1/12. fucosidosis with hypothyroidism: a case report.fucosidosis is a rare, autosomal recessive lysosomal storage disorder caused by a severe deficiency of alpha-l-fucosidase. Here we present a 27-month-old male who was referred to us for evaluation of developmental delay, which was first detected at age six months. His past medical history was also remarkable for recurrent pulmonary infections and myoclonic seiures. His family history revealed that he was the first living child from a consanguineous marriage. He had a younger sister who died at five months of age from pneumonia who had facial resemblance to the proband, developmental delay and a congenital heart defect. physical examination revealed length: 81 cm (25-50p), weight: 10.2 kg (25-50p), and head circumference: 49 cm (50-75p). He had a coarse face, hepatomegaly and generalized spasticity. His initial laboratory examination revealed negative urine screening column chromatography for mucopolysaccharidosis. His X-ray findings were consistent with mild form of dysostosis multiplex. Based on clinical and laboratory features, fucosidosis was suspected. Fucosidase enzyme activity was zero. In addition to fucosidosis, thyroid function tests indicated primary hypothyroidism. This is, to the best of our knowledge, the fourth case of fucosidosis diagnosed in turkey.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/12. Normal thyroglobulin and thyroperoxidase gene expression in thyroid congenital defective thyroglobulin synthesis.We have studied a member (JBM) of a family MO previously described, with congenital goiter, hypothyroidism, and presence of hyposialylated Tg in the follicular lumen. Other congenital goiters (MA and JNA) with virtual absence of Tg were studied similarly. The presence of apparently normal-sized Tg in JBM tissue was confirmed in the present study by radioimmunoassay, Sephacryl S300 column chromatography, immunoelectrophoresis, and SDS agarose gel electrophoresis. Dot blot hybridization analysis with Tg and TPO probes indicated that mRNA hybridization levels of JBM tissue were similar to control thyroid tissues. Congenital goiter tissues showed relatively lower TSH receptor mRNA content in comparison with normal thyroid tissues. dna was digested with five restriction endonucleases (Taq I, Eco Rv, Pvu II, Pst I, and Eco RI), and the results revealed polymorphisms previously described with the Tg gene. No significant differences in the TPO Pst I pattern were observed in comparison with control samples. We conclude that no major alterations of the Tg and TPO gene expression are detectable and that no significant deletions of these genes are present. The biochemical abnormality in the JBM Tg molecule may be a posttranslational error during the assembly of the protein.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/12. hypothyroidism resulting from generic levothyroxine failure.In today's cost-conscious health care system, generic preparations should be prescribed whenever possible provided that safety and efficacy are not compromised. Several reports, however, suggest that generic levothyroxine may not always be interchangeable with the proprietary preparations. Such interchangeability is critical because patients are likely to receive different brands of levothyroxine during the life of their treatment. We report a case of severe hypothyroidism that developed in a patient who had been well controlled before receiving a generic levothyroxine preparation. Analysis of the patient's tablet by high-pressure liquid chromatography showed that the levothyroxine content was approximately 30 percent less than its labeled content and outside current food and Drug Administration (FDA) requirements. It is likely that poor tablet bioavailability was a contributory factor. Euthyroidism was achieved with the same dose of a more potent and possibly more bioavailable brand-name product. Until levothyroxine products become more uniform and the FDA confers therapeutic equivalence, product substitution with expense as the principal consideration should be avoided.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/12. Factitious elevation of thyrotropin in a new ultrasensitive assay: implications for the use of monoclonal antibodies in "sandwich" immunoassay.Three patients who had falsely elevated serum TSH concentrations (initial values, 30.5, 74, and greater than 50 mU/L) in a mouse monoclonal immunoradiometric assay are reported. Two patients were treated for hypothyroidism inappropriately, and one underwent unnecessary diagnostic testing. Immunoaffinity chromatography of serum from one patient indicated that the serum TSH level was truly low. Addition of mouse serum or immunoglobulin g (IgG) or absorption of patient serum with solid phase-bound mouse IgG-1 reduced the TSH content in the serum of the three patients to undetectable levels. Blocking studies revealed that all patients had antibodies directed at mouse IgG-1, the subclass of mouse antibody present in the assay kit. The serum of one patient who had autoimmune disease with elevated serum Igs had much broader species cross-reactivity than that of another patient who had known exposure to rats and mice. We hypothesize that such antimouse antibodies can arise either from endogenous autoimmunity or exogenous animal exposure. serum TSH elevations also were found when the serum samples were tested in other mouse monoclonal immunoassays, underscoring the fact that antibody interference can potentially affect many assays used in endocrinology and other areas of medicine to make major diagnostic and therapeutic decisions. Clinicians must be aware of such interactions; relatively simple laboratory maneuvers can differentiate true from false results in assays of this type.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/12. Thyroid disease with monoclonal (immunoglobulin g lambda) antibody to triiodothyronine and thyroxine.A man with previous Graves' disease spontaneously developed hypothyroidism. He became euthyroid with T4 therapy, but developed inappropriately elevated serum levels of T3 and, to a lesser extent, T4. Gel filtration analysis (Sephadex G-150) of serum trace-labeled with [125I]T3 revealed binding to a high molecular weight fraction, distinct from normal T3-binding proteins. This abnormal activity cochromatographed with serum immunoglobulin g (IgG) by deae-cellulose chromatography and gel filtration, and was retained by the F(ab)2 fragment of IgG, indicating its true antibody nature. By isoelectric focussing, there was restricted heterogeneity of the [125I]T3-antibody complex (pI 9.0-9.1), and the antibody was identified as an IgG (lambda) monoclonal Ig by immune precipitation. Antigenic cross-reactivity with T4 was demonstrated by inhibition of hapten binding. The affinity of the antibody for T3 was high (Ka = 0.9 x 10(9) liter mol-1), and the T3 binding capacity of the antibody in serum was estimated as 1132 ng/dl, equivalent to 1.39 mg T3-specific IgG/liter (0.014% of the total serum IgG). This binding capacity was similar to the serum T3 values (1100-1300 ng/dl) at which transition from hypothyroid to euthyroid states was observed, as judged by clinical examination and measurement of serum TSH levels.