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S Benvenga

Publications and source records attributed to S Benvenga.

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

Post-traumatic selective hypogonadotropic hypogonadism.

A very small proportion of hypopituitarism is due to head trauma, which may have occurred from days to years earlier. In the literature we found only three cases (two males, one female) of post-traumatic hypopituitarism in whom the hormone deficiency was claimed to be restricted to the gonadotrophs and considered to be permanent after a period of follow-up ranging from less than one year to four years. Here we describe a 26 yr-old male patient who, eight years after a motorcycle accident, was evaluated for hypogonadism and followed-up for three years. Serum testosterone, basal and GnRH-stimulated FSH and LH remained undetectable over the first 22 months of follow-up. Then, basal and GnRH-stimulated gonadotropins moved progressively into the normal range. Basal and dynamic evaluation of the other anterior pituitary hormones was persistently normal. At the 15th month of follow-up there was a change in the pituitary CT scan, presumably due to pituitary revascularization. Therefore, our patient disproves that post-traumatic isolated gonadotropin deficiency is irreversible.

Accidents, Traffic↗
PubMed1997

A thyroid hormone binding motif is evolutionarily conserved in apolipoproteins.

High-density lipoproteins (HDL) are the major lipoprotein (Lp) plasma carriers of thyroid hormones, binding mediated by a specific interaction with their apolipoproteins (A-I, A-II, A-IV, C-I, C-II, C-III and E). The single binding site of these apolipoproteins is encoded by exon 3 (exon 2 for apoA-IV) of the respective gene and has amino acid sequence homology with regions of the three major thyroid hormone plasma transport proteins (TBG, TTR, and albumin) known to contain the corresponding hormone binding site(s). Within the hormone domain, we identified a 5-residue hydrophobic motif "Y, L/I/M, X, X, V/L/I" that is extremely well conserved in apolipoproteins. The exon-3 coded region of human apo E contains a hydrophobic pocket which is formed by Trp 34 and a number of neighboring leucines (residues no. 28, 30, 37 or 43). The location of this pocket overlaps strikingly that of the region (aa 26-40) where the said homology is maximal and where the motif YLRVW, (aa 36-40) lies. This hydrophobic pocket should represent the thyroid hormone site of apo E and, because of the said homology, should exist in the other HDL apolipoproteins. Because TBG and/or TTR are not present in all animal species, but Lp are, and because fish HDL bind thyroid hormones, I postulated that thyroid hormone binding to HDL apolipoproteins is conserved through the phylum. To this end, I evaluated the conservation of the 5-residue motif in all the apolipoprotein sequences known (PIR data bank no. 42) and tested the thyroid hormone binding properties of two animal apolipoproteins that were available (bovine apo A-I and rabbit apo E). I found that the conservation does exist and that the binding properties of the two animal apolipoproteins match those of the respective human counterpart. In addition, I found that the 5-residue motif is spared by naturally occurring mutations, which is not the case for other domains. I therefore conclude that the interaction of thyroid hormones with Lp represents the first plasma transport for these hormones that appeared in the animal world and that preservation of the structure of the hormone domain appears to be more important than preservation of other domains.

Amino Acid Sequence↗
PubMed1997

Thyroid hormone autoantibodies elicited by diagnostic fine needle biopsy.

