Effect of increased iodide intake on thyroid function in subjects on chronic lithium therapy

Thyroid function tests were obtained in 10 patients on chronic lithium therapy before and after the administration of potassium iodide 250 mg q.i.d. Mean serum TSH rose by 8.9 muU/ml and mean serum T3 rose from 70 to 101 ng/dl. Two patients became hypothyroid; a third showed a rise in TSH without any change in T3 or T4. A fourth patient developed hyperthyroidism probably secondary to the Jod-Basedow phenomenon. Pharmacologic doses of iodine should be administered with caution to patients on chronic lithium therapy.     

Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight of our patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. We conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop in the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.     

Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting-enzyme inhibitor (SQ 14,225, captopril) in hypertensive patients

Nineteen patents with treatment-resistant essential (13) or renovascular (6) hypertension were treated with an orally active inhibitor of angiotensin-converting enzyme, D-2-methyl-3-mercaptopropanoyl-L-proline (captopril), for periods up to 6 mo. The compound alone produced moderate to marked sustained reductions in blood pressure, often to normal levels. One patient who had a low renin level exhibited no significant response. In four patients with a partial response, addition of a diuretic produced satisfactory blood pressure control. No serious side-effects were noted. A syndrome of rash and fever was observed in two patients, which resolved following reduction of the dose or withdrawal of drug.The mechanism of action remains to be fully elucidated, but the data indicate that a major action involves suppression of the reninangiotensin-aldosterone system. Thus, the degree of blood pressure reduction was correlated (1) with the level of pretreatment plasma renin activity, (2) with the induced suppression of urinary aldosterone excretion, and (3) with the consequent changes in potassium balance and serum potassium. Sustained coverting-enzyme blockade produced natriuresis in a majority of patients on a normal sodium intake, a factor that may contribute to the blood pressure response.The evidence suggests that at the doses currently used the induced blockade of angiotensin II formation is incomplete, since during therapy aldosterone appears to remain responseive to physiologic changes in renin activity, although at a lower level. Indeed, reactive increases in renin secretion may, in some patients, diminish the antihypertensive action of the drug.These results with an oral agent over a longer time closely resemble the acute effects of the intravenous nonapeptide inhibitor. The effects of these two agents in turn are in many respects similar to those obtained with other agents that block the renin system, namely saralasin and beta-adrenergic blockers. Accordingly, from a conceptual standpoint, these new findings provide another dimension in the growing body of evidence, idicating a significant in involvement of the renin-angiotensin-aldosterone system in most hypertensive patients. This in turn provides the basis for a new approach to therapy based on the identification and containment of the renin factor by specific pharmacologic agents.     

Recovery of the thyroid function in patients with atrophic hypothyroidism and blocking type TSH binding inhibitor immunoglobulin

The prognosis of atrophic hypothyroidism with blocking type TSH-binding inhibitor immunoglobulin was studied. Among 45 patients (16 males and 29 females) with overt hypothyroidism (serum TSH greater than 40 mU/l) without goitre, thyroid autoantibody to microsomal antigen was positive in 38 or 84.4%, and 4 or 8.9% had TSH-binding inhibitor immunoglobulin, which was shown to be a TSH-stimulation blocking antibody by cAMP production assay using cultured porcine thyroid cells. Thyroidal radioactive iodine uptake was low and thyroid hormone replacement therapy was required. Long-term follow up of 2 patients with strongly positive TSH-binding inhibitor immunoglobulin for 2 to 7 years, however, revealed recovery of the thyroid function after steroid therapy or spontaneously with iodide restriction, respectively, correlating with decrease in both TSH-binding inhibitor immunoglobulin and TSH-stimulation blocking antibody activities. Thyroidal radioactive iodine uptake became normal and histological examination of the thyroid in one patient revealed well-preserved thyroid follicles with lymphocytic infiltration. Recovery of thyroid function can be expected with a decrease in TSH-binding inhibitor immunoglobulin activity in atrophic hypothyroidism, which is not necessarily the end stage of chronic thyroiditis.     

A case of Hashimoto's thyroiditis with thyroid immunological abnormality manifested after habitual ingestion of seaweed

An interesting case of iodide induced goitre with immunological abnormalities is described. The patient who was sensitive to synthetic penicillin had previously been treated for exudative pleuritis, congestive heart failure and acute renal failure. Following recovery, he began to ingest large amounts of seaweed after which he developed goitrous hypothyroidism. It was of interest that the serum level of gamma-globulin increased, and subsequently the antithyroid microsomal antibody became strongly positive, suggesting that thyroidal autoimmune processes had been precipitated. Biopsy of the thyroid gland revealed chronic thyroiditis, with evidence suggesting extreme stimulation by TSH. Hight thyroidal uptake of 131I, positive perchlorate discharge test and biochemical analysis of the thyroidal soluble protein showed severe impairment of hormone synthesis following continuous accumulation of excess iodide. While there is evidence suggesting that increased iodide may be an important factor in the initiation of Hashimoto's thyroiditis, this may result from the marked increased sensitivity of Hashimoto's gland to the effects of iodine. Thus an occult lesion could be unmasked in this manner. The mechanism by which iodide mediates this effect is not clear.     

Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism

We studied the effect of potassium perchlorate (KClO4) in patients with hypothyroidism due to amiodarone. The short term administration of KClO4 to six such patients led to prompt restoration of euthyroidism, while the three untreated patients remained hypothyroid for 2-6 months. Since KClO4 inhibits thyroid iodide transport, thereby blocking further entrance of iodide into the thyroid and decreasing intrathyroidal iodide content, amiodarone-associated hypothyroidism is probably secondary to the inhibitory effect of excess intrathyroidal iodine on thyroid hormone synthesis.     

The syndrome of multiple endocrine gland insufficiency

Addison's disease, when caused by idiopathic atrophy of the adrenal cortex, is frequently associated with other endocrine abnormalities. Primary hypothyroidism and hypogonadism have been reported in association with adrenal insufficiency; understandably, such cases may lead to diagnostic confusion with respect to possible pituitary disease.This case study concerns a woman who exhibited, in sequence and over a period of 17 years, hypogonadism, hypoadrenalism, diabetes mellitus and, finally, hypothyroidism. Originally misdiagnosed as having Sheehan's syndrome, she eventually became hyperpigmented. The true nature of her illness was then revealed to be primary insufficiency of multiple endocrine glands, with the demonstration of elevated levels of several pituitary hormones.Because multiple endocrine insufficiencies may coexist or develop with time, we suggest that a patient with a single documented endocrine deficiency be investigated initially and serially for additional glandular deficiencies.     

Comparison of RA 131I treatment protocols for Graves' disease

The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50-60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy.     

Reversible primary hypothyroidism and elevated serum iodine level in patients with renal dysfunction.

Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH greater than 10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen greater than 7.1 mmol/l and creatinine greater than 106 mumol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30 (83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67-15,591 micrograms/l, N = 19) and a high thyroidal radioactive iodine uptake (51.5 +/- 29.3% at 24 h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.     

A case of consciousness disturbance resulting from severe hypothyroidism due to chronic thyroiditis and excess iodine absorption

An 82-year-old Japanese man had consciousness disturbance due to severe hypothyroidism triggered by percutaneous absorption of iodine from an iodine-containing ointment used in diabetic gangrene treatment. Laboratory data revealed extremely high urinary iodine concentrations, and chronic thyroiditis-induced hypothyroidism. Excess iodine intake can also cause hypothyroidism. It was unlikely that iodine intoxication or Hashimoto's encephalopathy had caused the consciousness disturbance. The patient regained consciousness after discontinuing the use of the ointment and commencing thyroid hormone therapy. We conclude that consciousness disturbance resulted from severe hypothyroidism caused by chronic thyroiditis and excess iodine absorption.     

Echocardiographic characterization of the reversible cardiomyopathy of hypothyroidism

Nineteen patients with untreated hypothyroidism were evaluated by M-mode echocardiography. Asymmetric septal hypertrophy (ASH), defined as a ratio of interventricular septal thickness to left ventricular posterior wall thickness (IVS/LVPW) equal to or greater than 1.3, was identified in 17 cases. Additional abnormalities recognized by echocardiography included reduced amplitude of systolic septal excursion (SSex) [13 patients], reduced per cent of systolic septal thickening (%SST)[19 patients], reduced left ventricular outflow tract dimension (LVOT)[five patients] and systolic anterior motion of the mitral valve (SAM)[five patients]. These findings are similar to some of the echocardiographic features of idiopathic hypertrophic subaortic stenosis (IHSS). In 10 patients who returned to euthyroid state with L-thyroxine therapy, these abnormalities resolved. We conclude that long-standing hypothyroidism leads to a reversible cardiomyopathy, manifested by asymmetric septal hypertrophy with or without other echocardiographic features of a hypertrophic obstructive cardiomyopathy. This previously unrecognized features of hypothyroidism has important diagnostic and therapeutic implications.     

碘对大鼠甲状腺钠碘转运体mRNA表达及甲状腺功能的影响

观察不同碘摄入量对大鼠甲状腺钠碘转运体（NIS）mRNA、血清甲状腺激素、尿碘水平以及甲状腺组织碘含量的影响。低碘组NIS mRNA表达明显增强，而血清甲状腺激素、尿碘、甲状腺组织碘含量显著下降。高碘组NIS mRNA表达受到抑制，甲状腺激素有下降趋势。提示NIS是甲状腺自身调节的重要组成部分。高碘、低碘均可导致甲状腺功能低下。     

Hyperthyroidism induced by potassium iodide given in the course of 125I-fibrinogen test

Hyperthyroidism developed in three patients during the administration of potassium iodide given for the purpose of blocking the thyroid uptake of radioactive iodine liberated in the course of the 125I-fibrinogen test. In a consecutive series of 31 geriatric patients, who received potassium iodide for the same reason, biochemical hyperthyroidism developed in three instances and significant depression of thyroid function was observed in 10. The performance and the interpretation of the 125I-fibrinogen test are unaffected if iodide is not administered to the patient. The possible hazards to some patients of either induced hyperthyroidism or faulty assessment of thyroid function may be greater than the risk of thyroid irradiation. It is suggested that for the performance of the 125I-fibrinogen test potassium iodide need not be given to the elderly and should be given in a dose of 30 mg daily for two weeks to younger patients. Under certain circumstances potassium perchlorate may be a preferable drug for preventing the accumulation of radioactive iodine by the thyroid.     

