Iodine induced thyroid disease

Although iodine prevents goiter, enlarged thyroid glands continue to be detected in subjects, especially children, in spite of adequate iodine ingestion. Iodine may cause goiter in susceptible individuals by inhibiting the organic binding of iodine as is seen in adult asthmatics, neonates born of iodine ingesting mothers and in subjects residing along the littoral of Japan. Myxedema, especially in treated Graves' disease and Hashimoto's disease, may also be precipitated by iodine. On the other hand, iodine given to euthyroid subjects in areas of endemic goiter and to subjects with nontoxic nodular goiter may induce thyrotoxicosis by disclosing diffuse autonomously functioning thyroid tissue. An indirect adverse effect of iodine upon the thyroid gland may be manifested by lymphocyte glandular infiltrates and chronic thyroiditis which were sparse or absent in thyroid glands removed from subjects living in iodine deficient areas before iodine prophylaxis and therapy. Not only has the incidence of thyroiditis increased, but the histologic and clinical distinctions between treated Graves' disease and chronic thyroiditis have become indistinct. Experimentally, chronic thyroiditis has been produced in animals following large doses of iodine. Accumulated evidence supports the concept that iodine contributes to the genesis of chronic thyroiditis.     

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.     

Late post-partum hemorrhage after cesarean section due to rupture of a false aneurysm of the uterine pedicle

We report a 14 year-old girl with a huge adenomatous goiter in the left lobe in the thyroid gland reaching the aortic arch with elevated thyroglobulin. The tumor grew rapidly for two years since the initial diagnosis as an euthyroid hemilateral goiter. Ultrasonography revealed multinodular tumors and magnetic resonance imaging made clear the lower expanding site of the tumor. We recommend careful follow up of hemilateral diffuse goiters by ultrasonography for earlier detection of nodular changes as seen in our case.     

Diagnosis of infections caused by varicella zoster virus]

Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland. The majority of patients with Pendred's syndrome are euthyroid. We report on an unusual case of a patient with Pendred's syndrome presenting with amenorrhea and late-onset hypothyroidism.     

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.     

On target: a model to teach baccalaureate nursing students to apply critical thinking

The majority of thyroid tumors are not homogeneous histologically, this creating difficulties in interpretation of different carcinoma variants. The aim of the study was a complex comparative study of morphogenetic changes in carcinoma, adenoma and surrounding thyroid tissue. Surgical material from 48 patients operated because of nodular (multinodular) euthyroid goiter in Moscow Medical Academy in 1990-1997 was used. It was established that all the observations of early thyroid carcinoma diagnosed clinically as a nodular (multinodular) euthyroid goiter were represented by differentiated forms of thyroid carcinoma. Thyroid carcinoma was characterized by higher values of biomolecular markers as compared to adenomas and surrounding tissue. High values of c-myc expression in adenomas and surrounding tissue may indicate possible genetic rearrangements. A peculiar feature of carcinomas was the fact that deletions and replication errors in malignant tumors in this study were found simultaneously in the three genes investigated. As to different histological types of carcinoma, the most frequent deletions of the genes studied were observed in medullary and papillary-follicular carcinoma. High values of heterozygosity loss were found already in adenomas and surrounding tissues, this indicating the presence of the genetic changes already in the benign tumors and surrounding tissue.     

Outpatient management of patients with large multinodular goitres treated with fractionated radioiodine

The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating hormone and free thyroxine (+/- free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of 35 female and three male patients with a median age of 59 years (range 37-87 years). Prior to treatment 20 patients were biochemically hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and 29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to surgery.     

Lithium and its effects on the endocrine system, bones and peripheral nerves--a current review

Controlled studies in 1990-1992 with Danish, Sardinian, and Hongkong-Chinese patients consistently revealed a prevalence of goiter of about 50% in lithium treated patients. This is far beyond the frequency generally assumed for Germany, the whole country still known to be an endemic goiter area. Hypothyroidism as a side effect of lithium occurs in a clearly different group of patients and is much less frequent, the overall incidence being not substantially different from the incidence in the general population. But the risk of becoming hypothyroid as well as hyperparathyroid during lithium prophylaxis is markedly higher in women over 45 years of age, who in the general population are also prone to both endocrine dysfunctions. Lithium is considered to have a provoking role. Lithium is known to be accumulated in the bone and an impact on bone metabolism was shown in animal studies. The data reviewed prohibit the use of lithium during lactation and enforce strict indication in children. In adults the effect of lithium on bone should be considered only in osteomalacia and severe osteoporosis. This review is illustrated by the case of a 60-year-old woman, who after 4 years of successful treatment with lithiumcarbonate because of schizoaffective psychosis, developed a syndrome of hypercalcemia. Exstirpation of a parathyroid adenoma rendered her normocalcemic. Moreover, a pre-existing diffuse goiter had grown to a large nodular goiter within the course of her 5-year treatment. As she finally became paraparetic, she was admitted to our rehabilitation center for the diseases of the spinal cord. Her paraparesis may have been caused not only by the lithium-induced primary HPT, but in part by lithium itself. There are a few reports on lithium causing peripheral neuropathy at toxic levels. A transient deterioration of a pre-existing neuropathy, as in our case study, may have happened at lithium serum levels not far beyond the upper limit of 0.8 mmol/l.     

