Laszlo Hegedüs

Influence of thyroxine treatment on thyroid size and anti‐thyroid peroxidase antibodies in Hashimoto's thyroiditis

Summary. objective it has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimotos thyroiditis but no objective data are available. We have therefore Investigated the Influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxldase antibodies.

Acute effects of insulin on plasma noradrenaline and the cardiovascular system

It is now known that insulin has marked acute effects on plasma noradrenaline and the cardiovascular system. These effects of insulin are not due to hypoglycemia and occur without changes in plasma adrenaline. Intravenous injection of insulin in juvenile diabetics increased plasma noradrenaline and heart rate and decreased glomerular filtration rate, renal and peripheral blood flow, and plasma volume. Urinary excretion rates of beta-2-microglobulin and urinary volume decreased after insulin, whereas urinary albumin excretion increased. When blood glucose was maintained by glucose infusion after insulin, glomerular filtration rate and renal blood flow remained unaltered whereas plasma noradrenaline, heart rate, and urinary albumin excretion increased and beta-2-microglobulin excretion decreased. Decreases in glomerular filtration rate and renal blood flow after insulin are thus due to the fall in blood glucose. Rise in albumin excretion after insulin is probably of glomerular origin and not caused by the fall in blood glucose or by changes in renal hemodynamics. In patients with long-term diabetic nephropathy and albuminuria, insulin decreased albumin excretion (probably due to renal vasoconstriction) and plasma noradrenaline did not increase. In alloxan-diabetic rabbits the increase in heart rate after insulin was not abolished by autonomic blockade. In short-term streptozotocin-diabetic rats, muscle capillary endothelial cells showed a reduced number of free micropinocytotic vesicles. The number was nearly normalized 1 hr after intramuscular injection of insulin. The mechanism of action of insulin on plasma noradrenaline, heart rate, plasma volume, and urinary albumin excretion is not known. The rise in plasma noradrenaline after insulin may be compensatory to hypovolemia or to antagonizing effects of insulin on some actions of noradrenaline. The findings in streptozotocin-diabetic rats suggest that insulin may be essential for the normal function of capillary endothelial cells.

Observer variation in the clinical assessment of the thyroid gland

Abstract. In order to evaluate the reliability of clinical assessment of the thyroid gland, two specialists in endocrinology and two younger doctors independently examined 53 patients twice, and assessed whether they had a diffuse goitre, a multinodular goitre, a solitary nodule or a normal gland. In 30% of the patients all four observers were in agreement, whereas in 47% and 23% of the patients, two and three different diagnoses were given, respectively. Inter‐observer variation was determined and kappa values between −0.04 and 0.54 were found. Intra‐observer variation was smaller, revealing kappa values between 0.44 and 1.00. The present study suggests that clinical assessment of the thyroid gland may lead to misclassification of the type of thyroid disease, and thereby to a less than optimal choice of therapy.

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a)☆

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).

Oral glucose increases urinary albumin excretion in normal subjects but not in insulin-dependent diabetics.

An oral glucose load increased urinary albumin excretion significantly in six normal subjects (from a mean basal value of 4.6 microgram/min to 16.9 microgram/min at 30-90 min after oral glucose). Urinary excretion of beta-2-microglobulin did not change after oral glucose whereas urinary volume increased. Administration of the water vehicle did not increase albumin excretion. Oral glucose had no effect on urinary albumin excretion in six insulin-dependent diabetics. The effect of oral glucose was not identical to the changes observed after intravenous insulin because oral glucose urinary volume and did not change beta-2-microglobulin excretion whereas insulin decreased both parameters.

Thyroid gland volume and thyroid function during and after acute hepatitis infection

Thyroid function, the occurrence of goiter, and ultrasonically determined thyroid gland volume were investigated in 23 consecutive nonalcoholic patients with acute viral hepatitis during and six months after recovery, and compared with data obtained from 23 matched controls. Seven patients had clinically detectable goiter during disease, but only one after recovery (P less than 0.05). Median thyroid volume was 28 mL (range 15 to 42 mL) compared with 18 mL (range 12 to 27 mL) after recovery (P less than 0.001), and 17 mL (range 11 to 24 mL) in the controls (P less than 0.001). During acute hepatitis, serum levels of thyroxine, thyroxine binding globulin, and free thyroxine index were significantly increased while triiodothyronine and thyrotropin levels were unaltered and triiodothyronine resin uptake and free triiodothyronine index levels were decreased. After recovery all thyroid variables were normalized. In conclusion, acute liver disease was associated with a marked increase in thyroid volume, but the study did not clarify the mechanism underlying thyroid enlargement.

