potassium-perchlorate and Hypothyroidism

Amiodarone is an iodine-rich drug. Its chronic administration may lead to disturbances in thyroid hormone metabolism and/or overt gland dysfunction. It causes an increased in serum fT4, rT3, and TSH concentrations and a decreased serum level of fT3 without thyroid dysfunction. Amiodarone may induce thyrotoxicosis (AIT--Amiodarone-induced thyrotoxicosis) or hypothyroidism (AIH--Amiodarone-induced hypothyroidism) in some persons. AIT occurs more frequently in areas with low iodine intake. The excess iodine contributes to excessive thyroid hormone synthesis-type I AIT or may lead to thyroiditis and a destructive process of thyroid follicular cells, resulting in excess thyroid hormone release-type II AIT. The mixed form of AIT also occurs. Type I AIT should be treated with antithyroid drugs alone or in association with potassium perchlorate, type II AIT benefits from treatment with glucocorticoids, whereas the mixed form of AIT is most effectively treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. AIT often requires thyroidectomy after restoration of euthyroidism or radioiodine therapy, provided that 24-h thyroid radioactive iodine uptake values permit. AIH prevails in areas with high dietary iodine intake. It requires a discontinuation of amiodarone therapy and thyroid hormone (levothyroxine) replacement. It can remit spontaneously. Amiodarone and L-thyroxine therapy is also possible. Baseline thyroid function tests, thyroid antibodies, and imaging examinations such as thyroid ultrasound on initial evaluation and follow-ups every 6 months must be carefully monitored before starting amiodarone therapy.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Antithyroid Agents; Female; Glucocorticoids; Humans; Hypothyroidism; Perchlorates; Potassium Compounds; Pregnancy; Thyroid Gland; Thyroid Hormones; Thyroidectomy; Thyroiditis; Thyrotoxicosis

Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Brain; Cannabinoid Receptor Agonists; Disease Models, Animal; Dopamine Agonists; Dopamine Antagonists; Dronabinol; Haloperidol; Hypothyroidism; Imidazoles; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Perchlorates; Phenotype; Potassium Compounds; Receptor, Cannabinoid, CB1; Receptors, Dopamine D1; Receptors, Dopamine D2

Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner.

Topics: Acetylcholinesterase; Age of Onset; Animals; Anxiety; Avoidance Learning; Brain; Disease Models, Animal; Fear; Hypothyroidism; Isoenzymes; Male; Memory Disorders; Mice, Inbred BALB C; Motor Activity; Perchlorates; Potassium Compounds; Random Allocation

Thyroid hormones are essential for the maturation and functions of the central nervous system. Pain sensitivity is related to the thyroid status. However, information on how thyroid hormones affect pain processing and synaptic transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive threshold and synaptic transmission in the ACC were detected in the experimental hypothyroidism (HT) mice.. HT was induced by methimazole and potassium perchlorate in distilled drinking water for 4 weeks. The threshold of pain perception to hot insults, but not mechanical ones, decreased in hypothyroid mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks, thermal pain threshold recovered. Electrophysiological recordings revealed enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic transmission in the ACC. Supplementation with T3 or T4 significantly rescued this synaptic transmission imbalance. In the same model, HT caused the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down-regulated γ-aminobutyric acid A receptors in the ACC. Supplementation with T3 or T4 notably recovered the levels of above proteins.. These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC.

Topics: Animals; Disease Models, Animal; Excitatory Postsynaptic Potentials; Gyrus Cinguli; Hyperalgesia; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Mice; Mice, Inbred C57BL; Pain Threshold; Perchlorates; Potassium Compounds; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Thyroxine; Triiodothyronine; Up-Regulation

