iThyroid.com

[Calcitonin and parathyroid hormone secretion and calcium metabolism in patients with diffuse toxic goiter during treatment with lithium carbonate]

Author

Petrov NM

Source

Probl Endokrinol (Mosk), 30(1):22-6 1984 Jan-Feb

Abstract

Seventy-six patients (6 males and 70 females) with diffuse toxic goiter, stages I-II, received lithium carbonate as a thyrostatic drug. The drug dose ranged from 900 to 1500 g depending on the degree of the disease clinical symptoms. The treatment with lithium lasted 45 days. Before drug administration and on days 7, 15, 30 and 45 of treatment the content of triiodothyronine (T3), thyroxine (T4) and calcitonin was measured in the thyroid, that of parathyroid hormone (PTH) in the parathyroid gland, and that of thyrotropic hormone (TTH) in the pituitary. The concentration of ionized calcium in the serum, calcium excretion with urine, and tubular calcium reabsorption were measured concurrently. In patients with diffuse toxic goiter treated with lithium, calcium excretion with urine substantially reduced, whereas tubular reabsorption of calcium and phosphates increased. However, serum calcium concentration did not rise, remaining within normal during all the treatment periods. In the author's opinion, this was favoured by two factors: the lithium-induced increase in interstitial calcium absorption on the one hand and compensatory increase in PTH secretion on the other one. The decreased content of thyronines in the hemocirculation (T3, T4), a short-term elevation of TTH and calcitonin elevation in the blood and steady increase in PTH secretion were characteristic features of the time course of the hormonal parameters in patients with toxic goiter treated with lithium.

 

Title

Genistein but not staurosporine can inhibit the mitogenic signal evoked by lithium in rat thyroid cells (FRTL-5).

Author

Takano T; Takada K; Tada H; Nishiyama S; Amino N

Address

Department of Laboratory Medicine, Osaka University Medical School, Japan.

Source

J Endocrinol, 143(2):221-6 1994 Nov

Abstract

Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C. Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells. These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.

 

 

Title

Preliminary observation on the metabolism in spontaneous hereditary diabetic Chinese hamster (Shanyi colony).

Author

Hu M; Wu Y; Wu H

Address

Institute of Metabolism and Endocrinology, Second Affiliated Hospital, Hunan Medical University, Hunan Province, China.

Source

Chin Med J (Engl), 110(9):711-4 1997 Sep

Abstract

OBJECTIVE: To observe the changes of tissue lithium content and its relationship with glucose metabolism in spontaneous hereditary diabetic Chinese hamsters (SHDCH). METHODS: Twenty diabetic and ten normal Chinese hamsters were paired and separated randomly into four groups: controls (C), diabetics (D), controls treated with lithium carbonate (CT) and diabetics treated with lithium carbonate (DT). The lithium carbonate treatment was administrated with drinking water containing lithium carbonate (0.2 mg/ml). Blood glucose levels were determined at 0, 1, 3, 5, 6th month, and insulin levels at 1, 3, 6th month. The lithium contents in liver, kidney and muscles were determined at the end of 6th month, using wet digestion assay and ICP-AES. Concentrations of fructosamine, lactic acid, GPT, BUN were also evaluated. RESULTS: The data showed that in Group D the lithium levels in hepatic tissue were lower than in Group C (P < 0.05), and lithium contents in kidney and muscle also decreased. In Group DT, the lithium contents in tissues were higher than in Group D (P < 0.05) and similar to Group C. Blood glucose levels and fructosamine concentrations decreased while insulin and lactic acid levels did not alter significantly. GPT and BUN levels did not change in both Group CT and Group DT. CONCLUSIONS: There is lithium deficiency in hepatic, renal and muscular tissues from diabetic Chinese hamsters. Low-dose and six-month-treatments of lithium carbonate can improve tissue lithium deficiency and glucose metabolism, and do not damage liver and kidney functions.

 

Title

Lithium orotate in the treatment of alcoholism and related conditions.

Author

Sartori HE

Source

Alcohol, 3(2):97-100 1986 Mar-Apr

Abstract

The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere's syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS)

 

Title

Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism.

