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PubMed1992

Serum levels of free and bound testosterone in hyperthyroidism.

OBJECTIVE: The aim of this study was to improve knowledge about the relationships between free and bound forms of testosterone in serum and the major testosterone-binding proteins during hyperthyroidism. DESIGN: Nine men and 11 women were studied when hyperthyroid due to Graves' disease and again after at least 3 months of euthyroidism. MEASUREMENTS: The serum concentrations of free T3, free T4, TSH, sex hormone-binding globulin (SHBG), LH, progesterone and free, non-SHBG bound and total testosterone were determined. RESULTS: For both sexes, hyperthyroidism was associated with significant elevations of the mean total testosterone and sex hormone-binding globulin (SHBG) levels and significant depressions of the mean percentage and concentration of non-SHBG-bound testosterone and the mean percentage of free testosterone. For women, the mean free testosterone concentration was significantly lower during hyperthyroidism than during euthyroidism; no significant difference in mean free testosterone concentration was observed between hyperthyroid and euthyroid men. When the experimentally derived data were analysed according to a model based on the binding constants of testosterone with SHBG and albumin, the simulated results for each patient when hyperthyroid and euthyroid paralleled the actual results. However, the model consistently overestimated the actual amounts of non-SHBG-bound testosterone. There was a significant correlation between SHBG concentration and the severity of thyrotoxicosis as measured by the change in thyroid hormone levels between euthyroidism and hyperthyroidism. CONCLUSIONS: Our results support the following pathogenetic sequence: thyrotoxicosis leads to a rise in serum SHBG concentration which is accompanied by an increase in testosterone concentration, a fall in the concentration of non-SHBG-bound testosterone and little or no change in the concentration of free testosterone.

Adolescent↗

PubMed1995

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE: The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroidism led us to perform a study in order to compare a fixed dose regime comprising doses of 185 370 or 555 MBq based on gland size assessment by palpation only, with a calculated 131I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour 131I uptake determination. DESIGN: Prospective randomized study. PATIENTS: Two hundred and twenty-one consecutive hyperthyroid patients referred for 131I treatment. Four Patients who died for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remaining 163 patients (143 women) were studied, divided into subgroups according to the type of gland. They all received antithyroid drugs prior to 131I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS: Thyroid function variables were determined approximately 2 weeks before 131I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to 131I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of 131I was carried out. Thyroid volume was also estimated 12 months after 131I therapy in 78 of the 163 patients. Twelve months after the initial 131I dose patients could be classified as euthyroid, hyperthyroid or hypothyroid. RESULTS: Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthyroid. Seven of 78 (9%) in the calculated dose group and 6 out of 85 (7%, NS) in the fixed dose group were classified as permanently hypothyroid. Finally, 39 of 78 (50%) in the calculated dose group and 49 of 85 (58%, NS) in the fixed group were euthyroid at 12 months after 131I treatment. One year after 131I therapy thyroid volume was reduced from 59.3 +/- 9.2 (mean +/- SEM) to 36.2 +/- 6.6 ml (average reduction 39%) in the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 +/- 6.1 to 41.17 +/- 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS: A semiquantitative approach is probably as good as the more elaborately calculated radioiodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.

Adult↗

PubMed2004

Changes in endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism.

OBJECTIVE: This case-control study was carried out to assess the alteration of endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism. PATIENTS AND METHODS: The study subjects included 12 patients with hyperthyroidism and 39 apparently healthy individuals. We performed a subtotal thyroidectomy on the hyperthyroid patients. The endothelium-dependent arterial dilation was determined with a high-resolution ultrasound method in each patient at the hyperthyroid stage before treatment (stage H), the euthyroid stage induced immediately before surgery (stage E), and the transient hypothyroid stage 1 or 2 months after surgery (stage L). RESULTS: The flow-mediated arterial dilation decreased significantly from H to E and from E to L (P < 0.001). As compared with H, baseline blood flow decreased markedly at stages E and L (P < 0.001). The flow-mediated arterial dilation and baseline blood flow in the control subjects were very close to those at stage E of the hyperthyroid patients. The absolute change in the flow-mediated arterial dilation showed significant negative correlation with the changes in TSH (r =-0.86, P < 0.001), lipoprotein (a) [Lp(a)] (r =-0.77, P < 0.001) and low density lipoprotein (LDL) (r =-0.79, P < 0.001), and significant positive correlation with changes in fT3 (r =+0.88, P < 0.001). The absolute change in the baseline blood flow showed significant positive correlation with the change in fT3 (r =+0.85, P < 0.001) and significant negative correlation with the change in TSH (r =-0.63, P < 0.01). CONCLUSION: The endothelium-dependent arterial dilation increases significantly in untreated hyperthyroid patients, and decreases markedly after a subtotal thyroidectomy. Therefore, we conclude that the endothelium is more responsive to reactive hyperaemia in the hyperthyroid than the euthyroid state.

