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The role of the autonomic nervous system in the resting tachycardia of human hyperthyroidism.

The mechanisms that control resting heart rate in hyperthyroidism were evaluated in six patients before and after treatment with propylthiouracil. The patients were subjected to pharmacological blockade under resting conditions in two experimental sessions: first session, propranolol (0.2 mg/kg body weight); second session, atropine (0.04 mg/kg body weight) followed by propranolol (0.2 mg/kg body weight). All drugs were administered intravenously. Resting heart rate was significantly reduced from 100 +/- 6.5 beats/min to 72 +/- 2.5 beats/min (P less than 0.005) after clinical and laboratory control of the disease. After double blockade, intrinsic heart rate was reduced from 105 +/- 6.8 beats/min before treatment to 98 +/- 6.0 beats/min after treatment (P less than 0.025). The reduction in heart rate caused by propranolol was not significantly different before (-13 +/- 1.4 beats/min) and after (-9 +/- 1.0 beats/min) propylthiouracil. In contrast, atropine induced a higher elevation of heart rate after treatment (45 +/- 8.6 beats/min) than before treatment (26 +/- 4.0 beats/min). The present results suggest no appreciable participation of the sympathetic component of the autonomic nervous system in the tachycardia of hyperthyroidism, at least under the conditions of the present study. The small change observed in intrinsic heart rate, although significant, seems to indicate that this is not the most important mechanism involved in this tachycardia. Our results suggest that an important reduction in the efferent activity of the parasympathetic component participates in the mechanisms that modify resting heart rte in hyperthyroidism.

Adult↗

Hyperthyroidism mimicking increased intracranial pressure.

We report a 32-year-old woman presenting with progressive symptoms of increased intracranial pressure and slight enlargement of the ventricles on CT scan. The underlying cause was hyperthyroidism due to Graves' disease. With treatment to correct the hyperthyroid state, all symptoms rapidly disappeared. The rare onset of hyperthyroidism with symptoms indicating intracranial hypertension, and the possible pathophysiologic mechanisms are discussed.

Adult↗

Cholelithiasis and hyperthyroidism in a cat.

A 14-year-old domestic short-hair cat presented with a history of intermittent malaise and increased drinking. A diagnosis of hyperthyroidism and cholelithiasis was made by a combination of blood testing, radiography and ultrasonography. After medical management of hyperthyroidism, thyroidectomy and cholecystectomy were successfully performed. Removed choleliths were comprised of calcium carbonate and bilirubinate. Histopathological analysis of tissue suggested low grade pancreatic and hepatobiliary disease, as well as hyperthyroidism, might have contributed to stone formation.

Animals↗

Serum cholesterol esterification in hyperthyroidism and hypothyroidism.

The rate of serum cholesterol esterification was measured in twenty healthy subjects and compared to similar data obtained with seventeen hyperthyroid and ten hypothyroid subjects. No significant differences were noted in the rate of cholesterol esterification while differences in the fractional rates were highly significant (p less than 0.001); the hyperthyroid group being higher and the hypothyroid group lower than normal. There were no clear trends observed in the changes of the rate of cholesterol esterification upon therapy. However, the fractional rates always increased when hypothyroid patients became euthyroid and always decreased in hyperthyroid patients as the result of therapy.

Cholesterol↗

[Paraneoplastic hyperthyroidism in a patient with metastasizing teratocarcinoma and excessively high HCG].

Clinically manifest hyperthyroidism is a rare paraneoplastic syndrome in patients with excessive HCG production due to testicular cancer. A 40-year-old patient with right testicular cancer (teratoma, embryonal cell carcinoma), diffuse pulmonary metastases and high serum HCG levels presented with symptomatic hyperthyroidism. The patient received immediately thyrostatic therapy and 4 cycles of PEI chemotherapy (Cisplatin, Etoposide, Ifosfamide). Thyroid function had returned to normal by the beginning of the second course of chemotherapy. After right orchiectomy and resection of residual pulmonary masses which revealed vital tumor cells, two additional courses of chemotherapy were performed. The patient is well and without evidence of disease 11 months after therapy. All patients with testicular cancer and excessive HCG production should be evaluated for biochemical and clinical signs of hyperthyroidism and treated accordingly with antithyroidal medication and immediate cytoreductive chemotherapy.

Adult↗

Gadolinium as an alternative contrast agent during cardiac catheterization in patient with iodine-induced hyperthyroidism.

We report the first case of a male patient with iodine-induced hyperthyroidism and unstable angina pectoris in whom a diagnostic cardiac catheterization with gadolinium as contrast agent was chosen. The patient was hospitalized with an iodine-induced hyperthyroidism after angioplasty using an iodinated contrast agent. He presented with a continuous arrhythmia and unstable angina pectoris. A repeated cardiac catheterization using iodinated contrast agent was contraindicated. This case report shows that gadolinium is a useful alternative contrast agent for cardiac intervention in patients with iodine-induced hyperthyroidism.

Cardiac Catheterization↗

Correlation between glucose disposal and amino acids levels in hyperthyroidism.

Insulin is known to decrease plasma levels of both glucose and amino acids. We have designed a study to examine whether in hyperthyroidism, where insulin sensitivity is changed, correlation between glucose disposal and amino acids levels is maintained. We studied 5 normal (N) and 5 hyperthyroid (HTD) subjects, and measured glucose disposal rate and serum levels of plasma amino acids before and during insulin infusion utilizing the euglycemic hyperinsulinemic clamp technique. Insulin was effective in decreasing the levels of all amino acids in the plasma of all subjects. The mean amino acid decrease in response to insulin infusion rate of 10 mu/kg/min was 35 +/- 3% in N and 50 +/- 3% in HTD. The half maximally effective dose of insulin on glucose disposal was 43 +/- 3 and 69 +/- 9 uU/ml in N and HTD respectively (p < 0.05). The half maximally effective dose of insulin on decreasing plasma amino acids was 37 +/- 7 and 75 +/- 5 uU/ml in N and HTD respectively (p < 0.01). The concentration of insulin giving a half maximal effect on serum amino acids correlated with the half-maximally effective dose on glucose disposal rate (r = 0.72, p < 0.01). The maximal effect on total amino acid levels correlated with maximal glucose disposal (r = 0.76, p < 0.001). Similar results were observed with branched chain amino acids. We conclude that in hyperthyroidism glucose disposal and decrease in amino acids levels are closely correlated as in healthy subjects. This also confirms the association between glucose disposal and amino acids levels in a variety of insulin sensitive and resistant states.

Adult↗

Increase of serum somatomedin C in hyperthyroid patients with pregnancy.

In thyrotoxic women with pregnancy, serum somatomedin C (SmC) concentration was markedly elevated (mean +/- SD 13.57 +/- 4.66 U/ml) compared to thyrotoxic women without pregnancy (1.24 +/- 1.09 U/ml), non-pregnant euthyroid women previously treated for hyperthyroidism (0.87 +/- 0.30 U/ml), normal subjects with pregnancy (6.08 +/- 3.36 U/ml) and pregnant euthyroid women previously treated for hyperthyroidism (5.98 +/- 1.52 U/ml). Since SmC/growth hormone ratio was significantly more in thyrotoxic pregnant women than in normal pregnant women and euthyroid pregnant women previously treated for hyperthyroidism, and since human placental lactogen (HPL), human chorionic gonadotropin (HCG) and prolactin (PRL) do not crossreact with SmC antibody, it is suggested that excess thyroid hormone during pregnancy results in excessive hepatic somatomedin C production.

Adult↗

Increased release of gastrin in hyperthyroid rats in vitro.

The extrinsically denervated and vascularly perfused stomach of the hyperthyroid rat exhibits an increased basal gastrin release and an exaggerated response to stimulation with the b-agonist isoproterenol. The b-blocker propranolol does not inhibit the increased basal release of gastrin, but completely blocks the effect of isoproterenol. Vagal stimulation is not different between hyperthyroid and euthyroid rats. We conclude, that there are two mechanisms which are responsible for the increased release of gastrin in hyperthyroidism: firstly a direct effect of thyroid hormones on gastrin cells, and secondly an increase in sensitivity of gastrin cells towards b-adrenergic stimulation.

Animals↗

Insulin secretion and action in the hyperthyroid rat.

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.

Animals↗

Alteration of plasma and erythrocyte membrane lipid components in hyperthyroid rats.

Cholesterol and phospholipid have been measured in plasma and erythrocyte membrane of hyperthyroid rats. It has been found that while the former is reduced by about 30% in plasma and increased by the same amount in erythrocyte membranes, on the contrary, the latter increases by 35% in both plasma and red cell membranes. It seems that when serum triiodothyronine increases, a major cholesterol transfer occurs from plasma to erythrocyte. In this way, by the concomitant phospholipid increase, it is possible to avoid an alteration of the cholesterol/phospholipid molar ratio in the red cells, thus preventing their abnormal function in hyperthyroid rats. The proposal is made that an additional reason for the plasma cholesterol decrease in hyperthyroid subjects can be attributable to a net transfer of this compound from plasma to erythrocyte.

Animals↗

[Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy with octreotide].

