methimazole and Hypertrophy

The present study was undertaken to assess the effect of selenium (Se) on hypothyroidism induced by methimazole (MMI) in lactating rats and their pups. Rats were randomly divided into four groups of six each: group I served as a negative control which received standard diet; group II received orally MMI (250 mg L -1 ); group II received both MMI (250 mg L -1 , orally) and Se (0.5 mg/kg of diet); group IV served as a positive control and received Se (0.5 mg Na 2 SeO 3 /kg of diet). Treatments were started from the 14th day of pregnancy until postnatal day 14. In the MMI-exposed group, the body weight of 14-day-old pups diminished compared to controls; besides, a hypertrophy of the thyroid glands was observed. Co-administration of Se through the diet restored these parameters to near normal values. In the MMI-treated group, thyroid iodine contents and plasma thyroid hormone levels significantly decreased, while plasma TSH levels increased in pups and their mothers. These biochemical modifications corresponded histologically to closed follicles, increased vascularity and a reduction in colloid volume. Co-treatment with Se ameliorated these parameters. We concluded that the supplementation of Se in diet had beneficial effects on hypothyroidism during a critical period of life.

Topics: Animals; Antithyroid Agents; Feeding Behavior; Female; Humans; Hypertrophy; Hypothyroidism; Lactation; Male; Maternal Exposure; Methimazole; Pregnancy; Rats; Rats, Wistar; Selenium

Recent studies concerning the association between extraocular muscle (EOM) enlargement in thyroid-associated ophthalmopathy (TAO) and immunological and clinical activity have not been conclusive, probably due to a lack of uniform imaging methods (ultrasonography, computer tomography [CT] or magnetic resonance imaging [MRI]) and difficulties in the determination of EOM volume. The aim of the present study was to examine the significance of EOM enlargement as established by MRI-based volume determination, with reference to proptosis and the presence of autoantibodies, clinical activity and the duration of active disease.. We determined EOM volume using MRI in 15 patients concomitantly with the determination of TSH, thyroid hormones, thyrotropin receptor antibodies (TRab) thyroid peroxidase antibodies (TPOab) and clinical activity score (CAS) at entry. We also established the duration until cessation of clinically active TAO.. All 15 patients had bilateral EOM enlargement, but swelling of orbital fatty tissue was absent. Significant correlations between thickness of musculi rectales and proptosis, values of TRab, CAS, and duration of activity were observed.. Our results support the hypothesis of a role of thyrotropin receptor antibodies in the pathogenesis of TAO and suggest that only EOM enlargement is responsible for proptosis in TAO.

Topics: Adult; Antithyroid Agents; Autoantibodies; Exophthalmos; Female; Graves Ophthalmopathy; Humans; Hypertrophy; Iodide Peroxidase; Magnetic Resonance Imaging; Methimazole; Oculomotor Muscles; Receptors, Thyrotropin; Thyroid Hormones; Thyrotropin

This paper describes the effects of goitrogen-induced hypothyroidism on GH, prolactin and the testis size of rats. Hypothyroidism was caused by lifetime-rearing on goitrogen methimazole (MMI). This condition was brought on by adding 0.025% (Weight/ Volume) MMI to the mother's drinking water immediately after birth. Offspring, after weaning, were given the same food and drinking water as that of the mother until sacrified. Four experimental groups were designed: group 1, CMF (normal rat chow) and tap water; group 2, CMF with 0.025% thyroid powder and tap water; group 3, CMF and tap water containing 0.025% MMI and group 4, CMF with the thyroid powder and tap water containing 0.025% MMI. The rats were killed at 73 days of age after rearing under the 4 conditions described. Pituitary GH and PRL and serum PRL were significantly less in group 3 than in the others. Testis weight was the same for groups 3 (2.51 +/- 0.14 g; Mean +/- SD), 1 (2.76 +/- 0.07 g) and 2 (2.60 +/- 0.06 g). Increased testis weight was noted only in group 4 (3.25 +/- 0.1 g). The ratio of testis to body weight was significantly higher in group 3 than in the other groups. The authors concluded that hypothyroidism causes pituitary dysfunction with GH and PRL deficiency and also causes testis enlargement with age.

Topics: Animals; Antithyroid Agents; Body Weight; Female; Growth Hormone; Hypertrophy; Hypothyroidism; Male; Methimazole; Organ Size; Pituitary Gland; Pregnancy; Prolactin; Rats; Rats, Wistar; Testis; Thyrotropin; Thyroxine

We have investigated changes in the synthesis and localization of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during the induction of goitre in iodine-deficient rats, and during the subsequent involution of the gland following goitrogen withdrawal. Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. After twelve weeks the goitrogenic stimuli were removed and thyroids examined 4 weeks later. Circulating T4 levels became undetectable within two weeks of goitrogen administration while thyroid weight had increased five-fold. The thyroids continued to increase in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I mRNA showed a relative decline with prolonged goitrogen administration, and following thyroid involution the hybridization signal was similar to that seen in control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs were all present in growth-quiescent, control thyroids and those encoding IGFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroid involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and immunohistochemistry respectively, were found to co-localize predominantly in follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and peptide were localized to the parafollicular cells (C-cells) which were increased in number during involution. The results suggest that an increased expression of IGF-1 may contribute to early goitre formation, but that a relative increase in the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5 by C-cells suggests that it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.

Topics: Animals; Carrier Proteins; Gene Expression Regulation, Neoplastic; Goiter; Hyperplasia; Hypertrophy; Immunoenzyme Techniques; In Situ Hybridization; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor I; Male; Methimazole; Rats; Rats, Wistar; RNA, Messenger; Thyroid Gland; Thyroxine

It has been argued that the increase in size of the pituitary of castrated cockerels is due to hypertrophy of gonadotropic cells, some of which have been converted from other pituitary basophils. A counter argument could maintain that new gonadotropes are recruited from chromophobes that are replaced by mitotic division of undifferentiated cells. Since mitosis requires thymine for DNA replication, labelled thymine (H3-thymidine) incorporated in DNA identifies new cell formation. On this basis, the chicken pituitary does not produce enough new cells to account for the size differences associated with castration or methimazole treatment.

Topics: Adrenocorticotropic Hormone; Animals; Autoradiography; Chickens; DNA Replication; Growth Hormone; Hypertrophy; Male; Methimazole; Mitosis; Orchiectomy; Pituitary Gland; Prolactin; Testis; Thymidine; Thyroid Gland

By means of morphological, morphometrical and autoradiographical methods restorative processes in the parathyroid glands in 41 euthyroid and in 41 hypothyroid rats have been studied during 1-24 days after mechanical trauma of the glands or after hemithyroparathyroidectomy. Seven hypothyroid and 7 euthyroid rats serve as a control. Hypothyroidism is produced with daily injection of mercazolil (6 mg/kg) 3 weeks before the operation and during the time of the experiment. In nonoperated hypothyroid rats development of hypertrophy in parathyrocytes is noted. Prolonged injection of mercazolil weakens (posttraumatic regeneration) or completely suppresses (compensatory hypertrophy) mitotic activity of the glandular cells (in comparison with the euthyroid animals). Manifestation of hypertrophy in parathyrocytes of the hypothyroid rats in comparison with the corresponding control is also less, than against the background of euthyreosis.

Topics: Animals; Hyperplasia; Hypertrophy; Hypothyroidism; Male; Methimazole; Mitosis; Parathyroid Glands; Rats; Thyroidectomy

Topics: Adenocarcinoma; Adenoma; Animals; Female; Hyperplasia; Hypertrophy; Male; Methimazole; Neoplasms; Rats; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms