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PubMed2002

[Differentiated thyroid gland carcinoma in a scintigraphically hot thyroid nodule: diagnosis and interdisciplinary therapeutic management].

A hyperfunctioning differentiated thyroid carcinoma is a rare occurrence. Nevertheless, this diagnosis must be considered in a scintigraphically hot nodule if there is a clinical or sonographic suggestion of malignancy. The case of a 57-year old patient with hyperthyreosis and a scintigraphically hot thyroid nodule is presented. Further evaluation led to the diagnosis of a differentiated thyroid carcinoma with extensive lymph node and pulmonary metastases (pT2b, pN1b, pM1). The scintigraphically hot nodule corresponded to the primary tumor, whereas scintigraphic detection of the lymph node metastases was only possible postoperatively. Extensive resection of the lymph node metastases was achieved by the intraoperative application of a gamma probe (2nd operation). This allowed sufficient uptake of radioiodine in the pulmonary metastases for their detection and subsequent devitalisation by radioiodine therapy. Complete elimination of all tumour tissue was documented at a control follow-up after six months. Gamma probe-guided surgery may allow for additional removement of non-palpable lymph node metastases. In selected cases this may optimize the surgical results and thereby facilitate the subsequent radioiodine elimination of advanced differentiated thyroid carcinomas.

Adenocarcinoma, Follicular↗
PubMed2004

A novel 1297-1304delGCCTGCCA mutation in the exon 10 of the thyroid hormone receptor beta gene causes resistance to thyroid hormone.

INTRODUCTION: Resistance to the thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to hormonal action caused by mutations located in the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor beta (TRbeta) gene. PATIENT: The patient in this study, a 42-year-old Caucasian male, came to medical attention because he experienced atrial fibrillation. Clinical evaluation showed a small and diffuse goiter and biochemical tests revealed markedly elevated concentrations of total T4, total T3, and free T4, normal thyroid-stimulating hormone (TSH) values and slightly increased I131 thyroid uptake at 24 hours. The thyroperoxidase, thyroglobulin, and TSH receptor antibodies were positive. He was treated with cabergoline plus methimazole. This treatment was stopped because of the inconsistent response, monotherapy with tri-iodothyroacetic acid (TRIAC) was then prescribed after molecular diagnosis confirmed RTH syndrome. METHODS: The exons 9 and 10 of the TRbeta gene, including splicing signals and the flanking intronic regions of each intron, were amplified with PCR. DNA sequences from each amplified fragment were performed with the Taq polymerase-based chain terminator method and using the specific TRbeta forward and reverse primers. RESULTS: Direct sequence analysis of the exons 9 and 10 of the TRbeta gene revealed an eight basepair deletion, 1297-1304delGCCTGCCA in exon 10. The mutation produces a frameshift at amino acid 433 and introduces a stop codon TGA at position 461, 85 nucleotides downstream from deletion. This alteration was not detected in either the father or mother of the patient, suggesting a de novo mutation that was confirmed by DNA fingerprint analysis. CONCLUSIONS: In the present study we have identified a novel sporadic mutation corresponding to 1297-1304delGCCTGCCA deletion in the activating function 2 (AF-2) region of TRbeta. To our knowledge, this is the first time that the presence of a partial deletion of eight nucleotides in the TRbeta has been reported.

Adult↗
PubMedDate not supplied

[Color Doppler ultrasonography of the thyroid gland in diagnostics of autoimmune thyroiditis].

Diagnostics of thyroid gland pathology becomes more efficient with combined use of ultrasound and Doppler Ultrasonography. The article presents Color Doppler Ultrasonography data of 91 patients with hypertrophic and atrophic form of autoimmune thyroiditis. The obtained results showed considerable increase in resistive index in patients with chronic autoimmune thyroiditis and consequently the index can be used as diagnostic criterion of chronic autoimmune thyroiditis.

Adolescent↗
PubMed1989

The role of ultrasensitive thyroid-stimulating hormone measurement in the initial evaluation of thyroid function.

New ultrasensitive assays of thyroid-stimulating hormone (TSH) have been introduced recently and recommended as better first line tests of thyroid function. The previous biochemical thyroid function tests are reviewed, with details of their usefulness and limitations. The limitations of the new ultrasensitive TSH assays are also reviewed. Although there are advantages in using TSH compared to other tests, the cost versus benefits ratio have yet to be assessed. Clinicians should be aware of the limitations in any biochemical test of thyroid function and treatment should not be based on laboratory investigation alone.

