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PubMed1991

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

The concept of using thyroid-stimulating hormone (TSH) receptor antagonists in the management of Graves' disease is intriguing. Therefore, we investigated a TSH receptor antagonist derived from human chorionic gonadotropin (hCG) with respect to TSH receptor binding, adenylate cyclase activity, thyroid hormone release, and HLA class II antigen expression in vitro and in an in vivo model. A variant of hCG, asialoagalacto-hCG, like asialo-hCG and unlike hCG itself, inhibited both 125I-bTSH binding and cAMP response to bTSH in human thyroid membranes. However, like intact or deglycosylated hCG and unlike asialo-hCG, asialoagalacto-hCG displayed a limited affinity for hepatic asialoglycoprotein receptors, a likely marker for its in vivo turnover rate. It proved capable of inhibiting bTSH-stimulated thyroid hormone release in human thyroid slices as well as in the nude mouse bearing human thyroid transplants. It also prevented bTSH induced hypertrophy of transplanted thyrocytes. Further, HLA-DR expression induced by bTSH in the presence of gamma-interferon on human thyrocytes was inhibited. In conclusion, we present evidence that asialogalacto-hCG antagonizes bTSH actions on thyroid function and HLA-DR expression in human thyroid in vitro and, more importantly, in an in vivo model. Hence, the hCG variant described here or similar agents should warrant further exploration in the study and treatment of Graves' disease.

Adenylyl Cyclases↗

PubMed1975

[Clinical studeis on the regulatory system of thyroid hormone secretion and serum triiodothyronine. Part III. Studies on thyroid hormone change and its relationship when TSH in cases with subclinical hypothyroidism (Hashimoto's thyroiditis and 131I treated Graves' disease)].

Changes in thyroid hormone levels and their relationship with TSH in cases with Hashimoto's thyroiditis and 131I treated Graves' disease in subclinical hypothyroid state were investigated: 1) In 34 cases with Hashimoto's thyroiditis, TSH levels was 14.7 +/- 26.8 muU/ml (mean +/- s.d.), T3 144.5 +/- 33.6 Rg/100 ml; T4 6.7 +/- 2.4 MUG/100 ML; T3RU 25.4 +/- 3.2%; F.T.I. 2.0g +/- O.89; T3/T4 2.46+/- 1.04%. It was noted that TSH levels revealed significant positive correlation with T3/T4 (r=0.77); significant inverse correlation with F.T.I. (r= - 0.51); and non-significant inverse correlation with T3 levels (r= - 0.06). These results indicate that T3 might play a more important role than T4 in maintaining normal thyroid function (so-called T3 euthyroidism). This is probably based on metabolic disturbance of iodine which is common in Hashimoto's thyroid. In several cases with rather high normal basal T3 levels, no significant elevation in T3 was observed in spite of elevated TSH level following TRH administration. This might indicate that the thyroid is fully functioning and that no more reserve is left for the thyroid to respond further to elevated TSH. 2) In 30 cases with 131I treated Graves' disease, TSH concentration was 22.3 +/- 29.8 muU/ml (mean +/- s.d.); T3 100.7 +/- 35.4 ng/100 ml: T4 6.2 +/- 2.9 MUG/100 ML; T3RU 25.6 +/- 2.3%; F.T.I. 1.87 +/- 0.85; T3/T4 1.80 +/- 0.64. Significant inverse correlation was noted between TSH levels and F.T.I. as well as T3 levels. Although TSH levels showed significant positive correlation with T3/T4 (r=0.44), its degree of correlation was not as good as that with F.T.I. (r= - 0.71) and T3 (r= - 0.53). These results indicate that there is no preference in T3 production. From the responsiveness of thyroid and pituitary following TRH administration, assumption can be drawn that 131I treated Graves' patients, who became euthyroid, may in fact be on the way to hypothyroidism.

Follow-Up Studies↗

PubMed1991

Thyroid microsomal antigen in Graves' thyroid is not different from that in normal thyroid.

