11/27. Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis.We characterized the virtual absence of immunoassayable thyroglobulin (Tg) in the serum and thyroid gland of two siblings (MA, JNA) and one nephew (RSS) from a family without inbreeding or familial goiter. diagnosis of defective Tg gene expression was based on findings of normal PBI and low serum T4, low or normal serum T3, negative perchlorate discharge test, and virtual absence of the serum Tg response to challenge by bovine TSH. This conclusion was confirmed by analysis of proteins in the goiter extracts. Only minute amounts of immunoassayable Tg were detected by RIA (MA, 0.11; JNA, 0.19 mg/g tissue; compared to 70-90 mg/g in normal thyroid tissue). Gel filtration in Sephacryl S300 showed the absence of a normal Tg peak at 280 nm and concentration of label mostly on albumin. A minor intermediate peak of radioactivity was also detected, with the size of, approximately, normal Tg. sodium dodecyl sulfate-agarose gel electrophoresis indicated the absence of Tg dimer and monomer, and Western blotting and immunoelectrophoresis confirmed this finding. Dot blot quantification of Tg and thyroid peroxidase mRNA indicated decreased hybridization of the patients' mRNA (MA, 44%; JNA, 63%) with phTgM2 (Tg probe) and increased hybridization (MA, 191%; JNA, 182%) with the pM5 (thyroid peroxidase probe) compared with control thyroid tissue. Dot blot analysis of Tg mRNA from the two siblings weakly hybridized with 3' and 5' Tg probes. rna analysis by means of Northern transfer showed a clear signal of hybridization with Tg probe (phTgM1) in the 8- to 9-kilobase range, corresponding to the normal size Tg mRNA. No major polymorphisms were noted in Southern blotting, using seven restriction endonucleases. We conclude that no gross alteration of the 5' region of Tg gene was present in these patients. Ultrastructural examination of the thyroid tissue indicated that the rough endoplasmic reticulum was not augmented, nor were the cisternae of rough endoplasmic reticulum dilated. The defect observed in these goiters is diminished tissue concentration of Tg mRNA with defective translation. However, small amounts of functionally active Tg could be synthesized, iodinated, and immediately hydrolized, yielding mostly T3, owing to the intense tissue stimulation by TSH.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
12/27. airway obstruction due to goiter in older patients.It has been shown that goiters can progressively enlarge to compress the surrounding trachea or esophagus and result in incapacitating obstructive symptoms or potentially fatal airway obstruction. The potential of a goiter to become hyperactive also exists. Recently, we have seen three older patients with longstanding untreated "benign" goiters who presented difficult management decisions. Given the likelihood of progressive growth of a goiter and the increased life expectancy of these patients with goiters, it is essential to perform flow-volume loop studies while following these patients.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
13/27. Non-adenomatous inappropriate TSH hypersecretion and euthyroidism requires no treatment.The syndrome of inappropriate TSH secretion is described in a euthyroid girl and her father. Based on nuclear T3 binding studies in fibroblasts, generalized tissue resistance was associated with a lower binding affinity for T3 in nuclear extracts suggestive of a structurally abnormal receptor for T3. Early recognition of the syndrome and observation of the short-term response to thyroid medication prevented unnecessary trials of antithyroid medication and later radical ablative thyroid treatment.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
14/27. Computed tomography in amyloid goiter.Two cases of amyloid goiter showed diffuse decreased density of enlarged thyroid on CT. The diffuse decreased density of amyloid goiter on CT is thought to represent large amount of adipose tissue often found in amyloid goiter. When diffuse decreased density of the enlarged thyroid is recognized on CT, amyloid goiter should enter into differential diagnosis.- - - - - - - - - - ranking = 62.360155587237keywords = adipose (Clic here for more details about this article) |
