Comparative effects of desiccated thyroid gland and sodium salt of L-thyroxine in the treatment of hypothyroidism

The studies comparing the actions of dried thyroid gland (Thyroideum-Polfa) with L-thyroxine sodium (L-T4) were carried out in 20 female patients with hypothyroidism, including 19 patients with the primary hypothyroidism and 1 patient with hypothyroidism secondary to pituitary deficiency. Administration of the dried thyroid gland did not normalize blood serum T4 an TSH in any patient. Normal serum T4 or even slightly increased was achieved in all patients treated with L-T4. Serum TSH was normalized in 17 patients with the primary hypothyroidism. The following conclusions have been drawn: 1. Dried thyroid gland (Thyroideum-Polfa) is ineffective in the treatment of hypothyroidism. 2. Serum TSH remains elevated despite normal serum T3 in cases of the primary hypothyroidism with decreased serum T4 levels. 3. Sodium salt of L-thyroxine should be used for the treatment of hypothyroidism. 1-Triiodothyronine sodium may be used as an adjuvant therapy.     

Effect of thyroid hormone therapy on plasma insulin-like growth factor I levels in normal subjects, hypothyroid patients and endemic cretins

The effect of thyroid hormone therapy (L-T4 or L-T3) on plasma immunoreactive insulin-like growth factor I (somatomedin C, Sm-C) concentrations was studied in 8 normal controls, 14 primary hypothyroid subjects and in 7 patients with endemic cretinism. In normals basal levels of Sm-C (1.56 +/- 0.77 U/ml) increased to (2.46 +/- 1.0 U/ml; L-T4) and to (2.9 +/- 0.95 U/ml; L-T3). Plasma Sm-C basal levels were significantly lower in primary hypothyroid subjects (0.81 +/- 0.48 U/ml) and increased to 2.54 +/- 1.43 U/ml (L-T4) and to 2.16 +/- 0.83 U/ml (L-T3). A significant and positive correlation (r = 0.56) was found between Sm-C and serum T4 and T3 concentrations. Plasma Sm-C concentrations in endemic cretinism were initially normal in 4 patients, but low in the remaining 3 (mean +/- SD: 1.18 +/- 0.63 U/ml) and did not increase after 12 months (1.34 +/- 0.61 U/ml) or 18 months (1.01 +/- 0.43 U/ml) of L-T4 and L-T3 therapy. Plasma T4 levels and free T4 increased considerably in EC after therapy with a significant decrease in the previously elevated plasma TSH concentrations. The subnormal response of plasma Sm-C during effective thyroid thyroid hormone therapy could be an additional factor involved in growth failure of endemic cretins.     

Optimum replacement dose of thyroid hormone assessed by highly sensitive TSH determination in patients with congenital hypothyroidism

Serum thyroid hormone concentrations were measured in 100 samples from 25 patients with congenital hypothyroidism who were clinically well while receiving L-T4 therapy. Thyroxine concentrations were significantly higher than those of controls (p less than 0.01), while triiodothyronine was not significantly different. These samples were divided into four groups according to serum thyroid stimulating hormone concentrations as measured by highly sensitive immunoradiometric assay (IRMA-TSH). Serum thyroid hormone concentrations were compared among groups. The replacement dose of L-T4 and serum thyroid hormone in groups with undetectable IRMA-TSH were significantly higher than those in groups with normal or increased IRMA-TSH. These results show that serum thyroxine concentrations increase in most patients with congenital hypothyroidism on L-T4 therapy. Therefore, thyroxine concentrations above normal are not necessarily of clinical significance if IRMA-TSH is detectable. Undetectable IRMA-TSH might indicate the necessity for a reduction in the L-T4 replacement dose in patients with congenital hypothyroidism.     

Thyroid function and antimicrosomal antibody during the course of silent thyroiditis

The thyroid function and antithyroidal antibody were studied in 17 patients with silent thyroiditis unrelated to pregnancy. The antimicrosomal hemagglutination antibody (MCHA) was negative in ten of them (group I) and was positive in seven (group II). At one month after the thyrotoxicosis, thyroid function became normal in both groups. At two months after the onset of thyrotoxicosis, in group I T4 (8.1 +/- 1.8 micrograms/dl, Mean +/- SD), T3 (113 +/- 25 ng/dl) and TSH were normal. At that time T4 (2.8 +/- 2.2 micrograms/dl) was significantly decreased (p less than 0.001) compared with those of group I and the levels of TSH were strikingly increased in 6 patients in group II. The level of T3 (96 +/- 29 ng/dl) in group II was not different from that of group I. Therefore MCHA was negative in patients who did not develop hypothyroidism and MCHA was positive in patients who developed hypothyroidism. The development of hypothyroidism two months after thyrotoxicosis and positive MCHA are correlated. The Tg was elevated in 7 out of 13 patients (54%) with negative antithyroglobulin hemagglutination antibody and in the remainder was normal during thyrotoxicosis. The discrepancy between the level of Tg and thyroid hormones was discussed.     