Differences from normal in microsomal antigen (M-Ag) may be involved in the development of autoimmune thyroid disease. We compared the M-Ag in Graves' thyroid immunologically and biochemically to that in normal thyroid. The concentration of M-Ag, measured with an enzyme-linked immunosorbent assay, was significantly greater in the Graves' microsomes than in normal microsomes. Binding of a patient's microsomal antibody to Graves' microsomes was completely inhibited when the serum was first incubated with normal thyroid microsomes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting were done with a monoclonal antibody to denatured M-Ag. In both Graves' and normal thyroids, M-Ag existed as 107-, 101-, and 95-kDa peptides. After incubation with V8 protease, the residual antigenic peptide had a molecular weight of less than 60,000 and after incubation with trypsin, 95- and 87-kDa peptides and several smaller antigenic peptides were found. There were no significant differences in the pattern of normal and Graves' microsomes after digestion. Two-dimensional gel electrophoresis of Graves' microsomes showed that the isoelectric point for the 107-kDa peptide was at pH 7.2; that for the 101-kDa peptide was at pH 6.2, and that for the 95-kDa peptide was at 6.5. These values were not different from those observed for normal microsomes. These results indicate that M-Ag in Graves' thyroid does not differ from that in normal thyroid, and that microsomal antibodies in autoimmune thyroid disease probably do no arise from differences in the antigen.

Autoantigens↗

PubMed1988

[Clinical studies on abnormal thyroid stimulators in patients with Graves' disease. I. A sensitive assay for thyroid-stimulating antibodies using cultured porcine thyroid cells and polyethylene glycol precipitation of serum].

The activities of thyroid-stimulating antibody (TSAb) in serum from patients with Graves' disease were measured by a sensitive assay, using cultured porcine thyroid cells and the precipitation from serum with polyethylene glycol (PEG), and the activities were compared with those of thyrotropin binding inhibitor immunoglobulin (TBII), measured by the commercial assay kit. Porcine thyroid cells after digestion were cultured for 15-18 hours with TSH of 1-10,000 microU/ml or the precipitations of sera from normal subjects and patients with Graves' disease or Hashimoto's thyroiditis, and then the cAMP levels in the culture medium were determined by the commercial RIA assay kit (Yamasa). The precipitation was obtained by adding 0.5 ml of 30% PEG solution to 0.5 ml serum, and was resuspended with 0.6 ml of Hanks' medium without NaCl, containing 1.5% bovine serum albumin, 20mM Hepes and 0.5 mM 3-isobutyl-1-methylxanthine. The precipitation contained about 85% of immunoglobulin and 63% of albumin of the original amount of the serum, as well as substantial TSH, when the original serum contained TSH more than 40 microU/ml. When the PEG precipitations from 10 normal subjects were incubated with the thyroid cells of 4 X 10(5) cells, the cAMP releases into the medium ranged from 83 to 124%, when the mean value was calculated as 100%. Therefore, the cAMP release of more than 130% of the amount released into the culture medium incubated with normal IgG was judged as positive TSAb activity. The minimum detectable quantities were regarded as about 5 microU/ml TSH equivalent. TSAb and TBII activities were detected in 48 (92%) and 50 (96%) of 52 patients with untreated hyperthyroid Graves' disease, respectively, and either TSAb or TBII activities were detected in 16 (80%) of 20 patients with Graves' disease maintained in a clinically euthyroid state by treatment with antithyroid drugs. TBII was positive in 10(50%) of these patients. Some patients showed distinct discrepancies in these two activities, although there was a significant positive correlation between TSAb and TBII activities (r = 0.53, p less than 0.01) in patients with untreated Graves' disease. In these patients, TSAb activities showed a significant positive correlation with values for 99mTc thyroid uptake, determined 30 min after the injection. However, they did not show any significant correlation with serum T4 or T3 concentrations. Similarly, TBII showed significant correlations with goiter size and 99mTc thyroid uptake. To conclude, the present assay for TSAb is sensitive and reproducible.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb).

In this paper, we report a 49-year-old female with subacute thyroiditis who had thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) in serum. Although she was in the thyrotoxic phase and TSH was suppressed in May, 1990, her radioactive iodine uptake (RAIU) was not suppressed (35.5%) and a thyroid scan disclosed a diffuse goiter with no defect. Serum assays revealed the presence of TSAb, but TSBAb were negative. In August, 1990, the right lobe became undetectable by thyroid scan when the RAIU was 20.7% with the TSH level remaining suppressed. At that time, TSAb were negative, while TSBAb were positive. When the RAIU was 31.1% in October, 1990, both thyroid lobes became visible and the TSH level was normalized. TSBAb became negative, and although TSAb reappeared it later became undetectable. These results indicate that the changes in the patient's thyroid scan and RAIU were attributable to the presence of TSAb.