Author

Roca RP; Blackman MR; Ackerley MB; Harman SM; Gregerman RI

Address

Department of Psychiatry, Francis Scott Key Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Source

Endocr Res, 16(4):415-47 1990

Abstract

Acute psychiatric illness may be accompanied by transient hyperthyroxinemia. The mechanism of this phenomenon was examined by determining the role of thyrotropin (TSH) in the genesis of this state. Serial measurements of TSH, thyroxine (T4), free T4 index (FT4I), triiodothyronine (T3), and free T3 index (FT3I) were performed in 45 acutely hospitalized patients with major psychiatric disorders. Twenty-two (49%) patients exhibited significant elevations (greater than or equal to 2 SD above mean value of controls) of one or more thyroid hormone (or index) levels. Among depressed patients with elevated FT4I, TSH was higher (p less than .05) on the day of the peak FT4I than on the day of the FT4I nadir. There were significant positive correlations between psychiatric symptom severity and levels of FT4I among both depressed (p less than .01) and schizophrenic (p less than .025) patients. These data show that elevations of T4, FT4I, T3, and FT3I are common among psychiatric inpatients, especially early in their hospitalization, and that levels of thyroid hormones are correlated with severity of psychiatric symptomatology. TSH is higher early in the acute phase of illness and is not suppressed in the face of elevated thyroid hormone levels, a finding that distinguishes this phenomenon from ordinary hyperthyroidism. Elevations of peripheral thyroid hormone levels, particularly among depressed patients, may result from a centrally-mediated hypersecretion of TSH.

 

Title

The effects of lithium therapy on thyroid and thyrotropin-releasing hormone.

Author

Lazarus JH

Address

Department of Medicine, University of Wales College of Medicine, Cardiff, UK.

Source

Thyroid, 8(10):909-13 1998 Oct

Abstract

Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.

 

 

Title

Inhibitory effect of lithium on the release of thyroid hormones from thyrotropin-stimulated mouse thyroids in a perifusion system.

Author

Mori M; Tajima K; Oda Y; Matsui I; Mashita K; Tarui S

Address

The Second Department of Internal Medicine, Osaka University Medical School, Japan.

Source

Endocrinology, 124(3):1365-9 1989 Mar

Abstract

We studied the effect of lithium on the release of T3, T4, and cAMP from perifused mouse thyroids and on cAMP content in thyroid pieces. Lithium significantly inhibited T3 and T4 release from TSH-stimulated mouse thyroids. This inhibitory effect on thyroid hormone release was dependent on the concentration of lithium. Under continuous stimulation with TSH and 3-isobutyl-1-methylxanthine, both cAMP release and cAMP content were significantly decreased by lithium. In addition, we studied the effect of lithium on (Bu)2cAMP-stimulated thyroid hormone release. T3 and T4 release was stimulated by (Bu)2cAMP in a similar way to TSH. Lithium significantly inhibited (Bu)2 cAMP-stimulated T3 and T4 release from perifused mouse thyroids. These results suggest that lithium inhibits the action of TSH in the thyroid gland by both suppression of cAMP production and inhibition at a step beyond cAMP generation.

 

Title

Influence of lithium and exercise on serum levels of copper and zinc in rats.

Author

C´ordova A; Escanero JF

Address

Departamento de Fisiolog´ia, Colegio Universitario de Soria, Universidad de Valladolid, Soria, Spain.

Source

Rev Esp Fisiol, 47(2):87-90 1991 Jun

Abstract

The variations in serum levels of Cu and Zn induced by exercise in rats undergoing Li therapy are determined. The results show that exercise until exhaustion leads to a reduction in the Li concentration, which is more pronounced in rats subjected to training (to 50% maximum capacity) in the week before the test. The serum levels of Zn and Cu increased significantly with exhaustion in untrained rats, while there were no significant alterations in trained rats, except for serum Zn in those not treated with Li. The modifications in serum induced by exhaustion are lower in rats treated with Li. It is likely that Li and exercise have opposite effects on the tissue distribution of the two ions studied.

Author
    Corrigan FM; Besson JA; Ward 

Address
    Argyll & Bute Hospital, Lochgilphead, U.K.

Source
    Alcohol Alcohol, 26(3):309-14 1991

 Does the following study mean that lithium is involved in calcium/magnesium metabolism? 

 

Title

Role of trace elements Se and Li in drinking water on dental caries experience.

Author

Gauba K; Tewari A; Chawla HS

Address

Post Graduate Institute of Medical Education and Research, Department of Dentistry, Chandigarh, India.

Source

J Indian Soc Pedod Prev Dent, 11(1):15-9 1993 Mar

Abstract

Title

Lithium effects on calcium, magnesium and phosphate in man: effects on balance, bone mineral content, faecal and urinary excretion.