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/12. glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report.The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/12. Hereditary congenital goitre with thyroglobulin deficiency causing hypothyroidism.The thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21-year-old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12.9-20.0 micrograms/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80-220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3 T4 and MIT DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg-like proteins (RIA) in the thyroid soluble protein extract was only 16-122 micrograms/g (normal: 50-70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18-20S) thyroglobulin. Only one peak (3.6-4.1S) was obtained in the pooled soluble proteins supernatants. hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
8/12. Familial and sporadic thyroglobulin deficiency with goitre and hypothyroidism.The thyroid proteins and iodocompounds were analysed in the thyroid tissue of 4 patients with nontoxic goitre. Subtotal thyroidectomy was performed for tracheal compression. The thyroid components were labelled with a trace amount of 125I before operation. One patient had congenital goitre and hypothyroidism with cretinoid features. Three other patients belonged to the same family. Two had congenital goitre, one of them with subclinical and biochemical hypothyroidism. There was a range of thyroglobulin (TG) deficiency ranging from virtual absence of TG in the most affected patient to 17% of normal in the least affected one. There seemed to be an inverse relationship between TG content and clinical signs. Also with decreasing TG more iodocompounds were found in the 3-8 S region on gradient centrifugation. In the most affected patient all the radioactivity was in the 3-8 S region, in the least affected one it was all found in the 19 S and 27 S regions. The other patients had an intermediate pattern. The 3-8 S fraction contained albumin, IgG and some material which reacted like TG on immunoelectrophoresis except for the least affected patient. The iodine content was normal whereas the iodination of TG was low-normal or low. Iodotyrosines and iodothyronines were found in all glands analysed on column chromatography but only in the most heavily affected patient did the ratio iodotyrosines/iodothyronines seem to be elevated. Evidently TG was not necessary for hormone formation in this gland but the efficiency of the matrix seemed not to suffice for normal hormone production.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/12. Possible thyroidal involvement in a case of fabry disease.Endocrinological evaluations of a 48-year-old man with fabry disease revealed low levels of serum thyroid hormones and high levels of serum thyrotropin (TSH), indicating that the patient had primary hypothyroidism. Also, an exaggerated growth hormone (GH) response to hypoglycemic stimuli was observed. Thin layer chromatography of the lipid extract of the thyroid gland obtained by biopsy demonstrated marked accumulation of ceramide trihexoside (CTH) and ceramide dihexoside (CDH). These findings strongly suggest that thyroid hypofunction and hypothalamic dysfunction could be involved in fabry disease.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/12. Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies.A number of radioimmunotherapy (RAIT) trials with iodinated antibodies have shown a high variability in the radiation doses to the thyroid. Therefore, the aim of this study was to evaluate which factors influence these thyroid doses during RAIT with 131iodinated monoclonal anti-carcinoembryonic antigen (CEA) antibodies. Data from 36 patients with CEA-expressing tumours were analysed. The patients underwent RAIT with the 131I-labelled IgG1 anti-CEA antibody, MN-14 (Ka = 10(9) l mol-1) or its F(ab')2 fragment (activity range 45.8-220.0 mCi). The thyroid was blocked with 120 mg iodine (lugol's orSSKI solution) and 400 mg perchlorate per day, starting 1 day prior to the first study. blood clearance and molecular composition of labelled plasma compounds were determined by blood sampling and size-exclusion high-performance liquid chromatography analysis. The cumulated activities of tissues were determined from daily imaging and blood clearance data. Doses were derived from the MIRD scheme. Thyroid radiation doses showed a high variability, between 1.2 and 37.7 cGy mCi-1 (mean /- S.D.: 11.1 /- 8.3 cGy mCi-1), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was 2.4 /- 1.9 microCi mCi-1 (range 0.2-10.0 microCi mCi-1), which was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases. No correlation was found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the mAb preparation, rapid metabolic breakdown of the labelled antibody due to human anti-mouse antibodies (HAMA), or immune complex formation with circulating antigen. However, a relationship between the thyroid doses and the patients' compliance in taking their Lugol's and perchlorate blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (range from 31.1 h to virtual infinity), is indicated. No rising TSH titres or other signs of (latent) hypothyroidism were seen in these patients during a 2 year follow-up period. Longer follow-up was not possible because of the terminal condition of most of the patients. These data show that thyroid doses in an appropriately blocked individual given a standard, non-myeloablative dose of RAIT, are generally lower than those assumed to be required to cause late hypothyroidism. Even if higher activities are used, potential hypothyroidism may be overcome easily by hormone replacement. Thyroid doses are independent of parameters leading to an enhanced exposure of the thyroid to free radioiodine, suggesting that patient compliance in taking their blocking medication may be the most crucial factor for reducing thyroid doses in RAIT with 131I-labelled antibodies.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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