15/27. Coping with respiratory obstruction after thyroidectomy for giant goitres in northern nigeria.thyroidectomy for giant goitres in Northern nigeria is associated with a high incidence of postoperative asphyxia. tracheostomy may be a life saving procedure in these circumstances, but delay may prove fatal when its need arises insidiously. It is therefore better established prophylactically in patients who are more than likely to develop asphyxia, as in the case of preoperative complications followed by prolonged surgery. During the dry, dust-laden and desiccating Harmattan season of Northern nigeria, however, tracheostomy poses life-threatening dangers and should be established only in patients who need it for survival. Postoperative asphyxia can be minimised by adopting certain operative techniques which reduce the risks of postoperative haematoma and laryngeal oedema. Establishment of a thyroidectomy team for surgery and for postoperative management improves results.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
16/27. Familial partial target organ resistance to thyroid hormones.A 30-year old woman with a history of recurrent goiter, who had undergone two partial thyroidectomies, is described. She presented with tachycardia, nervousness and a fine tremor of the fingers. Initially, she had normal serum thyroid hormone levels: thyroxine (T4 (D)) 11.6 MUG/100 ML, triiodothyronine (T3) 138 ng/100ml, normal levels of binding proteins and a very high serum thyrotropin (TSH), 98 muU/ml. During follow-up T4 (D) increased to 17.2 mug/100 ml, T3 increased to 277 ng/100 ml, while TSH decreased to 11 muU/ml. There was an exaggerated response of TSH to a peak value of 550 muU/ml after intravenous administration of 200 mug thyrotropin-releasing hormone (TRH). Administration of 60 mg prednisolone daily resulted in a blunting of the response to TRH. Administration of 50 mug T3 daily for 1 month resulted in a fall in serum TSH from 98 to 50 muU/ml. Later, when the serum TSH level had fallen spontaneously to 20 muU/ml, administration of 100 mug T3 daily for two weeks resulted in a fall in serum TSH to 5.3 muU/ml. Treatment with 20 mg carbimazole daily for 3 weeks resulted in a decrease in serum T4 levels with a concomitant increase of serum TSH. There was no evidence of pituitary enlargement and other pituitary hormone levels were normal. All the relatives studied (father, sister, three children) had elevated T4 levels with normal basal TSH values. It is concluded from this study that our patient presents evidence of partial resistance to thyroid hormones.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
17/27. Low molecular weight thyroglobulin leading to a goiter in a 12-year-old girl.We characterized the abnormal thyroglobulin (TG) in the thyroid and serum of a 12-yr-old girl with a large sporadic multinodular goiter first noted at age 4 yr. She developed normally and had no clinical evidence of hypothyroidism. However, her serum T4 was less than 1.0 microgram/dl, T3 was 125 ng/dl, and TSH was 155 microU/ml. serum PBI was 9.7 micrograms/dl, and more than 90% was not extractable with butanol. The 24-h radioactive iodine uptake was 55%, not dischargeable by perchlorate. Hormone formation was tested by the administration of 131I before surgery. [131I]T4 and [131I]T3, but not 131I-labeled iodotyrosines, were present in the thyroidal venous blood. hydrolysis of 10,000 X g supernatants from three randomly obtained samples of the goiter revealed 66-77% of the 131I as iodotyrosines, 2-4% as iodothyronines, and 10-12% as undigestable material; the MIT to DIT ratio ranged from 3.1-8.7, and the T4 to T3 ratio ranged from 2.3-8.3. The TG level was 2.5 mg/g in the goiter and 9.4 micrograms/ml in the serum. The RIA displacement curves for the goiter and serum TG levels were both identical to the curve produced by normal human TG. The iodine contents of goiter and serum TG were 0.49% and 0.47% (wt/wt), respectively. The T4 to T3 ratio was lower in the goiter (approximately 5) than in the serum iodoprotein (approximately 45), whereas the calculation of the T4 to T3 ratio in the thyroidal secretion was less than 1. The goiter and serum TG bound normally to concanavalin a, indicating that they contained carbohydrate. When either serum- or goiter-soluble proteins were gel-filtered (Bio-Gel A-5m), TG immunoreactivity and stable iodine elution profiles were the same, suggesting that no significant amounts of other iodoproteins were present in the thyroid or circulation. Both serum and goiter TG elution volumes corresponded to mol wt of approximately 9 X 10(4). A sedimentation rate of 10-11 S was found for both goiter and serum TG. An abnormally low mol wt of 8.5-9.0 X 10(4) was determined by sodium dodecyl sulfate-electrophoresis, in good agreement with the estimates from gel filtration studies. A single band was present on sodium dodecyl sulfate-electrophoresis regardless of whether the TG was reduced before the analysis. Thus, it is very unlikely that the low molecular weight was due to partial hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS)- - - - - - - - - - ranking = 2keywords = fat (Clic here for more details about this article) |
