The substance basis of Poria ameliorates hypothyroidism other than hyperthyroidism based on proteomics and metabolomics.

Integrated metabolomics and proteomics analysis was carried out to study the effects of Poria and its split components (volatile oil, triterpenoid, oligosaccharide, amino acid, and crude polysaccharide) on rats of normal physiological model, hyperthyroidism model, and hypothyroidism model to explore the substance basis of Poria for hypothyroidism from the perspective of a holistic view in substance and energy metalism. The key pathways regulating substance and energy metabolism were screened, encompassing tricarboxylic acid cycle pathway, glycolysis/ gluconeogenesis pathways, biosynthesis of amino acid pathway, fatty acid biosynthesis pathway, pentose phosphate pathway, peroxisome proliferator-activated receptors pathway, etc Poria and its split components showed promoting effects on substance and energy metabolism in normal model, while showed amelioration effects on hypothyroidism model at different degrees, and had no significant improvement effects on hyperthyroidism in rats. Volatile oil, triterpenoid, and crude polysaccharide from Poria were regarded as substance basis of Poria ameliorating hypothyroidism other than hyperthyroidism. This work also revealed the feasibility of metabolomics and proteomics analysis to elucidate the effective substance basis of traditional Chinese medicine from a new viewpoint based on its effects on substance and energy metabolism.

Role of Selenium Intake for Risk and Development of Hyperthyroidism.

Purpose: To investigate the importance of dietary selenium (Se) for hyperthyroidism. Methods: We performed a more in-depth analysis of a large cross-sectional study of 6152 participants from two counties within the Shaanxi Province, China. These counties are characterized by different habitual Se intake. We investigated the effects of a different dietary Se supply (0.02, 0.18, 0.6, or 2.0 ppm Se) on disease development in a mouse model of Graves disease (GD). Results: The cross-sectional study revealed a comparable prevalence of hyperthyroidism, irrespective of Se intake, in both counties. However, an unexpected sex-specific difference was noted, and Se deficiency might constitute a risk factor for hyperthyroidism, especially in males. In a mouse model, pathological thyroid morphology was affected, and greater Se intake exerted some protecting effects on the pathological distortion. Circulating thyroid hormone levels, malondialdehyde concentrations, total antioxidant capacity, and the titer of GD-causing TSH receptor autoantibodies were not affected by Se. Expression analysis of the transcripts in the spleen indicated regulatory effects on genes implicated in the immune response, erythropoiesis, and oxygen status. However, the humoral immune response, including the CD4/CD8 or T-helper 1/T-helper 2 cell ratio and the concentration of regulatory T cells, was similar between the experimental groups, despite the difference in Se intake. Conclusions: Our data have highlighted a sexual dimorphism for the interaction of Se and thyroid disease risk in humans, with indications of a local protective effects of Se on thyroid gland integrity, which appears not to be reflected in the circulating biomarkers tested.

Cyclovirobuxinum D alleviates cardiac hypertrophy in hyperthyroid rats by preventing apoptosis of cardiac cells and inhibiting the p38 mitogen-activated protein kinase signaling pathway.

OBJECTIVE: To investigate the underlying mechanisms of cyclovirobuxinum D (Cvb-D) on alleviating cardiac hypertrophy in rats. METHODS: Sprague-Dawley rats were randomly divided into 5 groups: control group; levothyroxine-induced cardiac hypertrophy group (model); levothyroxine-induced cardiac hypertrophy + Cvb-D group (Cvb-D); levothyroxine-induced cardiac hypertrophy + captopril group (captopril); levothyroxine-induced cardiac hypertrophy + SB203580 group (SB203580), n=10 for each group. Rats were daily administered the respective drugs continuously for14 days by gastric gavage. A rat model of cardiac hypertrophy was established by intraperitoneal injection of levothyroxine to investigate whether Cvb-D protects against cardiac hypertrophy by inhibiting the p38 mitogen-activated protein kinase (MAPK) signaling pathway and preventing apoptosis of cardiac cells. RESULTS: Treatment with Cvb-D significantly deceased left ventricle hypertrophy, improved the histopathology, hemodynamic conditions, and cardiac function in rats with cardiac hypertrophy. Compared with the normal control group, in rats with cardiac hypertrophy, expression of bax in the heart and phospho-p38 MAPK protein levels were significantly up-regulated (P<0.01 or 0.05), whereas the bcl-2 protein level was down-regulated (P<0.01). In contrast, Cvb-D treatment reversed the changes in bax and phospho-p38 MAPK protein levels but increased the bcl-2 protein level (P<0.01 or 0.05), and these effects were similar to those of captopril and SB203580 (a specific p38MAPK inhibitor) treatment. Furthermore, both Cvb-D, captopril and SB203580 reduced mRNA expression of p38α, p38ß, c-fos, and c-jun mRNA, and Cvb-D had a stronger effect (P<0.01). CONCLUSION: These results demonstrate that Cvb-D protects against cardiac hypertrophy, which is possibly mediated by prevention of cardiac cell apoptosis and inhibition of the p38MAPK signaling pathway.

Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat.

Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth.

Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing.

Curcumin differentially regulates the expression of superoxide dismutase in cerebral cortex and cerebellum of L-thyroxine (T4)-induced hyperthyroid rat brain.

The present investigation was aimed to elucidate the effect of curcumin on lipid peroxidation (LPx) and superoxide dismutase (SOD) in L-thyroxine (T4)-induced oxidative stress in cerebral cortex and cerebellum of rat brain. Elevated level of LPx in cerebral cortex declined to control level on supplementation of curcumin to T4-treated rats. On the other hand, unaltered LPx level in T4-treated rats showed a significantly decreased level of LPx on supplementation of curcumin. The increased activity of SOD and translated products of SOD1 and SOD2 in cerebral cortex of T4-treated rats was ameliorated on supplementation of curcumin. The decreased activity of SOD and protein expression of SOD1 in cerebellum of T4-treated rats were ameliorated on administration of curcumin. On the other hand, SOD2 expression was not influenced either by T4-treated or by curcumin supplementation to T4-treated rats. Results of the present investigation reveal that the regulation of expression of SOD by curcumin in different regions (cerebral cortex and cerebellum) of rat brain is different under hyperthyroidism.

Vitamin E management of oxidative damage-linked dysfunctions of hyperthyroid tissues.

INTRODUCTION: Thyroid hormones affect growth, development, and metabolism of vertebrates, and are considered the major regulators of their homeostasis. On the other hand, elevated circulating levels of thyroid hormones are associated with modifications in the whole organism (weight loss and increased metabolism and temperature) and in several body regions. Indeed, tachycardia, atrial arrhythmias, heart failure, muscle weakness and wasting, bone mass loss, and hepatobiliary complications are commonly found in hyperthyroid animals and humans. RESULTS: Most thyroid hormone actions result from influences on transcription of T3-responsive genes, which are mediated through nuclear receptors. However, there is significant evidence that tissue oxidative stress underlies some dysfunctions produced by hyperthyroidism. DISCUSSION: During the last decades, increasing interest has been turned to the use of antioxidants as therapeutic agents in various diseases and pathophysiological disorders believed to be mediated by oxidative stress. In particular, because elevated circulating levels of thyroid hormones are associated with tissue oxidative injury, more attention has been paid to explore the application of antioxidants as therapeutic agents in thyroid related disorders. CONCLUSIONS: At present, vitamin E is among the most commonly consumed dietary supplements due to the belief that it, as an antioxidant, may attenuate morbidity and mortality. This is due to the results of numerous scientific studies, which demonstrate that vitamin E has a primary function to destroy peroxyl radicals, thus protecting polyunsaturated fatty acids biological membranes from oxidative damage. However, results are also available indicating that protective vitamin E effects against oxidative damage can be obtained even through different mechanisms.

[Application of herbal medicine alba in treatment of patients with the pathology of thyroid].

High prevalence of hyperplastic and autoimmune diseases of thyroid in Ukrainian population is determined by endemic deficit of iodine and selenium. The aim of this research was to assess the place of biologically-active additions on the basis of herbal material containing an iodine and selenium in prophylaxis and treatment of thyroid pathology. During the six month period 55 patients received herbal preparation Alba twice a day. The levels of TSH, volume of thyroid, the sizes of nodular goiter (ultrasound investigation) were measured before and at the end of the investigation. The levels of thyroid stimulating antibodies to TSH receptor (AB-r TSH) were evaluated in patients with hyperthyroidism. The results of Alba application showed that in patients with thyroid pathology (diffuse nontoxic goiter, hyperthyroidism and chronic thyroiditis) it was possible to reduce the volume of thyroid, normalize its function, and decrease the level of AB-r TSH in diffuse toxic goiter. We also found approximately 20 % shortening of the time needed to get target level of TSH and finally the duration of treatment of thyrotoxicosis.

