Analysis of Fas, FasL and Caspase-8 expression in thyroid gland in young patients with immune and non-immune thyroid diseases

INTRODUCTION: Apoptosis, programmed cell death is a regulating mechanism enabling the removal of superabundantly produced and unnecessary at the certain moment cells. Disturbances of the apoptosis regulation contribute to the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate expression of proapoptotic Fas/FasL and caspase-8 in thyroid tissues in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: Inclusion criteria of Graves' patients were: large goiter, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH < 0.45 microIU/mL for more the 2-3 months from an onset of the disease. Isolated thyrocytes were identified by indirect method: in the first stage mouse monoclonal antibodies (mAbs) anti-TPO were bound to rabbit anti-mouse antibodies IgG (Fab')2 labeled FITC. To obtained cellular suspension mAbs directed against apoptotic Fas/FasL molecules labeled with PE (Phycoerythrin) was added. All investigations were performed on Coulter EPICS XL flow cytometer. Detection of apoptotic proteins was confirmed by Western Blot and immunohistochemistry methods using mAbs in DAB chromogene visuality and marked by Mayer's haematoxylin. Evaluation of caspase-8 expression in thyroid follicular cells was performed by Western Blot test. RESULTS: The analysis of Fas and FasL expression on surface of thyroid follicular cells was higher in patients with Hashimoto's thyroiditis (38%, 26%) in comparison with patients with Graves' disease (18%, 14%). In case of patients with Hashimoto's thyroiditis significantly lower percentage of thyroid tissue infiltrating immune Fas+ (13%) and FasL+ (22%) T cells in comparison with Graves' patients (33%, 43% respectively) was observed . Identification of proapoptotic Fas and FasL molecules in the thyroid follicular cells revealed higher expression of both proteins in patients with GD (++,++) and HT (+++; +++, respectively) in comparison with NTNG patients (+/0; +/0). Caspase-8 expression was detected in band 55 kDa using Western Blot test in patients with thyroid autoimmune diseases. CONCLUSIONS: We conclude that alteration in the expression of proapoptotic proteins in thyroid follicular cells may play a role in pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to increased proliferation of thyroid follicular cells which is responsible for goiter formation.     

Thyroid cancer in patients with hyperthyroidism

OBJECTIVE: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. METHODS: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. RESULTS: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. CONCLUSION: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.     

血浆HSP60 和TSGF联合检测甲状腺癌的早期诊断价值

目的:究血浆热休克蛋白-60(HSP60)与肿瘤特异性生长因子(TSGF)联合检测对甲状腺癌的早期诊断价值。方法:于2011年1月~2015年11月期间选取254例甲状腺癌患者(定为甲状腺癌组)、156例结节性甲状腺肿患者(结节性甲状腺肿组)和202例健康者(健康组)为研究对象,采用ELISA法检测三组血浆HSP60、TSGF水平,分析其与甲状腺癌病理因素的关系及诊断的敏感度和特异度。结果:甲状腺癌组的血浆HSP60、TSGF水平均显著高于结节性甲状腺肿组以及健康组,且结节性甲状腺肿组高于健康组,差异均具有统计学意义(P0.05)。甲状腺癌患者血浆HSP60、TSGF水平与年龄、性别、临床分期均无相关性(P0.05)。血浆HSP60、TSGF单独诊断甲状腺癌的敏感度和特异度分别为68.75%、81.82%和83.33%、71.88%,两者联合诊断的敏感度和特异度则分别达到了88.89%和86.72%。结论:在甲状腺癌的早期诊断中,采用血浆HSP60和TSGF联合检测的方式可靠性较高,值得推广应用。     

Proliferative activity of papillary carcinoma and benign papillary hyperplasia of thyroid follicular cells

Papillary structures of follicular cells are observed in nodular goiter, cysts, hyperplastic areas of follicular tumors, Graves' disease, thyroiditis and carcinomas. The distinction of papillary carcinomas from benign lesions has important implication for clinical management. The aim of the study was to test a marker of proliferation activity (MIB-1) in the diagnosis of benign and malignant thyroid papillary proliferation. The study was carried out in 98 women with papillary carcinoma, nodular goiter. intracystic proliferation. Graves' disease and hyperplastic areas of follicular benign tumors. The formalin fixed, paraffin-embedded specimens were microscopically examined using HE staining and immunostaining with MIB-1 antibody (DAKO). The proliferative index (PI) was significantly higher in malignant than in benign papillary hyperplasia. Our results may provide additional information for differential papillary proliferation diagnosis by FNAB.     

