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Hyperthyroidism and the impalpable thyroid gland.

A retrospective analysis of 594 unselected cases of hyperthyroidism from one district was made to determine whether the thyroid gland had been palpable on presentation. The thyroid had been diffusely palpable in 374 patients (63%), nodular in 110 (19%) and impalpable in 96 (16%); there was no clinical record in 14 (2%) cases. Under 40 years of age a diffuse gland was usual, being present in 86% of cases. The proportion of nodular and impalpable glands both increased progressively with age comprising 30% and 48% respectively in patients older than 70 years. Grave's ophthalmopathy was present in 13% of hyperthyroid patients with diffuse glands, in 12% of those with impalpable glands, but in only 1.5% of those with nodular thyroids. Thyroid autoantibodies were found with a similar frequency in all three groups. There was a very good correspondence between clinical assessment of shape and nodularity of thyroid and the results of isotope scanning; the majority of patients with impalpable glands (86%) had a diffuse uptake of isotope. In the elderly hyperthyroid patient an impalpable thyroid gland is common and is not a factor to weight against the diagnosis.

Adolescent↗

Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies.

We report a 48-year-old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L-T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29.1 pmol/l after cessation of L-T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal less than 140%), while thyroid stimulation-blocking antibodies (TSBAb) determined by inhibition of TSH-induced cyclic AMP increase were positive at 96.1% (normal less than 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.9%), while TSBAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid-relating antibodies change in the course of the disease.

Antibodies↗

Effects of hyperthyroidism on binding proteins for steroid hormones.

Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) binding capacities were examined weekly in eight normally cycling women and three women taking birth control pills during a 5-week baseline period and after daily ingestion of 75 micrograms of L-triiodothyronine (T3) for 30 days. The SHBG binding capacity increased whereas the CBG binding capacity decreased after T3 therapy. The binding capacities of proteins for steroid hormones were measured in 18 hyperthyroid subjects (Graves' disease) prior to and after 3 months of antithyroid drug therapy. SHBG binding capacity in hyperthyroid men or women was higher, and CBG binding capacity lower than those in euthyroid subjects. Thus, during hyperthyroidism, binding capacities of sex hormone binding globulin and corticosteroid binding globulin vary in opposite directions. A statistically significant correlation between the ratio of the sex hormone binding globulin to the corticosteroid binding globulin and triiodothyronine levels was found (P less than 0.01). Therefore the ratio of the sex hormone binding globulin to the corticosteroid binding globulin might be potentially useful as a biochemical index of thyroid hormone action in peripheral tissues.

Adult↗

TSH binding-inhibiting antibodies in hyperthyroidism: relationship to clinical signs and hormone levels.

TSH binding-inhibiting antibody (TBIAb) activity was measured in 809 European patients with different forms of hyperthyroidism. Distribution of these TBIAb was skewed, with a peak in the range of normal controls, and an ill defined, not clearly separated peak at higher levels of TSH displacement. There was no unequivocal separation of two possible subgroups of hyperthyroidism (immunogenic and non-immunogenic). TBIAb distributions of patients with and without endocrine ophthalmopathy (EO) overlapped considerably. Although patients with Graves' disease, arbitrarily defined by the presence of endocrine ophthalmopathy or diffuse nuclide uptake by thyroid scanning, had mostly elevated TBIAb activity, 24.3% had values within the range of normal controls (mean + 2SD). Patients with diffuse thyroid uptake had significantly higher TBIAb levels than patients with nodular scan findings. In Graves' disease, TBIAb activity was positively correlated with the severity of endocrine ophthalmopathy, the size of the thyroid, and the serum levels of total and free triiodothyronine. There was no influence of age, sex, pretreatment, or regional iodine supply. These results suggest (1) that the clinical manifestations of Graves' disease are statistically related to TBIAb activity and (2) that separation of immunogenic and non-immunogenic forms of hyperthyroidism by means of TBIAb determination is unsatisfactory. The almost continuous distribution of TBIAb points to insufficient sensitivity of the present technique and raises doubts as to whether TBIAb values can be reliably classified as 'positive' or 'negative'.

Age Factors↗

Effect of 131I treatment on the calcitonin response to calcium infusion in hyperthyroid patients.