Autoantibodies↗

PubMed1977

Thyrotropin binding and long acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates.

The ability of various thyroid subcellular fractions to bind [125I]iodo TSH and to absorb long-acting thyroid stimulator (LATS) and thyroid stimulating immunoglobulins (TSI) activities was examined. Membranes purified from thyroid homogenates or isolated thyroid cells absorbed LATS/TSI activities and specifically bound [125I]iodo TSH. Purified thyroglobulin, nuclei, mitochondria and ribosomes did not bind [125I]iodo TSH nor did they absorb LATS/TSI activities. Cell sap obtained by gentle lysis of isolated thyroid cells failed to absorb LATS/TSI activities and to bind labeled hormone. However, freeze-thawing of the cells fragmented the membranes, releasing [125I]iodo TSH binding as well as LATS/TSI absorbing activities into the soluble (cell sap) fraction. The results suggest that the LATS/TSI antigen is of cell surface origin, includes the TSH receptor or larger membrane fragments containing the receptor, and that its release into the soluble fraction is due to the fragmentation of the thyroid membrane during homogenization and preparative procedures.

Animals↗

PubMed1991

Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases.

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.

Adolescent↗

PubMed1975

Subacute thyroiditis in a lateral thyroid gland: evaluation of the pituitary-thyroid axis during the acute destructive and the recovery phases.

Subacute thyroiditis in a lateral, ectopic thyroid has been previously unreported. A 4 10/12-YEAR-OLD GIRL HAD AN ENLARGING MASS IN THE LEFT UPPER ANTERIOR NECK. Initially, the serum concentration of T4 was normal, T3 was elevated, and TSH was undetectable without response to TRH. RAI uptake was 1%. The data were consistent with subacute thyroiditis. Twelve weeks later the serum concentration of T4 was low and TSH was elevated; thyroid replacement therapy was given for 20 weeks. When this was discontinued, there was an initial increase and then a decrease in the TSH values accompanied by an increase in serum concentrations of T3 and T4 to normal during eight weeks. One must consider a lateral ectopic thyroid gland in the differential diagnosis of masses in the neck. Physicians must be aware that temporary hypothyroidism occurs during the course of subacute thyroiditis.

Acute Disease↗

PubMed1991

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.

Adult↗

PubMed1991

Autoimmune thyroiditis with transient thyrotoxicosis: comparison between painful thyroiditis and painless thyroiditis.

Clinical and laboratory findings and long-term outcomes in 8 patients (7 women) with autoimmune thyroiditis (AT), aged 34-59 years, who had a painful tender goiter and a transient thyrotoxicosis with a low thyroid radioactive iodine uptake (RAIU), were compared with those in 15 patients (13 women) with painless thyroiditis (PT), aged 23-69 years. Six painful AT and 6 PT patients had a history of prior awareness of goiter. All patients with painful AT had a moderate or marked elevation of erythrocyte sedimentation rate and a positive result for C-reactive protein, while only 3 PT patients (group B) did. There were no significant differences between the mean age, duration of symptoms, white blood cell count, serum triiodothyronine (T3) and thyroxine (T4) concentrations, serum T3/T4 ratio and duration of thyrotoxicosis after the initial examination and prevalences of positive results for antithyroglobulin and -microsomal antibodies in the two diseases. Two of 8 painful AT patients showed a histologically chronic fibrous variant and 6 others showed chronic lymphocytic thyroiditis. All PT patients examined also showed lymphocytic thyroiditis. Two and 5 painful AT patients developed transient and persistent hypothyroidism, respectively, while 8 [7 in group A (normal ESR), 1 in group B] and 3 PT patients (1 in group A, 2 in group B) did, respectively. The mean serum thyroid-stimulating hormone level in the hypothyroid phase in painful AT patients was higher than that in PT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1978

Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with a thyrotropin receptor defect and in vivo stimulation of thyroid function.

