A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.
A patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid hormone will be given in an attempt to suppress her TSH.
10 patients with a single hyperfunctioning thyroid nodule each were studied for pituitary thyrotropin (TSH) suppression. They were judged to be euthyroid on clinical grounds. The total thyroxine (T4D), free thyroxine (FT4), total triiodothyronine (T3D), and free triiodothyronine (FT3) were normal in most of the patients. Incorporation of 131I into the hyperfunctioning thyroid nodules was not suppressed by the administration of physiological doses of T3. Basal serum TSH concentrations were undetectable (<0.5 - 1.0 μU/ml) in all patients. The metabolic clearance of TSH in one patient before and after excision of the thyroid nodule was unchanged (40 vs. 42 ml/min) whereas the calculated production rate was undetectable before the operation (<29 mU/day) and normal after (103 mU/day). These data, in one patient, suggest that the undetectable concentration of TSH in these patients is a result of suppressed TSH secretion rather than accelerated TSH clearance.
In eight patients, basal serum TSH concentrations failed to increase after the intravenous administration of 200 μg of thyrotropin-releasing hormone (TRH); minimal increases in serum TSH concentrations were observed in two patients. The suppression of TSH was evident despite “normal” concentrations of circulating thyroid hormones. The observation that normal serum concentrations of T4D, FT4, T3D, and FT3 may be associated with undetectable basal serum TSH concentrations and suppressed TSH response to TRH was also found in four hypothyroid patients given increasing doses of L-thyroxine and sequential TRH stimulation tests.
Activating somatic mutations in the thyrotropin (TSH) receptor have been identified as a cause of hyperfunctioning thyroid adenomas, and germline mutations have been found in familial nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. All mutations reported to date have been located in the transmembrane domain. We now report an example of an activating mutation in the extracellular, TSH-binding domain, found in a male infant with congenital hyperthyroidism due to a toxic adenoma. The pregnancy was remarkable for fetal tachycardia. Scintigraphic studies demonstrated a large nodule in the right lobe, and a hemithyroidectomy was performed at the age of 2 yr. Direct sequencing of the TSH receptor gene revealed a mutation in one allele resulting in a substitution of serine281 by isoleucine (Ser281--> Ile) in the extracellular domain. The mutation was restricted to the adenomatous tissue. Expression of the Ser281--> Ile mutation in vitro revealed an increase in basal cAMP levels. Affinity for TSH was increased by the mutation. These findings demonstrate that activating mutations can also occur in the extracellular domain of the TSH receptor, and support a model in which the extracellular domain serves to restrain receptor function in the absence of TSH or antibody-induced conformational changes.
Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.
Thyroid cysts and pseudocysts, or hemorrhagic cysts, are quite frequent thyroid pathologies. Surgical theraphy has always been the treatment of choice in this pathology, but percutaneous ethanol injection (PEI) is becoming still more common. PEI was originally used in the treatment of liver nodules and subsequently in solid, hyperfunctioning thyroid nodules, but today it is used exclusively in cysts. The aim of this study was to evaluate the efficacy of PEI in reducing thyroid cyst volume 12 and 84 months after treatment and to compare cost-benefit to that of surgical treatment. The study includes 110 consecutive patients, who all underwent PEI after cytological analysis had excluded the presence of neoplasia. All patients had refused surgical treatment. One patient died during the follow-up due to cerebral hemorrhage. Each patient received an average of 5.3 ± 2.7 PEI treatments. After 12 months, volume was reduced by 82.6% and after 84 months by 93.03%. Dysphonia occurred in 2 cases of which one resolved spontaneously and one received cortisone therapy. The cost of PEI treatment is considerably lower than the cost of surgical therapy (the cost saving in our patient population was about €200,000). PEI should therefore be preferred to surgical treatment due to its efficacy and lower cost.
Percutaneous ethanol injection therapy; Thyroid US; Thyroid cysts
The osteoporosis associated with human hyperthyroidism has traditionally been attributed to elevated thyroid hormone levels. There is evidence, however, that thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states, directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In order to determine whether low TSH levels contribute to bone loss in hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr-knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type mice, thereby demonstrating that the absence of TSH signaling contributes to bone loss. Further, we identified a TSH-like factor that may confer osteoprotection. These studies suggest that therapeutic suppression of TSH to very low levels may contribute to bone loss in people.
A patient initially presented with an autonomously functioning right thyroid nodule and transient hyperthyroidism which lasted for a few months. Several months after resolution of thyrotoxicosis, the patient had a recurrent episode of hyperthyroidism and was found to have a left hot nodule. The right hyperfunctioning nodule had become cold on scintigraphy, and its aspiration revealed haemorrhagic fluid suggesting haemorrhagic infarction as the mechanism of resolution of the first episode of hyperthyroidism. Again following resolution of the second episode of hyperthyroidism, the left hot nodule also became hypofunctioning on scintigraphy indicating that the spontaneous restoration to euthyroidism was secondary to infarction. Recurrent hyperthyroidism and resolution due to nodular infarction in a patient with a nodular goitre may mimic the more common causes of transient thyrotoxicosis and should be considered in the differential diagnosis of goitrous hyperthyroidism.