Adult↗

PubMed2005

Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder.

OBJECTIVES: Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism. METHODS: We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks of subsequently being readmitted with a resulting discharge diagnosis of hyperthyroidism were estimated in survival analyses. RESULTS: A study sample of 133,570 patients discharged with an index diagnosis was identified. Exactly 610 patients were later readmitted following diagnoses of hyperthyroidism. Patients with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism when compared to patients with depression. LIMITATIONS: The results apply only to hospitalized patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients hospitalized with bipolar disorder tend to be at greater risk of readmission with hyperthyroidism than suitable control patients.

Adult↗

PubMed1989

Electrophysiological abnormalities and enhanced reperfusion arrhythmias in the isolated hearts of hyperthyroid rats.

1. The influence of hyperthyroidism on electrophysiological characteristics and on reperfusion arrhythmias was examined in rat hearts. 2. Electrophysiological studies were performed with glass microelectrodes, and the experiments on reperfusion arrhythmias were done in isolated perfused hearts. 3. Ventricular muscle from hyperthyroid rats was more prone than that from euthyroid rats to develop triggered activity under conditions believed to cause myoplasmic Ca2+ overload. 4. The severity of reperfusion arrhythmias was significantly enhanced in hyperthyroid preparations as compared with euthyroid ones. 5. The enhanced reperfusion arrhythmias in hyperthyroid rats were significantly reduced by propranolol (3 x 10(-7) M), lignocaine (1 x 10(-5) M) and verapamil (3 x 10(-8) M), but not by nadolol (3 x 10(-7) M) or prazosin (3 x 10(-7) M). 6. These results suggest that increased heart rate due to hyperthyroidism and responses mediated via either alpha- or beta-adrenoceptors were not dominant causes of enhanced reperfusion arrhythmias in hyperthyroid hearts. 7. The increased tendency to develop triggered activity which was observed in the electrophysiological study, may be one possible explanation of enhanced reperfusion arrhythmias in hyperthyroid hearts.

Action Potentials↗

PubMed1978

Thyroid function tests in elderly hyperthyroid patients.

Several tests of thyroid function were performed in 35 hyperthyroid patients over the age of 65 (elderly). The results were compared to those of similar tests in 48 hyperthyroid patients under the age of 65 (young). Total serum thyroxine (T4) was within the normal range in 14 percent of the elderly and 11 percent of the young hyperthyroid patients. The free thyroxine index (FTI) was within the normal range in 11 percent of both groups. The triiodothyronine uptake (T3U) proved to be a poor test in both groups. Although elevation of the triiodothyronine (T3) level allowed a diagnosis of "T3-toxicosis" in 2 elderly and 3 young hyperthyroid patients, the T3 level was normal in 34 percent of the elderly and 13 percent of the young subjects. Correction of the T3 range for age reduced the number of normal T3 values to 12.5 percent in the elderly hyperthyroid patients. The 24-hour uptake of radioactive iodine was normal in 12 percent of the young hyperthyroid patients, 27 percent of the elderly patients with Graves' disease, and 70 percent of the elderly patients with toxic nodular goiter, despite recent readjustment of the normal range for the test. It is concluded that the diagnosis of hyperthyroidism in the elderly may be difficult and that no single test can be relied upon to exclude the diagnosis.

Adult↗

PubMed1985

The effect of age on blood pressure in hyperthyroidism.