[Herbs for calming liver and suppressing yang in treatment of hyperthyroidism with hyperactive liver yang: herbal effects on lymphocyte protein expression].

OBJECTIVE: To observe the herbal effects on hyperthyroidism patients with syndrome of hyperactivity of liver-Yang by method for calming the liver and suppressing Yang and investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of the curative mechanisms of calming the liver and suppressing Yang treatment. METHOD: A total of 48 hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were randomly divided into treatment group and control group. The treatment group was treated by method for calming the liver and suppressing Yang in accordance with traditional Chinese medicine (TCM) and the control group with thiamazole tablets for three periods of treatment The therapeutic effects, the score of TCM symptom, electrocardiogram (P wave), thyroid hormones and ultrasound were observed in both groups before and after the treatment. The side effects in the treatment course were observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrphoresis and matrix assisted laser desorption/ionizaton time-of-flight mass spectrometry. RESULT: The treatment group has the effect on stepping down the heart rate, cutting down the P wave amplitude changes, regulating the level of thyroid hormones and decreasing the volume of thyromegaly. There are not statistically significant between the treatment group and control group. However, the treatment group has obviously better effect on regulating TCM symptom and decreasing the side reaction than the control group (P<0.05). There are not statistically significant on the total effective between the treatment group and control group. The average spots in lymphocyte for normal people, before and after treating hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were (429 +/- 31), (452 +/- 28) and (437 +/- 36) spots respectively. Eight down-regulated protein expressions and 11 up-regulated protein expressions were obtained in the hyperthyroidism patients with syndrome of hyperactivity of liver-Yang and normal people. Five strengthened expressions of protein were also obtained in 8 down-regulated expressions of protein and 8 lower expressions of protein in 11 up-regulated expressions of protein before and after treating the migraine patients with syndrome of hyperactivity of liver-Yang. Ten of the total 8 differential protein spots were successfully identified by MALDI-TOF-MS. The functions of these proteins were involved in metabolism associated, transportation, antioxidation, sigal transduction and immume associated protein, etc. according to information provided by NCBI and MSDB database. CONCLUSION: In this study, the TCM complex prescription with herbs for calming the liver and suppressing Yang can regulate the thyroid hormones, improves TCM symptoms, and decrease the adverse reaction. It can possibly regulate lymphocyte protein expression.

Transient cytotoxicity of ¹³¹I beta radiation in hyperthyroid patients treated with radioactive iodine.

BACKGROUND & OBJECTIVES: Radioiodine ( 131 I) or radioactive iodine in low doses is used worldwide as the first line of management in the treatment of hyperthyroidism. Information is available on the extent and severity of cell damage after a high dose radioiodine ( 131 I) therapy for thyroid cancer, but information is scanty on its cellular effects, its extent and severity of cell damage after a low dose 131 I therapy. The present investigation was aimed to study the cytotoxic effects of a low dose 131 I therapy in varying doses as is normally being used in routine clinical practice in the treatment of various forms of hyperthyroidism. METHODS: Peripheral blood lymphocytes were analyzed in 32 hyperthyroid patients. All of them received 131 I in the form of sodium iodide solution orally. Blood lymphocytes were studied for the presence of chromosomal aberrations (CA) and micro nucleus (MN) using micronucleus assay. Blood samples of these patients were drawn prior to the treatment, on 7 th and 30 th days after the treatment. RESULTS: The results indicated a positive relationship between 131 I dose, CA and MN frequency. A statistically significant increase in CA and MN frequency in day 7 post- therapy and a decrease in mean levels of CA and MN on day 30 post-therapy were observed when compared to pre-therapy. INTERPRETATION & CONCLUSIONS: This study showed that the cytogenetic damage induced by 131 I in low doses i.e., less than 555MBq was minimal and reversible. Patients can be motivated to undertake this safe and easy procedure as a first line of therapy in the treatment of hyperthyroidism.

Two unusual cases of intractable hyperthyroidism responsive to octreotide: Munchausen syndrome or not?

