Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter.

PURPOSE: To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS: A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS: Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION: The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder.

Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre.

The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

The long-term outcome of thyroidectomy for sporadic non-toxic goitre.

To study the long-term outcome after thyroidectomy, 113 sporadic non-toxic goitre patients who underwent thyroidectomy in our hospital in the period 1974-1983, were studied. Five patients complained of recurrent goitre; a goitre was found on inspection and palpation in these five and in 15 others. There were no differences between the 20 patients with goitre and the 93 patients without goitre with regard to sex, age, duration of goitre, indication and type of thyroidectomy, postoperative thyroid hormone medication, period of follow-up, and T4, T3, or TSH plasma values at the time of follow-up examination. Twenty-three patients complained of voice changes since thyroidectomy. In a case control study, included in this follow-up study, 19 patients with goitre, i.e. thyroid size I and II as estimated by inspection and palpation (cases), and 16 patients without goitre, i.e. thyroid size OA and OB (controls), were studied in more detail. No difference between cases and controls was found in any of the above mentioned parameters that could explain the recurrence of goitre. Thyroid volume (median) was greater in the cases (34.1 ml, range 7.9-83.4) than in the controls (10.3 ml, range 2.5-48.7) (P less than 0.001), although a considerable overlap between the two groups was observed. One or more thyroid nodules were found in 89.5% of the cases and in 62.5% of the controls (NS). Serum thyroid growth stimulating immunoglobulin (TGI) was present both in cases (68%) and controls (50%). TGI was present in high titres in all five patients who complained about recurrent goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of thyroid volume measured by ultrasonography in the diagnosis of goitre.

UNLABELLED: Thyroid volume was measured by ultrasonography in 80 euthyroid patients with sporadic nontoxic goitre and in 50 healthy adults, all residing in non-iodine deficient areas. All patients were referred because of complaints of goitre and had been diagnosed as cases of goitre by inspection and palpation. The thyroid volume in 15 patients with goitre (19%) was within the normal reference range (4.9-19.1 ml). Fourteen of the 15 patients had thyroid nodules larger (mean diameter 2.9 +/- 1.1 cm) than those detected in nine of the healthy adults (mean diameter 0.8 +/- 0.6 cm; P less than 0.001). Thyroid size as estimated by inspection and palpation (grade OA to III according to Stanbury et al., 1974) was poorly related to thyroid volume measured by ultrasonography. IN CONCLUSION: (1) a thyroid volume within the normal reference range does not rule out the presence of nodular goitre; and (2) application of thyroid volume measurement by ultrasonography may prevent overestimation of goitre prevalence in epidemiological surveys.

The application of an immunoradiometric assay of plasma thyrotropin (TSH-IRMA) in molar pregnancy.

Plasma thyrotropin was measured by immunoradiometric assay (TSH-IRMA, "Sucrosep", Boots Celltech) in three patients with molar pregnancy. Two patients were hyperthyroid (increased plasma concentrations of FT4, FT4 index, and FT3 index), one patient was euthyroid (normal free thyroid hormone concentrations). TSH-IRMA values were below the detection limit (less than 0.1 mU/L) in the two hyperthyroid patients; the euthyroid patient had a TSH-IRMA value of 0.8 mU/L, within the reference range of normal subjects (0.5-3.3 mU/L). In vitro experiments demonstrated interference of the grossly elevated hCG levels in the TSH-IRMA, resulting in lower values. The observed interference was independent of ambient TSH concentrations, but related to hCG levels. We conclude that despite interference of hCG in TSH-IRMA the clinical usefulness of TSH-IRMA as a first-line test of thyroid function appears to be maintained in molar pregnancy.

Determinants of thyroid volume as measured by ultrasonography in healthy adults in a non-iodine deficient area.

Thyroid volume was measured by ultrasonography in 50 healthy adults (25 males, 25 females, age 20-70 years) living in the non-iodine deficient area of Amsterdam. Thyroid volume was 10.7 +/- 4.6 ml (mean +/- SD, range 2.7-20.4 ml). No relation was found between thyroid volume and any of the following parameters: plasma TSH, T4, T3, thyroglobulin (Tg), urinary iodine excretion, tobacco and alcohol consumption. Thyroid volume in males (12.7 +/- 4.4 ml) was greater than in females (8.7 +/- 3.9 ml, p = 0.0014), but no sex difference was observed in the ratio of thyroid volume to body weight (males, 0.16 +/- 0.05 ml/kg; females 0.13 +/- 0.06 ml/kg; NS). Thyroid volume was positively related to body weight, but not to age. We conclude that the sex difference in thyroid volume is due to the difference in body weight between males and females. Lean body mass is presumably the most important physiological determinant of thyroid size in subjects living in a non-iodine deficient area.

