Decreased thyroid hormone signaling accelerates the reinnervation of the optic tectum following optic nerve crush in adult zebrafish.

The regenerative capacity of the adult mammalian central nervous system (CNS) is poor and finding ways to stimulate long distance axonal regeneration in humans remains a challenge for neuroscientists. Thyroid hormones, well known for their key function in CNS development and maturation, more recently also emerged as molecules influencing regeneration. While several studies investigated their influence on peripheral nerve regeneration, in vivo studies on their role in adult CNS regeneration remain scarce. We therefore investigated the effect of lowering T3 signaling on the regeneration of the optic nerve (ON) following crush in zebrafish, a species where full recovery occurs spontaneously. Adult zebrafish were exposed to iopanoic acid (IOP), which lowered intracellular 3,5,3'-triiodothyronine (T3) availability, or to the thyroid hormone receptor ß antagonist methylsulfonylnitrobenzoate (C1). Both treatments accelerated optic tectum (OT) reinnervation. At 7days post injury (7dpi) there was a clear increase in the biocytin labeled area in the OT following anterograde tracing as well as an increased immunostaining of Gap43, a protein expressed in outgrowing axons. This effect was attenuated by T3 supplementation to IOP-treated fish. ON crush induced very limited cell death and proliferation at the level of the retina in control, IOP- and C1-treated fish. The treatments also had no effect on the mRNA upregulation of the regeneration markers gap43, tub1a, and socs3b at the level of the retina at 4 and 7dpi. We did, however, find a correlation between the accelerated OT reinnervation and a more rapid resolution of microglia/macrophages in the ON and the OT of IOP-treated fish. Taken together these data indicate that lowering T3 signaling accelerates OT reinnervation following ON crush in zebrafish and that this is accompanied by a more rapid resolution of the inflammatory response.

Efficacy of iopanoic acid for treatment of spontaneous hyperthyroidism in cats.

Iopanoic acid is an iodine containing oral cholecystographic agent that has been used to treat hyperthyroidism in humans and has recently been evaluated in an experimental model of feline hyperthyroidism. The aim of this study was to evaluate the efficacy of iopanoic acid in cats with spontaneous hyperthyroidism. Eleven cats were included in the study. Eight were treated initially with 50mg orally q 12h and three were treated with 100mg orally q 12h. Prior to treatment (baseline) and at 2, 4, and 12 weeks of treatment, owner questionnaires, physical exams, complete blood count, biochemistry analyses, and T(3) and T(4) concentrations were evaluated. The mean serum T(3) concentration decreased with treatment at all time periods compared to baseline. Mean T(4) concentrations were increased at weeks 4 and 12 compared to baseline. Five cats had a partial response during the initial 4 weeks of therapy, but the effects were transient and no significant improvements in clinical signs or physical exam findings were noted at any time period. Results suggest that iopanoic acid may be beneficial for acute management of thyrotoxicosis in some cats, but is not suitable for long-term management.

Effects and safety of iopanoic acid in cats administered levothyroxine.

The purpose of this study was to evaluate the safety and effect of iopanoic acid in 13 cats with hyperthyroidism induced by daily subcutaneous administration of 25microg/kg levothyroxine for a period of 42 days. On day 28 of levothyroxine administration, cats were randomly allocated to receive treatment twice daily with a placebo (control group; n=4), 50mg iopanoic acid (low dose group; n=5), or 100mg iopanoic acid (high dose group; n=4) for 14 days. Compared to the control group, T(3) concentrations were significantly decreased in both the low dose and high dose groups on days 35 and 42. T(3) concentrations in the low dose and high dose groups at days 35 and 42 were not different from day -8. The effect of iopanoic acid on clinical signs of hyperthyroidism was less apparent. Further clinical studies evaluating the long-term effect in cats with spontaneous hyperthyroidism are warranted.

Pharmacodynamic effect of iopanoic acid on free T(3) and T(4) levels in amiodarone-induced thyrotoxicosis.

