methimazole and Hypertension

Although simple febrile seizures are relatively common and benign in toddlers, it is important to rule out any underlying critical disease that necessitates further intervention and treatment. Thyroid storm, the extreme manifestation of hyperthyroidism, is relatively rare and not often considered in the differential diagnosis of a febrile seizure despite its high mortality rate. Here, we report 1 of the youngest patients with thyroid storm, who initially presented with a febrile seizure. After reevaluation, the 2-year-9-month-old patient was discovered to have thyromegaly, which led to recognition that her persistent tachycardia and widened pulse pressure were likely signs of thyrotoxicosis. Laboratory results were consistent with primary hyperthyroidism due to Graves' disease. Thyroid storm was then diagnosed on the basis of clinical features including gastrointestinal and central nervous system disturbances. Treatment with methimazole, propranolol, hydrocortisone, and Lugol's iodine solution was used. This medication regimen was safe and effective with restoration of a euthyroid state after 2 months and no recurrence of seizures. Improved awareness of hyperthyroidism and thyroid storm can lead to prompt diagnosis and treatment of this endocrine emergency, thus reducing mortality and morbidity. Pediatricians should consider this diagnosis in children with febrile seizures and suggestive vital signs and physical examination findings.

Topics: Child, Preschool; Female; Graves Disease; Humans; Hydrocortisone; Hypertension; Iodides; Methimazole; Propranolol; Seizures, Febrile; Tachycardia; Thyroid Crisis

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n=13) or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 ± 2.0 vs 108.8 ± 3.0 mmHg, p<0.001), SAP (157.3 ± 2.9 vs 135.7 ± 4.5mm Hg, p<0.001) and DAP (109.7 ± 1.9 vs 88.4 ± 2.6 mmHg, p<0.001) when compared to OWTD, and had lower HR (355.1 ± 8.9 vs 386.8 ± 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 ± 0.8 vs 4.0 ± 0.6 mmHg(2), p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems.

Topics: Animals; Baroreflex; Blood Pressure; Disease Models, Animal; Female; Heart Rate; Hypertension; Hypothyroidism; Male; Methimazole; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

Topics: alpha-Methyltyrosine; Antihypertensive Agents; Antithyroid Agents; Catecholamines; Enzyme Inhibitors; Female; Fluid Therapy; Graves Disease; Humans; Hypertension; Hypotension; Methimazole; Middle Aged; Pheochromocytoma; Time Factors

Topics: Adrenergic beta-Antagonists; Adult; Anesthesia, Intravenous; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Dexamethasone; Drug Therapy, Combination; Female; Graves Disease; Humans; Hypertension; Iopanoic Acid; Kidney Diseases; Methimazole; Preoperative Care; Propranolol; Tachycardia; Thyroidectomy

The best-known adverse hematologic reaction of methimazole is agranulocytosis. Aplastic anemia is extremely rare. The prognosis within the entity of aplastic anemias is surprisingly good, despite the severe and prolonged course of the disease. The present article reports the case of a 74-yr-old female patient who exhibited aplastic anemia with severe clinical symptoms 8 weeks after the initiation of methimazole administration. The hemorrhagic symptoms were aggravated by a coumarin overdose. Supportive hemotherapy and antibiotic treatment were supplemented with recombinant human granulocyte colony-stimulating factor and high-dosage corticosteroids. The granulocyte count normalized on day 5 of treatment, the platelet count exceeded the critical value on day 11, and on day 25 the patient was discharged in remission.

Topics: Aged; Anemia, Aplastic; Coumarins; Drug Overdose; Female; Granulocyte Colony-Stimulating Factor; Humans; Hypertension; Hyperthyroidism; Methimazole; Methylprednisolone; Platelet Transfusion; Recombinant Proteins

Hyperthyroidism and chronic renal disease occur commonly in geriatric cats, often in association with potentially life-threatening primary or secondary hypertension. Early treatment of hypertension minimizes damage to vital organs. This case illustrates the complexity of managing hypertension in a geriatric cat with both hyperthyroidism and renal disease.

Topics: Animals; Antihypertensive Agents; Antithyroid Agents; Cat Diseases; Cats; Diagnosis, Differential; Enalapril; Female; Hypertension; Hyperthyroidism; Kidney Diseases; Methimazole; Treatment Outcome

We describe a patient with right adrenal tumor detected incidentally. The tumor was diagnosed as pheochromocytoma by endocrinological and radiological studies, and was removed surgically. Graves' disease, which had been in remission for more than two decades after discontinuation of antithyroid drug treatment, relapsed during preoperative evaluation of pheochromocytoma when the patient was treated with alpha- and beta1-adrenergic antagonists. Administration of methimazole resulted in a rapid improvement of thyroid function and the patient remained euthyroid on small doses of methimazole. This case may suggest possible involvement of excessive catecholamine secretion and beta2-adrenergic receptor activation by pheochromocytoma in the relapse of Graves' disease.

Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Antithyroid Agents; Dose-Response Relationship, Drug; Doxazosin; Female; Graves Disease; Humans; Hypertension; Incidental Findings; Methimazole; Middle Aged; Pheochromocytoma; Propanolamines; Recurrence

In the present study we evaluated the effects of methimazole, an antithyroid drug, on blood pressure and other variables in the early and established phases of hypertension induced by the inhibition of nitric oxide synthesis with the oral administration of NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking water. Moreover, we also evaluated the acute pressor effect of L-NAME on systemic blood pressure in control and rats treated chronically with methimazole, administered via drinking water (30 mg/100 ml). Oral administration of methimazole maintained the blood pressure of L-NAME-treated rats at normal levels 25 days after induction of hypertension. However, after 25 days of methimazole treatment in rats made hypertensive with L-NAME (for 25 days), high blood pressure was similar in methimazole-treated and non-treated L-NAME rats, despite the fact that a hypothyroid state had been achieved in the methimazole-treated rats. Acute intravenous injection of L-NAME caused a similar increase in mean arterial pressure in control and methimazole-treated rats at the lowest dose; however, smaller pressor responses were observed with increasing doses in hypothyroid rats. These results clearly demonstrate that hypothyroidism induced by methimazole prevents, but does not reverse, L-NAME hypertension and reduces the acute pressor responsiveness to L-NAME administration.