BACKGROUND: The effective treatment for patients with resistant hyperthyroidism is difficult. METHODS: In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide. RESULTS: Cases 1 and 2 were both middle-aged women. They presented thyrotoxicosis with a low serum concentration of TSH and thyroidal radioactive iodine uptake (RAIU). The underlying causes, such as thyroiditis, metastatic thyroid cancer and struma ovarii were explored. Iodine-induced hyperthyroidism, particularly factitious hyperthyroidism was highly suspected, but there was no direct evidence to establish these diagnoses. In spite of good compliance, their thyrotoxicosis could not be controlled with large doses of PTU or MMI. ß-blocker, methylprednisolone, radio-iodine therapy and even thyroidectomy were all attempted and failed. Short-acting octreotide was first administered to case 1 and then to case 2. Thyroid function improved greatly within 3 days in both cases. The doses of octreotide were tapered down to twice a week with consistent efficacy. During the follow-up periods, case 1 required octreotide 0.1mg twice per week and case 2 is on thyroid replacement therapy due to hypothyroidism. The recurrences of hyperthyroidism in both cases were again rapidly controlled with the increased dose of octreotide in case 1 and re-started the usage of octreotide in case 2. CONCLUSIONS: The etiology of thyrotoxicosis in these 2 cases is not clear. In the absence of struma ovarii or wide-spread follicular thyroid cancer, factitious hyperthyroidism due to Munchausen syndrome should be considered first. The efficacy of the off-label use of octreotide in hyperthyroidism was highly effective (only) in these 2 cases.

[Clinical effect of prunrllae oral solution in treating hyperthyrea].

OBJECTIVE: To observe the clinical effects of prunrllae oral solution in treating hyperthyrea. METHOD: 56 cases with hyperthyrea were randomized into two groups; group A1 was treated by classic method, B1 was treated by classic method combined with prunrllae oral solution. The size, vessel caliber of thyroidea, volume of blood flow and blood flow rate pre-and post-treatment were measured by color supersonic, meanwhile, 20 normal thyroidea were measured as control group. RESULT: The size and vessel caliber of thyroidea of the two groups pre-treatment were obviously bigger than those of the control group, the volume of blood flow and blood flow rate were obviously slower than those of the control group (P < 0.001), the sizes of thyroidea of the two groups became smaller, especially the group B1 was more obvious, and there was no significant difference in the size of thyroidea between group B1 and control group. CONCLUSION: It is indicated that combined treatment of traditional Chinese medicine (prunrllae oral solution) and western medicine is superior to western medicine in treating hyperthyrea.

[Differentiated thyroid gland carcinoma in a scintigraphically hot thyroid nodule: diagnosis and interdisciplinary therapeutic management]. / Differenziertes Schilddrüsenkarzinom in einem szintigraphisch heissen Schilddrüsenknoten: Diagnostik und interdisziplinäres therapeutisches Vorgehen.

A hyperfunctioning differentiated thyroid carcinoma is a rare occurrence. Nevertheless, this diagnosis must be considered in a scintigraphically hot nodule if there is a clinical or sonographic suggestion of malignancy. The case of a 57-year old patient with hyperthyreosis and a scintigraphically hot thyroid nodule is presented. Further evaluation led to the diagnosis of a differentiated thyroid carcinoma with extensive lymph node and pulmonary metastases (pT2b, pN1b, pM1). The scintigraphically hot nodule corresponded to the primary tumor, whereas scintigraphic detection of the lymph node metastases was only possible postoperatively. Extensive resection of the lymph node metastases was achieved by the intraoperative application of a gamma probe (2nd operation). This allowed sufficient uptake of radioiodine in the pulmonary metastases for their detection and subsequent devitalisation by radioiodine therapy. Complete elimination of all tumour tissue was documented at a control follow-up after six months. Gamma probe-guided surgery may allow for additional removement of non-palpable lymph node metastases. In selected cases this may optimize the surgical results and thereby facilitate the subsequent radioiodine elimination of advanced differentiated thyroid carcinomas.

[Multi-modality therapy concept in metastatic follicular thyroid carcinoma with hyperthyroidism]. / Multimodales Therapiekonzept bei metastasiertem folliculären Schilddrüsencarcinom mit Hyperthyreose.

The coincidence of hyperthyroidism and thyroid carcinoma seldom occurs. Only few reports on functionally metastases of thyroid carcinoma have been published. We report a 59-year-old man who underwent subtotal thyroidectomy for toxic nodular goiter. Histological examination revealed a follicular thyroid carcinoma. After thyroidectomy and cervical lymphadenectomy the patient developed a strong hyperthyreosis. Scintigraphy showed strong radioiodine uptake in the sacrum. De-bulking resection of the metastasis followed by high-dose radioiodine treatment was performed. After radioiodine therapy the patient became euthyroid. Treatment of hyperthyreosis in metastatic thyroid cancer requires a multimodal therapeutic concept.