To better define the effect of age on blood pressure in patients with hyperthyroidism, the blood pressures of 321 patients with hyperthyroidism were compared with those of 324 euthyroid controls. Subjects were divided into four age groups by decade from 20 to 59 years. The systolic, but not diastolic, blood pressure in the patients with hyperthyroidism was significantly higher in all age groups. Among the euthyroid controls, the systolic blood pressure increased with age. However, no age-related increase was apparent among the hyperthyroid patients because of the relatively high systolic blood pressure in young patients. Effective antithyroid treatment reduced the systolic blood pressure significantly in hyperthyroid patients. The reduction of systolic blood pressure was greater in the younger hyperthyroid patients than that in the older ones, so that an age-related increase in systolic blood pressure was present after a euthyroid state had been achieved. These results provide evidence against the report that in hyperthyroidism, hypertension tends to occur in older patients, and suggest that the effect of excessive thyroid hormone on the systolic blood pressure may differ according to age.

Adult↗

PubMedDate not supplied

Hypertension in cats with chronic renal failure or hyperthyroidism.

The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in 28 cats with naturally occurring renal failure, 39 cats with hyperthyroidism, and 33 clinically normal cats. The mean systolic and diastolic blood pressures in the normal cats were 118.4 +/- 10.6 mm Hg and 83.8 +/- 12.2 mm Hg, respectively. In the cats with chronic renal failure, both the systolic (146.6 +/- 25.4 mm Hg) and diastolic (96.6 +/- 15.2 mm Hg) blood pressures were significantly higher (P less than 0.0001 and P less than 0.01, respectively) than in the normal cats. Elevations in systolic and/or diastolic blood pressure were recorded in 17 (61%) of the 28 cats with chronic renal failure. In the 39 untreated hyperthyroid cats, both the mean systolic (167.9 +/- 28.9 mm Hg) and diastolic (111.6 +/- 21.5 mm Hg) pressures also were significantly higher (P less than 0.0001) than normal. Increased systolic and/or diastolic blood pressure was recorded in 34 (87%) of the 39 hyperthyroid cats. In seven cats with hyperthyroidism that were reevaluated two to four months after successful treatment of the hyperthyroid state, there was a significant fall in mean systolic pressure (P less than 0.05) from a pretreatment value of 159.5 +/- 15.4 mm Hg to a posttreatment value of 132.0 +/- 1.62 mm Hg. Overall, the results of this study indicate that mild to moderate hypertension is common in cats with chronic renal failure and in cats with untreated hyperthyroidism. In addition, the hypertension appears to be reversible following successful treatment of the hyperthyroid state.

Animals↗

PubMed1982

Altered developmental changes of neuromuscular junction in hypo- and hyperthyroid rats.

1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo- and hyperthyroid rats from the age of birth (day 0) to day 35.2. Hypothyroidism in new-born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 muCi (131)I on day 1. Hyperthyroidism was induced by daily injection of thyroxine.3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5-8 days, while in hyperthyroid rats the elimination was accelerated by 2-3 days.4. The frequency of miniature end-plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0-5 to 1/sec on days 25-35. The m.e.p.p. frequency in hypothyroid rats was 25-65% of that in normal rats of the same age. In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration of m.e.p.p. measured on day 22-23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end-plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypo-or hyperthyroid rats.7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.

Acetylcholine↗

PubMed1979

Effect of hypoxia on mechanical properties of hyperthyroid cat papillary muscle.

It has been previously established that hyperthyroid myocardium exhibits increased performance under well-oxygenated conditions. To date, it is not known whether hyperthyroid cardiac muscle can maintain this increased performance during hypoxia. The responses of isolated right ventricular papillary muscles from hyperthyroid and euthyroid kittens to hypoxia were compared under isometric conditions at 31 degrees C. Under well-oxygenated conditions, the hyperthyroid cardiac muscle exhibited both an increased contractility and an accelerated rate of relaxation. A similar degree of acute hypoxic stress for 15 min resulted in a greater decrease in contractility in the hyperthyroid compared with the euthyroid papillary muscle as indicated by a greater fall in both peak tension development (2.2 +/- 0.25 from 4.2 +/- 0.2 vs. 0.9 +/- 0.15 from 3.2 +/- 0.4 g/mm2, P less than 0.01) and +dT/dt (12.9 +/- 2.3 from 25 +/- 3 vs. 4.0 +/- 0.6 from 14 +/- 1 g-s-1-mm-2, P less than 0.01). In addition, compared with the euthyroid data, hypoxia resulted in impaired myocardial relaxation in the hyperthyroid cardiac muscle. Thus, the hyperthyroid compared with the euthyroid papillary muscle exhibits both a greater decrease in contractility and an impairment of myocardial relaxation during hypoxia, indicating a greater susceptibility to a given hypoxic stress.