HISTORY AND FINDINGS: Magnetic resonance imaging (MRI) of the central nervous system was performed on a 72-year-old woman who was hyperthyroid without suppression of the thyroid-stimulating hormone (TSH) and had complained of a recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in diameter, in the anterior pituitary. The clinical symptoms were marked by a long-standing monosymptomatic illness of rapidly changing mood swings with depressive and manic phases. INVESTIGATIONS: Endocrinological-biochemical tests showed hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH: 2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a 5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified the mass as a retrosternal goitre. TREATMENT AND COURSE: As an operation on the anterior pituitary would have carried a high risk for the patient who was in a poor general condition and she had refused to be operated, treatment with octreotide, a long-acting somatostatin analogue, was initiated. This achieved a euthyroid state with partly suppressed TSH, and the patient's emotional swings ceased. CONCLUSION: If hyperthyroidism coexists with non-suppressed TSH levels, a TSH-producing hypophyseal adenoma should be considered in the differential diagnosis despite its rarity. Octreotide administration is an effective and safe treatment and is the method of choice, especially when there are contraindications to surgical resection of the anterior pituitary.

Adenoma↗

A marked upregulation of uncoupling protein 2 gene expression in adipose tissue of hyperthyroid subjects.

Recently, a family of uncoupling protein (UCP) genes has been discovered. The role of these genes is unknown, but it has been suggested that they are involved in regulating resting metabolic rate. In this study, we hypothesised that thyroid hormone status may influence the expression of UCP2 mRNA. The adipose tissue levels of UCP2 mRNA were measured in eight female subjects before and after treatment for thyrotoxicosis. All subjects in the hyperthyroid condition had markedly enhanced plasma levels of thyroxine (62.0 +/- 6.9 vs. 17.9 +/- 1.7, p = 0.012) and triiodothyronine (37.9 +/- 6.9 vs. 5.9 +/- 0.9, p = 0.012), accelerated heart rate (94 +/- 7 vs. 69 +/- 5, p = 0.012), decreased BMI (24.5 +/- 1.9 vs. 25.1 +/- 1.9, p = 0.025) and decreased percentage body fat (32.8 +/- 4.4 vs. 37.1 +/- 4.5, p = 0.018), as compared to the euthyroid state. Using RT-competitive-PCR, the UCP2 mRNA levels were found to be 2.5-fold upregulated in hyperthyroidism (10.4 +/- 1.7 vs. 4.2 +/- 1.3 amol/microg RNA, p = 0.012). In contrast, no difference in expression levels of the reference gene 18SrRNA was seen in the hyperthyroid versus the euthyroid state (317 +/- 49 vs. 279 +/- 25 amol/microg RNA, p = 0.48) but the difference in UCP2 mRNA levels between the hyper- and euthyroid state remained when UCP2 was related to 18SrRNA (p = 0.012). In conclusion, thyrotoxicosis markedly increases the expression of UCP2 mRNA in adipose tissue, which suggests a role for thyroid hormones in the regulation of this uncoupling protein in man.

Adipose Tissue↗

Cholesterol 7 alpha-hydroxylase activity in hypothyroidism and hyperthyroidism in humans.

Alterations of serum cholesterol levels are well recognized findings in hypothyroidism and hyperthyroidism. It remains unclear, whether thyroid hormones may affect serum concentrations of cholesterol through changes in the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolic conversion of cholesterol to bile acids. We determined serum concentrations of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one, which reflects cholesterol 7 alpha-hydroxylase activity in the liver, in 19 patients with hypothyroidism and in 10 patients with hyperthyroidism before and after treatment, respectively. In patients with hypothyroidism, serum concentrations of cholesterol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p < 0.0005), respectively, after replacement therapy with thyroid hormones. In contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/- 15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL-cholesterol were unchanged during substitution therapy. In patients with hyperthyroidism, serum concentrations of cholesterol and LDL-cholesterol increased by 27% (p < 0.01) and 39% (p < 0.01) after antithyroid treatment, respectively. Again, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one did not change significantly during treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/- 8.1 ng/ml before treatment, n.s.). These findings indicate that in humans, thyroid hormones influence serum lipid concentrations by other mechanisms than by affecting the activity of cholesterol 7 alpha-hydroxylase.

Adenoma↗

The relationship between lipoprotein(a) and low density lipoprotein receptors during the treatment of hyperthyroidism.

