High dosage thyroxine treatment in therapy and prevention refractory patients with affective psychoses

Natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) against k562 human tumor cell targets was studied in patients with Graves' disease and Hashimoto's thyroiditis. NK activity was measured in a standard 4-hour 51chromium (Cr) release assay. Cytotoxicity was expressed as lytic units (LU)/10(6) PBL. Significantly decreased NK cell activity was demonstrated in both groups of patients, with mean (+/- SE) lytic units of 10.3 (+/- 9.1) and 13.3 (+/- 10.3) for patients with Graves' disease and Hashimoto's thyroiditis, respectively, compared with 36.0 (+/- 26.3) for age- and sex-matched normal subjects. When patients with Graves' disease were analyzed according to their thyroid status; NK activity was significantly depressed in (1) hyperthyroid patients before treatment; (2) hyperthyroid patients receiving antithyroid therapy; and (3) euthyroid patients receiving antithyroid therapy, compared with normal subjects. Graves' disease patients who were hypothyroid after radioactive iodine therapy or thyroidectomy had normal NK activity. No significant differences between hyperthyroid and euthyroid patients or between hypothyroid patients and normal subjects were demonstrated. NK activity in patients with Graves' disease did not correlate with serum levels of thyroxine, the presence or severity of ophthalmopathy, or titers of serum thyroid antibodies. In patients with Hashimoto's thyroiditis there was no correlation between NK activity and goiter size, titers of antithyroid antibodies, or thyroid status. These findings suggest that depression of NK activity in both disorders is secondary to abnormalities of thyroid hormone secretion, although an effect of the underlying autoimmune reactions has not been excluded.     

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).     

Postpartum thyroiditis and Basedow disease

BACKGROUND: The postpartum period is characterized by a rebound in autoimmunity secondary to immune tolerance induced by pregnancy, creating favorable conditions for flare up of Graves' disease or autoimmune thyroiditis. Postpartum thyroiditis is a recognized clinical entity. CASE REPORT: Six years after onset of Graves' disease treated with antithyroid drugs, a 25-year-old woman had a high serum level of antithyroperoxidase antibodies a few months before she became pregnant. Six weeks after delivery, she developed signs of hyperthyroidism and goiter. The diagnosis of postpartum thyroiditis was retained. Her condition regressed spontaneously to euthyroidism then hypothyroidism. DISCUSSION: The therapeutic options involved underline the importance of distinguishing between Graves' disease and postpartum thyroiditis. The diagnosis of postpartum thyroiditis is based on history taking, clinical findings, and laboratory tests, especially isotope uptake.     

Is it hyperthyroidism? You can't always tell from the clinical picture

Hyperthyroidism usually causes a typical clinical syndrome in younger patients, but in some cases it presents with only minimal or atypical symptoms. This is especially true in older patients, who may have none of the typical signs, such as goiter. Differentiation between a euthyroid hyperthyroxinemic state and hyperthyroidism is crucial to avoid unnecessary treatment of persons with a normally functioning thyroid gland. In addition, distinguishing between causes of hyperthyroidism is important, because the treatments may be completely different. For example, in subacute thyroiditis, supportive care and observation are usually the only treatments needed, whereas in Graves' disease or toxic multinodular goiter, more definitive therapy is required.     

A study of thyroid disease in family practice

Thyroid disease is relatively common in family practice, yet is often undiagnosed or poorly managed. This study examines several aspects of thyroid disease in a large, semirural family practice setting and exemplifies the type of practical clinical research that can be done in family medicine. An overall prevalence of approximately one percent was determined for thyroid disease in this practice. In a series of 85 patients, the ratio of hypothyroidism:hyperthyroidism:euthyroid goiter was 9:2:1 respectively. Initial signs and symptoms recorded for these patients conformed closely to the findings in other large series. Eighty percent of the patients with idiopathic hypothyroidism never had enlarged glands, whereas 100 percent of the patients with hypothyroidism associated with Hashimoto's thyroiditis had enlarged glands. Laboratory aids such as serum thyroid stimulating hormone (TSH), anti-thyroid antibodies, and radioactive iodine uptake (RAIU) and scans were inadequately utilized. Medical and/or surgical consultation was obtained in 17.5 percent of patients with hypothyroidism, 80 percent of patients with hyperthyroidism, and 63 percent of those with euthyroid goiter. Currently 95 percent of the hypothyroid patients and 100 percent of the hyperthyroid patients are euthyroid.     