Animals↗

PubMed1995

Effects of hyperthyroidism on muscle blood flow during exercise in rats.

Hyperthyroidism is associated with exercise intolerance. Previous research, however, has shown that cardiac output is either normal or enhanced during exercise in the hyperthyroid state. We therefore hypothesized that blood flow to working skeletal muscle is augmented in hyperthyroid animals during in vivo submaximal exercise and, consequently, that noncardiovascular factors are responsible for intolerance to exercise. To test this hypothesis, rats were made hyperthyroid (Hyper) over 6-12 wk with injections of triiodothyronine (300 micrograms/kg). Hyperthyroidism was evidenced by left ventricular hypertrophy [euthyroid (Eut), 2.12 +/- 0.05 mg/g body wt; Hyper, 2.78 +/- 0.06; P < 0.005], 25-60% increases in citrate synthase activities in Hyper hindlimb muscles over those of Eut rats, and higher preexercise heart rates (Eut, 415 +/- 18 beats/min; Hyper, 479 +/- 19; P < 0.025). Regional blood flows were determined by the radiolabeled microsphere method, preexercise, and at 1-2 min of treadmill running at 15 m/min (0% grade). Total hindlimb muscle blood flow preexercise was unaffected (Eut, 31 +/- 4 ml.min-1.(100) g-1, n = 11; Hyper, 40 +/- 6, n = 9; not significant) but was higher (P < 0.025) in Hyper (127 +/- 17, n = 9) compared with Eut (72 +/- 11, n = 9) during treadmill running. During exercise, flows to individual muscles and muscle sections were approximately 50-150% higher in Hyper compared with Eut rats. Visceral blood flows were largely similar between groups. These findings indicate that hyperthyroidism is associated with augmented blood flow to skeletal muscle during submaximal exercise. Thus hypoperfusion of skeletal muscle does not account for the poor exercise tolerance characteristic of hyperthyroidism.

Animals↗

PubMed1996

Myosin heavy chain of immature soleus muscle grafts adapts to hyperthyroidism more than to physical activity.

The interaction of hyperthyroidism and the elements of physical activity on early regeneration of muscle grafts was investigated. Soleus muscle grafts were studied 15 days after graft operations in eu- and hyperthyroid rats. Hypotheses were tested regarding the adaptation of the myosin heavy chain (MHC) profile of grafts and nongrafted control muscles and whether the effect of hyperthyroidism would predominate over the opposing influence of recruitment and mechanical load on MHC of grafts. Denervation and myectomy of synergist muscles were employed to manipulate the elements of physical activity. Denervation decreased the expression of type I MHC, and hyperthyroidism furthered the shift toward a "fast" isoform profile. For example, in denervated grafts, type IIb was undetected in euthyroid rats and accounted for 31% of MHC in hyperthyroid rats. Compared with control muscles, grafts in the denervated and innervated-normal load groups demonstrated greater plasticity because the adaptive response of MHC to thyroid status was more pronounced. Hyperthyroidism predominated over the opposing influence of the elements of physical activity on the regulation of MHC expression in innervated plus overload grafts. For example, type I MHC was 86% of MHC profile of innervated plus overload grafts in euthyroid rats and was only 49% in hyperthyroid rats. In conclusion, a heightened plasticity for grafts was evidenced in denervated and innervated tissues, and the regulation of MHC by thyroid hormone predominated over that due to the elements of physical activity.

Animals↗

PubMed2000

McCune-Albright syndrome associated with non-autoimmune type of hyperthyroidism with development of thyrotoxic crisis.