Topics: Administration, Oral; Animals; Blood Pressure; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hypertension; Injections, Intravenous; Male; Methimazole; NG-Nitroarginine Methyl Ester; Rats; Rats, Wistar; Reference Values

1. The physiological relevance of cardiac and vascular alpha-adrenoceptors may increase in disease states in which beta-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus, disease states which alter beta-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the alpha 1-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via alpha-adrenoceptors.

Topics: Animals; Cardiovascular System; Diabetes Mellitus, Experimental; Disease Models, Animal; Hemodynamics; Hypertension; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Male; Methimazole; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Adrenergic, alpha-1; Triiodothyronine

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Topics: Animals; Blood Pressure; Body Weight; Cardiomegaly; Hypertension; Kidney; Male; Methimazole; Rats; Rats, Inbred Strains; Renin

This study evaluates the effects of methimazole, an antithyroid drug, on blood pressure, digoxin-like immunoreactive factor (DLIF) production and other variables related to salt and water metabolism in low-renal mass (LRM) hypertension. Drinking administration of methimazole (0.025%) from replacement of water by the 1% NaCl solution maintained the blood pressure of low-renal mass rats at normal levels during four weeks after hypertension induction. Serum and urinary excretion of DLIF were significantly increased in LRM rats with respect to controls; in all tests, the highest values of DLIF were found in LRM-methimazole treated (LRM-M) rats. Urinary excretion of DLIF showed positive correlations with diuresis and natriuresis in all three groups (control, LRM and LRM-M rats). However, the correlation between DLIF and sodium disappeared when both factors were expressed as a function of their concentrations. These results indicate that methimazole prevents LRM hypertension and suggest that DLIF might not represent the putative natriuretic hormone. Other findings were that methimazole-treatment reduced renal compensatory hypertrophy subsequent to subtotal nephrectomy, and did not modify the characteristic polyuria-polydypsia in this type of hypertension.

Topics: Animals; Blood Proteins; Cardenolides; Digoxin; Hypertension; Isotonic Solutions; Kidney; Male; Methimazole; Natriuresis; Potassium; Rats; Rats, Wistar; Saline Solution, Hypertonic; Saponins; Sodium Chloride; Water Deprivation

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar-Kyoto (WK) and Sprague-Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/mu LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV-dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and -dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV-dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiomegaly; Coronary Circulation; Diabetes Mellitus, Experimental; Food Deprivation; Heart; Hypertension; Male; Methimazole; Myocardial Contraction; Oxygen Consumption; Perfusion; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Thyroxine; Vascular Resistance

Topics: Adenosine Triphosphatases; Adenylyl Cyclases; Aging; Animals; Blood Pressure; Hypertension; Hypothyroidism; Methimazole; Myocardium; Rats; Sodium-Potassium-Exchanging ATPase

Thyroid activity of both male and female spontaneous hypertensive (SH) rats was studied by measurements of uptake and rate of release of 131-I, urinary excretion of 131-I, and thyroxine secretion rate (TSR). In addition, thyroid glands were removed at death and weighed. Radioactivity of the thyroid gland of male rats measured at intervals after administration of 131-I revealed a significantly reduced maximal uptake at 21.5 hr after injection and a reduced rate of release. The mean biological half-life of 131-I for the control group was 37.8 plus or minus 3.1 (SE) hr compared to 54.8 plus or minus 7.2 hr for hypertensives (P less than 0.05). Similar results were observed for females in that biological half-life of 131-I was 32.2 plus or minus 1.2 hr compared with 84.1 plus or minus 4.1 hr for hypertensives (P less than 0.01). Urinary excretion of 131-I by hypertensive rats at 24, 48, and 72hr after injection of 131-I did not differ from control in either experiment. Thyroid weight at autopsy was increased significantly above that of normotensive controls. TSR was measured indirectly in a third group of male spontaneously hypertensive and normotensive rats. TSR of control rats was estimated to be 0.97 mug T4/100 g body wt/day and 1.35 mug T4/100 g body wt/day for SH RATS. The results are consistent with the suggestion that the method for measurement of TSR in hypertensive rats gives an artifactually high value because TSH secretion is elevated.

Topics: Animals; Body Weight; Chick Embryo; Female; Hypertension; Injections, Intraperitoneal; Iodine; Iodine Radioisotopes; Male; Methimazole; Organ Size; Rats; Thyroid Gland; Thyroxine; Time Factors

Topics: Age Factors; Animals; Antithyroid Agents; Blood Pressure; Body Weight; Dinitrophenols; Female; Hypertension; Imidazoles; Male; Methimazole; Rats; Sodium Chloride; Stimulation, Chemical; Thyroidectomy; Triiodothyronine

Topics: Adult; Aged; Blood Pressure; Cholesterol; Female; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Middle Aged; Myxedema; Norepinephrine; Thyroid Hormones

Topics: Antithyroid Agents; Humans; Hypertension; Hypertension, Malignant; Methimazole