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.     

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.     

A case of calcinosis universalis successfully treated with low-dose warfarin

A 27-year-old male patient with calcinosis universalis resulting from dermatomyositis was successfully treated with low-dose warfarin. On his trunk and extremities, there were many subcutaneous calcified nodules, and knee flexion was difficult. After oral warfarin therapy for three years, the calcified nodules became smaller, and the knee mobility improved. His serum vitamin K level was abnormally high, decreased just after starting warfarin therapy, and then remained within the normal range. Since vitamin K has been known to play an important role in the Ca2+ binding process in bones or tissues, we suggest that this therapy is effective in reducing subcutaneous calcification through the vitamin K cycle.     

A rapid morphometric method for determining thyroid gland function

The incidence of postoperative hypothyrosis after subtotal resection of the thyroid for diffuse toxic goiter is rather high, 40-50% according to many authors. A method is suggested permitting assessment of the share of "active zones" during surgery. A certain amount of thyroid tissue is left with due consideration for this share, this amount being sufficient to attain an euthyroid state in the postoperative period.     

Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage

In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation the mean urinary iodine level was 0.18 +/- 0.02 micromol/l, and 10% of the subjects had a urinary iodine level below 0.08 micromol/l. Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine. and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However. within 4 or even 2 months, some subjects (15 % of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG Suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins. but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.     

Extinction coefficient of thyroglobulin

The extinction coefficient at 280 nm of the solution (pH 7,2-7,4) of thyroglobulin from normal thyroid and nodular euthyroid goiter was measured with the values of 0,6-0,7 to 0,9 ml.mg-1.cm-1. The value of E1%280 as function of the iodoamino acid content depends on the morphological state of the thyroid gland. A simple method for determination of the E1%280 value by measuring of the protein absorption spectrum is proposed.     

Pseudotumor form of hepatic distomatosis: successful treatment with praziquantel

Human Fasciola hepatica infection is usually discovered either early, during the acute (invasive) phase, or in the advanced phase, which is characterized by biliary complications. We report a case of liver distomatosis with nodular intra-hepatic lesions in a 58-year-old woman. Radiological investigations showed 3 nodular lesions in the VII segment, which were difficult to distinguish from liver metastases or liver abscesses. Distomatosis serology was positive with passive hemagglutination. After a 5-day treatment with praziquantel, clinical symptoms resolved quickly while serological tests became negative. Radiological images slowly decreased to a calcified scar at 13 months. No side-effects were noted. Praziquantel, whose efficacy in the common presentations of liver distomatosis has recently been demonstrated, also seems effective and well tolerated in case of nodular intra-hepatic lesions.     

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.     

Familial insensitivity of the pituitary and periphery to thyroid hormone: a case report in two generations and a review of the literature

A clinically euthyroid 2-yr-old girl was found to have diffuse goiter that measured 3 X 5.5 cm with a prominent systolic bruit. Serum free T4 (3.4 ng/dl) and serum T3 (360 ng/dl) remained elevated for the next 10 months even though she remained clinically euthyroid. Elevation of serum free T4 (3.0 ng/dl) and serum T3 (265 ng/dl) was also present in the 24-yr-old nongoitrous mother who had symptoms and signs of hypothyroidism. Following intravenous injection of TRH, basal TSH levels of 2.7 and 2.8 microunits/ml increased to peak values of 17 and 21 microunits/ml at 30 min in the daughter and mother, respectively. Administration of exogenous T3 followed by sequential testing with boluses of TRH revealed retention of TSH responsiveness in both daughter and mother during pretreatment with dosage regimens of T3 below 125 micrograms daily. Maintenance of TSH responsiveness to TRH in the presence of elevated levels of serum free T4 and serum T3 indicates relative pituitary insensitivity to thyroid hormone which could be overridden by increasing the circulating levels of serum T3 three to fivefold over the already elevated basal levels. The absence of clinical signs of thyrotoxicosis indicates peripheral insensitivity to thyroid hormone with elevated circulating concentrations presumptively compensating for the defect. Resistance to thyroid hormone in two generations of the same family suggests genetic inheritance, and is concordant with four earlier reports of familial aggregation in this syndrome.     