Steroid hormones exert profound effects on the development of brain areas controlling complex cognitive function in adulthood. One class, progestins, may contribute by acting on the progestin receptor (PR), which is transiently expressed in a critical layer of developing cortex: the subplate. PR expression in the subplate coincides with the establishment of ongoing cortical connectivity and may play an important organisational role. Identification of the factor(s) that regulate the precise timing of PR expression within subplate may help elucidate the function of PR. Thyroid hormone may interact with hormone response elements within the PR gene. The present study examined the effects of maternal hypothyroidism on levels of PR immunoreactivity (PR-IR) within the foetal subplate. Pregnant rats were made hypothyroid by the administration of methimazole and potassium perchlorate in drinking water. Maternal hypothyroidism significantly decreased PR-IR within the foetal subplate. Using the incorporation of 5-bromo-2'-deoxyuridine (BrDU) during subplate cell neurogenesis (embryonic day 13.5) to determine subplate cell survival in hypothyroid animals, we found that decreases in PR-IR cannot be attributed to significant subplate cell loss but are more likely the result of altered PR expression. Gestational thyroxine replacement to hypothyroid dams prevented the decrease in PR-IR within the subplate. These results identify thyroid hormone as a potential factor in the regulation of PR expression in the developing brain. These results are consistent with the idea that endocrine cross-talk between progesterone and thyroid hormone may be one mechanism by which maternal hypothyroidism alters normal cortical development.

Topics: Animals; Cerebral Cortex; Female; Hypothyroidism; Immunohistochemistry; Methimazole; Perchlorates; Potassium Compounds; Pregnancy; Pregnancy Complications; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Progesterone; Thyroxine

Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.

Topics: Animals; Body Weight; Cerebellum; Cluster Analysis; Disease Models, Animal; Gas Chromatography-Mass Spectrometry; Hypothyroidism; Male; Metabolic Networks and Pathways; Metabolome; Metabolomics; Mice; Mice, Inbred BALB C; Microarray Analysis; Perchlorates; Potassium Compounds; Principal Component Analysis; Reproducibility of Results

Amiodarone-induced hypothyroidism (AIH) may occur in patients with or without underlying thyroid disorders. In the latter, restoration of euthyroidism, after amiodarone discontinuation, can be facilitated and accelerated by a short course of potassium perchlorate (KClO4). However, it is unknown whether KClO4 may exert similar effects on thyroid function of AIH patients if amiodarone treatment is continued.. To evaluate the effects of KClO4 on thyroid function in AIH patients (without underlying thyroid disease) while continuing amiodarone treatment.. An open, prospective study of 10 consecutive AIH patients without underlying thyroid abnormalities referred to a tertiary referral center, and treated with KClO4 (600 mg/day) for a period of 26+/-13 days (range, 15-45 days). An additional, historical group of 12 consecutive patients with subclinical AIH left untreated while continuing or after withdrawing amiodarone was retrospectively evaluated as to the outcome of thyroid function.. Serum free T4, free T3, and TSH concentrations were measured at booking, during KClO4 treatment and after withdrawing the drug.. In the prospective study, KClO4 treatment restored euthyroidism in all patients within 28+/-11 days (range, 15-45 days). After KClO4 withdrawal, however, all patients became hypothyroid again after 45+/-15 days (range, 30-60 days). Two patients developed mild leukopenia (1 case) or a slight increase in serum creatinine levels (1 case), which promptly normalized after KClO4 withdrawal. In the historical group, followed for at least 12 months, euthyroidism was spontaneously and stably achieved after an average of 6 months in 5 patients in whom amiodarone could be discontinued, while subclinical hypothyroidism persisted in 7 patients in whom amiodarone had to be continued.. KClO4 very effectively restores normal thyroid function in AIH patients without underlying thyroid abnormalities, despite the fact that amiodarone therapy is continued. However, euthyroidism does not persist after KClO4 is withdrawn; in addition, spontaneous recovery of euthyroidism does not seem to occur in this subset of AIH patients, unless amiodarone is discontinued. Therefore, also in view of its potential side-effects, KClO4 cannot be recommended as a first-line treatment for AIH if amiodarone needs to be continued, while LT4 replacement is recommended under these circumstances, with periodical reassessment of thyroid function.

Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Female; Humans; Hypothyroidism; Male; Middle Aged; Perchlorates; Potassium Compounds; Prospective Studies; Retrospective Studies; Thyroid Gland; Time Factors

Mutations of the thyroperoxidase (TPO) gene have been reported as being the most severe and frequent abnormality in thyroid iodide organification defect (IOD) causing goitrous congenital hypothyroidism. The objective of this study was to screen and subsequently identify TPO gene mutations in patients with congenital hypothyroidism with evidence of total iodine organification defects (TIOD) or partial iodine organification defect (PIOD) as defined by the perchlorate discharge test. Seven goitrous patients with TIOD and seven patients with PIOD, from three and five unrelated families, respectively, were studied. We were able to detect different TPO genes mutations in patients with TIOD and PIOD. In TIOD families the results were as follows: (1) a homozygous GGCC insertion at exon 8, position 1277 (family 1); (2) compound heterozygosity with a GGCC insertion at exon 8 (1277) and a nucleotide substitution in exon 11 (2068G>C) (family 2); (3) compound heterozygosity with the mutation 2068G>C in exon 11 and a C insertion in exon 14 between positions 2505-2511 (family 3). In patients with PIOD we have detected: (1) only one heterozygous mutation in two families (4 and 5), in exons 11 and 10 (2084G>A and 1780C>A); (2) a compound heterozygous condition in one family (family 6), with mutations, respectively in exons 8 and 10 (1242G>T and 1780C>A); (3) only polymorphisms (family VII) and (4) a heterozygous mutation in the first base of the border exon/intron 9 +1G>T (family VIII). We did not detect inactivating mutations in exons 11, 16, and 21 of the THOX2 gene where mutations have been previously described. We concluded that homozygous and compound heterozygous mutations found in TIOD characterized the autosomal recessive mode of inheritance and will translate a nonfunctional protein or a protein that may not reach the apical membrane. As for PIOD, the majority of the studied kindreds had only heterozygous mutations and/or polymorphisms. It is conceivable that these TPO gene sequence alterations may partially affect the functional state of the translated protein or affect its transport to the apical membrane.

Topics: Adolescent; Adult; Base Sequence; Congenital Hypothyroidism; DNA Transposable Elements; Dual Oxidases; Flavoproteins; Genes, Recessive; Genetic Testing; Goiter; Heterozygote; Homozygote; Humans; Hypothyroidism; Iodide Peroxidase; Iodides; Mutation; NADPH Oxidases; Perchlorates; Polymorphism, Genetic; Potassium Compounds; Thyroid Gland

Thyroid gland ectopy is the most common cause in infants with congenital hypothyroidism (CH). Its association with iodine organification defect, as suggested by positive perchlorate discharge test (PDT) has been reported. However, whether such an association represents a true or transient defect has not yet been determined. This finding has an important clinical, epidemiological, and genetic implications.. To determine the natural history of iodine organification defect in patients with CH caused by thyroid ectopy detected by neonatal screening.. Prospective longitudinal study.. King Khalid University Hospital, Riyadh, Saudi Arabia.. PDT was performed, at the time of diagnosis and follow-up, in infants who showed an enlarged ectopic thyroid gland with a Tc-99m pertechnetate uptake of 2% or more.. Of 115 neonates with ectopic thyroid glands, 19 showed an enlarged gland with Tc-99m uptake ranging from 2 to 3.2%. Perchlorate discharge test was performed in 13 of these and was consistent with iodine organification defect in nine. Repeated PDT in seven patients showed normal values.. The results of the authors' study indicate the transient nature of the iodine organification defect and suggest that a delay in the developmental of synthetic mechanisms occur in the dysgenetic glands.