To determine whether the low density lipoprotein (LDL) receptor pathway is involved in the catabolism of plasma lipoprotein (a) [Lp(a)], serum lipids, Lp(a), and LDL receptor activity were measured in seven patients with hyperthyroidism before and after methimazole treatment given hyperthyroidism is associated with enhanced LDL receptor activity. LDL receptor activity in patients was estimated by the equation using the serum concentrations of apolipoprotein (apo) B and C-II. When euthyroidism was achieved after treatment, not only did serum total cholesterol, high density lipoprotein-cholesterol, apo B, and LDL-cholesterol (LDL-Ch) levels rise, but Lp(a) significantly increased and calculated LDL receptor activity significantly decreased. The changes in LDL receptor activity were significantly correlated with the changes in LDL-Ch as expected, but not with changes in Lp(a). These results suggest that the serum concentration of Lp(a) is lowered in hyperthyroidism, probably by a mechanism other than the enhanced activity of the LDL receptor, and that the LDL receptor pathway is involved in the catabolism of Lp(a) to a limited extent.

Apolipoproteins↗

[Periodic paralysis as the first manifestation of hyperthyroidism].

HISTORY AND CLINICAL FINDINGS: A 19-year-old man had mild diarrhoea at the time that suddenly one night he was unable to turn in his bed and the following morning could not move his arms and legs for 4 hours. Neither he nor any family members had previously had any paralysis. Physical examination was unremarkable except for mild tachycardia and first-degree goitre. INVESTIGATIONS: A provocation test with glucose (3 g/kg) and insulin (0.1 IU/kg) caused renewed paralysis for several hours, serum potassium falling from 4.3 to 3.4 mmol/l. The paralysis was reversed on oral potassium (40 mmol) Thyroid function tests revealed hyperthyroidism with an increased concentration of free thyroxine (25.5 pg/ml) and free triiodothyronine (9.7 pg/ml), while thyroid-stimulating hormone was decreased (0.07 mU/I), supporting the diagnosis of autoimmune thyroiditis. TREATMENT AND COURSE: Thyrostatic treatment was started with thiamazole (10 mg every other day). There was no further periodic paralysis and another provocation test was negative. CONCLUSION: Fleeting paralysis is often misdiagnosed as being psychogenic. Potassium abnormalities are the most common cause but are only rarely associated with hyperthyroidism. This case of thyrotoxic hypokalaemic paralysis was probably based on a genetic defect of muscle fibre membrane manifesting itself only in the presence of hyperthyroidism.

Adult↗

[Comparison between the intravenous TRH-test and the T4-thyroid suppression test for the diagnosis of borderline hyperthyroidism].

In a prospective study of 60 patients with T3 and/or T4 values within +/- 10% of the upper limit of normal, the suppressibility of thyroid storage values before and after oral administration of 3 mg L-thyroxine was tested and compared with the results of an intravenous TRH test. In 46 patients the results of the two methods agreed (77%): in 31 patients (52%) radioiodine uptake could not be suppressed nor TSH stimulated in the TRH test. Physiological suppression of the storage values in normal TSH stimulation after TRH as a sign of completely euthyroid function was present in 15 (25%). In the remaining 14 patients, 13 had a suppressed TRH test. In all patients radioiodine uptake could be suppressed either normally (above 50%) or partially (20-30%). A normal T4 suppression test in the absence of TSH rise after TRH indicates that biologically active TSH is circulating, even though not demonstrated by radioimmuno-assay. A normal T4 suppression test is an important argument against treating a given case of hyperthyroidism. The T4 suppression test reveals smooth gradation between euthyroid and hyperthyroid states. If the TRH test is normal one can assume a physiological T4 suppression test and no further tests are needed. If the TRH test is negative and there is only slight elevation of the thyroid hormones, the T4 suppression test is indicated before definitive treatment of hyperthyroidism is initiated.

Adult↗

[Conservative treatment of hyperthyroidism (author's transl)].

Antithyroid medication was given to 158 patients with hyperthyroidism over a period of 3 to 60 months. After cessation of therapy patients were followed up for 18 to 90 months. Permanent euthyroidism was seen in 70 patients (44.3%) after stopping treatment, however, 88 patients (55.7%) showed recurrence of hyperthyroidism occurring 1 to 56 months after ceasing treatment. In more than 50% recurrence of hyperthyroidism was within the first 3 months and in almost 80% within the first year after end of treatment. There was no connection either between the length of thyrostatic treatment and the recurrence rate or between the length of treatment and recurrence time. Comparison of patients with and without recurrence according to various parameters prior, during and after thyrostatic treatment indicates that there is a high risk of recurrence in patients with 1) nodular and (or) large goitres, 2) marked clinical symptomatology and delayed attainment of a euthyroid state after starting conservative treatment, and 3) the symptom of sweating remaining uninfluenced by antithyroid treatment.

Antithyroid Agents↗