Author

Plenge P; Rafaelsen OJ

Source

Acta Psychiatr Scand, 66(5):361-73 1982 Nov

Abstract

Calcium, magnesium and phosphate metabolism was studied in lithium-treated patients, using a metabolic balance technique. Two groups of patients participated in the study: 1) Patients who were to start on a prophylactic lithium treatment, and 2) Long-term lithium-treated patients whose treatment was to be terminated. Lithium treatment produced a positive balance in both calcium, phosphate and magnesium. By continuous lithium treatment the effect on magnesium wore off, whereas the effect on calcium and phosphate persisted. In urine, lithium induced a decrease in both calcium and phosphate excretion, whereas the excretion of magnesium was increased. Bone mineral content was measured by photon absorption, and lithium treatment resulted in a decrease in bone mineral content occurring within the first 6 months of lithium treatment. In the patients, bioavailability of the Li2CO3 preparation was found to be about 95%, and the patients contained about one 24-h dose of lithium just before the next dose of lithium was administered.

 

Title

Mechanism of lithium action: in vivo and in vitro effects of alkali metals on brain superoxide dismutase.

Author

Shukla GS

Source

Pharmacol Biochem Behav, 26(2):235-40 1987 Feb

Abstract

Intraperitoneal administration of lithium (2 mEq/kg/day) was found to increase the superoxide dismutase (SOD) activity in certain brain regions after 24 hours (2 injections) and 3 days (once a day) of exposure. In vitro addition of wide range of lithium (0.1 to 8 mEq) to enzyme preparation as well activated cortical SOD activity; however, at 10 mEq concentrations an inhibition was observed. The increase in SOD activity did not appear to be region specific as under both in vivo and in vitro conditions lithium enhanced enzyme activity in all the tested brain regions. The effects of intraperitoneal administration of 2 mEq/kg rubidium and cesium for 24 hr (2 injections) and 6 days (once a day) were also studied on central SOD. Both the alkali metals were not found to produce any significant alteration in the cortical enzymic activity. When the in vitro effects of these monovalent alkali metals were tested, only 2 mEq rubidium was found to increase cortical SOD; however, cesium and potassium at similar concentration did not produce any appreciable effects. It appears from the data that lithium-induced increase in brain SOD activity is not an unspecific effect of alkali metals. SOD enzyme disposes cytotoxic superoxide radicals which, if not removed, could impair the normal functioning of cellular membrane and produce a variety of psychedelic compounds as well. The activation of central SOD by lithium would enhance the disposal process of superoxide radicals whose pathological concentrations may be present in affective disorders. The mechanism of lithium-induced activation of SOD, at present, is not known.

 

Title

Putative role for lithium in human hematopoiesis.

Author

Barr RD; Koekebakker M; Brown EA; Falbo MC

Source

J Lab Clin Med, 109(2):159-63 1987 Feb

Abstract

Ingestion of lithium salts increases production of neutrophil granulocytes from the bone marrow in human subjects when the concentration of the ion in blood is within the range 5 to 10 X 10(-4) mol/L. Results of preliminary dose-response experiments appeared to indicate that nanomolar levels of lithium stimulated clonal proliferation of granulocyte precursors from normal bone marrow in vitro, suggesting the possibility that this element may contribute to the physiologic regulation of blood cell formation in humans. The present studies confirm that the influence of lithium on hematopoiesis is evident in vitro at concentrations equivalent to that demonstrable in normal blood (2 to 4 X 10(-7) mol/L). Furthermore, such effects are not cell lineage specific, being observed also in clonogenic cultures of erythroid and eosinophil granulocyte progenitor cells, and the phenomenon attributed to lithium is a property shared with rubidium and cesium salts. These findings point to a role for lithium and its elemental relatives in the biophysical mechanisms involved with the control of human blood cell production.

 

Title

Effect of lithium on hepatic lipid peroxidation and antioxidative enzymes under different dietary protein regimens.

Author

Tandon A; Dhawan DK; Nagpaul JP

Address

Department of Biochemistry, Panjab University, Chandigarh, India.

Source

J Appl Toxicol, 18(3):187-90 1998 May-Jun

Abstract

Lithium in the form of lithium carbonate was administered at a dose level of 1.1 g kg(-1) food to rats fed normal (18% protein), low-protein (LP; 8%) and high-protein (HP; 30%) diets for a period of 1 month. A highly significant (53%) increase in the level of lipid peroxidation (LPO) was observed in protein-deficient rats but this increase was marginal in rats fed an HP diet (18%). Lithium treatment of rats fed a normal diet caused a marked decrease (22%) in LPO. Lithium administration to rats fed an LP diet also reduced the raised levels of LPO to the extent of 16%. Furthermore, lithium treatment normalized the HP-induced increase in the levels of LPO. The activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were reduced significantly in protein-deficient rats. On the other hand, an HP diet caused a decrease in SOD activity only. The activities of GPx and catalase were appreciably enhanced in lithium-treated rats. Lithium treatment to LP-fed rat markedly increased GPx activity and brought the decreased levels of SOD and catalase to within normal limits. Lithium administration to HP-fed rats did not cause any significant alteration in the activities of these antioxidative enzymes.

