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Role of FNA in the medical management of minimally enlarged thyroid.

Fine-needle aspiration (FNA) of thyroid is a cost-effective and simple diagnostic tool in the initial screening of patients with thyroid nodules. But, its role in a clinically normal thyroid or a minimally enlarged thyroid in a symptomatic patient suspected of having thyroid dysfunction is unknown. With our 2-yr experience in a setup of a tertiary health care hospital in a developing country, we have aimed to implement a management protocol using FNA thyroid done without ultrasound guidance and TSH estimation done during the same visit in symptomatic patients suspected of having thyroid pathology but presenting with no goiter or having minimally enlarged thyroid with no palpable nodules. The thyroid enlargement in 172 cases were graded with the criteria endorsed by WHO, Pan American Health Organization, and International Council for Control of Iodine Deficiency Disorders into grade 0, 1, and 2. The cases were evaluated cytologically and correlated with TSH values according to the algorithm formulated by the authors. FNA was diagnostic in 86.6, 98, and 100% in grade 0, 1, and 2 goiters, respectively. 52.3% (n = 90), 19.8% (n = 34), 16.9% (n = 29) of cases were diagnosed as Hashimoto's thyroiditis (HT), colloid goiter (CG), and lymphocytic thyroiditis (LT). Sixteen had a combination of LT and CG (n = 6), HT and CG (n = 6), papillary carcinoma (n = 2), and diffuse hyperplasia (n = 2). No statistically significant difference (P = 0.4586) was noted between the groups of patients with grade 0 and grade 1-2 goiter, who underwent FNAC. 38.95% of patients (n = 67) with TSH values greater than 10 microIU/ml and considered hypothyroid showed features of HT/LT at FNA. 23.83% (n = 41) having TSH values between 5 and 10 microIU/ml (subclinical hypothyroidism) also showed features of HT/LT at FNA. Both groups were treated with thyroxine. 35.46% (n = 61) of cases with TSH values within normal range (0.5-5.1 microIU/ml) and considered euthyroid showed a spectrum of lesions at cytology other than HT and LT. They are being followed up to detect them at an early stage of subclinical hypothyroidism. Only 13 cases (7.5%) who were serologically euthyroid showed HT/LT and are being followed-up. Thus, the authors advocate FNA of the thyroid as a single simple cost-effective office procedure in the medical management of all nonpalpable/minimally enlarged thyroid in patients suspected of having thyroid pathology and/or in combination with TSH values. FNA helps in early detection of subclinical hypothyroidism, which is of utmost importance in pregnant women and further makes possible availability of baseline values for future reference. With the implementation of this protocol of FNA thyroid without imaging, we affirm that the practice of cytology which differs in different geographic areas and from country to country depending on economy and availability of infrastructure can be made more user-friendly.

Adolescent↗

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Child, Preschool↗

The various effects of amiodarone on thyroid function.

Amiodarone, a benzofuranic-derivative iodine-rich drug used mostly for tachyarrhythmias, often causes changes in the peripheral metabolism of thyroid hormones mainly due to the inhibition of 5'-deiodinase activity: an increase in serum thyroxine and reverse triiodothyronine, and a decrease in serum triiodothyronine concentrations. Overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH), occurring in 14% to 18% of patients receiving long-term treatment, may develop both in apparently normal thyroid glands and in glands with preexisting abnormalities. AIH is mainly due to the failure to escape from the acute Wolff-Chaikoff effect, and, in patients with thyroid autoimmune phenomena, to concomitant Hashimoto's thyroiditis. AIT is due to excess iodine-induced thyroid hormone synthesis (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), although mixed forms often occur. Treatment of AIH consists of levothyroxine replacement therapy while continuing amiodarone therapy; alternatively, amiodarone can be discontinued, if possible, and the natural course toward euthyroidism can be accelerated by a short trial of potassium perchlorate. In type I AIT, the simultaneous administration of thionamides and potassium perchlorate is the treatment of choice, while in type II AIT steroids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. The low thyroidal 131I uptake usually makes radioiodine therapy not feasible, while thyroidectomy is a valid alternative in cases resistant to medical therapy.