Subclinical hyperthyroidism is usually associated with Graves' disease or toxic nodular goiter. Here we report a family with hereditary subclinical hyperthyroidism caused by a constitutively activating germline mutation of the thyrotropin receptor (TSHR) gene.
The proband was a 64-year-old Japanese woman who presented with a thyroid nodule and was found to be euthyroid with a suppressed serum TSH. The nodule was not hot. Although antibodies to thyroid peroxidase and thyroglobulin antibodies were present, TSHR antibodies were not detected by TSH-binding inhibition or by bioassay. Two of her middle-aged sons, but not her daughter, also had subclinical hyperthyroidism without TSHR antibodies. Without therapy, the clinical condition of the affected individuals remained unchanged over 3 years without development of overt hyperthyroidism.
A novel heterozygous TSHR point mutation causing a glutamic acid to lysine substitution at codon 575 (E575K) in the second extracellular loop was detected in the three family members with subclinical hyperthyroidism, but was absent in her one daughter with normal thyroid function. In vitro functional studies of the E575K TSHR mutation demonstrated a weak, but significant, increase in constitutive activation of the cAMP pathway.
Although hereditary nonautoimmune overt hyperthyroidism is very rare, TSHR activating mutations as a cause of subclinical hyperthyroidism may be more common and should be considered in the differential diagnosis, especially if familial.
Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.
To study the effectiveness and safety of USG-guided ethanol sclerotherapy in cystic thyroid nodules.
Materials and Methods:
USG of the thyroid gland was performed in 54 patients suspected to have a thyroid nodule on clinical examination. All patients with a predominantly cystic nodule (i.e., when >2/3rd of the nodule was cystic) were included in the study. Ethanol was injected into the cyst under USG guidance. The amount of ethanol injected was about 50% of the amount of aspirated fluid. Follow-up USG was done every month for 3 months; ethanol was re-injected when there was no significant reduction in the cyst volume. The initial cyst volume was compared with the final volume; statistical significance was assessed using the paired t-test.
USG revealed predominant cystic nodules in 16 of the 54 patients. Fifteen patients were selected for the study. Following ethanol sclerotherapy, four out of the 15 patients (26.6%) showed complete disappearance of the cyst and nine (60%) showed significant reduction in the cyst volume (i.e., reduction of cyst volume by ≥50% of initial volume). Only two patients did not show significant reduction in cyst volume; both these patients had nodules with an initial volume of ≥20 cc. There were no complications attributable to ethanol injection during follow-up.
Ethanol sclerotherapy is an effective and safe treatment for benign cystic thyroid nodules with volumes of <20 cc. Cystic nodules with volume >20 cc may need more number of alcohol injections and longer follow-up.
Cystic thyroid nodules; ethanol sclerotherapy
Seventy-eight clinically euthyroid patients with atrial dysrhythmias, either established or paroxysmal, and sixty-three patients in sinus rhythm with coronary disease were screened for hyperthyroidism using thyroid function tests including the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH). All had normal levels of serum thyroxine (T4) apart from three with dysrhythmias who were found to have hyperthyroidism. Twenty per cent of patients with atrial dysrhythmias and 10% of those in sinus rhythm had exaggerated TSH response to TRH. Thirty-six per cent of patients with an exaggerated response of TSH to TRH had significant titres of thyroid auto-antibodies compared with 15% with positive antibodies in those with normal TSH response to TRH. Auto-immune thyroid disease may be more closely related to heart disease than has previously been recognized. Rapid atrial dysrhythmias may occur in the presence of a normal serum thyroxine, high levels of TSH and positive thyroid antibodies.
We performed genetic immunization of outbred NMRI mice, using a cDNA encoding the human thyrotropin receptor (TSHr). All mice produced antibodies capable of recognizing the recombinant receptor expressed at the surface of stably transfected Chinese hamster ovary (CHO) cells, and sera from most of the immunized mice blocked TSH-dependent stimulation of cAMP accumulation in cells expressing the TSHr. Five out of 29 female mice showed sign of hyperthyroidism including elevated total T4 and suppressed TSH levels. The serum of these mice contained thyroid-stimulating activity, as measured in a classic assay using CHO cells expressing recombinant TSHr. In contrast, only 1 male out of 30 had moderately elevated serum total T4 with undetectable TSH values. The hyperthyroid animals had goiters with extensive lymphocytic infiltration, characteristic of a Th2 immune response. In addition, these animals displayed ocular signs reminiscent of Graves’ ophthalmopathy, including edema, deposit of amorphous material, and cellular infiltration of their extraocular muscles. Our results demonstrate that genetic immunization of outbred NMRI mice with the human TSHr provides the most convincing murine model of Graves’ disease available to date.