J Clin Endocrinol Metab 1999 Feb;84(2):499-503

Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism.

Bogazzi F, Bartalena L, Brogioni S, Scarcello G, Burelli A, Campomori A, Manetti L, Rossi G, Pinchera A, Martino E

Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Italy.

Effectiveness of radioiodine for Graves' hyperthyroidism depends also on its intrathyroidal persistence. The latter is enhanced by lithium by blocking iodine release from the thyroid. One hundred ten patients with Graves' hyperthyroidism were randomly assigned to treatment with radioiodine or radioiodine plus lithium, stratified according to goiter size (< or =40 or >40 mL) and evaluated for changes in thyroid function and goiter size, at monthly intervals, for 12 months. Cure of hyperthyroidism occurred in 33 of 46 patients (72%) treated with radioiodine and in 45 of 54 patients (83%) treated with radioiodine plus lithium. The probability of curing hyperthyroidism was higher and its control prompter (P = 0.02) in the radioiodine-plus-lithium group. Patients with < or =40-mL goiters had similar persistence of hyperthyroidism (13%), but lithium-treated patients had hyperthyroidism controlled earlier (P = 0.04). Among patients with >40-mL goiters, hyperthyroidism was cured in 6 of 15 patients (40%) treated with radioiodine alone and in 12 of 16 patients (75%) treated with radioiodine plus lithium (P = 0.07), and cure occurred earlier in the latter (P = 0.05). Goiters shrank in both groups (P < 0.0001), more effectively and promptly (P < 0.0005) in the radioiodine-plus-lithium group. Serum free T4 and T3 levels increased shortly after therapy only in the radioiodine group (P < 0.01). Lithium carbonate enhances the effectiveness of radioiodine therapy, in terms of prompter control of hyperthyroidism, in patients with small or large goiters. In the latter group, lithium also increases the rate of permanent control of hyperthyroidism.

Preoperative treatment of intractable hyperthyroidism with acute lithium administration.

The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests.

Oomen HA, Schipperijn AJ, Drexhage HA

[Lithium therapy and hyperthyroidism: disease caused or facilitated by lithium? Review of the literature apropos of a case of hyperthyroidism preceded by transient hypothyroidism].

Sadoul JL, Kezachian B, Freychet P

Clin Exp Pharmacol Physiol 1998 Oct;25(10):795-9

s

Acute lithium administration impairs the action of parathyroid hormone on rat renal calcium, magnesium and phosphate transport.

Carney S, Jackson P

Faculty of Medicine & Health Sciences, University of Newcastle, New South Wales, Australia.

1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The present study evaluated the acute effect of Li+ on renal electrolyte transport, particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats. 3. The acute administration of Li+ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+ and Mg2+ excretion was only increased in the intact group. Fractional excretion (FE) of Ca2+ and Mg2+ increased from 2.2 +/- 0.2 to 3.5 +/- 0.3% and 12 +/- 2 to 18 +/- 2%, respectively (P < 0.01). 4. In further experiments in TPTX rats, Li+ administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FECa of 3.8 +/- 0.2% was reduced to 1.4 +/- 0.2% and 1.7 +/- 0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li+ an FECa of 4.0 +/- 0.2 was decreased to 2.8 +/- 0.2 and then 1.9 +/- 0.3% with the same PTH concentrations. 5. The inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7 +/- 0.2 vs 1.6-1.8 mmol/L). The FEMg results were comparable. 6. These results demonstrate that Li+ directly inhibits PTH-mediated renal reabsorption of Ca2+ and Mg2+ and also blunts PTH-mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li+ treatment may be a consequence of reduced renal Ca2+ reabsorption.

In previous posts I mentioned my ER reaction to a drug called Fosomax for osteoporosis. My symptoms were like that of a serious thyroid storm, but the blood test indicated a normal TSH level during this attack. This drug is a type sodium and I swear I felt like I was choking to death from salt, I drank gallons of water feeling as if it were necessary to stay alive. No one knows what happened to me medically speaking. I was then put on Paxil to render the attacks they thought to be panic, but I know better and panic attacks don't turn your eyes blood red, raise your BP 50points, Pulse 35points, skin rash, etc. for 5 to 8 hours. It would begin after I would eat, anything with a sodium content over 100mg. would set it off! I have never been so scared, I have been off of Paxil now for 2 months with no problems so far.