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Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.

Circulating analytes used in the exploration of thyroid function are TSH and free thyroid hormones (FT4 and FT3). TSH is used as first line analysis in diagnosis because a normal value excludes almost always a thyroid dysfunction. However in the follow up of a treatment for hypo- or hyperthyroidism, free hormones are to be determined since TSH reaction is delayed and does not reflect precisely the restoration of euthyroidism. The measurement of anti-thyroperoxidase antibodies (anti-TPO) will show the presence of an autoimmune thyroiditis and that of thyroid stimulating antibodies (TSI) will establish the diagnosis of Graves' disease. The measurement of circulating thyroglobulin has no place in the diagnostic of thyroid dysfunction nor in the evaluation of a goitre but it is now the golden standard in the follow up of patients with a differentiated thyroid cancer after surgery and radioiodine ablation in patients without antithyroglobulin antibodies. Echography is the first line examination to evaluate thyroid morphology. It shows tiny thyroid nodules and gives precious informations on their structure, as well as paremchymatous diffuse abnormalities associated with thyroiditis. Thyroid scintigraphy with 99mTc allows establishing the functional characteristics of thyroid nodules (warm or cold) and to precise the origin of a thyrotoxicosis (autonomous toxic nodule vs Graves-Basedow, sub acute or silent thyroiditis). Whole body scintigraphy is mandatory after radioiodine treatment with 131I in order to visualize possible metastasis and establish their avidity for iodine.

Thyroglobuline (Tg) is a large molecule of high molecular weight mainly indicated in monitoring differentiated thyroid cancer (DTC), its measurement remains difficult. We report the case of a patient who underwent total thyroidectomy for a poorly differentiated thyroid insular carcinoma. Despite several (131)I treatments, a progressive elevation of serum Tg is observed. A control performed in another laboratory using an immunoradiometric assay (IRMA Cisbio) returns an undetectable value (< 0,2 mg/L). A new sample was simultaneously sent to different laboratories. Three nonisotopic immunometric assays showed high values of Tg while the IRMA assay, considered the gold standard, gave a result below the detection threshold. The absence of Tg antibodies and of anti-mouse antibodies was confirmed. The IRMA Kit manufacturer agreed to carry out an expertise. After changing their detection antibody, the presence of a high Tg was demonstrated, in agreement with non-isotopic techniques. The expertise conclusion was a lack of detection by the IRMA Tg assay. This incident was notified to AFSSAPS by the manufacturer.

Thyroid carcinomas represent the most common endocrine malignancy, and several biological markers are proposed according to the different types of this cancer: for papillary cancer, thyroglobulin constitutes an excellent prognostic factor and rearrangements of ret oncogene can be useful in diagnosis. In sporadic medullary carcinoma, calcitonin is a diagnosis marker of choice, and coupled with ACE, can prevent relapse. Regarding familial medullary carcinoma, mutation screening in ret oncogene leads to early detection of new cases.

Malignant transformation of struma ovarii is exceptional (less than 1%). The histolological diagnosis of malignancy is difficult especially in the well differentiated forms. Immunohistochemistry is highly contributive in the anaplastic forms. The prognosis is relatively favorable except for the metastatic and undifferentiated forms. We report a case of malignant struma ovarii with metastasis observed in a 65-year-old woman who died rapidly from her disease. In light of this observation, we discuss the diagnositic, management and outcome features of these particular tumors.

Radioodine-131 has an important place in the management of well-differentiated thyroid cancer. Patient preparation for radioiodine-131 administration must be rigorous and is based on the stimulation of endogenous TSH production, which requires a hypothyroid state after withdrawal of suppressive T4-therapy. The introduction of recombinant human TSH would simplify the protocol of preparation and improve the quality of life of patients. The diagnosis place of radioiodine-131 knew significant changes following the introduction of the serum thyroglobulin measurement. This tumour marker has a central role in the strategy of follow-up and tends to be the principal element of indication for a diagnosis exploration with radioidine-131. The systematic ablation of thyroid remnants remains controversial particularly in patients with good prognosis factors; the efficacy of low activities is also still debatable. The optimal follow-up strategy and the indication of remnant ablation must take in account the prognosis factors of survival and recurrence. Radioiodine-131 therapy permits frequently the cure of distant metastases, particularly in infraradiological pulmonary forms. This fact outlines the importance of an early detection of tumour recurrence based on the conjunction of radioiodine-131 and thyroglobulin. Side effects of radioiodine-131 therapy are generally limited if the precautionary measures are well applied; leukaemia constitutes the main risk but this complication is very uncommon and occurs after a high cumulative activity.

Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants or as squamous metaplasia of follicular epithelium. In a retrospective study of 1 390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2) : p <0, 01). The number of SCN rises with increasing number of sections examined. No statistical differences were found with age or thyroid disorders and presence of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases, neuroendocrine cells (calcitonin and/or calcitonin gene related peptide, chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The different cell types of SCN fitted with the ultimobranchial remnant theory. Thus, some rare carcinomas (like mixed medullary and vesicular carcinoma or mucoepidermoid carcinoma) might originate from SCN.

By its dual gamma and beta emission, 131I permits both external detection and selective irradiation of residual or metastatic differentiated thyroid carcinoma. Indications based on the evaluation of prognostic factors and on the quality of surgical excision are more advisable than systematic use. Useless, even harmful after unilateral surgery decided because of a very good prognosis, 131I is recommended according to several retrospective studies for post surgical ablation of the remnants, the detection and the treatment of the recurrences and the distant metastases. The use of therapeutic doses in patients with an isolated elevation of thyroglobuline (Tg) without any clinical or radiological signs favors early diagnosis and cure of metastases with negative diagnostic scintigraphy. Dosimetric considerations and radioprotection measures must be guided by specific rules concerning radiometric material, adapted rooms and skilful personnel. Scintigraphic detection must be done in the best technical conditions. Protracted follow-up is based on Tg dosages and 131I whole body scintigraphies. Early diagnosis of metastases and positive response to 131I irradiation influence favorably remission rates. Even if a complete remission is not achieved, repeated treatments by a specialized team improve the quality of survival for metastatic patients.

The authors studied the diagnostic interest of cell cultures in thyroid tumors. They cultivated 10 tumours (4 papillary carcinomas, 5 medullary carcinomas and 1 sarcoma-looking tumour). In 7 cases, cultures yielded nothing more than pathologic examination. Nonetheless the study allowed to detect a double secretion (calcitonin and thyroglobulin) in 2 medullary carcinomas which turned out to be mixed proliferations. It also detected a production of thyroglobulin by the sarcoma. They think that cell cultures may have a diagnostic interest besides pathologic examination, allowing precise study of secretory features of the tumors.

We present a new case report of "Insular" thyroid carcinoma. The first series was published, in 1984, by Carcangiu et al. The propensity for local recurrence and early distant metastases explains the poor prognosis of this carcinoma and demands aggressive therapy at the time of diagnosis. This includes radical surgery, radiotherapy with possible chemotherapy. Clinical and pathological arguments suggest that this carcinoma could be an intermediate stage in the process of loss of differentiation of some thyroid neoplasms.

We reconstituted functional follicles from isolated cells, after embedding in a collagen matrix. Therefore we could carry out many investigations. We showed that the cells embedded in collagen reorganized into functional follicles secreting thyroglobulin (Tg) visualised in the intra-follicular compartment, and triiodothyronine (T3) after TSH stimulation. We used these reconstituted follicles for testing several drugs, amiodarone, propranolol and some anaesthetic drugs (thiopental, midazolam and ketamine). We observed that all these drugs inhibited partially or totally, according to the dose administered, the follicular production of Tg and T3. We also found that the follicles reconstituted from thyroid Grave's tissues gave an abnormal secretion of Tg and T3. Finally we created in Rennes a human thyroid model that permits the exploration of pathologic tissues and that may be used in pharmacotoxicology.

