.3 to 1.1 micrograms/L) with prolonged TRH. These observations suggest that cranial irradiation may cause hypothalamic hypothyroidism with TSH with decreased bioactivity, and that prolonged TRH administration may restore normal bioactivity.

Adult↗
PubMed1995

Mechanism of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in human nonfunctioning pituitary tumors.

Several evidence suggest that pituitary adenylate cyclase activating polypeptides (PACAP-38 and -27) could function as hypophysiotropic factors. Both peptides interact with either the type I receptor, which preferentially binds the two PACAPs and has a much lower affinity for vasoactive intestinal polypeptide (VIP) or the type II receptor, which binds the two PACAPs and VIP with a nearly equal affinity. In addition to the stimulation of adenylyl cyclase (AC) activity, in different cell types PACAP causes an increase of cytosolic calcium levels ([Ca2+]i), consequent to phospholipase-C activation. In the present study, we investigated the effect of PACAP on cAMP formation and [Ca2+]i levels in 16 human nonfunctioning pituitary adenomas (NFPA). PACAP-38 increased cAMP formation in all tumors; the peptide stimulated either AC activity in membrane preparations from 26 +/- 10 to 214 +/- 179 pmol/mg prot/min (P < 0.01) or cAMP efflux from 12 +/- 5.4 to 73.2 +/- 32 pmol/well (P < 0.01) in cultured cells. The effect, detectable at concentrations higher than 1-10 pM, was maximal at 0.1-10 nM. While PACAP-38 and PACAP-27 were nearly equally effective and potent, 100-fold higher concentrations of VIP were required to obtain similar AC activation. GHRH and CRH were ineffective in any NFPA. The PACAP effect was not antagonized by a VIP antagonist, while PACAP fragment 6-27 amide partially reduced the stimulatory effects of both PACAP-27 and VIP in 2 out of 3 tumors tested. PACAP-38 caused a [Ca2+]i rise in cells obtained from 7 NFPA (from 110 +/- 34 to 151 +/- 40 nM [Ca2+]i, P < 0.05) while in the remaining 7 the peptide was ineffective at any concentrations tested (from 1 nM to 10 microM). In the responsive tumors, PACAP-38 effect was not consequence of phospholipase-C activation since removal of extracellular Ca2+ as well as blockade of L-type Ca2+ channels by dihydropyridine antagonists abolished [Ca2+]i increase triggered by the peptide. These data indicate that PACAP is by far the most potent activator of cAMP formation in NFPA and suggest a possible modulatory action of this peptide on cell growth.

Adenoma↗
PubMed1995

Circadian variations of thyrotropin bioactivity in normal subjects and patients with primary hypothyroidism.

Circadian rhythm of TSH secretion is characterized by a pronounced nocturnal increment that is not followed by the expected rise of circulating thyroid hormone levels. These findings suggest that the nocturnal TSH surge may be constituted by molecules with reduced bioactivity. We, therefore, investigated TSH bioactivity (measured as cAMP accumulation in FRTL-5 cells) and its carbohydrate structure (by Concanavalin A affinity chromatography) in different blood pools taken during the day and night from seven normal subjects and from one patient with mild (mPH) and five with severe primary hypothyroidism (sPH). Patients with sPH were also studied during low dose L-T4 treatment. Cosinor analysis showed a significant TSH circadian rhythm in the control group and in L-T4-treated sPH patients. The nocturnal TSH surge was not followed by any increase in free thyroid hormone levels. In normal subjects, the daytime ratio of TSH bioactivity to immunoreactivity (TSH B/I) was higher than the nocturnal one [1.4 +/- 0.6 (+/- SD) vs. 1.1 +/- 0.6; P < 0.02]. The same pattern was observed in the only mPH patient (1.0 +/- 0.2 vs. 0.7 +/- 0.1; P < 0.01), but not in the sPH patients (0.8 +/- 0.3 vs. 0.7 +/- 0.1; P = 0.3). L-T4 administration to sPH patients caused the daytime TSH B/I to increase and restored the day/night difference in the TSH B/I (1.0 +/- 0.3 vs. 0.8 +/- 0.3; P < 0.02). Concanavalin A chromatography showed that a higher percentage of less mature forms of TSH are secreted during the night. These data indicate that TSH molecules secreted during the night are less bioactive and differently glycosylated than those circulating in the same individual during the day, thus explaining why thyroid hormone levels do not rise after the nocturnal TSH surge. In sPH patients, the TSH circadian rhythm is restored during L-T4 administration, and day/night differences in TSH B/I similar to those recorded in normal subjects are observed.

Adult↗
PubMed1995

Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a.