Influence of chronically altered thyroid status on the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase in female inbred lewis rats.

The activity of liver mitochondrial flavoprotein-dependent glycerol-3-phosphate dehydrogenase (GPDH) is considered a reliable marker of thyroid status in acute and short-lasting experiments. The aim of this study was to ascertain whether GPDH activity could also be used as an index of thyroid status during chronic experiments over several months. We therefore analyzed GPDH activity in liver mitochondria of female inbred Lewis rats with thyroid status altered for 2 to 12 months. Hyperthyroid state was maintained by triiodothyronine (T (3)) or thyroxine (T (4)) administration, while methimazole was employed for inducing hypothyroidism. We found a seven- and three-fold increase of GPDH activity in female rats after T (3) or T (4) administration, respectively, compared to euthyroid females (8.9 +/- 2.3 nmol/min/mg protein), whereas administration of methimazole reduced the enzyme activity almost to one-third of the euthyroid values. These changes were not significantly influenced by the duration of hyperthyroid or hypothyroid treatment. We conclude that the level of the rat liver GPDH activity could serve as a useful marker for evaluation of hyperthyroid and hypothyroid status in chronic long-lasting experiments on female inbred Lewis rats.     

Serum T3 level in the patients with hyperthyroidism after therapy.

Serum T3 level in various thyroid diseases was determined in unextracted serum with the Dainabot kit for T3 RIA. The serum T3 level in 33 normal subjects was 0.8-1.6 ng/ml. It was 5.7 +/- 3.5 ng/ml (mean +/- S.D.) in 36 hyperthyroid patients, and undetectable to 0.8 ng/ml in 21 hypothyroid patients. Generally the serum T4 and serum T3 decreased in parallel after radioiodine therapy for hyperthyroidism. However, in some cases the serum T3 level remained high in spite of normalized serum T4 after radioiodine therapy. This state indicated "T3-toxicosis", and hyperthyroidism was apt to recur. When thyroid function was observed for 2 years following radioiodine treatment, the ratio of serum T3 (T3 level before treatment/T3 level after treatment) decreased more significantly as compared with the ratio of serum T4 in euthyroid cases. Serum T3 provides a more sensitive index of thyroid function than serum T4 in euthyroid states after radioiodine or anti-thyroid drug therapy. The present data indicate that the serum T3 level and the T4/T3 ratio are valuable aids in the estimation of prognosis of hyperthyroid patients after various treatments.     

D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.

The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from this study and from parallel invitro investigations that the effect of propranolol on the conversion of T4 to T3 is unrelated to its beta-adrenergic blocking activity, and that at low therapeutic doses propranolol may exert appreciable "membrane-stabilising" effects in vivo.     

Thyroid hormone regulation of cell migration and oxidative metabolism in polymorphonuclear leukocytes: clinical evidence in thyroidectomized subjects on thyroxine replacement therapy

Migration and superoxide anion (O2-) generation were studied in polymorphonuclear leukocytes (PMNs) from 14 athyreotic patients, previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice: in hypothyroidism (visit 1) and after TSH-suppressive L-T4 replacement therapy (visit 2). Random migration and N-formyl-Met-Leu-Phe (fMLP) 0.1-microM induced chemotaxis were similar in cells from patients at both visit 1 and visit 2 and from healthy controls. On the contrary, resting O2- generation in cells from patients was significantly lower than control values, both at visit 1 and 2. At visit 1, fMLP 0.1 muM-induced O2- generation was significantly lower than control values, while phorbol-myristate acetate (PMA) 100-ng/ml induced O2- generation was similar in cells from patients and from controls. At visit 2 both responses increased, resulting in fMLP-induced O2- generation superimposable to control values and PMA-induced O2- generation significantly higher with respect to both visit 1 and cells from controls. In vitro exposure of PMNs from healthy subjects to L-T4 did not affect O2- generation in resting cells, and significantly increased that induced by fMLP or PMA only at high, supra-physiological concentrations. Neither TSH nor T3 had significant effects at any of the concentrations tested. The present results document the existence of a correlation between thyroid status and oxidative metabolism of human PMNs, which is however unlikely to depend upon a direct action of thyroid hormones on these cells.     

Changes in plasma fibronectin levels in thyroid diseases

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.     