An evaluation of the thyroxine content in thyroglobulin and different derived thyroxine-containing peptides by enzyme immunoassay is presented. Results correlate very well with those obtained by ion-exchange chromatography which served as a reference method: r = 0.997, p less than 10(-6). Enzyme immunoassay is more rapid and sensitive than ion-exchange chromatography and then suitable for routine use. Furthermore, this paper shows, for the first time, that enzyme immunoassay can be used to perform direct thyroxine estimation in small peptide (Mr less than 2,500) without previous total enzymatic hydrolysis.

Iodoaminoacid content (iodothyronines, T3 and T4, and iodotyrosines, MIT and DIT) has been determined in enzymatic hydrolysates of thyroglobulin Tg 19S of different iodine content (0.3-0.9%) isolated from equilibrium labeled rats. Preparative equilibrium centrifugation in RbCl density gradients of pure thyroglobulin was used to obtain protein fractions of largely different iodine content (0.2-1.2% I). Thin layer chromatography of total hydrolysates demonstrated that the distribution of iodoaminoacids depends on the total iodine content of each fraction. It is concluded, in agreement with previous results, that the native structure of Tg is an important factor in the regulation of hormone biosynthesis and that even at low iodination levels of Tg. T3 and T4 are synthesized.

The authors have developed an indirect immunofluorescence technique for histochemical detection of thyroglobulin and have tested it on 66 tissue sections. Fluorescence reflecting the presence of thyroglobulin was elicited in 57 samples of differentiated thyroid tissue, including healthy or hyperfunctional tissue and primary or metastatic papillary or follicular carcinomas. Thyroglobulin was found to be distributed heterogeneously between different areas and different cells. It may occupy the whole cell, the apex, the colloid substance and sometimes extracellular spaces. No fluorescence was present in non-thyroid tissues. This technique could be applied mainly to the diagnosis of thyroid carcinomas, where 25 metastases have been examined by this method, and to clear cell carcinomas. In these two cases, thyroglobulin appeared to be a good marker of tumoral tissue.

A case of vacuolated (signet-ring) cell microfollicular adenoma of the thyroid is presented and confronted to the pertinent literature. It is a rare lesion. Its histologic aspect, featuring vacuolated cells and microfollicules, sometimes clover-shaped, and the results of the mucin stains and thyroglobulin immunostaining confirm the follicular-cell nature of the tumor and exclude primary mucin-producing tumors of the thyroid. Arrest of folliculogenesis appears to be the basic mechanism of histogenesis in our case.

We report on the 466 nucleotides long, extreme 3' end of the ovine thyroglobulin (Tg) mRNA. The nucleotide sequence and the deduced carboxyl terminal region of the protein have been compared with those reported in other species. Comparison with hog peptides known to contain all the triiodothyronine (T3) of the mature Tg suggests that the antepenultimate amino acid, a tyrosine residue could be involved in hormone formation. This also agree with the data reported for bovine and murine Tg.

6 thyroid gland and 3 cervical lymph node clear-cells carcinomas are investigated by means of indirect immunofluorescence detection of thyroglobulin. Immunofluorescence was positive only in 1 case, which was a primitive thyroid carcinoma. In 7 other cases, its negativity pointed at the metastatic nature of the lesion, from a clear cell carcinoma of kidney (in 4 cases, nephrectomy was very remote, and in 3 cases, the renal lesion was discovered after our examination of the thyroid tumour). One observation showed negative staining reaction, and was a propagation of a parathyroid carcinoma to the thyroid gland. It is concluded that thyroglobulin can be used as an immunohistochemical marker to establish whether a clear cell cervical tumour originates from thyroid gland, or is a metastatic neoplasm.

A direct radioimmunoassay for human serum thyroglobulin (TG) has been developed. The lower limit of detection of the assay was 7.5 ng/ml. The serum values in normal subjects were between 0 and 44 ng/ml (n = 34, 21 female subjects, 13 male subjects). In 22 of the 34 subjects, TG was not detectable. The mean value of TG in a group of 19 subjects with multinodular goiter was 115.8 +/- 62.7 ng/ml (mean +/- SD). A group of 16 thyrotoxic individuals also had an elevated TG concentration (107 +/- 71 ng/ml). The serum TG levels in 6 patients with differentiated thyroid carcinoma with metastases were much more elevated than in any other clinical situation (3430 +/- 1100 ng/ml). In patients with thyroid cancer in clinical remission (n = 9), the TG levels were normal. In 2 patients with non-differentiated thyroid tumors, TG was not detectable. The major methodological problem in TG determination is the presence of anti-TG autoantibodies which may interfere with the radioimmunoassay.