We describe the effects of iopanoic acid on daily levels of free triiodothyronine (FT(3)) and free thyroxine (FT(4)) in a patient with progressive type II amiodarone-induced thyrotoxicosis (AIT) who was undergoing thyroidectomy. The patient was a 59-year-old man who was undergoing amiodarone therapy while awaiting cardiac transplantation; the use of beta blockers and corticosteroids to control the AIT was contraindicated in this patient. Prior to thyroidectomy, the patient was started on iopanoic acid at 1.0 g twice a day; in response to gastrointestinal side effects, the dosage was subsequently reduced to 0.5 g twice a day. The patient responded to iopanoic acid with a rapid decrease in his FT(3) level and slight increase in his FT(4) level. This control of thyrotoxicosis allowed for an uneventful thyroidectomy, which was later followed by successful cardiac transplantation. Based on our findings in this single case, we believe that iopanoic can be used to rapidly lower FT(3) levels and to treat symptoms of thyrotoxicosis in a preoperative setting. We also discuss the different pharmacodynamic effects that iopanoic acid has on FT(3) and FT(4) levels.

Amiodarone-induced thyrotoxicosis. A review.

Amiodarone (AM), a potent class III anti-arrhythmic drug, is an iodine-rich compound with a structural resemblance to thyroid hormones triiodothyronine (T3) and thyroxine (T4). At the commonly employed doses, AM causes iodine overload up to 50-100 times the optimal daily intake, which may be responsible of a spectrum of effects on thyroid function often counterbalancing its heart benefits. Although most patients on chronic AM treatment remain euthyroid, a consistent proportion may develop thyrotoxicosis (AM-induced thyrotoxicosis, AIT) or hypothyroidism. AIT is more prevalent in iodine-deficient areas and is currently subdivided in two different clinico-pathological forms (AIT I and AIT II). AIT I develops in subjects with underlying thyroid disease, and is caused by an exacerbation by iodine load of thyroid autonomous function; AIT II occurs in patients with no underlying thyroid disease and is probably consequent to a drug-induced destructive thyroiditis. Mixed or indeterminate forms of AIT encompassing several features of both AIT I and AIT II may be also observed. The differential diagnosis between AIT I and AIT II (which is important for the choice of the appropriate therapy) is currently made on radioiodine uptake (RAIU), which may be high, normal or low but detectable in AIT I, while is consistently very low or undetectable in AIT II and on colour-flow Doppler sonography (CFDS) showing normal or increased vascularity in AIT I and absent vascularity in AIT II. Quite recently, studies carried out in our Units at the University of Cagliari (Italy) showed that sestaMIBI thyroid scintigraphy may represent the best single test to differentiate AIT I (showing increased MIBI retention) from AIT II (displaying no significant uptake). Treatment of AIT is dependent from its etiology. AIT usually responds to combined thionamides and potassium perchlorate (KClO4) therapy, AIT II generally responds to glucocorticoids, while indeterminate forms may require both therapeutic approaches. In patients with AIT I definitive treatment of hyperthyroidism by administration of (131)I, initially not feasible for the low RAIU and/or the risk of thyrotoxicosis exacerbation, is advised after normalization of iodine overload. To control severe AIT additional treatment with lithium carbonate, the use of short course of iopanoic acid and plasmapheresis have been also proposed. In cases resistant to medical treatment and/or in patients with severe cardiac diseases who cannot interrupt AM or require quick AM reintroduction, total thyroidectomy (possibly carried out by minimally invasive video-assisted technique) may be proposed after rapid correction of thyrotoxicosis with combination of thionamides, KClO4, corticosteroids and a short course of iopanoic acid.

Effects of different treatments for hyperthyroidism on the hypothalamic-pituitary-adrenal axis.

To investigate the effects of iopanoic acid (IA) and carbimazole on increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in hyperthyroidism, we studied 14 women with hyperthyroidism caused by Graves' disease (n + 11) or toxic multinodular goitre (n + 3) before and after carbimazole or IA treatment. Seven normal women comprised the control group. Changes in thyroid-stimulating hormone, total and free thyroid hormones, arginine vasopressin (AVP), urinary free cortisol, adrenocorticotrophin (ACTH) and cortisol in response to human corticotrophin-releasing hormone (hCRH; 100 microg, i.v.) were estimated under basal conditions and after treatment with IA (3 g/day; n + 7) for 7 days or carbimazole (30 mg/day; n + 7) for 1 month. A higher ACTH response, with normal cortisol secretion, was observed in hyperthyroid patients in response to hCRH compared with the control group. After 7 days treatment, IA induced a significant reduction in total tri-iodothyronine (T(3)) and free T(3) to normal levels and a stronger ACTH response to hCRH, whereas plasma and urinary cortisol levels remained unchanged. Patients treated with carbimazole showed normalization of thyroid hormone levels, a reduction in basal and stimulated ACTH secretion and higher urinary free cortisol levels compared with pretreatment levels. Neither IA nor carbimazole treatment had any effect on AVP levels in hyperthyroid patients. In conclusion, hyperthyroid patients showed HPA axis hyperactivity of central origin with reduced cortisol responses, which were reversed by carbimazole treatment. The differential effects of IA and carbimazole on HPA function indicate that thyroid hormones have a role in modulation of the HPA axis.