The role of ultrasonography in thyroid disease

Ultrasound examination of the thyroid gland is widely used in the diagnosis of thyroid disease. This test is easy and rapid to perform, widely available and the results are readily interpreted. Using ultrasound the image of foci of disease within the gland are easily identified, especially using high frequency probes which enable solid nodules up to approx 3 mm to be revealed with 10 MHz probes. In non-nodular thyroid disease the ultrasonic structure guides the diagnosis (thyroiditis, Graves' disease). During the follow-up of thyroidectomised patients ultrasound can easily reveal postoperative anatomic variations and an early diagnosis can be obtained of any signs of local recurrence of the primary disease. Only hemiagenesia and hypoplasia can be accurately evaluated in congenital disease, whereas in the event of the persistence of the thyroglossal duct the latter can only be diagnosed if it presents a cystic evolution. Thyroid ectopia cannot be identified and must be studied using thyroscintigraphy, preferably performed using 131I as the isotope. The acquired pathology is classified into phlogistic processes, diffuse or nodular hyperplasia, benign and malignant neoplasia. This classification is widely accepted by virtually all authors. In thyroiditis, ultrasound may facilitate the diagnosis of De Quervain's non-suppurative sub-acute thyroiditis (TANS) and Hashimoto's chronic thyroiditis, although always in association with clinical and laboratory tests. The most frequent thyroid pathology is without doubt goitre. This disorder may occur in a non-nodular (widespread goitre with an endemic or sporadic pattern) or nodular form which may be single or multiple. The term goitre is used to indicate the increased volume of the thyroid gland independently of the causes which have provoked it. Common goitre is defined as being endemic when in some geographic area 10% of the general population or 20% of the school-aged population suffers from thyroid hyperplasia (areas of goitrogenic endemic disease). Graves' disease may be included in the group of thyroid hyperplasia diseases, although it is distinguished from the simple versions by the marked glandular hyperactivity which creates manifest hyperthyroidism. In this pathology ultrasonography must be supplemented by colour-Doppler wherever possible. Thyroid nodules are subdivided in terms of their echostructure into 5 types: liquid, mixed (prevalently solid or prevalently liquid), hyperechogenic solid, isoechogenic solid and hypoechogenic solid. The characteristics of benign nodules are: hypoechogenic structure, regular edges, complete and uniform hypoechogenic peripheral halo.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sexual behavior in married women with chronic gynecologic inflammation]

In patients with the first manifestation of hyperthyroidism of Graves' disease, antithyroid drug treatment is the therapy of first choice. Treatment has to be carried out depending on iodine supply of the individual patient with the lowest possible drug dose. Controls of treatment have to be done in short intervals (every 2 weeks) until euthyroidism is reached, afterwards controls of thyroid function have to be done every three months. After euthyroidism is established, the combination of antithyroid drug therapy with thyroid hormones may be useful to avoid hypothyroidism or goiter development during treatment in contrast to a monotherapy with antithyroid drugs. Antithyroid drug treatment has to be carried out for one year. The remission rate of patients does not increase with higher doses of antithyroid drugs or a longer treatment duration. The determination of TSH receptor antibodies does not help predicting a relapse of hyperthyroidism of Graves' disease in the individual patient at the end of treatment. Regular follow-up controls after antithyroid drug treatment are necessary to recognize relapse of Graves' disease in time.     