Amiodarone↗

A patient with Graves' disease who developed hypothyroidism associated with thyroid stimulation blocking immunoglobulin during anti-thyroid drug therapy.

A girl, 12 years of age, developed Graves' disease compounded with rheumatic fever and idiopathic thrombocytopenic purpura. Thrombocytopenia improved under short-term treatment with steroids and her mitral valvular insufficiency, due to the rheumatic fever, disappeared 4 years later. Initially, she had been treated with propylthiouracil (PTU) for 28 months. She suffered a relapse 9 months after stopping PTU and so she was given further PTU therapy. However, hypothyroidism developed 11 months after the initiation of therapy and continued, though further PTU treatment was discontinued. She now receives 1-thyroxine and maintains a euthyroid state. At the onset of the patient's hyperthyroidism, the TSH-binding inhibitor immunoglobulin (TBII) and the thyroid stimulating antibodies (TSAb) were found to be positive. During the remission period, only the thyroid stimulation blocking immunoglobulin (TSBI) was weakly positive. At relapse, only TBII was mildly positive. When hypothyroidism developed, both TBII and TSBI were positive, and TSAb was negative in all testings of her diluted IgGs. The patient's TBII and thyroid dysfunction were unaffected by high-dose intravenous gammaglobulin therapy or by treatment with prednisolone 0.5 mg/kg/day for 2 weeks. In conclusion, the emergence of TSBI during or after anti-thyroid drug therapy might possibly lead to hypothyroidism in patients with Graves' disease.

Antithyroid Agents↗

[The effect of laryngectomy and postoperative radiotheraphy on thyroid gland functions].

OBJECTIVES: We investigated the frequency of hypothyroidism in patients treated with total laryngectomy, hemithyroidectomy-isthmectomy, and postoperative radiotherapy for T3 or T4 larynx cancers. PATIENTS AND METHODS: Twenty-nine male patients (mean age 54 years; range 43 to 72 years) with T3 or T4 larynx cancers were prospectively included in the study. Preoperatively, thyroid function tests were normal in all the patients. Following radiotherapy, serum thyroid-stimulating hormone (sTSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels were measured every three months at least for a year. Detection of an increased level of sTSH together with decreased or normal levels of FT3 and/or FT4 indicated clinical and subclinical hypothyroidism, respectively. The relationship was assessed between hypothyroidism and both age and radiotherapy dosage. Statistical analyses were made with the use of the Student's t- test and Mann-Whitney U-test. RESULTS: Following radiotherapy, thyroid function tests remained normal in 12 patients (41%), while 12 patients (41%) and five patients (18%) developed subclinical and clinical hypothyroidism, respectively. No significant relationship was found between age and thyroid dysfunction (p>0.05), whereas radiotherapy dosage was found in significant relationship with the development of hypothyroidism (p<0.05). CONCLUSION: Due to high rates of subclinical or clinical hypothyroidism following combined therapy, thyroid functions should be closely monitored in patients undergoing laryngectomy for T3 or T4 larynx cancers.

Adult↗

[Is a TSH screening for the diagnosis or exclusion of functional thyroid autonomy meaningful?].

A normal baseline TSH serum concentration is accepted as excluding thyroid dysfunction. The present study examined the usefulness of that concentration as a screening test for functional autonomy. 310 patients were retrospectively examined. They were all clinically euthyroid and had normal peripheral thyroid hormone concentrations. The positive predictive value for the confirmation of autonomy was 55.5%, the negative predictive value for the exclusion of autonomy 87.7%, using 0.5 mU/l as a lower limit. The probability for the presence of thyroid autonomy in patients with a TSH serum concentration below 0.3 mU/l was 72.5%.

Female↗

Insecticide-induced inhibition of thyroid activity in the fish Oreochromis mossambicus and recovery in insecticide-free water.