Antibodies against thyroid gland peroxidase and thyroglobulin in various thyroid diseases

Autoantibodies to thyroperoxidase (anti-TPOAb) and thyroglobulin (anti-TgAb) were measured in 564 patients with various thyroid disorders and in 59 healthy subjects using chemiluminometric immunoassay. The frequency of elevated titers was 8.6% in healthy subjects, 76.2% in patients with untreated hyperthyroidism and diffuse goiter, 80.7% in patients with relapse of hyperthyroidism. 83.4% of patient with hyperfunction changed spontaneously to hypothyroidism and 71.5% of patients with hypothyroidism and goiter had antibodies above the normal range. Unexpectedly low prevalence of autoantibodies were detected in patients with primary myxoedema without goiter (48.2%) and in patients with endocrine ophthalmopathy and euthyroidism (33.2%). In the subgroup of patients with hyperthyroidism under methimazole treatment we found an incidence of positivity of 56% and the mean of positive values was lower compared with the untreated ones. In 42.8% of patients with hyperthyroidism and diffuse goiter treated successfully by methimazole, surgery or radioiodine elevated concentrations of antibodies could be detected, however they were in remission for more than five years. 197 (82.4%) of the patients with positive antibody titers showed higher concentrations to peroxidase compared with thyroglobulin. 57.9% of serum samples positive for anti-TPOAb were negative for anti-TgAb, whereas 9.4% of samples positive for anti-TgAb were anti-TPOAb negative. The diagnosis of thyroid autoimmunity could generally be based on measurement of anti-TPOAb with additional measurement of anti-TgAb in special cases.     

Calcitonin and calcium content of the blood of patients with thyroid pathology

The blood calcitonin and calcium content was studied in 38 patients with thyrotoxicosis, 20 subjects with endemic euthyroid goiter and 7 persons with primary hypothyrosis. The blood calcium and calcitorim levels were not changed in males and females with endemic euthyroid goiter in comparison with those of 19 healthy controls. Calcitonin content was markedly decreased in patients with hypothyrosis. Calcium level was significantly increased in males, remaining practically unchanged in females. Calcium and calcitonin levels were dependent on thyrotoxicosis severity. Calcitonin content remained unchanged in moderate thyrotoxicosis and lowered in the severe stage of the disease. The blood calcium level remained unchanged both in males and females suffering from severe thyrotoxicosis and in males with the moderate form of the disease. Calcium content diminished in the blood serum of females with moderate thyrotoxicosis.     

The results of epidemiological studies concerning iodine deficiency and goiter in Poznań Region (Poznań coordinating center)

The studies concerning iodine deficiency and occurrence of goiter, being a fragment of the program covering different parts of Poland, included 2620 children of age between 7 and 12 years attending randomly chosen schools situated in towns and villages of Poznań, Pila, Leszno, Konin, Kalisz, Bydgoszcz and Zielona Góra districts. Among the children studied, 1009 children (522 boys and 487 girls) attended town schools, and 1611 (774 boys and 837 girls) country schools. All children were subjected to anamnesis by using a standard questionnaire. Also physical examination of the thyroid aimed at the evaluation of size and morphology of the gland was carried out by palpation (according to the obligatory WHO scale) and by ultrasonography. Urine samples were taken from the majority of children for the determination of urinary excretion of iodine. In 736 (28.1%) of the studied children an enlargement of the thyroid was found. Among these children 253 are inhabitants of towns (this number represents 27.8% of all urban children studied) and 483 are inhabitants of villages (30% of all rural children studied). In 92.7% of cases the goiter could be classified as type IB according to WHO and in 56 cases it was of nodular character. There was a clear relation between the incidence of goiter and the age of the children studied. Frequency distribution of goiter in the individual age groups was as follows: for urban children--21.8% in age group of 7-8 years, 23.5% in age group of 9-10 years and 29.7% in age group 11-12 years, and for rural children the corresponding values were 21.1%, 30.2% and 38.2%. Mean urinary iodine excretion was 96 micrograms/L (median 84 micrograms/L) for urban children, and 87 micrograms/L (median 64 micrograms/L) for rural children. Among 2620 answers concerning the use of iodized salt in the household, only 980 (37.1%) were positive. In towns, the use of iodized salt declared about 41% of families and in villages about 35%. Altogether, among 736 cases of goiter, 464 are children not using iodized salt. Only in 272 cases goiter appeared despite the use of iodized salt. The data concerning family occurrence of goiter and the type of iodized salt used can be treated as approximate because of subjective character. According to the results obtained, the region covered by the study falls according to the WHO and ICCIDD classification to the category of an area of mild iodine deficiency requiring more intensive iodine prophylaxis.