Evaluation Studies as Topic↗
PubMed1989

[Thyroid function in severe non-thyroidal diseases].

The aim of the present study was to find out whether a change in the function of the pituitary-thyroid axis can be revealed in a relatively homogenous group of hematological patients. To clarify this problem serum levels of total-thyroxine and triidothyronine, free-thyroxine and free-triiodothyronine, reverse-triidothyronine and thyrotropin were detected in these patients. The majority of subjects with chronic myelogenous leukemia (in the remission phase) have normal pituitary-thyroid function, however a change in the peripheral metabolism of thyroxine can be revealed. Longitudinal studies in patients with acute myelogenous leukemia indicate that in some cases with the progression of the disease serum TSH and thyroid hormone levels decrease referring to secondary hypothyroidism and in these cases the measurement of serum free-thyroxine content by an analogue tracer method is not recommended. On the basis of the investigational results it is stated that in hematological patients the pituitary-thyroid function is influenced by the phase of illness and by the results of the given treatment.

Humans↗
PubMed1981

[Thyroid gland diseases in old age. Clinical aspects and therapy. Part 2: Hypothyroidism, bland struma, thyroid gland neoplasms].

Because of the slow lingering course of this disease, the diagnosis of hypothyroidism is generally made by chance particularly because the euthyroidism can change unobserved into manifest hypothyroidism. In old age the course of hypothyroidism may be oligosymptomatic: only adynamia and abnormal susceptibility to cold may be diagnosed. Because of the augmented oxygen requirement of tissues during therapy with thyroid hormones the medical treatment of hypothyroidism has to start - especially in old age - with a fractional part of the final dose. In old age bland struma more and more changes to nodular struma, where small autonomic areas are often developed. Conservative therapy with thyroid hormones predominates in this case. Radioiodotherapy is indicated when medical treatment has been without success and operation is contraindicated because of high risk. Cancer of the thyroid is important - with respect to differential diagnosis - especially in older patients. Cancer of the thyroid is most common in patients aged between 50-70 years, and the anaplastic carcinoma is the most frequently observed malignant growth of old age. Concerning therapy, a radical operation comes into consideration; if radical operation is combined with too high risks, remaining tissue may be treated by radioiodotherapy without danger.

Aged↗
PubMed1995

[Study on different imaging time of late 201Tl thyroid imaging to differentiate malignant from benign thyroid nodules].

This study was undertaken to clarify better time to initiate the late 201Tl thyroid imaging to differentiate malignant thyroid nodules from benign ones. Thyroid images were obtained at 5 min, 1 and 3 hr after i.v. injection of 74 MBq of 201Tl chloride. The early (5 min) and late (1 or 3 hr) 201Tl images were compared in pathologically proven 38 malignant and 48 benign nodules of 83 patients. The lesion activity (LA) on the early image was visually graded as no uptake (-), slight uptake less than the surrounding thyroid tissue uptake (STTU) (+/-), uptake equal to the STTU (+), and uptake more than the STTU (++). The change of LA relative to the STTU from the early image to the late image was visually graded as decreasing (D), unchanged (U) or increasing (I) pattern when the LA was (+/-) to (++). The benign or malignant possibility at 1 hr and 3 hr in each lesion pattern was as follows: When the LA was (-) or D, the benign possibility was 95% (35/37) and 85% (39/46). When the LA was I, the malignant possibility was 96% (27/28) and 91% (21/23). When the LA is U, the diagnosis was equivocal: malignancy; 43% (9/21) at 1 hr and 59% (10/17) at 3 hr. The positive LA had a tendency to decrease with time irrespective of tumor character. The 1 hr image was statistically better than the 3 hr image as a late image. Comparative diagnosis of 5 min and 1 hr images with the criteria of I and U lesions being malignant and others being benign seems to be the best not to overlook malignant nodules: negative predictive value 95% and sensitivity 95%.

Diagnosis, Differential↗
PubMed1995

Characteristics of thyroid ultrasound pictures in children with nodular thyroid changes effected by radionuclides.