We report on a patient having McCune-Albright syndrome (MAS) associated with non-autoimmune hyperthyroidism associated with thyrotoxic crisis. Polyostotic fibrous dysplasia developed at age 8, and café-au-lait pigmentation was noted on the skin. At age 18, he developed hyperthyroidism with multiple adenomatous changes. The hyperthyroidism had been controlled with an antithyroid drug, but the antithyroid medication was discontinued by the patient at age 23. One year later, thyrotoxic crisis developed with fever, convulsions and loss of consciousness. Thyroid function tests showed serum concentrations of free T(4) of 5.1 ng/dl, and serum TSH of <0.1 microU/ml. Serum thyroglobulin concentrations were markedly increased (1,280 ng/ml). Three major thyroid-related autoantibodies (TSH receptor antibody, antithyroglobulin, and antimicrosomal antibodies) were not detected in serum. Serum GH concentrations were increased, and not suppressed by the glucose tolerance test, but increased paradoxically by TRH. The thyrotoxic crisis was ameliorated by treatment with a beta-adrenergic receptor-blocking agent, glucocoroticoid, iodine, antithyroid drug, and antibiotics. The cause of thyroidal defect in our patient is not considered to be autoimmune hyperthyroidism, but hyperthyroidism due to constitutive activation of G(s)alpha by inhibition of its GTPase. This paper describes, as far as we know, the first case of MAS associated with thyrotoxic crisis. Because hyperthyroidism in this patient recurred quickly after discontinuation of the antithyroid drug, the mode of treatment for MAS-associated hyperthyroidism appears to be total surgical ablation or repetitive radioiodine therapy.

Adult↗

PubMed2003

Relationship of stressful life events, anxiety and depression to hyperthyroidism in an asian population.

BACKGROUND: Psychological disturbances are well-known disorders in patients with hyperthyroidism, with anxiety and depression being the most commonly described. Stressful life events may play an important role in the relationship of anxiety, depression and hyperthyroidism. We assessed the associations of these disorders by three-part rating scales, including the Hamilton Rating Scale for Anxiety (HAM-A) indicating anxiety, the Zung Self-Rating Depression Scale (Zung Scale) indicating depression and the Social Readjustment Rating Scale (SRRS) indicating external stress from life events in this study. METHODS: Eighty-six outpatients who visited an endocrine clinic with suspicion of thyroid disease and 18 healthy volunteers were enrolled in the study. In all of these individuals, thyroid functions were assessed and questionnaires were completed during an interview. RESULTS: The outpatients with hyperthyroidism (n = 39) had higher scores of HAM-A (15.7 +/- 1.1 vs. 8.0 +/- 0.8, p < 0.001), Zung scale (46.2 +/- 1.5 vs. 37.5 +/- 1.4, p < 0.001) and SRRS (92.9 +/- 13.5 vs. 56.9 +/- 8.4, p = 0.015) than those with euthyroidism (n = 47). The scores of the three-part rating scales were also higher in the outpatients with hyperthyroidism than in healthy volunteers (n = 18), with no significant differences between the outpatients with euthyroidism and healthy volunteers. CONCLUSION: In patients with hyperthyroidism, anxiety, depression and stressful life events were more severe than in those with normal thyroid function. There were no correlations between these psychological disorders and thyroid function tests of the subjects with hyperthyroidism. The role of psychotherapy in the development of hyperthyroidism deserves further investigations.

Adult↗

PubMed1987

Effects of beta-blocking agents on urinary excretion of 3-methylhistidine during experimental hyperthyroidism in rats.

Beta-blocking agents are increasingly used as preoperative treatment of hyperthyroid patients. Relatively little is known about the effects of these drugs on metabolic alterations in hyperthyroidism. The aim of this investigation was to study the effects of two different beta-blocking agents on the urinary excretion of 3-methylhistidine (3-MH) during experimental hyperthyroidism in rats. Experimental hyperthyroidism was induced by daily intraperitoneal injections of triiodothyronine (T3; 100 micrograms/100 g body weight) for 3 days. Control animals were injected with corresponding volumes of solvent. Groups of rats received food enriched with metoprolol (8.8 mmol/kg of diet) or propranolol (3.3 mmol/kg of diet) or food without additions. Urinary 3-MH excretion was increased by about 40% during experimental hyperthyroidism. A similar increase of 3-MH excretion was found in animals receiving T3 + metoprolol, whereas the excretion of 3-MH was reduced to control level in hyperthyroid rats receiving propranolol. No effects of metoprolol or propranolol on 3-MH excretion were found in control animals. Although the source of 3-MH cannot be exactly defined, the present results indicate that increased proteolysis in skeletal muscle and/or other tissues during experimental hyperthyroidism was reduced by propranolol.