Zn concentration in thyroid tissue and whole blood of women with different diseases of thyroid

The Zn concentration in thyroid tissue and whole blood of patients with Graves’ disease, thyroid cancer, and nodular goiter disease was determined using the total-reflection X-ray fluorescence method. The dependence of obtained concentrations on the clinical stage of the examined disease, histopathological grading, and kind of analyzed material (thyroid tissue and blood) was studied. The determined concentration of Zn was the lowest in the thyroid tissue of patients with thyroid cancer (23.1 μg/g) and it was the highest in the case of Graves’ disease (41.7 μg/g), whereas in the blood samples, the reverse results were found (7.1 μg/g and 4.8 μg/g, respectively). The physical basis of the method used, the experimental setup, and the procedure of sample preparation are described.     

Expression of Bcl-2 family proteins in thyrocytes from young patients with immune and nonimmune thyroid diseases

The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves' disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.     

Inactivation of human thyroid stimulator by human thyroid extract.

To determine whether the thyroid stimulating activity of IGG of patients with Graves' disease is associated with the reaction with a putative human thyroid antigen, the inactivation of the property of IgG to stimulate cAMP generation in human thyroid slices incubated in vitro was studied by pretreating the IgG with human thyroidal particulate fraction. In the preliminary experiment, it was demonstrated that to cause cAMP generation stimulation, on incubation period of 120 min is required to allow the IgG to penetrate the tissue. When human thyroid slices were incubated with normal IgG without or with pretreatment by human thyroid particulate fraction obtained from 100 mg tissue, cAMP content in the slices was 142 +/- 25 or 138 +/- 26 f moles/mg, respectively, indicating that basal thyroidal cAMP levels were not influenced at all by normal IgG even after pretreatment with thyroid particulate fraction. When the slices were incubated with gG of Graves' disease without or with the similar pretreatment, cAMP content was 320 +/- 31 or 140 +/- 25 f moles/mg, respectively, demonstrating an almost complete inhibition of the activity of the IgG to cause cAMP generation stimulation.     

Arterial hypertension associated with hyper and hypothyroidism]

45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. Conclusions: 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established.     

Decreased nerve growth factor levels in hyperthyroid Graves' ophthalmopathy highlighting the role of neuroprotective factor in autoimmune thyroid diseases

Nerve growth factor (NGF), which is a neurotrophic factor, is involved in autoimmune and inflammatory processes. Serum NGF levels were investigated in 131 patients with autoimmune (95 with Graves' disease, of whom 57 had ophthalmopathy, 19 with Hashimoto's thyroiditis) and nonimmune thyroid diseases (17 with toxic nodular goitre), and 20 controls. NGF levels were measured via enzyme-linked immunosorbent assay. Twenty-nine positive cases for NGF were detected: 21 cases in Graves' disease, 7 cases in Hashimoto's thyroiditis, no case in toxic nodular goitre and one case in controls. NGF levels were higher in patients with Graves' disease and particularly with Hashimoto's thyroiditis compared with controls (1786.47+/-34.79 pg/ml and 1996.27+/-77.71pg/ml vs 1579.16+/-57.45pg/ml, P<0.049 and P<0.0001, respectively). Increased NGF levels associated with Graves' hyperthyroidism and correlated with FT(3) (P<0.01). Patients with the presence of antibodies against TSH receptor showed higher NGF levels than those with no antibodies (1938.61+/-56.44pg/ml vs 1712.12+/-54.22pg/ml, P<0.009). Decreased NGF levels were demonstrated in hyperthyroid Graves' ophthalmopathy compared with those without eye symptoms (1746.65+/-51.98pg/ml vs 1910.47+/-55.62pg/ml, P<0.036). NGF may be involved in the pathomechanism of autoimmune thyroid diseases. Decreased NGF levels in hyperthyroid Graves' ophthalmopathy highlight the importance of NGF in the neuroprotection of orbital tissues.     