97 children with thyroid nodules found through screening programs in regions of White Russia (Belarus) affected by fallout from the Chernobyl disaster underwent thyroid ultrasound examination by one team at a central reference hospital. 46 of these children were operated on. 31 of these had thyroid carcinoma (30 papillary carcinoma, 1 follicular carcinoma), 9 adenoma, 3 nodular goitre, 2 thyroiditis and one colloid goitre. Sex distribution was equal in the carcinoma group while in all other groups females prevailed. In younger age groups (3-6 and 7-10 years) carcinomas were found more often than adenomas and cysts. A carcinoma was present most likely if there were a single nodule with a volume of more than 1.5 cm3, inhomogeneous echo structure, unclear, hypoechogenic margins, and enlarged regional lymph nodes.

Adenocarcinoma, Follicular↗
PubMed1997

Fine needle aspiration cytology of papillary carcinoma thyroid with Hashimoto's thyroiditis--report of two cases.

Two cases of papillary carcinoma of thyroid with clinically unsuspected Hashimoto's thyroiditis were diagnosed on Fine Needle Aspiration Cytology (FNAC) in females aged 22 yrs, and 57 yrs., who presented with a solitary thyroid nodule. The frequency of carcinoma in Hashimoto's thyroiditis varies between 0.5 to 23.7%, depending on the stringency of diagnostic criteria applied. We believe that this possibility must be kept in mind when ever an aspirate of a solitary nodule shows profuse lymphocytes and Hurthle cells.

Adult↗
PubMed1997

[Agenesis of the thyroid lobe associated with Hashimoto's thyroiditis].

A thyroid hemiagenesis in association with Hashimoto's thyroiditis and mild hypofunction in a 40 years woman, is described. It is an unusual association. The clinical, hormonal, immunological, instrumental and cytological diagnosis has been established. The importance of the scintigraphic pattern and the differential diagnosis with other pathological situations, such as Plummer's disease and several destroying processes, is emphasized. It is suggested that thyroid hemiagenesis has not to be regarded as clinically insignificant, in consideration of a possible association with pathologies of the normally developed lobe (Graves' disease, myxoedema, goiter, Hashimoto's thyroiditis, and especially neoplastic degeneration) or with nonthyroid diseases (hyperparathyroidism).

Adult↗
PubMed1995

Interdependence of corticosterone and thyroid hormones in toad larvae (Bufo boreas). II. Regulation of corticosterone and thyroid hormones.

Typically, the role of corticosterone(B) in metamorphosis is considered secondary to that of thyroid hormone, with B having only enhancing effects. In the current study, we demonstrate that the relationship between the thyroid hormones and B is much more complex and that thyroxine (T4) may depend on B for some of its functions. Tadpoles of the western toad (Bufo boreas) were treated with various combinations of corticosterone (B), thyroxine (T4), triiodothyronine (T3), a goitrogen (thiourea; Thio), and a corticoid synthesis inhibitor (metyrapone; MTP). Hormones were extracted from individual tadpoles and whole-body hormone levels determined by radioimmunoassay. B-treatment decreased the ratio of T4 to T3, suggesting that B increased the conversion of endogenous T4 to T3. In addition, B-treatment in combination with T4 resulted in high whole body-levels of T3. B also caused a decrease in whole body-thyroid hormone levels (T4 and T3), suggesting negative feedback on the hypothalamo-pituitary-thyroid axis and T3 had a similar effect, decreasing whole body-T4 levels. T4-treatment, but not T3, increased whole body-B levels and MTP-treatment in combination with T4 prevented the stimulatory effect of T4 on B production. MTP-treatment alone blocked all steroid metabolism of [3H]progesterone by the inter-renal in vitro, and lowered whole body-B levels three-fold in vivo. Thio-treatment reduced thyroid hormone levels and also resulted in decreased B. Finally, we suggest that these results demonstrate a system in which T4 may regulate its own potency: increasing T4 stimulates B production, which increases the conversion of T4 to its more active form T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1996

Thyroid function and serum thyroid binding proteins in prepubertal and pubertal children with chronic renal insufficiency receiving conservative treatment, undergoing hemodialysis, or receiving care after renal transplantation.

OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean +/- SE) in the three groups of patients (294 +/- 18, 303 +/- 18, and 323 +/- 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 +/- 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 +/- 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 +/- 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 +/- 41.9, 121 +/- 5.7, and 123 +/- 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 +/- 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 +/- 0.82, 2.13 +/- 0.13, and 2.01 +/- 0.20 nmol/L respectively) was significantly lower than in prepubertal control subjects (3.04 +/- 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 +/- 47 and 4950 +/- 1230 nmol/L, respectively). Serum levels of total thyroxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or endstage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment.

Adolescent↗
PubMed1992

The association of thyroid dyshormonogenesis and deafness (Pendred syndrome): experience of the Victorian Neonatal Thyroid Screening Programme.

Between 1977 and 1989, the Victorian Neonatal Thyroid Screening Programme detected five subjects with thyroid dyshormonogenesis and sensorineural deafness. These patients have been diagnosed as having Pendred syndrome. In two of the children, thyroid function tests which were initially abnormal at birth returned to normal spontaneously without treatment. However, hypothyroidism subsequently recurred and the children required thyroxine therapy. These two children could have been mistakenly diagnosed as having transient hypothyroidism. The detection of five patients with Pendred syndrome illustrates the importance of audiological assessment in all babies with thyroid dyshormonogenesis in whom there is increased uptake of isotope on thyroid scanning. In our experience, hearing loss in patients with Pendred syndrome may be progressive over time, so that repeated audiological assessments are necessary.

Deafness↗
PubMed1997

Thyroid regulation of NADPH:cytochrome P450 oxidoreductase: identification of a thyroid-responsive element in the 5'-flank of the oxidoreductase gene.

The current study demonstrates that T3-activated transcription of the NADPH:cytochrome P450 oxidoreductase (P450R) gene is dependent on the thyroid hormonal status of the animal, with both transcriptional and post-transcriptional pathways being important in regulating the cellular P450R mRNA level. The region required for transcriptional activation of the P450R gene by T3 has been identified. Nuclear run-on experiments demonstrated that the effects of T3 on P450R transcription are dependent on thyroid status, with a transcriptional enhancement obtained in T3-treated hypothyroid rat liver (1.8-fold increase) but not in T3-treated euthyroid animals. Transient cotransfection of P450R promoter/chloramphenicol acetyl transferase (CAT) constructs and the thyroid hormone receptor beta1 (TR beta1) expression plasmid into rat hepatoma H4IIE cells resulted in a 2.4-fold induction of promoter activity that was both T3 and TR beta1 dependent. Analysis of promoter deletion constructs identified a P450R-thyroid response region (P450R-TRE; bases, -564 to -536) containing three imperfect direct repeats of the thyroid response motif, AGGTCA. Mutational analysis further established that T3 induction was dependent only on the upstream direct repeat, having the sequence AGGTGAgctgAGGCCA. Footprint analysis showed that all three motifs were protected by proteins present in rat liver nuclear extracts, and a direct interaction between P450R-TRE and T3 receptors TR alpha1 and TR beta1 was demonstrated by gel-shift analysis. In vitro binding studies with P450R-TRE revealed the formation of heterodimeric complexes when TR alpha1 was coincubated with either the retinoic X receptor alpha or nuclear extract from rat liver, COS, or H4IIE cells. In addition, placement of the P450R-TRE upstream of the T3-nonresponsive heterologous thymidine kinase promoter resulted in a 2.7-fold transcriptional enhancement that was both T3 and TR beta1 dependent. Previous studies have demonstrated that T3 augments P450R mRNA levels approximately 20-30-fold and approximately 12-fold, respectively, in hypothyroid and euthyroid rats. Hence, for the hypothyroid state, transcriptional and post-transcriptional events contribute to the T3-induced mRNA increases; however, the marked increase in message level in T3-treated euthyroid animals depends primarily on post-transcriptional pathways.

Animals↗
PubMed1991

Demonstration of the existence of the alternatively spliced form of thyroid peroxidase in normal thyroid.