Topics: Choristoma; Congenital Hypothyroidism; Female; Humans; Hypothyroidism; Infant, Newborn; Male; Neonatal Screening; Perchlorates; Potassium Compounds; Prospective Studies; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Thyroid Function Tests; Thyroid Gland; Tongue Diseases

Forty children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography.. In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently.. Scintigraphy revealed athyrosis in 7 children. In 11 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been considered by ultrasound. In 50% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed.. This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Topics: Child; Child, Preschool; Congenital Hypothyroidism; Female; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Perchlorates; Potassium Compounds; Radionuclide Imaging; Retrospective Studies; Thyroid Gland; Ultrasonography

The kidney androgen-regulated protein (KAP) gene exhibits a cell-specific hormonal regulation of its expression in the epithelial cells of proximal tubules of mouse kidney, where T3 is required for constitutive expression in the straight segments and androgens for expression in the convoluted ones. By using different models of hypothyroidism, we demonstrate that maximal androgen-mediated induction of the gene depends on thyroid hormone as well. This constitutes a specific event, since vitamin D3 cannot mimic the effects of T3, albeit their remarkable functional relationship. It is also shown that while congenital hypothyroid hyt/hyt male mice, exposed to maternal T3 in the gestational period, exhibit diminished but existent androgen-dependent cortical responses, mice exposed to goitrogens during gestation and postnatally are unable to express the gene even at postnatal day ninety. Impairment of KAP cortical expression in hypothyroid animals does not correlate with lower levels of androgens or androgen receptor expression.

Topics: Animals; Antithyroid Agents; Dihydrotestosterone; Epithelium; Female; Gene Expression Regulation, Developmental; Hypothyroidism; Kidney; Male; Methimazole; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Orchiectomy; Perchlorates; Potassium Compounds; Pregnancy; Proteins; Receptors, Androgen; RNA, Messenger; Testosterone; Thyroid Hormones; Thyroxine

A number of radioimmunotherapy (RAIT) trials with iodinated antibodies have shown a high variability in the radiation doses to the thyroid. Therefore, the aim of this study was to evaluate which factors influence these thyroid doses during RAIT with 131iodinated monoclonal anti-carcinoembryonic antigen (CEA) antibodies. Data from 36 patients with CEA-expressing tumours were analysed. The patients underwent RAIT with the 131I-labelled IgG1 anti-CEA antibody, MN-14 (Ka = 10(9) l mol-1) or its F(ab')2 fragment (activity range 45.8-220.0 mCi). The thyroid was blocked with 120 mg iodine (lugol's orSSKI solution) and 400 mg perchlorate per day, starting 1 day prior to the first study. Blood clearance and molecular composition of labelled plasma compounds were determined by blood sampling and size-exclusion high-performance liquid chromatography analysis. The cumulated activities of tissues were determined from daily imaging and blood clearance data. Doses were derived from the MIRD scheme. Thyroid radiation doses showed a high variability, between 1.2 and 37.7 cGy mCi-1 (mean +/- S.D.: 11.1 +/- 8.3 cGy mCi-1), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was 2.4 +/- 1.9 microCi mCi-1 (range 0.2-10.0 microCi mCi-1), which was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases. No correlation was found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the mAb preparation, rapid metabolic breakdown of the labelled antibody due to human anti-mouse antibodies (HAMA), or immune complex formation with circulating antigen. However, a relationship between the thyroid doses and the patients' compliance in taking their Lugol's and perchlorate blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (range from 31.1 h to virtual infinity), is indicated. No rising TSH titres or other signs of (latent) hypothyroidism were seen in these patients during a 2 year follow-up period. Longer follow-up was not possible because of the terminal condition of most of the patients. These data show that thyroid doses in an appropriately blocked individual given a standard, non-myeloablative dose of RAIT, are generally lower than those assumed to be required to cause late hypothyroidism. Even if higher activities are used, potential hypothy

Topics: Adenocarcinoma; Adult; Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Carcinoembryonic Antigen; Female; Humans; Hypothyroidism; Immunoglobulin G; Indium Radioisotopes; Iodides; Male; Mice; Patient Compliance; Perchlorates; Potassium Compounds; Radiation Dosage; Radiation Injuries; Radioimmunotherapy; Thyroid Gland; Thyrotropin