The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).
Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.
Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.
Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.
Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-β subunit gene expression. We have previously shown that retinoid X receptor–selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-β promoter activity in vitro. The RXR-γ isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-γ isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-γ–deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-γ–deficient mice were relatively resistant to exogenous T3. RXR-γ–deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-γ, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-γ isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.
An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed.
Thyroid stimulating hormone (TSH), Free Thyroxine (FT4) and Free Triiodothyronine (FT3) were assayed in 505 women of this region. 60 women had previous history of thyroid disease. The remaining 445 women formed the “Disease free group”. A “Reference group” was obtained by excluding women with previous and present history of thyroid dysfunction. Of the total 505 women examined 15.8% had thyroid dysfunction and 84.2% were euthyroid. 11.5% were hypothyroid (9.5% sub-clinical) and 1.8% hyperthyroid (1.2% clinical). The geometric mean TSH for the total population was 2.65 μIU/ml. It was significantly (p=0.025) lower in the reference population 2.17 μIU/ml. There was no significant difference in the FT3 and FT4 values between groups. 19% of women over 60 years had elevated TSH above 4.5 μIU/ml. The 2.5 and 97.5 percentiles of the reference population was 1.1–5.2 μIU/ml. 6.1% of women in the reference group had TSH levels above the reference intervals. Hypothyroidism particularly sub-clinical hypothyroidism is predominantly present amongst women in this iodine sufficient region. Evaluation of thyroid status could help in early detection and treatment.
Thyroid function; Hypothyroidism; Sub-clinical hypothyroidism
Among 76 patients who had had a subtotal thyroidectomy for hyperthyroidism from one to seven years previously recurrent hyperthyroidism was found in three and hypothyroidism in 13. The remaining 60 subjects were clinically euthyroid but a raised level of serum thyroid-stimulating hormone (TSH; greater than 5-0 mu U/ml) was found in 39. Analysis of the data showed that their serum thyroxine was significantly lower than in the subjects with a normal TSH. The serum triiodothyronine (T-3) was similar in both groups. It is concluded that subjects with a raised TSH remain clinically euthyroid by maintaining a normal serum T-3 concentration. There was no evidence of any long-term progressive deterioration of thyroid function after subtotal thyroidectomy.
The double antibody radioimmunoassay of serum thyroid-stimulating hormone (TSH) allows measurement of circulating levels of the hormone in most normal subjects. The serum TSH level in normal subjects is 1·6 ± 0·8μU/ml. Patients with non-toxic goitre and acromegaly have normal TSH levels. Values are always raised in hypothyroid patients (with primary thyroid disease) and are significantly lowered in those with hyperthyroidism. Of the many stimuli used in an attempt to raise TSH levels in normal adult subjects only three—synthetic thyrotrophin-releasing hormone, ethinyloestradiol, and carbimazole plus iodides—have been effective. The major clinical application of the TSH immunoassay lies in the diagnosis of minor degrees of hypothyroidism. An impaired response of serum TSH to synthetic thyrotrophin-releasing hormone should also help in the diagnosis of hypopituitarism affecting TSH production.
Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise.
This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed.
On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism.
Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences.
hyperthyroidism; GTD; HCG
Iodide that is essential for thyroid hormone synthesis is actively transported into the thyroid follicular cells via sodium/iodide symporter (NIS) protein in vertebrates. It is well known that NIS expression in thyroid is regulated by the thyroid statuses mainly through thyroid stimulating hormone (TSH). Although NIS mRNA expressions in extrathyroidal tissues have been qualitatively reported, their regulation by thyroid statuses has not been well clarified.
Male ICR mice aged four weeks were assigned into three groups (control, hypothyroid, and hyperthyroid). Hypothyroid group of mice were treated with 0.02% methimazole in drinking water and hyperthyroid group of mice received intraperitoneal injection (4 μg L-T4 twice a week) for four weeks. NIS mRNA expression levels in the tissues were evaluated using Northern blot hybridization and quantitative real-time RTPCR (qPCR). Additionally, end-point RTPCR for the thyroid follicular cell-characteristic genes (TSH receptor, TSHR; thyroid transcription factor-1, TTF1; and paired box gene 8, Pax8) was carried out.
By Northern blot analysis, NIS mRNA was detected in thyroid and stomach. In addition to these organs, qPCR revealed the expression also in the submandibular gland, colon, testis, and lung. Expression of NIS mRNA in thyroid was significantly increased in hypothyroid and decreased in hyperthyroid group. Trends of NIS mRNA expression in extrathyroidal tissues were not in line with that in the thyroid gland in different thyroid statuses. Only in lung, NIS mRNA was regulated by thyroid statuses but in opposite way compared to the manner in the thyroid gland. There were no extrathyroidal tissues that expressed all three characteristic genes of thyroid follicular cells.