The occurrence of thyroid abnormalities and the appearance of organ- and non-organ-specific autoantibodies during long-term recombinant interferon alpha-2a (IFN-alpha) therapy were studied in 86 and 51 consecutive outpatients with hepatitis C and B virus-related chronic active hepatitis (CAH-HCV and CAH-HBV), respectively. Most patients had longstanding community-acquired hepatitis. At baseline, 9.3% of CAH-HCV and 3.9% of CAH-HBV patients showed clinical and/or biochemical signs of thyroid dysfunction. The remaining patients were euthyroid, although anti-thyroid autoantibodies were found in 33/78 (42.3%) of CAH-HCV and in 5/49 (10.2%) of CAH-HBV patients. During IFN-alpha treatment, increased anti-thyroid autoantibody levels were seen in 40% of CAH-HCV initially negative patients, while they became detectable in no more than 10% of CAH-HBV patients. Interferon-alpha-induced hypo- or hyperthyroidism was recorded in 12 of 35 CAH-HCV patients treated for 12 months (34.3%). Only one CAH-HBV patient developed hyperthyroidism. High titers of anti-nuclear autoantibodies (ANA) were recorded at enrollment in 5/36 (13.8%) of CAH-HCV and in 3/16 (18.7%) of CAH-HBV patients. Only one CAH-HCV patient displayed anti-parietal cell antibodies (PCA). After IFN-alpha treatment, ANA were found in 10/28 (35.7%) and PCA in 2/28 (7.1%) of CAH-HCV patients, while an additional CAH-HBV patient developed PCA, but not ANA. However, no signs of systemic autoimmune disease were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evidence for the secretion of thyrotropin with enhanced bioactivity in syndromes of thyroid hormone resistance.

Resistance to thyroid hormone (RTH) is a rare genetic disorder associated with diverse mutations in the thyroid hormone receptor beta-gene. TSH-dependent thyroid hyperstimulation, leading to goiter and elevated thyroid hormone levels, is a characteristic feature of RTH. However, about 60% of untreated resistance patients have circulating TSH levels within the normal range, raising the possibility that the biological activity of TSH is altered. We, therefore, assayed the bioactivity of circulating TSH in 11 patients from 8 different kindreds with RTH, measuring cAMP production in Chinese hamster ovary cells transfected with the recombinant human TSH receptor as well as in FRTL-5 cells. The ratio of biologically active vs. immunoreactive TSH (B/I) was significantly higher in RTH patients than in 8 normal controls [TSH B/I, 4.2 +/- 0.9 (range, 2.2-11.9) vs. 1.3 +/- 0.2 (range, 0.6-2.1)]. TSH released in response to TRH had a bioactivity similar to that of circulating TSH under basal conditions. On the contrary, supraphysiological doses of T3 normalized the B/I ratio of circulating TSH. Concanavalin-A chromatography of TSH from RTH patients showed the presence of circulating forms with altered carbohydrate branching. Our data indicate that the bioactivity of circulating TSH in thyroid hormone resistance syndromes is enhanced and can be normalized after T3 administration. These findings may account for the occurrence of goiter and elevated thyroid hormone levels in RTH patients despite normal serum TSH concentrations.

Adult↗
PubMed1994

Variable biological activity of thyroid-stimulating hormone.

Thyroid-stimulating hormone (TSH), like the other pituitary glycoprotein hormones, is produced and secreted as a mixture of isoforms, the majority of which represent differences in oligosaccharide structure and possess different bioactivity. When samples are quantified simultaneously by immunometric assay and bioassay, the ratio between bioactivity (B) and immunoreactivity (I) may serve as an index of the overall potency of TSH. Variations of the TSH B/I ratio have been documented in both physiological and pathological conditions associated with alteration of the two most important mechanisms controlling TSH synthesis and secretion, i.e. TRH release and the thyroid hormone feedback system. Major examples of this assumption are the low TSH bioactivity found in samples from patients lacking TRH and thus bearing a hypothalamic hypothyroidism, and the enhanced bioactivity that is invariably found in TSH from patients with thyroid hormone resistance. Moreover, variations of TSH bioactivity have been recorded in normal subjects during the nocturnal TSH surge, in normal fetuses during the last trimester of pregnancy, in patients with primary hypothyroidism and in patients with TSH-secreting pituitary adenoma and non-thyroidal illness. In conclusion, the secretion of TSH molecules with altered bioactivity plays an important pathogenetic role in various thyroid disorders, while in some particular physiological conditions the bioactivity of TSH may vary in order to adjust thyroid hormone secretion to temporary needs.

Animals↗
PubMed1994

[Serum levels of the carboxyterminal telopeptide of type I collagen in patients with thyroid disorders].

Serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) levels, marker of bone resorption, were evaluated in 35 patients with hyperthyroidism (age range: 21-68 years) and in 35 with hypothyroidism (age range: 28-69 years). Data obtained were compared with those recorded in an age and sex matched control group. In patients with hyperthyroidism, serum ICTP levels were significantly higher than in controls (mean +/- SE: 9.1 +/- 0.7 vs 4.1 +/- 0.3 ng/ml; p < 0.0001). In patients with untreated hypothyroidism ICTP levels were significantly reduced (2.5 +/- 0.2 ng/ml, p < 0.0001); seven patients with hypothyroidism, evaluated after substitutive L-thyroxine treatment, showed a significant increase of ICTP levels (6th month: 5.9 +/- 0.7 ng/ml, p < 0.02). Taking into consideration all the data recorded in patients with both hyper- and hypothyroidism, serum ICTP levels were positively correlated with those of free T3 and free T4 and negatively correlated with those of TSH. In conclusion, our data show that repeated determinations of ICTP levels, which directly reflect the bone resorption activity, might be usefully employed in the evaluation of bone turnover in patients with thyroid disorders.

Adult↗