Quantitative thyroid scanning using low doses of technetium-99m sodium pertechnetate was performed on 147 infants (55 males and 92 females) with congenital hypothyroidism detected through the national neonatal screening programme. Thirty-two (21.8%) were athyrotic, while 62 (42.2%) had an ectopic thyroid and 53 (36%) had a eutopic gland with increased 99mTc uptake (mean 17%; range, 5%-38%). The perchlorate discharge test (PDT) was performed in nine of the infants with ectopic glands and 15 with eutopic glands; the findings were consistent with an organification defect in 22 cases (seven ectopic and 15 eutopic). Thyroid scintigraphy and PDT can add useful aetiological, genetic and prognostic information in the clinical evaluation of infants with congenital hypothyroidism detected by neonatal screening.

Topics: Choristoma; Congenital Hypothyroidism; Female; Humans; Hypothyroidism; Infant, Newborn; Iodine Radioisotopes; Male; Neonatal Screening; Perchlorates; Potassium Compounds; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Thyroid Function Tests; Thyroid Gland

Changes in the pituitary cells involved in amphibian metamorphosis were studied in Bufo arenarum tadpoles with inhibited thyroid function. After hatching, larvae were treated for 5 months with potassium perchlorate (KClO4), a goitrogenic substance known to prevent absorption of iodine from water or food, resulting in impaired thyroid hormone synthesis. Treated larvae continued to grow but halted their development in premetamorphosis, showing hyperplastic thyroid glands with disorganized follicles lacking colloid. Thyrotrop (TSH), lactotrop (PRL), somatotrop (GH), and corticotrop (ACTH) cells were stained immunocytochemically and the changes observed were evaluated morphometrically using an automatic image analyzer. Pars distalis volume increased in treated larvae. Morphometric results showed that, in treated tadpoles, TSH and PRL cell populations and cell volumes increased compared to normal larvae at the same stage. Changes in the GH and ACTH cell morphometry were slight. These results indicate that in Bufo tadpoles, after chronic thyroid hormone withdrawal, TSH, PRL, GH, and ACTH cells are able to develop and that thyroid hormones exert a strong feedback control on the synthesis and storage of TSH and PRL.

Topics: Adrenocorticotropic Hormone; Animals; Bufo arenarum; Cell Count; Cell Size; Feedback; Female; Growth Hormone; Hypothalamo-Hypophyseal System; Hypothyroidism; Image Processing, Computer-Assisted; Immunohistochemistry; Larva; Male; Metamorphosis, Biological; Neuropeptides; Perchlorates; Potassium Compounds; Prolactin; Thyroid Gland; Thyrotropin

Hypothyroidism followed by hyperthyroidism is described in two patients treated by amiodarone. Euthyroidism was rapidly restored after treatment with antithyroid drugs and potassium perchlorate. The physiopathology of amiodarone-induced hypothyroidism is discussed. Withdrawal of amiodarone is advised in the case of both hypothyroidism and hyperthyroidism.

Topics: Aged; Aged, 80 and over; Amiodarone; Antithyroid Agents; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Perchlorates; Potassium Compounds

The antiarrhythmic drug, amiodarone, induces thyroid dysfunction, which is potentially dangerous in cardiac patients. After discontinuation of the drug it takes several months before euthyroidism is restored. The potent antithyroid drug, potassium perchlorate (KClO4), is used successfully to treat amiodarone-induced thyrotoxicosis, but it is less well known as potential treatment in amiodarone-induced hypothyroidism. In this case report we describe the successful use of two courses of KClO4 treatment in a cardiac patient with severe amiodarone-induced hypothyroidism. The mechanisms responsible for the amiodarone-induced hypothyroidism and rationale for the use of KClO4 in this condition are discussed.