The histological and histochemical state of the thyroid gland of Oreochromis mossambicus was analyzed after 20 days' exposure of the fish to BHC (p less than 0.001 ppm). Histological changes after exposure included acolloidal and atrophied follicles and goitre formation. Follicular and nuclear diameter and the E/T ratio were significantly (p less than 0.001) higher than in the corresponding controls. The above insecticide led to thyroid dysfunction. The histochemical characteristics of the gland also changed after BHC treatment. When exposed fish were transferred to normal, clear, dechlorinated water, the altered follicles displayed remarkable recovery of activity and thyroid function returned to almost the same state as in normal controls. Histological and histochemical evaluation at 10-day intervals revealed healthy functional restitution of the gland, indicating that BHC-induced changes are reversible.

Animals↗

[Effects of amiodarone on thyroid function].

Amiodarone has been used in cardiology for more than 20 years as an anti-angina and anti-arrhythmia agent. In the seventies, variations in thyroid hormone and TSH concentrations were described in treated patients. Only recently, however the pathogenic mechanisms leading to dysthyroidism in long-term treatment have been described. Today, the gravity of amiodarone-induced hyperthyroidism has been greatly reduced due to a better understanding of the underlying mechanisms and better surveillance of thyroid function. In clinical practice, the following attitude can be proposed. Thyroid exploration should be completed before prescribing amiodarone: clinical examination should emphasize personal or familial history in search of dysthyroidism or goitre; hormone assays (TSH, free T4) are needed to eliminate any latent thyroid dysfunction, particularly hyperthyroidism with little or no clinical manifestation but sometimes the causal factor in cardiac symptomatology; search for a significant level of anti-thyroperoxidase antibodies can reveal underlying chronic thyroiditis. After prescription, clinical surveillance and TSH assay should be performed at 3 months then every 6 months during treatment. After withdrawal, surveillance should be continued with check-ups at 6 and 12 months.

Amiodarone↗

[Thyroid gland hemiagenesis with Graves' disease].

A case of Graves' disease occurring in a patient with hemiagenesis is presented. The detection of the rare occurrence of a congenital hemiagenesis is often made by either clinical symptoms of thyroid dysfunction or anatomical abnormalities such as nodular goiter. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning and ultrasonography of an absent lobe. Anti-thyroid antibody studies documented the presence of Graves' disease within the remaining lobe.

Diagnosis, Differential↗

Effect of domperidone on serum TSH and growth hormone in thyroid patients.

In euthyroid female patients, the release of TSH from the pituitary increases in response to domperidone, a dopaminergic-receptor blocking agent of peripheral action. The rate of increase varies with the functional state of the thyroid, as confirmed by results obtained in cases of euthyroidism, primary hypothyroidism, subclinical hypothyroidism and subclinical hyperthyroidism. Observations suggest that the more vigorous feedback-mechanism modulates the dopaminergic regulation of TSH-secretion at a high degree of sensitivity. Stimulation with 1-dopa intensifies the release of growth hormone from the pituitary which is, however, of lesser degree in hyperthyroid or hypothyroid than in euthyroid individuals. The GH-response to 1-dopa is enhanced by administration of propranolol, but the maximum serum GH levels in response to stimulation with 1-dopa are significantly lower in hyperthyroid than in euthyroid individuals. Administration of domperidone leaves the serum GH levels unaffected in euthyroid and hyperthyroid subjects, but causes a significant increase in a number of patients with primary hypothyroidism. The results suggest that the dopaminergic system plays a part in the regulation of TSH and GH secretion, asserting itself partly as a direct effect on the pituitary, and that the dopaminergic regulation may be affected by thyroid dysfunction.

Adult↗

Bone and joint manifestations of hypothyroidism.