18/27. A new case of familial partial generalized resistance to thyroid hormones: study of 3,5,3'-triiodothyronine (T3) binding to lymphocyte and skin fibroblast nuclei and in vivo conversion of thyroxine to T3.A clinically euthyroid 30-yr-old man with high serum levels of both total (T4, 14.5 micrograms/dl; T3, 272 ng/dl) and free (FT4, 33 pg/ml; FT3, 9.7 pg/ml) thyroid hormones and inappropriately normal TSH levels, both basally and after TRH stimulation, is described. Peripheral indices of thyroid hormone action and the patient's clinical status were not modified by the prolonged administration of supraphysiological doses of both T4 (up to 900 micrograms/day) and T3 (up to 80 micrograms/day), which decreased but did not completely abolish the TSH response to TRH. However, the TSH response to TRH was normally blunted by dexamethasone administration, which also reduced serum T4 and T3 levels to normal. T3 binding to nuclei of mononuclear leukocytes and cultured skin fibroblasts was normal. The overall pattern demonstrates that the patient was affected by partial peripheral resistance to thyroid hormone action. Study of the patient's family revealed the same hormone pattern in the patient's father, suggesting an autosomal dominant mode of inheritance. An in vivo study performed after the iv injection of tracer doses of [125I]T4 and [131I]T3, demonstrated increased production rates (PR) of both T4 [PR, 113.0 micrograms/day X m2; normal subjects, 55.4 /- 12.3 (mean /- SD); n = 13] and T3 (PR, 41.1 micrograms/day X m2; normal subjects, 16.3 /- 2.7). In vivo conversion of T4 to T3 was also evaluated in the patient; a nearly normal T4 to T3 conversion factor was found (0.3108 vs. 0.2576 /- 0.0422 in normal subjects). In four hyperthyroid patients, the T4 to T3 conversion factors were similar (0.2932 /- 0.0600), while the PRs of T4 and T3 were increased (PR of T4, 308.6 /- 85.6; PR of T3, 110.3 /- 35.0 micrograms/day X m2) compared to those in the normal subjects.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
19/27. A 138-nucleotide deletion in the thyroglobulin ribonucleic acid messenger in a congenital goiter with defective thyroglobulin synthesis.Two siblings (HSN and AcSN) with congenital goitrous hypothyroidism were investigated in terms of clinical, biochemical, and molecular biology. diagnosis of defective thyroglobulin (Tg) was based on findings of low serum T4, low normal or normal serum T3, a negative percholate discharge test, and the virtual absence of the serum Tg response to challenge by bovine TSH. Only minute amounts of Tg-related antigens were detected by RIA in the goitrous tissue (HSN, 0.82 mg/g, compared to 70-90 mg/g in normal thyroid tissue), as confirmed by sodium dodecyl sulfate-agarose gel electrophoresis that indicated the virtual absence of Tg. The Tg messenger ribonucleic acids (mRNAs) from controls and HSN thyroid tissue were first reverse transcribed and then divided into several portions from positions 57-8448; the resulting complementary DNAs were, in turn, amplified by reverse polymerase chain reaction. The amplification of nucleotides 5165-6048 from control thyroid tissue Tg mRNA showed a fragment of 884 base pairs (bp). In contrast, the fragment present in the HSN was /- 750 bp and lacked the normal fragment. The sequencing of the smaller fragment revealed that 138 bp were missing between positions 5590-5727 of the HSN Tg mRNA. This deletion does not affect the reading frame of the resulting mRNA and is potentially fully translatable into a Tg polypeptide chain that is shorter by 46 residues. A cysteine residue is maintained by the junction between the proximal T from leucine 1831 and the distal GT from cysteine 1877. dna genomic polymerase chain reaction amplification excludes a deletion in the Tg gene and indicates that the deleted 138-nucleotide sequences lie in the same exon. The functional consequences of the deletion are not entirely clear, but it is conceivable that the excision of this segment of the Tg molecule could affect the protein structure, resulting in its premature degradation, very low colloid storage, and diminished thyroid hormone production rate.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
20/27. Amyloid goitre and hypothyroidism secondary to cystic fibrosis.Although cystic fibrosis (CF) is still the most frequently fatal childhood disease, many adults now survive into their third and fourth decades. Uncommon complications of chronic diseases, such as amyloidosis, while infrequent, may now appear during the course of CF in adulthood. We present a case of a patient with CF who was diagnosed with hypothyroidism due to amyloid deposits in the thyroid.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
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