Identification of IGF-I in the calvarial suture of young rats: histochemical analysis of the cranial sagittal sutures in a hyperthyroid rat model.

Premature closure of cranial sutures has been known as one of the complications of juvenile or congenital hyperthyroidism. Thyroid hormone is an anabolic agent for bone formation in the early stages of childhood development. In children, excess thyroid hormone acts as an acceleration factor for the skeletal bone, whereas in adult hyperthyroidism, it causes bone mineral loss due to the high turnover rate of bone formation and consequently bone resorption. In addition, there are numerous literature descriptions concerning the interactions among bone metabolism, hormones, and growth factors, among which insulin-like growth factor I (IGF-I) is the most abundantly found growth factor in osteoblasts and in bone models in vivo. We therefore investigated whether or not the cranial sutures show accelerated closure and how the local growth factors or cytokines participate and function in local bone metabolism after administration of exogenous excess thyroid hormone in a rat model. A total of 60 female Wistar rats, aged 10 days, were divided into two groups, the triiodothyronine (T3)-treated group (n = 30, T3 0.1 microgram/gm of body weight per day) and the control group (n = 30, saline vehicle only), and were maintained and subsequently sacrificed at 15, 30, and 60 days. The parameters of cranial width derived from the morphologic measurements of the skull indicated that the lambda-asterion distance at 30 days and the pterion-bregma distance at 60 days in the T3-treated group were significantly decreased compared with those of the control group. Furthermore, the fluorescent histologic findings showed fluorescent labeling with no interruption along the suture edges, suggesting continuous bone formation, and displayed narrowing of the suture gap of the sagittal suture in the T3-treated group. Tartrate resistant acid phosphatase staining showed very little osteoclastic activity in the sagittal suture, especially in the T3-treated group. The intensity of immunohistochemical staining of IGF-I was markedly increased in the suture margins of the T3-treated group. There were no significant differences observed either in the skull base measurements or in the histologic and histochemical findings of the skull base or the coronal suture between the groups. More significantly, excess administration of thyroid hormone enhanced the cranial sagittal suture closure; therefore, it was proposed that local IGF-I plays an important role in sagittal sutural bone formation.

Tyrosine content, influx and accumulation rate, and catecholamine biosynthesis measured in vivo, in the central nervous system and in peripheral organs of the young rat. Influence of neonatal hypo- and hyperthyroidism.

The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.

[Phospho-calcium and bone metabolism in hyperthyroidism in adults]. / Le métabolisme phospho-calcique et osseux au cours de l'hyperthyroïdie de l'adulte.

The abnormalities of calcium-phosphorum metabolism observed in hyperthyroidism (tendency to hypercalcaemia with subsequent functional hypoparathyroidism, increase in serum alkaline phosphatase and in hydroxyprolinuria) essentially result from excessive mobilization of bone calcium and phosphates by the thyroid hormones themselves. Histomorphometric studies have shown that the skeletal repercussions of hyperthyroidism are almost constant. There is, in particular, excessive bone remodelling due to increased bone-forming and bone-resorbing cellular activities. However, since bone resorption is quantitatively more stimulated than bone formation, the physiological bone loss is accelerated and is only partly repaired by re-establishment of the normal thyroid function.

The effect of hyperthyroidism induced by thyroideum siccatum on the central nervous system: an electron microscopic study.

Ten adult male rats were administered orally with thyroideum siccatum every day to produce a hyperfunctional state of thyroid hormone. They were examined electron microscopically for the fine structure of the brain. Clinically, experimental rats lost in weight, manifested a hyperactive, irritative attitude, and were in an aggressive state. Electron microscopically, the nerve cells showed a slight increase in the number of mitochondria in the frontal cortex, spiral and petaloid variation of ER in the thalamus. The specific findings in the experimental rats were variations of synapse observed in the frontal and temporal cortex, gyrus hippocampi, and thalamus, centering around the hypothalamus. They included meandering of the presynaptic membrane, formation of vacuoles by the presynaptic membrane, saccate projection of this membrane to the postsynapse, and changes in vacuoles which were torn off and fell into the dendrite. These variations occurred in the synaptic membrane and ER, probably because synthesis of the membrane had been accelerated remarkably by the action of thyroid hormones. They were considered to have brought about abnormalities to the conductive and transmission system. They seemed to be closely related with emotional disturbances and psychic symptoms, since such variations were particularly apparent in the hypothalamus.

Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. II: Bone histomorphometry.

Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.