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism.

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. 99mTc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I [5.4 +/- 0.8% (+/- SE) at 60 min] was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by 99mTc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients. 2) The organification defect induced by iodine excess is greater in iodide-induced hypothyroidism than in eu- or hyperthyroidism. These findings may be explained by the increased TSH secretion in hypothyroidism and/or by decreased thyroidal concentration of an unknown specific iodinated compound (whose concentration and action vary with the total organic iodine content of the thyroid) that mediates the inhibition of iodide transport.

Thyroid hormones in acute myocardial infarction.

Thyroid hormones were serially measured over a 2-week period in thirty-four consecutive patients with acute myocardial infarction (AMI). A transient increase in plasma rT3 and a decrease in plasma T3 was found, with the maximum changes occurring on the third day after the onset of AMI. The changes in plasma rT3 and T3 were greater in the seventeen patients with a complicated AMI (mean peak SGOT 145 mu/l) than in the seventeen patients with an uncomplicated AMI (mean peak SGOT 79 mu/l). A correlation was found between infarct size (as estimated by the peak SGOT value) and the following indices: delta r T3, delta T3, highest rT3/t3 and highest rT3/T4 ratios. A transient increase in plasma TSH (peak on days 4 and 5) and in plasma T4 and FT4 index (peak on days 6 and 7) was also observed, whereas T3 resin uptake (T3U) decreased. These findings suggest that the following sequence of events occurs in thyroid hormone metabolism during AMI: (1) inhibition of the 5'-deiodination of T4, resulting in increased plasma rT3 and decreased plasma T3 values, and in a lower metabolic clearance of T4. (2) Increased secretion of TSH (provoked by the lower T3 levels) resulting in increased thyroidal secretion of T4 and T3, which is then switched off by the negative feedback of thyroid hormones on the pituitary.

The relation between gastrin, gastric acid and thyroid function disorders.

Hypergastrinaemia was found in 11 out of 24 untreated hyperthyroid patients (Graves' disease or nodular goitre). Seven patients had a co-existent (autoimmune) atrophic gastritis. In the remaining 17 patients plasma T3 was positively related to plasma gastrin, and negatively to gastric acid output; there was no relation between gastrin levels and acid output. Acid instillation into the stomach revealed a normal negative feedback of acid upon gastrin release. Sixteen hyperthyroid patients were restudied when euthyroid. Plasma gastrin decreased from 171 (51-1188) ng/l before treatment to 69 (39-392 ng/l after treatment (P < 0.002), and maximal acid output increased from 1.55 (0.00-22.75) to 8.03 (0.00-26.60) mmol H+/h (P < 0.01) (median values; range in brackets). However, in 4 patients with complete achlorhydria before and after treatment plasma gastrin decreased to the same extent as in the patients with gastric acid secretion. We conclude that thyrotoxic hypergastrinaemia cannot be fully explained by the low gastric acid output in hyperthyroidism.

The value of an intravenous TRH test for the diagnosis of tumoural prolactinaemia.

The plasma Prl response to 200 micrograms TRH iv was evaluated in 6 hyperprolactinaemic women without radiological evidence of a pituitary tumour (group I), in 15 hyperprolactinaemic women with dubious (group II) and in 17 normo- or hyperprolactinaemic women with clear (group III) radiological abnormalities, in 18 normo- or hyperprolactinaemic men with clear radiological abnormalities (group IV), and in 4 women and 3 men with hyperprolactinaemia and sellar destruction who had been treated in the past for pituitary adenoma (group V). The responses were compared with those obtained in a control group of 83 (42 women, 41 men) normoprolactinaemic healthy individuals. The Prl response was defined as a ratio (R2): the 20 min value minus the 0 min value, divided by the 0 min value. The median R2 values were: female controls 5.1, male controls 3.1, group I 0.1, group II 0.2, group III 0.3, group IV 0.55, group V females 0.45 and males 0. It is concluded that 1) subjects suspected of harbouring a microprolactinoma (groups I and II) demonstrate absent or attenuated responses similar to those found in patients with definite prolactinomas and 2) a value of plasma Prl 20 min after 200 micrograms TRH iv greater than 3.5 times the basal level (R2 > 2.5) rules out the presence of a prolactinoma.

Propranolol inhibits the in vitro conversion of thyroxine into triiodothyronine by isolated rat liver parenchymal cells.

A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation. Carbimazole (50 microM) has no effect on the conversion process, whereas propylthiouracil (50 microM) inhibits the conversion. The beta-adrenoceptor blocking agent propranolol lowers the conversion ratio when added in concentrations of 580 and 1160 microM, but has no inhibitory effect when 290 microM is added.