Hypothyroidism is frequently accompanied by musculoskeletal manifestations ranging from myalgias and arthralgias to true myopathy and arthritis. A case is presented in which an arthropathic process in the hip was the isolated finding in a young man who was severely hypothyroid. Previous literature on bone and joint manifestations of hypothyroidism is reviewed, with emphasis on cases where such manifestations were the presenting symptoms of thyroid dysfunction. Most cases of arthropathic changes in adult-recognized hypothyroidism involved the knees and hands, while the hip and the epiphysis of the femoral head appear more commonly involved in children. Thyroid hormones have known effects at the cellular level on proliferation and differentiation of bone and cartilage. The hypothyroid state appears to induce abnormalities in these tissues, which result in such clinical manifestations as epiphyseal dysgenesis, aseptic necrosis, possibly crystal-induced arthritis, and an arthropathy characterized by highly viscous noninflammatory joint effusions primarily affecting the knees, wrists, and hands. Neuropathic and myopathic symptoms accompanying hypothyroidism may manifest as joint region abnormalities when in fact there is no underlying arthropathy.

Adult↗

Demonstration of immunoglobulin G, A, and E autoantibodies to the human thyrotropin receptor using flow cytometry.

Human TSH receptor (TSHR) autoantibodies with biological activity result in thyroid dysfunction, but antibodies that simply bind do not. We have applied flow cytometry to the measurements of IgG, IgA, and IgE immunoreactivity to the TSHR in patients with Graves' disease (GD) and thyroid eye disease (TED) and in normal controls. CHO cells stably expressing the extracellular domain of the TSHR with a glycophosphatidylinositol anchor were produced and found to express approximately 4 times as many receptors, but of similar affinity, as JP09 in TSH binding studies. Substantial increases in median fluorescence and peak channel fluorescence were obtained by flow cytometry using TSHR monoclonal antibodies on the glycophosphatidylinositol cells. IgG autoantibodies were demonstrated in 55 of 65 untreated GD patients, 3 of 25 normal subjects, and 4 of 8 atypical TED sera (negative for TSHR autoantibodies with biological activity) by flow cytometry and correlated poorly with thyroid-stimulating antibodies. IgA antibodies were present in 1 of 12 normal, 1 of 7 treated GD with TED, and 3 of 8 atypical TED sera. IgE binding was observed in 1 of 12 normal, 2 of 8 treated GD without TED, 1 of 6 treated GD with TED, and 0 of 8 atypical TED sera. In conclusion, we have demonstrated autoantibodies that bind directly to the TSHR in the majority of GD patients and in 50% of patients with atypical TED and a small number of normal controls lacking TSHR antibodies that affect function. Although predominantly IgG lambda, TSHR autoantibodies of the IgA and IgE isotypes are also detectable.

Adult↗

Early-onset thyrotoxicosis after unrelated cord blood transplantation for acute myelogenous leukemia.

Thyroid dysfunction is a common complication after allogeneic hematopoietic stem cell transplantation (SCT). However, thyrotoxicosis as defined by elevated serum-free thyroxine (FT4) or free triiodothyronine (FT3) levels together with low thyroid-stimulating hormone (TSH) levels is rare after SCT. Here we describe 2 patients who developed thyrotoxicosis within the first 50 days after unrelated cord blood transplantation (CBT). Patient 1 is a 32-year-old woman with acute myelogenous leukemia (AML)-M5a who underwent CBT. On day +41, she developed tachycardia. On day +48, FT4 increased to 2.2 ng/dL and TSH was suppressed to less than 0.1 microU/mL. Antithyroid peroxidase antibody was positive. On day +83, FT4 spontaneously decreased to 1.4 ng/dL. Patient 2 is a 42-year-old man with AML-M4 who underwent CBT. On day +42, he developed tachycardia. On day +48, FT3 increased to 4.75 pg/mL and TSH was suppressed to 0.02 microU/mL. Antithyroid peroxidase antibody was positive. Eight months after CBT, his thyroid function spontaneously returned to normal. The presence of antithyroid peroxidase antibody suggested that immune-mediated reactions might be associated with the development of thyrotoxicosis after CBT in our patients. The present study shows that thyrotoxicosis can occur during very early periods after CBT.

Adult↗

[Amiodarone-induced thyrotoxicosis: case report and review of the literature].