Based on the knowledge that diagnostic fine needle biopsy of the thyroid (FNAB) results in a prompt increase in circulating thyroglobulin (Tg); we evaluated whether Tg is indeed the postulated antigen for circulating antibodies against thyroid hormones (THAb). Preliminarily, we verified that FNAB causes the release into the bloodstream of iodinated, heterologous, and thus potentially immunogenic, molecules of Tg. Of the initially enrolled 400 patients, 214 had a number of blood drawings sufficient to evaluate over time (before FNAB and 1-3 h, 3 days, 15 days, 30 days, 3 months, 6 months, and 12 months after FNAB) the following parameters: THAb of both IgM and IgG classes, Tg antibodies (TgAb; by a sensitive immunoradiometric assay), and Tg (in the 156 patients who were TgAb negative). We found the following. 1) Serum Tg most often peaks 1-3 h after FNAB (61 +/- 45% of the baseline level; mean +/- SD). 2) Only 7% of the initially TgAb-negative patients converted to positive, and only 12% of those initially positive had an increase in the levels of TgAb. 3) THAb were detected in 0 of 400 patients before FNAB, but were found in 9 of 214 (4.2%) after FNAB. This proportion is 2 orders of magnitude higher than that (149 of 369,000 or 0.04%) found in consecutive patients attending European thyroid clinics. Of the 9 cases, 6 had Hashimoto's thyroiditis (HT), 2 had euthyroid colloid goiter, and 1 had Hurthle cell carcinoma. In the 5 of 9 cases who were TgAb negative, the post-FNAB increment in Tg was 21-99%, i.e. lower than that of the majority of patients (101-12,500%). 4) THAb were of the IgM class in all 9 (6 against T3 and 3 against T4), and were accompanied and/or followed up to 3 months after FNAB by IgG-THAb of the same specificity (2 against T3 and 1 against T4) in 3 cases. In a fourth case, IgM-T3 were followed by a long-lasting synthesis of IgG-T3 (i.e. up to 1 yr post-FNAB). All 4 cases with IgG-THAb had HT and remained TgAb positive. 5) In the 2 HT and the 3 non-HT patients with undetectable TgAb, THAb were of the IgM class only. 6) In the HT group, 2 risk factors for the development of post-FNAB THAb appeared to be pre-FNAB TgAb levels below 400 U/mL that did not increase after FNAB and Tg released from a colloid nodule. We conclude that Tg release from the thyroid is sufficient to elicit THAb synthesis. In patients with autoimmune thyroid disease (HT), this synthesis occurs with a frequency 10-fold higher than that in patients with nonautoimmune thyroid diseases (21% vs. 2%). However, in only a fraction of patients with autoimmune disease, who need to be TgAb positive by a sensitive assay, the primary immune response (IgM) is followed by a secondary one (IgG). As, once present, this secondary response is long lasting in only a minority of our patients, we think that this could contribute to the rarity of naturally occurring THAb.

Antibody Specificity↗
PubMed1997

Endemic goiter.

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Goiter, Endemic↗
PubMed1996

Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism.

Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration elution patterns of cholesterol and triglycerides were evaluated in the total lipoprotein fractions (TLF) obtained from 10 healthy blood donors and 7 patients with hypothyroidism of brief duration. TLF (d < 1.210 kg/L) shown to be free of plasma T4 transport proteins (TBG, TTR, HSA) was equilibrated with 0.3 nM 125I-labeled T4, T3 or reverse T3 (rT3) and chromatographed on Sepharose CL-6B. Percent distribution of rT3 among the Lp subtypes was similar in the two groups (in normals: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HDL in hypothyroid subjects bound significantly more T4 (98.7 +/- 0.4 vs. 91.2 +/- 0.3%) and T3 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondingly less T4 and T3 was bound to VLDL and LDL. Whereas rT3 elution coincided with the major HDL cholesterol peak (202 +/- 17 kDa) and was the same in the two groups, both T4 and T3 eluted with smaller HDL particles and differed between hypothyroid and normal subjects. T4 eluted with somewhat larger HDL particles in hypothyroid subjects (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T3 eluted with smaller HDL (94 +/- 30 kDa vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothyroid subjects had a slightly but significantly greater mass than in normals (241 +/- 28 kDa vs. 218 +/- 14 kDa). The HDL elution patterns also differed: in normals there were from 3 to 6 minor peaks on either side of the major peak, whereas in hypothyroid subjects there were only 0 to 2 minor peaks. In conclusion, iodothyronines bind to relatively small size HDL subfractions and these are different for T4, T3, and rT3; hypothyroidism of brief duration induces both quantitative and qualitative changes in iodothyronine distribution among lipoproteins and alters the microheterogeneity of HDL-cholesterol.

Adult↗
PubMed1995

A quick method to detect circulating anti-thyroid hormone autoantibodies.

The aim of this study was to evaluate the feasibility of a chromatographic method to easily detect circulating anti-thyroid hormone autoantibodies (THBA), to calculate their affinity constant and the total thyroid hormone (TH) levels in presence of THBA. This method was applied to sera from 4 subject with suspected THBA and 20 controls (10 normal subjects and 10 patients with thyroid dysfunctions). After a short incubation with 125I-T3 or T4 tracer solution containing 8-anilino-1-naphthalenesulfonic acid as inhibitor of the binding of TH to plasma proteins without affecting THBA binding, the samples were chromatographied on prepacked Sephadex LH 20 columns and eluted with TRIS buffer to separate free TH from THBA-bound TH. Samples were considered THBA positive when radioactivity values in TRIS eluates were higher than in controls. THBA-bound TH were subsequently eluted with methanol and used to calculate the total TH present in patients with THBA. After a validation test using two standardized methods, we propose this method to quickly detect TH-BA in samples with suspected spuriously high values of free and total TH.

Anilino Naphthalenesulfonates↗
PubMed1995

Delayed intestinal absorption of levothyroxine.