Intact rat thyroid lobes incubated in vitro release recently synthesized thyroglobulin (Tg) into the media at a faster rate than they release thyroglobulin stored in follicular structures. Differential release of this Tg fraction cannot be explained by morphological alterations in thyroid architecture during incubation. This rapidly excreted fraction exhibits a low density on rubidium chloride gradients characteristic of poorly sialylated and poorly iodinated thyroglobulin, comigrating on rubidium chloride gradients with thyroglobulin isolated from tunicamycin treated glands. This poorly sialylated and poorly iodinated thyroglobulin is itself unaffected in its density or release into the media by tunicamycin treatment. Tg isolated from the media of tunicamycin treated glands has nearly the same low iodine and low sialic acid content as rat serum thyroglobulin and does not incorporate radiolabelled glucosamine. This fraction thus appear to duplicate properties of low glycosylated-low iodinated thyroglobulin released from thyroid cells in organisms that have no follicular structures and no follicular storage process as well as from thyroid tissue in patients with thyroid disease states, particularly thyroid tumors. Thus it is proposed a "short loop" pathway of low-glycosylated low-iodinated thyroglobulin directly into circulation, that bypasses and is not stored in the follicular lumen, the "long loop".

Thyroglobuline (Tg) biosynthesis has been studied in an adult fresh water lamprey Lampetra planeri (Bloch), by injection in coelomic cavity or by in vitro incorporation in follicles of branchial region of various radioactive labels: 125I-, 3H-leucine, 3H-mannose, 3H-galactose, N-acetyl mannosamine and 3H-N-acetylglucosamine. Labelling by all theses substances, present in Tg of mammals, proceeds efficiently in two hours. It has been demonstrated that the cyclostome studied synthetizes a 18 S iodinated glycoprotein analogous to Tg of higher vertebrates by its molecular size. It contains all the same hexose and N-acetyl derivatives of these in its sugar moiety and the same iodinated aminoacids. Purified 18 S Tg of the lamprey has been prepared; it is very poor in iodine (127I) and has a very low T3 and T4 content.

Porcine and ovine thyroglobulins were purified from fresh glands by slice extraciton, precipitation with buffered ammonium sulfate and Sepharose 6B gel filtration using 0.1 M sodium phosphate buffer pH 7.2 at all steps. In contrast to thyroglobulin obtained from frozen glands, the proteins purified from unfrozen glands only showed the 19 S and 12 S species by electrophoresis in sodium dodecylsulfate polyacrylamide gels. After full reduction and S-alkylation, no qualitative changes were observed in e gel electrophoresis patterns as compared to the unmodified proteins. Species of apparent molecular weight corresponding to the native 12 S subunit was the major component strongly suggesting a mol. wt. of about 330 000 for the elementary peptide chains of pig and sheep thyroglobulin. This was confirmed by sedimentation equilibrium analyses in 6 M guanidinium. HCl, 0.1 M sodium phosphate pH 7.2 OF FULLY REDUCED AND S-alkylated thyroglobulins which showed a weight average molecular weight of 310 000 daltons.

A specific double antibody radioimmunoassay for the measurement of Thyroglobulin (HTg) in human serum was developed according to the method of Van Herle. The sensitivity of the assay is 2.5 ng/ml. The mean concentration of HTg in 47 normal subjects was 15,1 ng/ml. Elevated HTg levels were found in patients with Graves' disease (12 cases) and in patients with metastases of differentiated thyroid carcinomas (14 cases). In patients with metastases of differentiated thyroid carcinoma the Tg level increases under stimulation by endogenous TSH. Sera obtained after total thyroid ablation for thyroid carcinoma did not contain demonstrable amounts of HTg. This technique was also applied to the assay of HTg in thyroid tissue.