Urinary iodide excretion in Japanese people and thyroid dysfunction]

In order to assess the Japanese dietary iodine intake, we examined the urinary iodine excretion of those on an ordinary Japanese diet chosen at random and observed whether the thyroid function might affect the amounts of urinary iodine excretion. The subjects consisted of cases of untreated hypothyroidism and chronic thyroiditis (CT) and euthyroid controls who were healthy people or had non-thyroidal disorders such as diabetes mellitus or hypertension. Eight cases of hypothyroidism were composed of 3 cases of secondary hypothyroidism with empty sella syndrome and 5 cases of primary hypothyroidism and 32 patients with CT have been maintained in euthyroid states with T4 medication. We selected 32 cases of sex and age-matched healthy people as controls. The mean levels of excreted urinary iodine were 465.6 micrograms/day in the healthy controls and 471.8 micrograms/day in patients with CT, respectively. Urinary iodine excretion was significantly correlated to serum inorganic iodide in both controls and CT patients, of which correlation coefficients were +0.35 and +0.5, respectively. Urinary iodine and serum inorganic iodide ratios (U/S) in hypothyroidism were significantly (p less than 0.05) depressed compared with those in CT. The present study indicated that recent Japanese dietary iodine intake was estimated to be approximately 470 micrograms/day and that the urinary iodine excretion would be influenced not only by iodine intake but also by thyroid function.     

Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring. Therapeutic considerations

Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)     

Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: a review.

Ingestion of potassium iodide (KI) offers effective protection against irradiation of the thyroid after accidental exposure to radioactive iodine. This prophylaxis aims at rapidly obtaining maximal thyroid protection without adverse effects. This article reviews studies on iodine kinetics in humans and on the efficacy of KI in protecting the thyroid. In adults with normal thyroid function, ingestion of 100 mg of iodide just before exposure to radioactive iodine blocks at least 95% of the thyroid dose. If exposure persists after iodide ingestion (100 mg), the percentage of averted dose may decrease significantly. Daily ingestion of a dose of 15 mg of KI would then maintain the thyroid blockade at a level above 90%. The efficacy of iodide and the occurrence of antithyroid effects also depend on external and individual factors such as dietary iodine intake, thyroid function, and age. The KI dosage regimen should be adjusted for age at exposure. For the fetus, the newborn, children, and adolescents, the risk of radiation-induced thyroid cancer in case of accidental exposure to radioactive iodine justifies KI prophylaxis, despite the risk of hypothyroidism, especially in newborns. For the elderly, the benefits of KI may be lower than the risk of iodine-induced hyperthyroidism.     

Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations

OBJECTIVE The present study was designed to investigate the prevalence of thyroid dysfunction and Its relation to thyroid autoantibodies and urine iodide concentration in apparently healthy people residing in Sapporo, a city of northern Japan, where the iodine intake is high. DESIGN AND SUBJECTS Serum TSH and thyroid autoantibodies, and urine iodide were measured in 4110 people (2931 men and 1179 women) (age 456 ± 103 years (mean ± SD)) who were recruited at the hospital for medical examinations. RESULTS The thyroid autoantibodies were positive in 6.4% of males and 13.8% of females with an age-related increase. Of the people with positive antibodies, 87.2% had normal TSH values (0.15–5.0 mU/l) as measured by a sensitive assay. The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves' disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidenced by supranormal TSH, was 0.68% for males and 3.13% for females with an age-related increase. Of those with hypothyroidism, 45.5% were autoantibody positive. The overall prevalence of Hashimoto's thyroiditis was 13.11% for females and 6.15% for males. The urine iodide levels of hypothyroidism with a positive autoantibody of 38.5 (17.7–83.9)μmol/l and a negative autoantibody of 34.9 (17.9–67.9) μmol/l were both significantly higher than that of normal subjects (26.9 (14.6–49.6) μmol/l) (P <0.01). When iodine intake was restricted for 6–8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group. CONCLUSIONS This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing latent hypothyroidism.     

Studies of hypothyroidism in patients with high iodine intake

Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type). In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type). In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [50.0 +/- 12.2% (+/- SD) vs. 4.3 +/- 3.2%; P less than 0.01], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6. Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again. Two patients had a history of habitual ingestion of seaweed (25.4 and 43.1 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily. The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland. These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.     

Lithium-associated thyrotoxicosis

Primary hypothyroidism developed in a 57-year-old woman treated for eight years with lithium carbonate for manic-depressive illness, and nine months later she became thyrotoxic. Although autoimmune disease appeared to be responsible, lithium was suspected to play a contributory role in both phases of her illness. This is the first reported case of hyperthyroidism following hypothyroidism in a lithium-treated patient. The 24 reported cases of lithium-associated thyrotoxicosis and the possible mechanisms that may explain this poorly understood phenomenon are also reviewed.