Normal rat thyroid membranes adsorb neurotoxicity when incubated with purified tetanus toxin. Membranes from a rat thyroid tumor with a thyrotropin receptor defect adsorb very little neurotoxicity when similarly evaluated. This inability of the tumor membranes to adsorb neurotoxicity is correlated with a defect in their ability to bind both 125I-labeled tetanus toxin and [125I]iodothyrotropin. The effect of tetanus toxin on the release of radioiodine from the thyroids of appropriately prepared mice has been measured by adapting methods used for the bioassay of thyrotropin. One minimum lethal dose of tetanus toxin given sc caused a significant release of radioiodine into the blood of mice 48 h after injection. In mice subjected to the stress of prior bleedings or anesthesia, the release of radioiodine from the thyroid by tetanus toxin was accelerated, i.e., the increase in blood radioiodine could be measured 24 h after injection. These results again suggest that tetanus toxin may interact with thyrotropin receptors on thyroid plasma membranes. The "sympathetic overactivity syndrome" seen in some patients with tetanus and the syndrome characterized as "thyroid storm" in patients with Graves' disease are discussed as they may relate to these observations.

Animals↗

PubMed1979

Adenyl cyclase activity in human thyroid plasma membranes from normal human thyroid tissue and thyroid adenomas.

The adenylcyclase (AC) activity of crude human thyroid plasma membranes were studied in some detail and conditions for optimal cyclic AMP-production established. Membranes from eight "cold" and two "hot" thyroid adenomas were investigated and compared to membranes from corresponding normal, paranodular tissues. The investigated membranes were found to contain similar basal AC activities, which were stimulated three to five times with TSH and 20--30 times with fluoride. Further, no difference in the TSH-sensitivity of AC from normal and "cold" adenomas could be detected. Thyrotrophin 0.02 mU/ml caused a measurable and 0.15 mU/ml a half-maximal stimulation of the cAMP-production. The data indicate, that disturbances of thyroid hormone production characteristic of thyroid adenomas, are not caused by alterations of the TSH-AC system and suggest that in a thyroid cell the degree of thyroid hormone synthesis do not alter the amount of plasma membrane-bound adenylcyclase.

Adenoma↗

PubMed1976

Autoimmune murine thyroiditis. VIII. Role of different thyroid antigens in the induction of experimental autoimmune thyroiditis.

Mice of the C57Br strain, which are susceptible to the induction of autoimmune thyroiditis with mouse thyroglobulin, and C57Bl mice, which are resistant, were immunized with human and rabbit thyroglobulins in Freund's complete adjuvant. Susceptible strain C57Br developed higher degrees of thyroid infiltration than the resistant strain. The results indicate that the responses to xenogeneic (foreign) thyroglobulins parallel allogeneic and syngeneic (mouse) thyroglobulin. BSVS mice, which are highly susceptible to thyroiditis, were immunized with mouse thyroid extract from five different mouse strains including syngeneic antigen. Recipients of C57Bl and DBA thyroid extracts showed lower indices of pathology than recipients of similar extracts from C3H, BSVS and non-inbred CF-1 mice. The results suggest that there is a difference in the immunogenicity of mouse thyroid extracts from different strains. Purified thyroglobulin was prepared from congenic strains B10.D2 (H-2d, resistant) and B10Br (H-2k, susceptible). H-2k thyroglobulin gave a greater response in both H-2k and H-2d mice than H-2d thyroglobulin.

Animals↗

PubMed1991

[Effectiveness of iodine prophylaxis and frequency of thyroid enlargement (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the Szczecin region after the Czernobyl accident].

The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the area of Szczecin (2350 females and 2217 males). The population was chosen randomly, according to a simple drawing scheme. All subjects were clinically examined using standardised questionnaires. In 3468 persons (including 1807 girls and women, 1661 boys and men) apart form clinical examination, the assessment of thyrotropin, thyroxine and triiodothyronine in serum and frequency of antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated. The data indicate that 94% of children in Szczecin's region received the prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only 17% of the adults received iodine. The most common preparation was Lugol solution given in a single dose. Among all persons who received iodine, only in 5% of subjects the side effects were noted (mostly in children), including symptoms of gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid side effects (thyroid pains). In examined population the high frequency of thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years) was found. The frequency of clinical diagnosis of thyroid disease was higher in women than in man (most often the diffuse goiter, rarely the nodular goiter). The frequency of thyroid enlargement and clinical diagnosis of thyroid disease was not dependent on prophylactic iodine intake. The iodine prophylaxis did not influence on thyroid hormones and TSH serum levels and on frequency of antithyroid antibodies.

Adult↗

PubMed1991

The effect of xenotransplantation of human thyroid tissue following radioactive iodine-induced thyroid ablation on thyroid function in the nude mouse.