Effect of iopanoic acid on radioiodine therapy of hyperthyroidism: long-term outcome of a randomized controlled trial.

CONTEXT: Telepaque [iopanoic acid (IA)] is believed to rapidly ameliorate hyperthyroidism; however, it may preclude subsequent 131I therapy, possibly delaying it for several months. OBJECTIVE: Our objective was to see how early patients, made euthyroid with Telepaque, can be treated with 131I and to compare their short- and long-term outcome with patients treated with 131I, after making them euthyroid with carbimazole and beta-blockers. DESIGN: We conducted a randomized controlled trial. SETTING AND PATIENTS: We studied 200 hyperthyroid patients at a tertiary care teaching institute. INTERVENTIONS: The IA group received Telepaque, 500 mg/d orally, for 7 d and then no medication for 1 wk followed by 131I therapy if radioiodine neck uptake had recovered. The control group received 30-40 mg oral carbimazole daily until patients became euthyroid followed by 131I. MAIN OUTCOME: After 1 wk of Telepaque therapy and 6 wk of carbimazole, almost all patients became clinically and biochemically euthyroid, and 86 and 94% of patients were ready for 131I therapy after 1 and 2 wk off Telepaque, respectively. The cure rate, defined as euthyroid plus hypothyroid, after the first dose of 131I in controls and the IA group was 80 and 76.2%, respectively (P = 0.54). Thirty-two percent among controls and 25% in the IA group became hypothyroid within 1 yr (P = 0.33); thereafter, the annual rate of hypothyroidism was about 2% in both groups. After a mean follow-up duration of 11 yr, 58% of patients in the control group and 51% in the IA group were hypothyroid. CONCLUSIONS: Telepaque rapidly ameliorates hyperthyroidism without jeopardizing the subsequent radioiodine therapy, and the outcome of radioiodine therapy in this subset of patients is in no way different compared with those prepared by carbimazole.

Rapid preoperative preparation for severe hyperthyroid Graves' disease.

Thyroidectomy (TX) is no longer the preferred choice for the therapy of hyperthyroid Graves' disease but is an alternative in patients who are noncompliant with or have reactions to antithyroid drugs, have moderate to severe ophthalmopathy, have large goiters, or who refuse (131)I therapy and/or long-term antithyroid drug therapy. Seventeen clinically and biochemically severely thyrotoxic patients (16 female, mean age of 35 yr), all but one with large goiters, underwent TX after rapid preparation. The potent inhibitors of the deiodination of T(4) to T(3), iopanoic acid (IOP) (500 mg twice a day) and dexamethasone (DEX) (1 mg twice a day), were given with propylthiouracil or methimazole, when possible, and beta-blockers. Thyroid function tests were obtained before treatment and at TX. All patients were thyrotoxic (mean +/- SE: T(4), 21.6 +/- 1.2 micro g/dl; free T(4) index (FTI), 10.3 +/- 0.8; total T(3), 510 +/- 48 ng/dl). IOP and DEX rapidly lowered T(3) values (P < 0.0001; total T(3), 147 +/- 13 ng/dl) with a smaller but significant (P < 0.05) decrease in T(4)/FTI (T(4), 17.9 +/- 1.3 micro g/dl; FTI, 7.9 +/- 0.6). All patients were clinically euthyroid before surgery. None developed hypoparathyroidism, laryngeal nerve damage, or worsening of ophthalmopathy after surgery. The restoration of hyperthyroid Graves' disease to euthyroidism is rapidly accomplished with IOP and DEX, beta-blockers, and, when possible, antithyroid drugs. This is especially relevant in noncompliant patients with large goiters.