OBJECTIVE: The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. DESIGN: Determination of basal calcitonin levels and calcitonin secretory reserve before and after 131I administration. PATIENTS: Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment. MEASUREMENTS: Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. RESULTS: The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9 +/- 2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6 +/- 0.7 and 1.6 +/- 0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. CONCLUSION: Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency.

Adult↗

Prevalence of subclinical hyperthyroidism and relationship between thyroid hormonal status and thyroid ultrasonographic parameters in patients with non-toxic nodular goitre.

OBJECTIVE: Basal plasma T4, T3 and TSH concentrations are usually normal in patients presenting with non-toxic nodular goitre. Using the evaluation of TSH response to TRH in a large series of such patients living in an area with normal iodine intake, we evaluated the prevalence of subclinical hyperthyroidism and the relationship between thyroid hormonal status and ultrasonographic parameters. PATIENTS: A prospective study of 242 consecutive patients (group I), referred with non-autoimmune nodular goitre, normal plasma free T4, total T3 and TSH levels, without (subgroup IA, 222 patients) or with (subgroup IB, 20 patients) clear-cut autonomous area(s) on scintigraphy. These patients were compared to 135 controls (group II). MEASUREMENTS: Plasma free T4 (FT4), total T3 (T3T) and TSH measurements. Evaluation of TSH response to TRH (delta level of increased TSH = peak TSH level during TRH test-basal TSH level), thyroid scintigraphy and morphological characteristics (number and total volume of nodule(s) and volume of extranodular tissue) determined by ultrasonography. RESULTS: In subgroup IA, (1) the mean (+/- SEM) basal TSH level (0.94 +/- 0.04 mU/I) and the mean value of increased TSH after TRH (4.92 +/- 0.34 mU/I) were lower (P < 0.001) than in group II (1.28 +/- 0.05 mU/I and 7.24 +/- 0.25 mU/I, respectively). The prevalence of SH (delta level of increased TSH below the mean -3 SD in controls) was 17.2%; (2) the mean FT4 level and the mean T3T value were not different (P > 0.05) from those of group II. In subgroup IB, (1) the mean basal TSH level (0.57 +/- 0.11 mU/I) and the mean increment of TSH after TRH (2.81 +/- 0.62 mU/I) were lower (P < 0.001) than in subgroup IA. The prevalence of subclinical hyperthyroidism was 75.0%; (2) the mean FT4 level (17.2 +/- 0.9 pmol/I) was not different from that in group II. However, the mean T3T value (1.99 +/- 0.01 nmol/I) was higher (P < 0.001) than in group II (1.65 +/- 0.05). In group I, subgroup IA and IB, there were significant (P < 0.05, at least) correlations between the numbers of nodules and both basal TSH levels and delta values of increased TSH or FT4 levels or T3T values. No correlations were found between other ultrasonographic data and plasma thyroid parameters. CONCLUSIONS: This study demonstrates a high prevalence of subclinical hyperthyroidism in patients presenting with non-toxic nodular goitres and suggests that the number of nodules, but not their total volume, is an important factor in the development of this condition.

Adolescent↗

Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism.

OBJECTIVE: There is recent evidence that both exogenous and endogenous subclinical thyrotoxicoses are associated with decreased bone mineral density. Scanty information is available on bone metabolism in these conditions when euthyroidism is restored. We evaluated the effect of anti-thyroid drug treatment on bone metabolism in endogenous subclinical hyperthyroidism. DESIGN: Prospective follow-up study over 2 years during treatment with methimazole, with an untreated control group. SUBJECTS: Sixteen post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre, eight of whom were treated with methimazole. MEASUREMENTS: Serum concentrations of free T4, total T3, TSH, osteocalcin, urinary excretion of hydroxyproline and forearm bone mineral density were measured at regular intervals. RESULTS: Significant changes in serum osteocalcin concentration or urinary hydroxyproline excretion were not observed in either group. Distal, but not proximal, forearm bone mineral density, expressed as a percentage of the base-line value, was significantly (P < 0.05) higher in the treated than in the untreated subjects in the second year of treatment. CONCLUSION: Treatment with methimazole in post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre can prevent excessive loss of bone, at least in the distal forearm.

Bone Density↗

MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan.