We have attempted to determine whether xenotransplanted human thyroid tissue into nude mice would act as a physiological substitute for the mouse thyroid gland after the mice had been rendered hypothyroid, using radioactive iodine (131I). The dosage of 0.2 millicuries of 131I was given to each mouse. The xenotransplantations of human thyroid tissue, i.e., normal, Graves' and nontoxic multinodular goitre, were carried out three weeks after radioactive ablation. The values of TSH in all mice rose to high levels (71 +/- 15.6 ng/ml, +/- SD) by three weeks after 131I administration. The TSH values in the mice declined rapidly and reached normal levels by 3-5 weeks after xenotransplantation. In addition, the serum T4 values were generally in the euthyroid range by 3-6 weeks after xenotransplantation. There were no marked differences in the changes of serum T4 and TSH when the three groups were compared. These results indicated that the xenografted human thyroid tissue permitted a return to a normal feedback system as reflected by normal serum TSH and T4 values in the animals. The Graves' thyroid tissue reverted to normal physiological function when removed from its human (abnormal) immune environment, signifying that Graves' thyrocytes are mere passive captives to immune events. This model should prove to be useful in the study of human thyroid physiology and pathophysiology.

Animals↗

PubMed1991

[Papillary thyroid carcinoma in a median ectopic thyroid associated with intra-abdominal thyroid tissue].

A 17-year-old female underwent surgical removal of a painless submental lump presumed to be a median cervical cyst. Histology showed a papillary thyroid carcinoma with invasion of the surrounding connective tissue. A 99m-technetium scan, performed in preparation for a planned total thyroidectomy, demonstrated no thyroid tissue. On subsequent 123-iodine scanning there was an area of increased uptake about 3 cm above the larynx, but no normal thyroid tissue. Histological sections, obtained during further surgical exploration of the base of the tongue, showed scattered thyroid cell rests in the lingual muscles. Whole-body scanning, carried out in connection with administration of radioiodine for ablation of remaining thyroid tissue, disclosed an unexpected area of increased uptake in the epigastrium. Sonography and CT scans failed to demonstrate any corresponding morphological abnormality. Following a further dose of radioiodine 4 months later, no areas of increased uptake were noted.

Abdominal Neoplasms↗

PubMed1991

Binding of peripheral blood and thyroidal T lymphocytes to thyroid cell monolayers: possible role of "homing-like" receptors in the pathogenesis of thyroid autoimmunity.

The specific binding of blood lymphocyte populations to non-antigenic receptors on high endothelial cells in peripheral lymphoid organs is well established. Such "homing" receptors in target tissues may also play a role in the early phase of organ specific autoimmunity. In this study binding of peripheral blood and thyroid-derived T cells to human thyroid (THY) cells was examined. Binding was measured as the percentage 51Cr-labelled T cells bound to THY monolayers. Interferon-gamma (IFN-gamma) enhanced the binding of peripheral blood T cells (PBL-T) from patients with Graves' disease (GD) and normals, but not from patients with Hashimoto's thyroiditis (HT), to allogeneic THY monolayers. The binding of T cells from patients with HT to untreated allogeneic THY monolayers was significantly greater than that for T cells from patients with GD or normals. TSH inhibited the IFN-gamma enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n = 5) and autologous (n = 4) THY monolayers. Intra-thyroid T cells (ITL-T) bound to autologous THY monolayers significantly more than PBL-T from the same patient, while ITL from patients with HT or Graves' disease bound more than their PBL-T to both allogeneic and autologous THY monolayers. ITL-T, but not PBL-T, bound significantly more to autologous THY than to autologous thyroid-derived fibroblast monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1976

Comparative ultrastructure of thyroid, tongue and eyelid lesions in the neuroma phenotype of medullary carcinoma of the thyroid: association of amyloid with fibroblasts in thyroid tumor and in mucosal neuromas.

Electron-microscopic and histochemical studies of thyroid tumor, tongue neuromas and eyelid neuromas from the lesions of a patient with medullary thyroid carcinoma were compared. In the thyroid tumor, a significant number of the C cells showed heterogeneity of granule types; no C cells, however, were identified in the tongue and eyelid neuromas. Amyloid was clearly shown by Congo red staining in the thyroid neoplasm and in the tongue neuromas. In all tissues, amyloid fibrils were found to be ultrastructurally closely associated with fibroblasts. These fingings suggest that the fibroblast rather than the C cell may have played the important role in the deposition of amyloid in this patient's thyroid carcinoma.

Amyloid↗