Topics: Amiodarone; Humans; Hypothyroidism; Male; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Thyroid Gland

Amiodarone-induced thyrotoxicosis (AIT) occurs most frequently in patients with underlying thyroid disease and is generally believed to be due to the iodine contamination of amiodarone and iodine released by the metabolism of the drug. We and others have suggested that the thyrotoxicosis may also be secondary to amiodarone-induced thyroiditis. To further determine the etiology of AIT, we administered large doses of iodides [10 drops saturated solution of potassium iodide (SSKI) daily] to 10 euthyroid patients long after an episode of AIT believed to be due at least in part to amiodarone-induced thyroiditis. Six of these 10 patients had an abnormal iodide-perchlorate discharge test before SSKI administration, indicating a subtle defect in the thyroidal organification of iodide. During SSKI administration, 6 patients developed marked iodine-induced basal and/or TRH-stimulated serum TSH elevations, 2 had suppressed basal and TRH-stimulated TSH values, and 2 had normal TSH responses compared to SSKI-treated euthyroid subjects with no history of amiodarone ingestion or thyroid disease. Serum T4 and T3 concentrations remained normal and unchanged during SSKI administration in both the AIT patients and control subjects. These results strongly suggest that excess iodine may not be the cause of the hyperthyroidism associated with amiodarone therapy, especially in those patients with probable amiodarone-induced thyroiditis. Furthermore, like patients with a previous history of subacute thyroiditis and postpartum thyroiditis, the present results suggest that some patients with a previous history of AIT may be at risk to develop hypothyroidism when given excess iodine.

Topics: Amiodarone; Female; Humans; Hypothyroidism; Iodine; Iodine Radioisotopes; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Thyrotoxicosis; Time Factors

Postpartum thyroiditis (PPT) is common and occurs in 1.7 to 16.7% of pregnant women, depending upon the study population. Most of these women develop transient hypothyroidism and thyroid function usually returns to normal. We have studied 11 euthyroid women with a previous history of PPT to determine the incidence of subtle defects in thyroid function measured by iodide-perchlorate (I-ClO4) discharge tests and TRH tests and to determine whether these women would develop iodide-induced hypothyroidism. Seven (64%) had positive I-ClO4 discharge tests and 5 (46%) had an abnormally high TSH response to TRH. Thyroid antimicrosomal and antithyroid peroxidase were positive in 8 women (73%) with a previous episode of PPT. The administration of pharmacological amounts of iodide (10 drops of saturated solution of potassium iodide daily) for 90 days to these 11 women resulted in elevated basal and TRH stimulated serum TSH concentrations in 8 (72.7%) compared to TSH values during iodide administration to women who had never been pregnant. Antimicrosomal and antithyroid peroxidase concentrations did not change during iodide administration. These findings strongly suggest that euthyroid women with a previous episode of PPT have permanent subtle defects in thyroid hormone synthesis and are inordinately prone to develop iodide-induced hypothyroidism, similar to findings previously reported in euthyroid subjects with Hashimoto's thyroiditis, with a previous episode of painful subacute thyroiditis, or previously treated with radioactive iodine or surgery for Graves' disease.

Topics: Adult; Analysis of Variance; Autoantibodies; Cohort Studies; Female; Humans; Hypothyroidism; Iodide Peroxidase; Iodine Radioisotopes; Microsomes; Perchlorates; Potassium; Potassium Compounds; Potassium Iodide; Puerperal Disorders; Thyroid Function Tests; Thyroid Gland; Thyroiditis; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

The binding of vasoactive intestinal peptide (VIP) and stimulation of adenylate cyclase by VIP were studied in intestinal epithelial cells during hypothyroidism. Experimental hypothyroidism was induced in rats by the administration of KC10(4). The binding capacity, but not the affinity, of VIP receptors decreased in the hypothyroid rats. Besides, the stimulation of cyclic AMP production by VIP was also diminished in cells from hypothyroid rats. These observations indicate a decrease of the responsiveness of intestinal epithelial cells to VIP in the hypothyroid status, suggesting a role of the peptide in the pathophysiologic mechanism of intestinal manifestations during hypothyroidism.