MELAS syndrome is a form of mitochondrial myopathy with manifestations of seizure, stroke-like syndrome, lactic acidosis, ragged red muscle fibres and mitochondrial encephalopathy. The syndrome has been reported in association with a variety of endocrine and metabolic disorders including diabetes mellitus (DM), hypothalamo-pituitary hypofunction, hypothalamic growth hormone deficiency and delayed puberty. Mitochondrial DNA (mtDNA) point mutation may be the major pathological defect. However, association of MELAS syndrome with hyperthyroidism has not previously been reported. A case is reported from Taiwan of a 32-year-old woman suffering from MELAS syndrome with associated DM and hyperthyroidism. When the latter was diagnosed in April 1988, the patient underwent subtotal thyroidectomy. There was no family history of thyroid disease. Because of repeated seizures, she had computed tomography (CT) and magnetic resonance imaging (MRI) of the brain which showed focal, low-density lesions over the cerebral hemispheres. Both serum and cerebral spinal fluid lactic acid levels were elevated. Mild elevations of serum T4 and T3 and a high titre of TSH receptor antibody were still present. Hyperglycaemia was noted during hospitalization and DM confirmed by oral glucose tolerance test. Muscle biopsy showed ragged red fibres. DNA analysis showed an A-to-G transition at the 3243rd nucleotide position of the tRNA(Leu(UUR)) gene of the mtDNA from the patient. Quantitative polymerase chain reaction (PCR) and restriction analysis revealed that about 60% of the blood mtDNA was of mutant type. The patient received antithyroid drugs for hyperthyroidism, diet control for DM and anti-epileptic drugs for seizure.

Adult↗

Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for subclinical hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months' duration with two parallel groups. PATIENTS AND METHODS: Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. RESULTS: At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0.003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0.050) was observed. No improvement in the SDQ score was observed. CONCLUSION: In summary, quality of life in patients with DTC and long-term subclinical hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.

Fatigue↗

Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for subclinical hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. PATIENTS: Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). MEASUREMENTS: We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. RESULTS: At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. CONCLUSION: In summary, glucose and lipid metabolism in patients with DTC and long-term subclinical hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.

Adult↗

Effect of hyperthyroidism and propylthiouracil treatment on liver biochemical tests.

Liver biochemical test (LBT) changes can be commonly observed in hyperthyroid patients. Those kinds of changes could also be observed because of propylthiouracil (PTU) therapy. We prospectively evaluated LBT changes because of PTU use for 1 year in patients who had been diagnosed with hyperthyroidism first. We studied 64 patients who had been diagnosed with hyperthyroidism. These patients took at least 1-year PTU treatment. We analysed LBT at diagnosis and after 2 and 12 months of treatment with PTU. Prior to PTU treatment, 30 (46.8%) of the 64 patients had at least one LBT abnormality. We observed at least one LBT abnormality in 11 (32%) patients after 2 months and nine (26%) patients after 12 months of treatment with PTU in 34 patients whose CBT were normal before treatment. We did not observe any deterioration in clinical picture and bilirubin levels. Elevated serum LBT during the pretreatment and PTU treatment period is common and usually transient and asymptomatic. PTU could be used for long times by lowering the dose and close follow-up in patients who have elevated LBT during the pretreatment and after PTU treatment period.

Adult↗

Hypercalcaemia and hypertransaminasaemia in a child with hyperthyroidism.

Hypercalcaemia and hypertransaminasaemia are well recognized and not infrequent findings in hyperthyroidism in adults. Both conditions are seldom reported in children. Here we report the case of a 4-year-old girl with hyperthyroidism associated with hypercalcaemia and hypertransaminasaemia which were reversed after euthyroid state was achieved. We recommend that serum calcium and liver function should always be monitored in children with hyperthyroidism.

Calcium↗

Effect of surgical stress on serum thyroid hormones in hyperthyroidism.

The effect of elective non-thyroidal surgery on serum total and free triiodothyronine (T3), reverse T3 and thyroxine (T4) has been studied in one patient with mild, untreated typical hyperthyroidism, one with mild T3 toxicosis and in four euthyroid patients. The high T3 level of typical hyperthyroidism became normal post-operatively, decreasing to 47% of the mean pre-operative level 24 hours after surgery, while total reverse T3 doubled. In euthyroid subjects T3 decreased to 57 +/- 6 (SEM)% of the pre-operative level 24 hours after surgery, associated with a doubling of reverse T3. The patient with T3 toxicosis, whose surgical stress was less severe, showed a 17% decrease in T3 without change in reverse T3. Because the inverse post-operative changes in T3 and reverse T3 described in euthyroid subjects also occur in typical hyperthyroidism, measurement of serum T3 may be diagnostically unreliable after surgical stress.