We report a case of amiodarone-induced thyrotoxicosis, and a broad review of the literature. Amiodarone is a drug widely used in cardiovascular medicine. Since it is iodine-rich, it may cause changes in thyroid function tests in some patients under chronic treatment. In 14-18% of amiodarone-treated patients, there is overt thyroid dysfunction (hypothyroidism or thyrotoxicosis). We here describe thyrotoxicosis, which can be distinguished in two subtypes differing in pathogenesis and treatment. Type I is primarily related to an excess of iodine-induced thyroid hormone synthesis in an abnormal thyroid gland, and the main medical treatment consists of the simultaneous administration of thionamides and potassium perchlorate. Type II is due to amiodarone-related destructive thyroiditis and glucocorticoids are therapy of choice. Mixed forms frequently exist. Due to the low thyroidal iodine uptake, radioiodine therapy is usually not efficacious. Surgical treatment can be performed in cases resistant to medical therapy.

Adult↗

Thyroid screening tests in psychiatric inpatients.

This study reports on a retrospective evaluation of the current practice of screening for thyroid dysfunction in an adult psychiatric inpatient program. Sixty-four percent of 342 admissions were tested during their hospital stay. Although 13.7% of tests yielded abnormal values on one or more of the thyroid indices, only 0.9% resulted in a diagnosis of hypothyroidism. None of the other abnormal test results led to any specific action being taken. The present pattern of use of thyroid function screening as observed in this study does not appear optimal. Issues in the selection of thyroid screening tests, and the value of the results obtained are discussed.

Adult↗

Immunoglobulins of patients recovering from Yersinia enterocolitica infections exhibit Graves' disease-like activity in human thyroid membranes.

Substantial evidence suggests a link between infections with Yersinia enterocolitica (YE) and Graves' disease. We have now examined the sera of 72 patients recovering from YE infection for immunoglobulins that interacted with the TSH receptor in human thyroid membranes. Compared with controls, in concentrations between 1 and 4 mg/mL, patient IgG produced a significant, concentration-dependent inhibition of TSH binding (p less than 0.001) and stimulation of adenylate cyclase activity (p less than 0.005-0.05). Whereas IgG from normal individuals caused no stimulation of adenylate cyclase, IgG from controls caused some concentration-dependent displacement of TSH, as previously reported. However, IgG from convalescents of YE infections was significantly more potent than normal IgG in reducing the binding of TSH to the membrane. Thus, at each examined concentration, YE patients' IgG displaced more TSH than IgG from normal controls. For each milligram per milliliter increment of IgG in the assay, patients' IgG caused a 10.2% inhibition of TSH binding (r -0.90, p less than 0.001), significantly greater than that seen with normal IgG (p less than 0.02). The present studies provide the first demonstration that IgG of patients recovering from YE infections react with the human TSH receptor. The antibodies presumably are produced against the TSH-binding protein present in YE. However, in view of lack of evidence for thyroid dysfunction in the sera of patients recovering from yersiniosis and the presence of TSH-binding proteins in other bacteria, we postulate that infection with YE is neither necessary nor sufficient to cause thyroid autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

The clinical spectrum of postpartum thyroid disease.

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.

Adult↗

Case report: silent thyroiditis after adrenalectomy in a patient with Cushing's syndrome.

A case of silent thyroiditis after unilateral adrenalectomy for treatment of Cushing's syndrome is reported. The left adrenocortical adenoma was resected. Glucocorticoid was replaced after the operation and was gradually tapered. Thyrotoxic symptoms with painless goiter occurred 9 months after the adrenalectomy when a replacement dose of prednisolone was tapered to 5 mg/d. Plasma-free thyroid hormones increased and thyrotropin was suppressed. Thyroidal uptake of radioactive iodine was extremely low. Both titers of antimicrosomal and antithyroglobulin antibodies stayed at high levels throughout the observation period from the preoperative stage. Normalization of thyroid functions was obtained 3 months after the onset of thyrotoxicosis with beta-adrenergic blocker alone. It was speculated that exposure to a large amount of endogenous and supplementary exogenous glucocorticoid protected the patient's immune system from autoimmune attack of thyroid antigens and that tapering of the supplementary glucocorticoid caused exacerbation of immune responses, resulting in overt thyroid dysfunction even 9 months after adrenalectomy.

Adrenalectomy↗