A case of Graves' disease associated with an autonomously functioning thyroid nodule (AFTN) (Marine-Lenhalt syndrome) which spontaneously became a cold nodule

We report a 31-year-old female with Graves' disease associated with an autonomously functioning thyroid nodule (AFTN) (Marine-Lenhalt syndrome) in which the AFTN spontaneously became a cold nodule. Initially the patient was thyrotoxic and had diffuse goiter with an elevated radioiodine uptake. She became euthyroid following six months of antithyroid drug therapy, and in addition to diffuse goiter, the solitary hot nodule was palpable in the left lobe. Fourteen months later, hyperthyroidism recurred and the thyroid scan revealed diffuse radioiodine uptake with a cold area in the nodular region. The resected nodule showed extensive degeneration and the histological diagnosis was follicular adenoma with Graves' disease. We discussed the significance of recognizing the syndrome and also compared the frequency of spontaneous degeneration in AFTN and in solitary cold nodules.     

Incidental thyroid carcinoma in thyrotoxic patients treated by surgery

BACKGROUND AND AIMS: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. METHODS: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997-2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n=245) had toxic multinodular goiter (TMG), 16.8% (n=63) had toxic adenoma (TA) and 17.9% (n=67) had Graves' disease. RESULTS: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves' disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. CONCLUSION: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves' disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.     

Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of Graves' disease and nodular goiter.

Cytokines might be involved in the immunological flare up, seen in some patients after 131I-treatment. Therefore, we measured serum levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interleukin-6 soluble receptor (IL-6sR) and Intercellular-adhesion-molecule-1 (ICAM-1) as well as tumor necrosis factor (TNF-alpha) after 131I-treatment of Graves' disease and nodular goiter. Seven patients with Graves' disease, eight with toxic nodular goiter and seven with non-toxic nodular goiter, were followed after 131I-treatment. The patients were treated in the euthyroid state. Blood samples were drawn at day 0, 4, 7, 21 and after 3 months. Significant increases were seen in free T4 index (FT4I), free T3 index (FT3I) and thyroglobulin (Tg) within the first weeks, and TSH simultaneously decreased. None of the cytokines demonstrated any change during follow-up, neither in the entire group nor in subgroups. FT4I and FT3I correlated significantly to ICAM-1. In conclusion, our data suggest that there does not seem to be prolonged cytokine activation after 131I-treatment for thyroid disorders.     

Suppression of thyroid cell growth by serum IgG in Graves' disease.

To determine whether serum immunoglobulin in addition to epidermal growth factor (EGF) augment growth in human thyroid cells, effects of these factors on thyrocytes were tested using IgG derived from 34 patients with Graves' disease and 12 normal subjects. The cell growth was estimated by [3H]-thymidine uptake, cell cycle determined by FACS analysis and the expression of c-fos mRNA in monolayer thyrocytes enzymatically prepared from Graves' thyroid. The addition of IgG taken from patients with Graves' disease inhibited the [3H]-thymidine uptake compared to that taken from control subjects. IgG taken from Graves' disease suppressed EGF-induced increase of S + G2/M phase in cell cycle and the expression of c-fos mRNA, while those taken from normal subjects did not affect at all. [3H]-thymidine uptake was more suppressed by IgG from patients with a smaller-sized goiter than by those with a larger-sized one. There was a negative correlation between the suppression of [3H]-thymidine uptake and levels of TBII (p less than 0.05). There was no correlation between the degree of suppression and the levels of T3, T4, TSAb, TSBAb or MCHA. Thus, in conclusion, IgG derived from sera of Graves' may inhibit the growth of Graves' thyrocytes, leading to the determination of the goiter size.     