Adult↗

Atrial fibrillation and arterial embolism in hyperthyroidism.

Atrial fibrillation or flutter was present in 70 of 381 patients with uncontrolled hyperthyroidism; return to stable sinus rhythm occurred in 39 with antithyroid and antiarrhythmic treatment. One third of the patients who reverted did so in the first week of treatment while still hyperthyroid. As expected, reversion was more likely in younger patients, and in those with arrhythmia of recent onset, without evidence of other heart disease. Eight patients with arrhythmia had proven (five) or probable (three) major arterial embolic episodes. Four of these eight patients died. Embolism tended to occur at an early stage, during uncontrolled hyperthyroidism, in patients with both atrial fibrillation and cardiac failure. These findings suggest that prophylactic anticoagulation may be appropriate in this high risk group, although more extensive studies are necessary before effective prevention of embolism can be claimed.

Adolescent↗

Hyperthyroidism complicating pregnancy: results of treatment by antithyroid drugs in 77 pregnancies.

Seventy-seven pregnancies (79 infants) complicated by hyperthyroidism were seen at three Dublin Maternity Hospitals during a 25 year period. Hyperthyroidism was diagnosed following conception in 14 pregnancies. Treatment was with carbimazole alone in 73 pregnancies, in a usual dose of 5 to 10 mg daily. The total fetal loss was 15.2 per cent with a perinatal loss of 5.1 per cent. The perinatal loss in patients treated with carbimazole alone was 4.1 per cent (excluding one death due to congenital malformation). Four infants (5.1 per cent) had goitre and 57 (85.1 per cent) of the surviving infants were above the 25th centile for gestational age. Spontaneous premature labour occurred in 7 pregnancies (9.1 per cent). There was a relative excess of infants with a birth weight less than the 25th centile, of neonatal goitre and premature labour after pregnancy in which treatment was started following conception. Hyperthyroidism complicating pregnancy can be treated effectively with antithyroid drugs given alone and in the minimal effective dose.

Antithyroid Agents↗

Effect of hyperthyroidism on fibre-type composition, fibre area, glycogen content and enzyme activity in human skeletal muscle.

Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca2+- and Mg2+-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.

Adult↗

Hyperthyroidism in the elderly.

In 65 elderly hyperthyroid patients (age range 50-78 years), sex differences, signs and symptoms and thyroid function were studied and the data were compared with those on 48 young hyperthyroid patients (age range 20-29 years). The incidence of hyperthyroidism was 3.5 times higher in females than in males among the young patients, whereas it was approximately equal in males and females among the elderly patients. Signs and symptoms conformed with the textbook description in the young subjects but not in the elderly ones. Measurements of serum triiodothyronine (T3) and thyroxine (T4) proved useful in preventing false diagnoses in elderly patients with atypical symptoms. In some elderly subjects with marginal increases of serum T3 and T4 concentrations, measurement of serum thyroid-stimulating hormone (TSH) after administration of thyrotropin-releasing hormone (TRH) was required to achieve an accurate diagnosis. Serum T3 and T4 levels and the thyroidal uptake of radioiodine were slightly but not significantly lower in the elderly than in the young patients. A high titer of circulating thyroid auto-antibody in the elderly may be related to this slight decrease in thyroid function. Serum T3 levels were significantly lower in the elderly than in the young subjects; this suggests impairment of peripheral monodeiodination of T4. Any abnormal serum levels of T4, T3, and TSH before and after administration of TRH could easily be restored to normal by treatment with antithyroid drugs in the elderly patients.

Adult↗

Hyperthyroid chorea in an elderly woman associated with sole elevation of T3.

A 72-year-old woman presented with chorea, mild tachycardia, and elevation of T3RIA. T4 was not elevated until the third determination. Chorea resolved with treatment of hyperthyroidism. This case represents the first case of T3 hyperthyroid chorea and the oldest patient with hyperthyroid chorea described in the literature. It demonstrates yet another subtle way in which thyroid disease can present in the elderly.

Aged↗