Iopanoic acid in the management of neonatal Graves' disease.

OBJECTIVE: Traditionally, neonatal thyrotoxicosis has been managed with antithyroid drugs and/or iodine as well as sedatives, propranol and digitalis when necessary. The purpose of this study was to evaluate the management of neonatal thyrotoxicosis using the radio-contrast agent iopanoic acid. METHODS: We managed five cases of neonatal thyrotoxicosis. All infants were treated initially with propranolol (1.7 mg/kg/day) and iopanoic acid 250 to 500 mg every third or fourth day. RESULTS: In all cases, clinical signs improved and T(3) and T(4) levels decreased dramatically within 24 to 72 hours. No toxic side effects were noted. CONCLUSION: Neonatal thyrotoxicosis can be managed successfully using iopanoic acid. Iopanoic acid is essentially free of side effects and need only be administered every 3 to 4 days. When administered until (transplacental) maternal TSI has been metabolized by the neonate, iopanoic acid maintains euthyroid status with no risk of hypothyroidism. With conventional therapy, propylthiouracil (PTU) must be administered three times a day. PTU also carries a significant risk of toxic side effects and a week or more of therapy is required to correct the hyperthyroid state and may induce hypothyroidism.

Treatment of hyperthyroidism associated with thyrotropin-secreting pituitary adenomas with iopanoic acid.

TSH-secreting tumors comprise less than 2% of all pituitary adenomas. All patients present with hyperthyroidism with a detectable TSH level, and a majority have macroadenomas. Oral cholecystographic agents (e.g. iopanoic acid) potently inhibit the activation of T(4) to the more potent T(3). They have been used successfully to treat primary thyroidal hyperthyroidism and thyroxine overdose. However, they have not been employed in the treatment of central hyperthyroidism. We report, herein, the first two patients with thyrotropinomas, in whom iopanoic acid (Telepaque) has been used perioperatively to safely and rapidly achieve euthyroidism. In case 1, free T(3) index improved from a value of 634 to 175 (normal range 78-162) after 3 d of therapy with iopanoic acid. In case 2, free T(3) by dialysis improved from 697 pg/dl (10.7 pmol/liter) to 195 pg/dl (3.0 pmol/liter) (normal range 210-440 pg/dl; 3.2-6.7 pmol/liter) after 7 d of therapy with iopanoic acid.

Rapid preparation of severe uncontrolled thyrotoxicosis due to Graves' disease with Iopanoic acid--a case report.

PURPOSE: To report the rapid preoperative preparation of a case of thyrotoxicosis due to Graves' disease resistant to medical treatment. CLINICAL FEATURES: A 14-yr-old boy presented with a history of progressive swelling in the neck. Signs and symptoms were compatible with hyperthyroidism. Thyroid function tests revealed: serum T4 296.5 nmol.L(-1), serum T3 6.06 nmol.L(-1) and serum thyroid-stimulating hormone < 0.15 mIU.L(-1). The diagnosis of thyrotoxicosis due to Graves' disease was made. Therapy was instituted with carbimazole 30 mg.day(-1) and propranolol 80 mg.day(-1), which were gradually increased to carbimazole 80 mg.day(-1) and propranolol 120 mg.day(-1), without response. Preparation was attempted by adding Iopanoic acid 500 mg four times a day and dexamethasone 0.5 mg four times a day in addition to the above drugs for five days. T3 levels declined to 1.8 nmol.L(-1), but the serum T4 remained elevated. Symptoms of hyperthyroidism persisted but with decreased intensity. As the patient could not be made euthyroid, surgery was planned to relieve the symptoms. Anesthesia was uneventful except for intraoperative and postoperative tachycardia, which was managed successfully with esmolol. CONCLUSION: In life threatening thyrotoxicosis refractory to medical treatment, Iopanoic acid may be used as an adjuvant to antithyroid drugs for rapid preparation of the patient prior to surgery.

Acute decrease in circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis.