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases

We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves’ disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves’ disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves’ disease. The low selenium levles in the thyroid tissue may increase thyroid cancer risk.     

Changes in serum autoantibodies to thyroid peroxidase during antithyroid drug therapy for Graves' disease

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.     

Anterior pituitary cell antibodies detected in Hashimoto's thyroiditis and Graves' disease

An immunofluorescence study using unfixed cryostat sections of rat pituitary glands was carried out on sera from 34 patients with Hashimoto's thyroiditis, 28 patients with Graves' disease, 10 patients with thyroid adenoma and 50 healthy subjects. After absorption of sera with rat liver tissues, 19 of 34 patients retained reactivity to anterior pituitary cell antibodies (PCA, 55.8%). On the other hand, immunofluorescence in anterior pituitary cells was faint and detected in only 2 of 28 patients with Graves' disease (7.1%) after absorption of their sera with rat liver aceton powder. A similar result was also obtained when PCA were compared in the sera of Hashimoto's thyroiditis and Graves' disease with high titers of thyroid microsomal autoantibodies. PCA were detected neither in the sera of patients with thyroid adenoma nor in the healthy subjects. The present study suggests that PCA were considerably more prevalent in Hashimoto's thyroiditis than in Graves' disease.     

Tissue calmodulin levels in normal and Graves' thyroids

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.     

Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly

The incidence of palpable goiters, the thyroid functional state and thyroid radioisotope uptake was analyzed retrospectively in 80 patients with acromegaly and 80 patients with prolactinomas. 71% of all patients with acromegaly had an enlargement of the thyroid (goiter); 49% of them had diffuse and 39% nodular goiters. The incidence of goiters in patients with prolactinomas from the same iodine deficient geographic region was only 35% (82% diffuse and 18% nodular). 17.5% of acromegalic patients underwent thyroid surgery before diagnosis of growth hormone excess. 17.5% of acromegalic patients with goiters had autonomous areas in their thyroids and 5% were clearly hyperthyroid. Goiters developed slightly more often in females (74%) than in males (67%). The mean preoperative growth hormone level was higher in acromegalic patients with goiter. The incidence of goiters was positively correlated with the documented time of elevated growth hormone concentration in serum. Two patients with exaggerated response of thyrotropin (TSH) (delta TSH greater than 20 mU/l) to the application of thyrotropin-releasing hormone (TRH) had no goiters. On the other hand most patients (61%) with goiters had a low TSH-response to TRH (delta TSH less than 10 mU/l) representing in part occult autonomy of thyroid function. No patient with prolactinoma has had previous thyroid surgery nor thyroid autonomy. One patient with prolactinoma suffered from Graves' disease and none of the acromegalic patients had this disease. We finally conclude that the elevation of growth hormone leads to increased incidence of euthyroid and hyperthyroid (autonomous) goiters independently of the influence of TSH.     

Plasma atrial natriuretic peptide in patients with Graves' disease

In order to clarify the effect of thyroid hormone on the plasma atrial natriuretic peptide (ANP) concentration, 14 patients with Graves' disease and 6 normal control subjects were studied. They were all under constant sodium intake because dietary sodium is known to affect the amount of plasma ANP. Sodium intake remained constant at 171 mEq daily for five consecutive days at which time the ANP concentration was measured. Graves' disease patients were tested both before and after surgery. The preoperative, hyperthyroid ANP level concentration in Graves' disease patients was 6.7 +/- 2.3 fmol/ml compared to a significantly lower level of 4.2 +/- 1.4 fmol/in normal control subjects. Seven days after surgery when Graves' disease patients became euthyroid their ANP markedly decreased to 4.2 +/- 2.9 fmol/ml. In the present study we were able to confirm that under a constant sodium diet, high plasma ANP in patients with Graves' disease was reduced after surgery when they became euthyroid. Results also suggest that high circulating ANP might play an important role in sodium and water metabolism and hemodynamic changes in hyperthyroidism.