Hyperthyroidism: diagnosis and management of Graves' disease

Hyperthyroidism, or thyrotoxicosis, results when the body's tissues are exposed to excessive levels of thyroid hormone. Hyperthyroidism affects 2% of women but only one-tenth as many men. Graves' disease is the most common form of hyperthyroidism, often occurring in young adults. It is an autoimmune disorder with an important genetic component. Hyperthyroidism's hallmarks include goiter and myriad signs and symptoms related to increased metabolic activity in virtually all body tissues. Increased sensitivity to circulating catecholamines adds to the clinical picture. Diagnosed by patient history, physical examination, and laboratory tests, Graves' disease is treated with antithyroid drugs, radioactive iodine, and/or surgery, plus supportive therapy. A good treatment outcome can be expected; long-term follow-up is indicated.     

Increased iodine uptake by obese strain thyroid glands transplanted to normal chick embryos

The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis. Since a defect or abnormality of the thyroid gland may be involved in this disease experiments were performed to compare the iodine uptake of OS with normal thyroid glands. To minimize the interaction of the OS immune system with the thyroid gland during these studies, thyroids were removed from 16-day-old embryos and transferred to the chorioallantoic membrane (CAM) of 9-day-old normal White Leghorn (NWL) embryos. NWL thyroid glands were transferred to the same CAM. Six days later the 20-hr 131I uptake of the transplants was determined. Twenty OS thyroid lobes had a mean 131I uptake of 2960 +/- 740 cpm, whereas the NWL thyroids incorporated significantly less iodine (890 +/- 160 cpm; p less than 0.025). These results, along with a previous report suggest that an abnormality of the thyroid gland might be an important factor in the development of autoimmune thyroiditis.     

Iodine-induced hyperthyroidism: occurrence and epidemiology

We have critically reviewed the available information on iodine-induced hyperthyroidism (IIH) from published sources and other reports as well as the experience of the authors in Tasmania, Zaire, Zimbabwe, and Brazil. Administration of iodine in almost any chemical form may induce an episode of thyrotoxicosis (IIH). This has been observed in epidemic incidence in several countries when iodine has been given as prophylaxis in a variety of vehicles, but the attack rate as recorded has been low. IIH is most commonly encountered in older persons with long standing nodular goiter and in regions of chronic iodine deficiency, but instances in the young have been recorded. It customarily occurs after an incremental rise in mean iodine intake in the course of programs for the prevention of iodine deficiency, or when iodine-containing drugs such as radiocontrast media or amiodarone are administered. The biological basis for IIH appears most often to be mutational events in thyroid cells that lead to autonomy of function. When the mass of cells with such an event becomes sufficient and iodine supply is increased, the subject may become thyrotoxic. These changes may occur in localized foci within the gland or in the process of nodule formation. IIH may also occur with an increase in iodine intake in those whose hyperthyroidism (Graves' disease) is not expressed because of iodine deficiency. The risks of IIH are principally to the elderly who may have heart disease, and to those who live in regions where there is limited access to medical care. More information is needed on the long-term health impact of IIH or "subclinical" IIH, especially in the course of prophylaxis programs with iodized salt or iodinated oil in regions where access to health care is limited.     

Preventive iodine administration and iodine excretion in the Vienna area and in the forest quarter

In order to reduce the still substantial iodine deficiency in the Austrian population, compulsory iodisation of salt was increased in 1990 from 10 mg potassium iodide/kg salt to 20 mg potassium iodide/kg. In this investigation we evaluated the adequacy of iodine supply in Vienna and the Waldviertel, a rural region northwest of Vienna. Daily iodine excretion (which reflects daily iodine intake) was investigated in 92 persons from the Waldviertel (all without thyroid gland pathology) and 110 persons from Vienna (54 with unremarkable thyroid glands, 56 with endemic goiter). Daily iodine excretion was higher in persons from the Waldviertel (161 +/- 90.7 micrograms/24 h, p < 0.05) than in those from Vienna (with healthy thyroid glands 126.4 +/- 42.9 micrograms/24 h and with goiter 117.2 +/- 60.5 micrograms/24 h, resp.). In both populations iodine supply as defined by the WHO (excretion of > 150 ug iodine/day) was inadequate. The recommended level was not achieved in 50% of the persons from the Waldviertel region and in 75% of persons from Vienna (healthy thyroid glands 76%, goiter: 75%). Iodine deficiency (intake < 100 micrograms/24 h) was present in 42% persons from the Waldviertel and in 31% and 24% persons, respectively, from Vienna with unremarkable thyroid glands and goiter. We conclude that although the iodine content of salt was increased, an iodine deficiency was present in a considerable portion of the population of an industrialized country (approximately 40% of persons from a rural region and 30% from the city of Vienna).     

Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis

Vascular endothelial growth factor (VEGF) is one of the angiogenic factors. We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis. The serum concentrations of thyroid hormones, TSH, TSH receptor antibodies, and VEGF were also examined. There was a significant increase in serum VEGF levels in patients with untreated GD and goitrous HT compared with those in healthy subjects. The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT. There was a significant correlation between serum VEGF levels and the ratio of intrathyroidal vascular area and thyroid area in untreated patients with GD who had a goiter larger than or equal to 40 cm3. There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter. Serum VEGF levels decreased significantly in these patients after treatment; this was accompanied by a significant decrease in intrathyroidal vascular area and thyroid volume. Our study demonstrates that VEGF appears to play an important role in intrathyroidal angiogenesis in patients with GD and goitrous HT.     

Glucocorticoids decrease c-fos expression in human nasal polyps in vivo

The aim of this work was to correlate color duplex sonography (CDS) patterns and thyroid histology in hyperthyroid Graves' disease (GD) patients. Sixteen patients with relapsed GD were studied. Before starting a new cycle of medical therapy with methimazole in decreasing doses for 3 to 6 months (baseline study), the patients underwent functional, autoimmune, and CDS studies. The same studies were carried out again just before surgery (presurgical study) after medical therapy had produced a normalization of thyroid hormone serum levels. The thyroid glands were histologically examined and their patterns were compared with CDS patterns. Thirty-three normal subjects were used as a control group. At baseline, 6 patients (group I) had intraparenchymal homogeneous vascular color spots or diffusely distributed over the parenchyma lobe or in areas alternating with avascular zones (CDS-A pattern). In 8 patients (group II) the thyroid had vascular bands with avascular or poorly vascularized parenchymal areas (CDS-B pattern). In 2 patients, the 2 patterns were present in the same thyroid (A-B pattern or mixed pattern). In these 2 patients the histological aspects were more similar to the CDS-B pattern than the CDS-A pattern. The 2 groups of patients differed in the velocity of systolic peak (VP) that was significantly higher in group I than in group II. In the presurgical study, no changes relative to CDS patterns were observed in patient groups I and II. The VP did not show any appreciable modifications in either group of patients. The thyrotropin-stimulating antibodies (TRAb) returned to normal levels in group II, but not in group I. The 2 CDS patterns, observed in the baseline study, were histologically characterized either by a richly vascularized parenchyma with prevalent endothelial hyperplasia (parenchymatous goiter, CDS-A) or by fibrotic septation with prevalent vascular intimal hyperplasia (CDS-B). In conclusion, this CDS study in GD patients showed 2 distinct vascular patterns. The thyroid glands were histologically characterized by either a richly capillary vascularized parenchyma (parenchymatous goiter, CDS-A aspect) or by fibrotic septation with prevalent intraseptal arteriolar-like hyperplasia (fibrous goiter, CDS-B aspect). Such differences may be secondary to a different duration of hyperthyroidism and/or intensity of TRAb thyroid stimulation.     

Hyperthyroidism and carcinoma of the thyroid gland

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.     

Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as hypoxia-selective cytotoxins

A role of psychic stress in precipitating hyperthyroid Graves' disease has been suggested, but the evidence in support of this pathogenetic mechanism is conflicting. In this study we investigated the possible occurrence of Graves' disease in patients with panic disorder, a psychiatric condition characterized by recurrent endogenous stress. The study group included 87 consecutive patients suffering from panic disorder since 1 to 30 years: 17 males (mean age 31.3, range 26-43 years) and 70 females (mean age 37.6, range 15-73 years). Two hundred and sixty-two normal subjects with no present or past history of psychiatric disorder served as controls. Patients were submitted to a full evaluation of the thyroid that included physical examination, assays for free thyroid hormones, TSH, thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb) antibodies, and thyroid echography. The prevalence of circulating TgAb and/or TPOAb in patients with panic disorder did not differ from that in the control group. Twelve patients with panic disorder (13.7%) had circulating TgAb and/or TPOAb, but none had TRAb. Three out of 12 patients with thyroid antibodies, indicating a genetic susceptibility to autoimmune thyroid disease, had a family history of clinical thyroid autoimmunity, and 4 of them had a hypoechogenic pattern of the thyroid at ultrasound suggesting autoimmune thyroiditis. None of the patients with panic disorder had a previous history of hyperthyroidism. On examination, clinical hyperthyroidism or endocrine ophthalmopathy were not found in any of them. A small goiter was appreciated by palpation in 16 patients (18.3%). Free thyroid hormones and TSH were within the normal range in all patients but one: a 55-year old lady with normal serum free thyroid hormones and undetectable TSH. During an 18-month follow-up she did not develop hyperthyroidism and her TSH spontaneously returned in the normal range. Considering the individual duration of panic disorder, evidence for previous or present Graves' hyperthyroidism was not found for a total of 478 patient-years of exposure to recurrent endogenous stress in the whole study group, and for a total of 39 patient-years in patients with a genetic susceptibility to autoimmune thyroid disease. In conclusion, we found that recurrent endogenous stress did not precipitate Graves' hyperthyroidism in a series of 87 patients with panic disorder, encompassing a total of 478 patient-years of exposure to stress. Failure to activate the hypothalamic-pituitary-adrenal axis by endogenous stress due to panic disorder as opposed to exogenous stress due to life-events might explain why panic disorder does not precipitate Graves' hyperthyroidism.     

History of autologous blood transfusion in neurosurgical operations]

Two Caucasian patients are described who had destructive postpartum thyroiditis (PPT) before the subsequent onset of Graves' hyperthyroidism (GH). HLA class II DQ typing in these two subjects identified putative susceptibility alleles previously detected in GH and PPT. Although PPT destructive thyroiditis preceding the development of GH is relatively uncommon, the occurrence of both these syndromes in the same patient suggests the possibility of an etiological role for thyroid antigen release and genetic susceptibility as pathogenic factors in the development of Graves' disease.     

Purification and crystallisation of the autoantigen thyroid peroxidase from human Graves' thyroid tissue

Milligram quantities of the human membrane autoantigen thyroid peroxidase (TPO) have been purified to a high degree of homogeneity by a combination of detergent solubilisation, monoclonal antibody affinity, and ion exchange chromatography, from pooled Graves' disease thyroid glands. The purified TPO of greater than 90% purity was enzymatically active as judged by its ability to oxidise guaiacol. Crystals of TPO have been grown from solutions of the protein solubilised in sodium deoxycholate, in the presence of ammonium sulphate. The crystals exhibited birefringence under polarised light, indicative of molecular order. Crystallisation of this large, membrane autoantigen represents the first step in delineating the complete three-dimensional structure of a human autoantigen involved in destructive thyroiditis.     

Autoimmune hypothyroidism

Most of the acquired hypothyroidisms are related to chronic lymphocytic thyroiditis which reduce the functional thyroid parenchyma, determine acquired organification disorders or rarely generation of blocking anti-TSH receptor antibodies. In subjects with genetic predisposition, autoimmunization against the thyroid involves recognition of thyroid antigens, cooperation between B and T lymphocytes and production of cytokines. Biologic markers of antithyroid autoimmune disorders are now widely available. Nevertheless therapeutic approach of autoimmune hypothyroidisms is still symptomatic: thyroid hormone is able to correct hypothyroidism, to reduce the volume of goiter if present and also to lower the biological evidence of thyroid autoimmunity.