OBSERVER VARIATION IN THE SCINTIGRAPHIC DIAGNOSIS OF SOLITARY COLD THYROID LESIONS

In order to evaluate the reproducibility of the diagnosis of solitary cold thyroid lesions, two specialists in nuclear medicine and two specialists in endocrinology independently twice read 240 thyroid 99mTc pertechnetate scintigrams. No significant difference or interaction between the results obtained from the right and the left lobe was found. A solitary cold lesion was diagnosed in 100 of the 480 lobes; however, in only 30 did all four observers agree upon the diagnosis. Interobserver variation was determined by pairwise comparison of observers. The observed agreement was between 0.91 and 0.94. After adjusting for expected chance agreement, kappa values between 0.57 and 0.70 were found. Intraobserver variation was smaller than interobserver variation, revealing agreement rates of 0.93–0.96 and kappa values between 0.71 and 0.77. Agreement was related to large lesions, lesions located centrally in the lobe, and ovoid‐shaped lesions. Clinicians should be aware to what extent they can rely on the information they use in their decisions. The considerable inconsistency in the evaluation of cold lesions on thyroid scintigrams should be taken into consideration, and calls in question the value of using thyroid scintigrams for deciding whether a patient should be referred for operation or biopsy.

Goiter and Uremia

Laszlo Hegedüs, MD, Department of Internal Medicine and Endocrinology F, Herlev Hospital, DK-2730 Herlev (Denmark) Dear Sir, We read with great interest the article by Sennesael et al. [1] addressing among others the question of goiter frequency in uremia. While we agree with their results and conclusions on free thyroid hormone concentrations, the data presented on thyroid size evaluation does not (for a number of reasons) allow any conclusion to be drawn as to the possible goitrogenic effect of uremia. Attention has to be drawn to the inexactness and irreproducibility of the clinical evaluation (palpation) of thyroid size [2] and it has to be stressed that such an evaluation does not with any reliability allow a quantitative evaluation of thyroid size. This could have been achieved by using ultrasound [3] and is necessary if one wishes to demonstrate alterations in thyroid size in a range of thyroid volume where no goiter is evident. Therefore, an increase in thyroid volume could well have been demonstrated, in the study by Sennesael et al. [1], in spite of the failure to demonstrate a difference in goiter frequency between patients and controls. In fact this is exactly what we found in a recent investigation on this topic [4]. Furthermore, the necessity of matching the patients with the controls in respect to a number of variables has been shown to be of crucial importance if one wishes to compare goiter frequency with any reliability. Thus, sex, age and body weight [3], liver disease and alcoholism [5], smoking habits [6] and changes within the menstrual cycle (unpublished) all influence thyroid gland volume and thereby goiter frequency. The suggested geographical variations in goiter frequency in uremia has tentatively been attributed to differences in daily iodine intake and excretion. However, daily urinary iodine excretion is very similar in Brussels (60 μg/day [1] and Copenhagen (80 μg/day) [7] further supporting the view that enlargement of the thyroid gland is related primarily to uremia and not environmental factors. The explanation for the conflicting findings might, therefore, rather be the inexactness of the clinical evaluation of goiter, stressing the importance of an objective assessment of thyroid size. Some authors have found that as many as 20–40% of patients with hyperparathyroidism had thyroid lesions of surgical significance [8] and we have shown that 9 of 23 consecutive patients with primary hyperparathyroidism had goiter and increased thyroid gland volume measured ultrasonically [9]. In view of the known association of uremia and hypercalcemia and hyperparathyroidism it is possible that the subjects with goiter (in our as well as other studies) were the ones with hypercalcemia and/or hyperparathyroidism. The goiter could possibly also be caused by mistaking grossly enlarged parathyroid glands for thyroid tissue. Such a palpatory distinction between the two tissues is certainly afflicted with much uncertainty.