We report four female patients with nodular goiter (in two of the four due to Hashimoto's thyroiditis) and one male patient with frank hypothyroidism due to Hashimoto's thyroiditis in whom TSH-suppressive or replacement L-T4 therapy failed to suppress or, respectively, normalize serum TSH. As is typical in our country, our patients took L-T4 15-20 min before a light breakfast. Gastrointestinal or other diseases and drugs known to interfere with the intestinal absorption of L-T4 were not the cause of this failure. The gastrointestinal absorption test of L-T4 (1000 micrograms) was performed in four patients; in three patients it revealed peculiar abnormalities in that (i) the absorption peak was > 70% but occurred at 4 hr vs an average of 2 hr in 12 euthyroid controls (EC) and 3 hr in the 10 primary hypothyroid controls (HC); (ii) 50% of the maximal absorption occurred at 110 min vs 45 min in EC and 50 min in HC; (iii) the maximal increment in T4 absorption was between 90 and 120 min (+111%) vs between 30 and 60 min in EC (+312%) and HC (+354%). In sum, only the first part of the absorption curve of T4 was shifted to the right (in three of the four women) and this shift was more pronounced and extended to the second part of the curve in the fourth patient; in this last patient absorption peak was 44% at 180 min. Based on these results, we obtained full suppression or normalization of TSH by postponing breakfast for at least 60 min after T4 ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Homology of calcitonin with the amyloid-related proteins.

We present evidence for a structural homology between the amino acid sequence of calcitonin (CT)--the fibrillar protein of the amyloid deposits of medullary thyroid cancer--and that of other 12 amyloid-related proteins (ARP). Seven of the 32 residues of CT are conserved in at least five ARP, and five of these seven amino acids belong to the stretch Gly2-Gln14. Gln14 is conserved in all 12 ARP and Cys7 in all eight ARP containing cysteine. The concentration of the homology in the N-terminal half of CT goes along with the knowledge that is the C-terminal region the one more important for the hormonal action of CT. Since an imbalance between synthesis and catabolism of a given ARP is believed to be the general pathogenetic mechanism of amyloidosis, the intratumoral deposition of CT in the form of amyloid fibrils would be due to the overproduction of a protein structurally similar to the ARP.

Amino Acid Sequence↗
PubMed1994

Thyroid hormone binding to isolated human apolipoproteins A-II, C-I, C-II, and C-III: homology in thyroxine binding sites.

Thyroid hormone binding to lipid-free apolipoprotein (apo) A-II, C-I, C-II, and C-III isolated from human plasma was investigated by photoaffinity labeling with [125I]T4 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both the monomeric and polymeric forms were specifically labeled. Inhibition by 10 microM unlabeled L-T4 was > or = 50%, suggesting affinity constants in the nM to microM range; the least inhibition was seen with apoA-II. Unlabeled D-T4 and reverse T3 (rT3) gave the same inhibition as unlabeled L-T4. Inhibitors of thyroid hormone binding to plasma proteins showed a different inhibitor potency with each apolipoprotein and a pattern different from that seen with T4 binding globulin (TBG) and transthyretin (TTR). Also in contrast to TBG, where only unsaturated nonesterified fatty acids (NEFA) are effective inhibitors, both unsaturated and saturated NEFA as well as other lipids inhibited T4 labeling. The flavonoid EMD 21388 was ineffective, confirming that it is a selective inhibitor of T4 binding to TTR. T4 binding to the apoCs was confirmed by the quenching of tryptophan fluorescence by unlabeled L-T4. (ApoA-II was not studied since it lacks tryptophan). Since the self-association of apolipoproteins involves interaction between amphipathic alpha-helices, and since the polymeric forms show specific T4 binding properties as in the parent monomer, the T4-binding domain appears to be outside the alpha-helical domain, as previously seen with apoA-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1994

Three new mutations of thyroid hormone receptor-beta associated with resistance to thyroid hormone.

Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) of the human thyroid hormone receptor-beta gene were observed in six individuals affected by the syndrome of resistance to thyroid hormone. All three mutations occurred in a heterozygous pattern and caused the following changes in the mature form of the receptor protein: Asp322 to Asn, Glu333 to Gln, and Lys443 to Asn, respectively. The first and third point mutations arose in two unrelated families from eastern Sicily, whereas the second concerned an individual from southern Calabria, apparently presenting a sporadic form of the resistance syndrome. The clinical and biochemical features of resistance to thyroid hormone, both before and after the administration of thyroid hormones, highlight the striking intrafamilial heterogeneity in the phenotypical presentation of the syndrome.

Adolescent↗
PubMed1994

Endemic goiter.

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Animals↗