We have investigated whether the alternatively spliced form of thyroid peroxidase (TPO), which has been shown clearly to occur in Graves' thyroid, is present in normal thyroid. We have performed a polymerase chain reaction on cDNAs prepared from normal thyroid mRNAs using primers 100 bases up-stream and down-stream from the 171 nucleotides that have been shown to be spliced out. Size analysis of the polymerase chain reaction products by agarose gel electrophoresis revealed bands at 0.2 and 0.37 kilobases (kb), sizes predicted to be obtained when the two forms of TPO cDNA are present. This was confirmed by hybridization with a 32P-labeled probe corresponding to the 20 nucleotides of the junction site. After stringent washing, the 0.2-kb band gave a clear positive signal, which was stronger than that of the 0.37-kb band despite the latter cDNA being more abundant. This demonstrates clearly that the alternatively spliced form of TPO exists in normal thyroid. Its significance is discussed.

Base Sequence↗
PubMedDate not supplied

Cancer in the thyroid is not always thyroid cancer.

Most clinicians assume that a thyroid mass which appears to be malignant is most likely a tumour arising from thyroid cells. We present a case where the thyroid malignancy was associated with a degree of systemic clinical and biochemical disturbance which suggested alternative diagnoses, and in which fine-needle aspiration revealed that the patient had a thyroid lymphoma. Gastric biopsy showed that this was a primary gastric diffuse B cell lymphoma. Subsequent management provided a number of challenging and overlapping problems, and the patient eventually died from this high-grade malignancy. We review the prevalence, presentation, diagnosis and management of lymphomas presenting as thyroid masses, and underline the problems in management when there is multi-system disease.

Journal Article↗
PubMedDate not supplied

Thyroid suppression test with a single oral dose of levothyroxine in the diagnosis of functional thyroid autonomy.

OBJECTIVE: To propose a modified form of thyroid suppression test with use of a single oral dose of levothyroxine (35 mg/kg). METHODS: After a baseline scintigram, 23 patients with nodular goiter suspected of autonomous function (warm or hot nodules, subnormal or undetectable thyrotropin levels, or both findings) and 14 normal subjects underwent a repeated scintigram 4 days after administration of levothyroxine. We evaluated triiodothyronine (T(3)), free thyroxine, and thyrotropin before and on the first, second, third, fourth, and seventh days after administration of the individualized dose of levothyroxine. RESULTS: The 99th percentile of postsuppression uptake in normal subjects was determined, and an uptake >12.4%, a 131 I concentration restricted to the nodule, or both factors were adopted as the criteria for diagnosis of an autonomously functioning thyroid nodule. Twelve patients were considered to have autonomously functioning nodules, and 11 patients were considered to have nonautonomous nodules. Baseline thyrotropin levels in patients with autonomous nodules did not differ significantly from those in patients with nonautonomous nodules. No signs or symptoms of toxicity were detected during the test, but all study subjects had increased free thyroxine values, and seven had high levels of T(3). CONCLUSION: The thyroid suppression test with 35 mg/kg of levothyroxine is an effective method for the diagnosis of an autonomously functioning thyroid nodule, is nontoxic, and avoids the inaccurate use of the medication occasionally observed with T(3). Even sensitive methods of thyrotropin determination cannot replace this test in the evaluation of autonomous thyroid function.

Journal Article↗
PubMed1990

Peripheral blood T lymphocyte sensitization to thyroid microsomal antigen from patients with Graves' disease negative for circulating anti-thyroid microsomal antibodies.

We have studied thyrocyte HLA-DR expression induced by supernatants of peripheral blood mononuclear cells (PBMC) stimulated by thyroid microsomal antigen (TMA), as an index of sensitization of the T lymphocyte in autoimmune thyroid diseases; we have studied PBMC from 11 normal control persons and 19 patients with Graves' disease (GD) in whom serum anti-thyroid microsomal antibodies (AMA) were either not detectable (9 patients) or were positive (10 patients). Thyrocyte HLA-DR induction in response to TMA-treated PBMC supernatants from GD was significantly different from that of normal controls (p less than 0.05, ANOVA). TMA-stimulated GD PBMC supernatants increased thyrocyte HLA-DR index [TMA 1 ng/ml, SI 143 +/- 82 (mean +/- SD), p less than 0.05], but normal PBMC supernatants did not. However there was no significant difference in response in terms of the thyrocyte HLA-DR expression induced by TMA-stimulated PBMC supernatants between AMA seronegative vs seropositive GD. These results suggest the possibility of some dissociation of the activities of T lymphocytes and B lymphocytes in patients with GD in response to thyroid microsomal antigen with or without anti-thyroid microsomal antibodies.

Adult↗