Adrenergic beta-Antagonists↗

PubMed1992

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.

Adult↗

PubMed2002

Cloning of the cat TSH receptor and evidence against an autoimmune etiology of feline hyperthyroidism.

Cats are the only nonhuman mammalian species with a high incidence of hyperthyroidism, and a better understanding of the pathogenesis of feline hyperthyroidism is of clinical relevance for veterinary medicine. The etiology of this disease in cats remains controversial. Both an intrinsic autonomy of growth and function of follicular cells as well as an autoimmune-related mechanism have been proposed. To explore the role of the autologous TSH receptor (TSHR) in the pathogenesis of hyperthyroidism in cats, we cloned the coding sequence of the feline TSHR by RT-PCR. The open reading frame consists of 2292 nucleotides and encodes a 763-amino acid protein, one amino acid less than the human TSHR. Species comparison reveals that the cat TSHR is most closely related to the canine TSHR, with 96% identity and 97% similarity in amino acid sequence. cAMP accumulation, inositol phosphate production, and TSH binding were similar in the feline TSHR, compared with the human receptor. Analogous to the human TSHR, the cat TSHR also displays basal constitutive activity. To test the possibility that hyperthyroid cats develop antibodies that stimulate the autologous receptor, transfected cells expressing the feline TSHR were treated with sera or purified IgG obtained from 16 hyperthyroid cats. There was no increase in cAMP-dependent luciferase activity in the hyperthyroid cats, suggesting the absence of stimulatory autoantibodies. These sera were also negative for TSH-binding inhibitory Igs in an RRA. At least in the animals included in this study, there is no evidence for the presence of circulating thyroid stimulating factors as a mechanism underlying the pathogenesis of feline hyperthyroidism, and the findings support a model involving intrinsic autonomy of thyroid follicular cell growth and function.

Amino Acid Sequence↗

PubMed2006

Increase in incidence of hyperthyroidism predominantly occurs in young people after iodine fortification of salt in Denmark.

CONTEXT: To prevent goiter and nodular hyperthyroidism, iodine fortification (IF) of salt was introduced in Denmark in 1998. We prospectively registered all new cases of overt hyperthyroidism in two areas of Denmark before and for the first 6 yr after iodine fortification. METHODS: We used a computer-based register of all new cases of hyperthyroidism in two population subcohorts with moderate iodine deficiency (Aalborg, n = 310,124) and mild iodine deficiency (Copenhagen, n = 225,707), respectively. Data were obtained 1) before IF (1997-1998); 2) during voluntary IF (1999-2000); 3) during the early (2001-2002) period of mandatory IF; and 4) during the late (2003-2004) period with mandatory IF. RESULTS: The overall incidence rate of hyperthyroidism increased [baseline, 102.8/100,000/year; voluntary IF, 122.8; early mandatory IF, 140.7; late mandatory IF, 138.7 (P for trend <0.001)]. Hyperthyroidism increased in both sexes (P < 0.001) and in all age groups: 0-19, 20-39, 40-59, and 60+ yr (P for trend <0.001). The increase was relatively highest in young adults aged 20-39 yr: late mandatory IF (percent increase from baseline), age 20-39, 160%, P < 0.001; age 40-59, 29%, P < 0.01; age 60+ yr, 13%, P = not significant. CONCLUSION: Even a cautious iodization of salt results in an increase in the incidence rate of hyperthyroidism. Contrary to current concepts, many of the new cases were observed in young subjects, and are presumably of autoimmune origin. Furthermore, monitoring is expected to show a decrease in the number of elderly subjects suffering from nodular hyperthyroidism.

Adolescent↗