Topics: Animals; Cyclic AMP; Epithelium; Hypothyroidism; Intestinal Mucosa; Intestines; Kinetics; Male; Perchlorates; Potassium; Potassium Compounds; Rats; Rats, Inbred Strains; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

We report a case of a patient with hypothyroidism due to amiodarone. The short-term administration (1 g/die for 10 days) of potassium perchlorate (KClO4) led to normalization of serum thyroid hormone concentrations and marked reduction of thyrotropic hormone. The reduction of KClO4 (400 mg/die) and its following withdrawal led to reappearance of hypothyroidism signs. No side-effects or toxic reactions occurred during KClO4 therapy. This anion competitively inhibits thyroid iodide transport, reducing intrathyroidal iodide content and removing thyroid hormone synthesis inhibition. We suggest KClO4 therapy when amiodarone-associated hypothyroidism impairs a pre-existent cardiac disease and when a quick restoration of euthyroidism is necessary. Nevertheless, we emphasize that its effect can be transitory in cases of short-term treatment or low doses.

Topics: Aged; Aged, 80 and over; Amiodarone; Female; Humans; Hypothyroidism; Perchlorates; Potassium; Potassium Compounds; Thyroid Gland

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidism was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.

Topics: Adult; Aged; Female; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Predictive Value of Tests; Prognosis; Thyroid Function Tests; Thyroid Hormones; Thyrotropin

Topics: Adult; Amiodarone; Female; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Male; Perchlorates; Plasmapheresis; Potassium; Potassium Compounds; Propylthiouracil; Thyroid Hormones; Thyroidectomy; Thyroxine

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.

Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Female; Humans; Hypothyroidism; Male; Middle Aged; Perchlorates; Potassium; Potassium Compounds; Thyrotropin; Thyroxine; Time Factors

In this study we investigated further the antigoitrogenic effect of ClO4 in rats on a low iodine diet (LID) and 6-propyl-2-thiouracil (PTU). The thyroid weight of rats on the mixed goitrogen was initially similar to that of animals on PTU, decreasing to values obtained in rats treated with ClO4 alone by 10 days. Despite the differences in thyroid weight, rats treated during an identical period with PTU or mixed goitrogen develop hypothyroidism to a comparable degree as far as can be assessed by the thyroidal 127I content, plasma T4, T3 and TSH concentrations, and pituitary TSH content. Moreover, it was observed that there were differences in plasma insulin and glucose levels in these hypothyroid animals. The plasma insulin and glucose levels of rats on PTU are comparable to those found in control rats. In rats on mixed goitrogen, both plasma insulin and glucose levels are initially maintained within the normal ranges, and then decline over the subsequent days of treatment. Within the treatment period studied here, plasma insulin and glucose levels were higher for rats on PTU than for animals on ClO4, PTU + ClO4, or thyroidectomized (Th) animals. We have obtained further evidence of the hypothyroid state of rats on these goitrogen regimens based on measurements of pituitary and plasma GH levels and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). The PTU-treatment decreased the liver alpha-GPD activity to a comparable degree to that of mixed goitrogen. Moreover, both PTU + ClO4 and PTU-treatment resulted in a state of hypothyroidism intense enough to induce effects on growth, and plasma and pituitary GH levels comparable to that of Th animals. However, the values for rats on mixed goitrogen appear to be below the PTU data. The present findings appear to be consistent with the view that TSH is not the unique factor determining the size of the resulting goitre. The results are discussed in relation to the hypothesis that: 1) the antigoitrogenic effect of ClO4 could be associated with changes in the ability of the thyroid tissue to bind TSH, or with a step beyond TSH binding, and 2) the different endocrine and metabolic states of rats on PTU or PTU + ClO4, shown by their different plasma insulin, GH and glucose levels, may play an important role in determining the thyroid weight response to TSH.

Topics: Animals; Blood Glucose; Goiter; Growth Hormone; Hypothyroidism; Insulin; Male; Organ Size; Perchlorates; Potassium; Potassium Compounds; Propylthiouracil; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Hormones