In thyrotoxicosis there is an impaired GH response to GHRH, normal GH responsiveness to GHRP-6 and lack of synergistic GH response after simultaneous administration of both peptides. We have previously shown that the GHRH-induced GH release in these patients increases after an acute reduction of circulating T3 values with administration of iopanoic acid, a compound that inhibits peripheral conversion of T4 to T3. We have now studied the effect of a decrease in serum T3 levels on the GH response to GHRP-6 (1 microg/kg) plus GHRH (100 microg) in 9 hyperthyroid patients before and after 15 days of treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (600 mg/day). Nine normal subjects were also studied. In all hyperthyroid patients iopanoic acid induced a rapid decrease and normalisation of serum T3 levels. In these subjects peak GH (microg/l; mean +/- SE) and AUC (microg/l x 120 min) values after GHRP-6 plus GHRH were significantly higher on day 15 compared to pretreatment values (peak, 18.3 +/- 3.0 vs 13.4 +/- 1.9; AUC, 1227.9 +/- 212.9 vs 968.5 +/- 160.4; p<0.05). Despite the significant enhancement of the GH responsiveness to GHRP-6 plus GHRH after treatment with iopanoic acid, this response remained significantly blunted when compared to controls both in terms of peak GH (18.3 +/- 3.0 vs 83.7 +/- 15.2; p<0.05) and AUC values (1227.9 +/- 212.9 vs 4956.5 +/- 889.3; p<0.05). In conclusion, our results show that an acute decrease of circulating T3 levels enhances, but does not normalise, the GH response to GHRP-6 plus GHRH in thyrotoxicosis. This could suggest that circulating T3 does not have a major role in the mechanisms involved in the synergistic effect of these peptides.

Perioperative management of the thyrotoxic patient.

Preoperative thyrotoxicosis is a potentially life-threatening condition that requires medical intervention before surgery. Most patients are undergoing thyroidectomy for persistent thyrotoxicosis, usually Graves' disease, either having contraindications to or failing medical therapy. Fewer patients are undergoing nonthyroidal surgery that is likely urgent or emergent. The choice of treatment depends on the time available for preoperative preparation, the severity of the thyrotoxicosis, and the impact of any current or previous therapies. Generally treatment is directed at a combination of targets in the thyroid hormone synthetic, secretory, and peripheral pathway with concurrent treatment to correct any decompensation of normal homeostatic mechanisms. Thionamides are the preferred initial treatment unless contraindicated, but do require several weeks to render a patient euthyroid. beta-Blockers should always be used unless absolutely contraindicated because they improve thyrotoxic symptoms especially of the cardiovascular system. Other agents including iodine and steroids can be used if rapid preparation is required or more severe thyrotoxicosis is present. The goal of therapy is to render the patient as close as possible to clinical and biochemical euthyroidism before surgery. Overall, the morbidity and mortality of adequately prepared patients is low.

Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study.

Amiodarone-induced thyrotoxicosis (AIT) may occur either in the presence of underlying thyroid disease (type I AIT) or in apparently normal thyroid glands (type II AIT). Type II AIT, a destructive thyroiditis, often favorably responds to glucocorticoids. Iopanoic acid (IopAc) is an iodinated cholecystographic agent that inhibits deiodinase activity and reduces the conversion of T(4) toT(3). It has recently been reported that cholecystographic agents restore euthyroidism in patients with type II AIT. We describe the results of a prospective randomized study conducted in 12 patients with type II AIT treated with either iopanoic acid (group A, n = 6) or glucocorticoids (group B, n = 6). Serum free T(3) levels normalized rapidly in both groups after 7 d, from 0.75 +/- 0.20 ng/dl (11.5 +/- 3.1 pmol/liter) to 0.46 +/- 0.10 ng/d (7.1 +/- 1.7 pmol/liter), P < 0.01, and from 0.58 +/- 0.10 ng/dl (9.0 +/- 1.2 pmol/liter) to 0.34 +/- 0.03 ng/dl (5.2 +/- 0.5 pmol/liter), P < 0.003, in groups A and B, respectively (P = NS). Serum free T(4) levels reduced at 6 months in group B [from 2.70 +/- 0.32 ng/dl (35.1 +/- 4.1 pmol/liter) to 1.0 +/- 0.04 ng/dl (13.4 +/- 0.6 pmol/liter), P < 0.0001] but not in group A (from 2.90 +/- 0.6 ng/dl (38.0 +/- 7.5 pmol/liter) to 2.30 +/- 0.4 ng/dl (35.6 +/- 6.1 pmol/liter, P = 0.39; P = 0.005 group B vs. group A). All patients in both groups became euthyroid and had their amiodarone-induced destructive thyroiditis cured as defined by normalization of both serum free T(4) and free T(3) levels, during both drugs therapy. However, patients in group B were cured more rapidly than patients in group A (43 +/- 34 d vs. 221 +/- 111 d, respectively, P < 0.002). This study shows that, albeit both drugs are effective, glucocorticoids are probably the drug of choice for more rapidly curing type II AIT.

Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters.

OBJECTIVE: The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). METHODS: Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Iopanoic acid rapidly controls type I amiodarone-induced thyrotoxicosis prior to thyroidectomy.

Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal thyroid glands (Type II AIT) or in the presence of sub-clinical thyroid abnormalities (either autonomous goiter or latent Graves' disease; Type I AIT). Mixed forms also occur. While Type I AIT is due to iodine-induced excess thyroid hormone synthesis, Type II AIT is a form of amiodarone (possibly iodine) -induced destructive thyroiditis. Type I AIT is usually treated by combined thionamide and potassium perchlorate therapy, but may be resistant to therapy. On the other hand, Type II AIT often responds favorably to glucocorticoids and may not require further therapy once euthyroidism has been restored. Not infrequently, however, AIT (especially Type I) is resistant to conventional treatment, and several weeks or months may elapse before euthyroidism is restored. Thyroidectomy has been carried out in Type I AIT patients, but thyroid surgery in thyrotoxic patients, especially those with underlying cardiac problems, carries a high surgical risk. In this study we describe 3 patients with Type I AIT, who were successfully treated with a short course of iopanoic acid (IOP), an oral cholecystographic agent, which is rich in iodine and is a potent inhibitor of 5'-deiodinase, resulting in a marked decrease in the peripheral tissue conversion of T4 to T3, in preparation for thyroid surgery. Euthyroidism was rapidly restored in 7-12 days, allowing a subsequent safe and uneventful thyroidectomy in all cases. These patients were then treated with L-T4 for their hypothyroidism and amiodarone was safely re-instituted. We suggest that IOP is the drug of choice in the rapid restoration of euthyroidism prior to definitive thyroidectomy in patients with drug resistant Type I AIT.

Clinical review 129: Oral cholecystographic agents and the thyroid.

Oral cholecystographic agents (OCAs) are known to affect thyroid hormone metabolism by acting as potent inhibitors of type I and type II deiodinases, blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine released from the drug blocks thyroid gland secretion of thyroid hormone. These properties make OCAs a potentially useful drug therapy in patients with hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are not useful for long-term treatment, which is usually followed by exacerbation of hyperthyroidism with continued use. The lack of significant side effects makes these drugs an excellent short-term option in situations where a rapid clinical improvement is critical.

Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients.

OBJECTIVE: Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion. DESIGN: Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.). PATIENTS: Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years. MEASUREMENTS: GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method. RESULTS: Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly higher on day 15 (24.4 +/- 3.8) than those observed on days 0 (14.2 +/- 1.6), 4 (15.2 +/- 3.0) and 7 (19.6 +/- 5.0). There was a 79% increase in this response on day 15 compared with the pre-treatment period. Hyperthyroid patients had a blunted GH response to GHRH on days 0, 4 and 7 in comparison with control subjects. However, on day 15, no differences were observed between the area under the curve (mean +/- SE mU/l.120 min) in thyrotoxic patients (1770 +/- 306) and in the control group (3300 +/- 816). IGF-I and albumin levels did not change during iopanoic acid administration. CONCLUSIONS: The results show that an acute reduction in serum T3 levels elicits an increase in GH responsiveness to GHRH in hyperthyroidism. Although the mechanisms involved in this process are still unknown, it is possible that T3 influences GH responsiveness to GHRH via hypothalamic somatostatin release. Alternatively, T3 could have a direct effect at the pituitary somatotroph, modulating GHRH intracellular pathways.

Successful treatment of massive acute thyroid hormone poisoning with iopanoic acid.

We report a toddler with massive thyroid hormone poisoning in whom the addition of iopanoic acid to the treatment regimen (propylthiouracil and propranolol) resulted in a dramatic clinical and biochemical improvement. Iopanoic acid is a safe and effective drug in the treatment of massive thyroid hormone poisoning in children.