NIS mRNA expression in the thyroid gland was up-regulated in hypothyroid mice and was down-regulated in hyperthyroid mice, suggesting that NIS mRNA in the thyroid gland is regulated by thyroid statuses. In contrast, NIS mRNA expression in extrathyroidal tissues was not altered by thyroid statuses although it was widely expressed. Lack of responsiveness of NIS mRNA expressions in extrathyroidal tissues reemphasizes additional functions of NIS protein in extrathyroidal tissues other than iodide trapping.
The extent to which hypothyroidism affects renal function in patients with heart failure remains incompletely explored, despite the known adverse prognostic implications of renal dysfunction in these patients.
In a pilot retrospective study, we evaluated 75 patients (age, ≥18 yr) with left ventricular ejection fractions <0.40. Forty-five patients had normal thyroid function (thyroid-stimulating hormone [TSH], 0.35–5.5 μIU/mL) and 30 had hypothyroidism. The group with hypothyroidism was subdivided into 17 patients who had controlled hypothyroidism (TSH, 0.35–5.5 μIU/mL) and 13 who had uncontrolled hypothyroidism (TSH, >5.5 μIU/mL). Renal function, measured in terms of glomerular filtration rate, was analyzed once in each patient, and the populations were statistically compared, with P <0.05 conferring statistical significance.
Baseline characteristics in all groups were similar. Mean glomerular filtration rate was better in patients with normal thyroid function than those with hypothyroidism (75.45 ± 31.48 vs 63.95 ± 21.43 mL/min/1.73 m2; P=0.032). There was no significant difference between patients with controlled hypothyroidism (66.89 ± 24.18 mL/min/1.73 m2) and those with normal thyroid function (P=0.131). In patients with uncontrolled hypothyroidism, mean glomerular filtration rate (60.2 ± 17.4 mL/min/1.73 m2) was significantly worse than in patients with normal thyroid function (P=0.015).
We found that heart-failure patients with insufficiently treated hypothyroidism have worse renal function than do patients whose thyroid function is normal or whose hypothyroidism is effectively treated. Larger studies will be needed in order to evaluate this conclusion further. We recommend that hypothyroidism in heart-failure patients be strictly controlled, lest it affect prognosis adversely.
Comorbidity; glomerular filtration rate; heart failure/complications/epidemiology/mortality; hypothyroidism/complications/physiopathology; kidney/physiopathology; kidney function tests; prognosis; risk factors; thyroid function tests; thyroid diseases/complications; thyroid hormones/physi-ology
The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.
A 9-year-old girl was euthyroid with a small goitre, exophthalmos, scaphocephalic skull, minor sketelal abnormalities, and raised serum thyroid hormone concentrations. Other members of the family did not have goitres and their thyroid hormone levels were normal. From age 3 years the patient was treated for Graves's disease, but after 4 years treatment was stopped because of enlargement of the goitre. Despite increased serum thyroxine (T4), free T4 (FT4), and triiodothyronine (T3), basal serum TSH, and the TSH response to thyrotropin-releasing hormone (TRH) were normal. Pituitary refractoriness was present because full suppression of the TSH response to TRH was achieved only after daily administration of 500 micrograms thyroxine. Urinary excretion of hydroxyproline, and the activity of red cell glucose-6-phosphate dehydrogenase remained normal when excess T4 was administered, demonstrating the tissue resistance to thyroid hormones. Peripheral lymphocytes were found to have nuclear receptors for T3 with normal affinity, but the relatively low binding capacity indicated that the biochemical defect might be a deficiency of nuclear receptor protein. The findings in this patient differ somewhat from previously reported cases of peripheral resistance to thyroid hormones.
Serum thyrotrophin (TSH) was estimated by double-antibody radioimmunoassay in 200 children aged 2 months to 16 years with normal thyroid function. There was no apparent variation in TSH with age or sex and only 4 children had TSH levels greater than 5 muU/ml. High TSH values were obtained in 9 children with primary hypothyroidism, in 3 children with thyroiditis, and in one girl with a lingual thyroid. Moderately raised TSH was found in 3 girls with thyroiditis, 2 brothers with goitres due to enzyme defect, and a girl with an ectopic thyroid. In one girl with a defect of iodine organification and in 3 boys with thyroxine binding globulin deficiency the TSH levels were normal despite very low serum thyroxine values. Serum TSH was also estimated in 20 children during treatment for primary hypothyroidism. 3 of these children showed slightly raised TSH levels despite apparently adequate replacement therapy with L-thyroxine. One girl showed a very high TSH level 3 weeks after treatment had been temporarily withdrawn.