Hepatic dysfunction in primary hypothyroidism

Twenty-seven patients with primary hypothyroidism were studied to evaluate the relationship between hepatic function and thyroid hormone deficiency in this disorder. In hypothyroidism, hypergammaglobulinemia was found in 71%, elevated glutamic oxaloacetic transaminase (GOT) in 48%, high lactic dehydrogenase (LDH) in 58%, hypercholesteremia in 52% and low elimination rate constant of indocyanin green (KICG) in 44%. In each criterion of liver function, these patients were divided into two groups, normal level and abnormal level group, respectively. T3 and T4 in patients with abnormal levels of GOT, glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gamma-GTP), leucine aminopeptidase (LAP), alkaline phosphatase (ALP) and 45 minutes retention rate of bromsulphalein (BSP) were not different from those in the normal level group. However, T3 and T4 in patients with abnormal levels of LDH, cholesterol, cholinesterase (ChE) and KICG were lower than those in the normal level group. The abnormal KICG group had a statistically higher cardio-thoracic ratio (CTR) than the normal group (65.7 +/- 18.8% vs 50.4 +/- 8.3%, p less than 0.05). In patients with pericardial effusion, CTR was 65.9 +/- 14.6%, while that in patients without pericardial effusion was 49.9 +/- 7.5% (p less than 0.05). These abnormalities of liver function were normalized in all cases after hormone replacement therapy. Liver biopsy in three cases disclosed normal liver in two cases and mild infiltration of monocyte into Glisson's capsule in one case.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Galactorrhea in subclinical hypothyroidism

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.     

Decline of T3 and elevation in reverse T3 induced by hyperglucagonemia: changes in thyroid hormone metabolism, not altered release of thyroid hormones

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum Triiodothyronine (T3) and a rise in reverse T3 (rT3) in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is suppressed by exogenous administration of L-thyroxine (L-T4) in appropriate dosage, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in euthyroid healthy subjects after administration of L-T4 for 12 weeks. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4 and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.01) and a marked rise in rT3 (P less than 0.01) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Therefore, this study demonstrates that changes in serum T3 and rT3 caused by hyperglucagonemia may be secondary to altered thyroid hormone metabolism in peripheral tissues and not due to altered release by the thyroid gland, since the release of thyroid hormones is suppressed by exogenous L-T4 administration.     

Lowering of T3 and rise in reverse T3 induced by hyperglucagonemia: altered thyroid hormone metabolism, not altered release of thyroid hormones

Recently we reported that hyperglucagonemia induced by glucagon infusion causes a decline in serum T3 and a rise in reverse T3 in euthyroid healthy volunteers. These changes in T3 and rT3 levels were attributed to altered T4 metabolism in peripheral tissues. However, the contribution of altered release of thyroid hormones by the thyroid gland could not be excluded. Since the release of thyroid hormones is inhibited in primary hypothyroidism and is almost totally suppressed following L-thyroxine replacement therapy, we studied thyroid hormone levels for up to 6 hours after intravenous administration of glucagon in subjects with primary hypothyroidism who were rendered euthyroid by appropriate L-thyroxine replacement therapy for several years. A control study was conducted using normal saline infusion. Plasma glucose rose promptly following glucagon administration demonstrating its physiologic effect. Serum T4, Free T4, and T3 resin uptake were not altered during both studies. Glucagon infusion induced a significant decline in serum T3 (P less than 0.05) and a marked rise in rT3 (P less than 0.05) whereas saline administration caused no alterations in T3 or rT3 levels. Thus the changes in T3 and rT3 were significantly different during glucagon study when compared to saline infusion. (P less than 0.01 for both comparisons). Since, the release of thyroid hormones is suppressed by exogenous LT4 administration in these subjects; we conclude that changes in serum T3 and rT3 observed following glucagon administration reflect altered thyroid hormone metabolism in peripheral tissues and not altered release by the thyroid gland.     

Relationships between plasma CoQ10 levels and thyroid hormones in chronic obstructive pulmonary disease

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q 10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. On the other hand, a low-T3 syndrome, due to reduced peripheral conversion from the prohormone T4, is observed in different chronic diseases: this condition is considered an adaptation mechanism, usually not to be corrected by replacement therapy. In order to perform a metabolic evaluation, we have studied a group of 15 patients, aged 69-82 ys, affected by chronic obstructive pulmonary disease (COPD), comparing respiratory indexes, thyroid hormones and CoQ10 levels (also normalized with cholesterol levels) in patients with low (group A) or normal (group B) free-T3 (FT3) concentrations. We found that CoQ10 levels were significantly higher in patients of group A than in B (0.91+/- 0.03 vs 0.7 +/- 0.04 microg/ml respectively); the same difference was observed when comparing the ratios between CoQ10/cholesterol in the two groups (200.16 +/- 8.96 vs 161.08 +/- 7.03 nmol/mmol respectively). These preliminary data seem to indicate that low T3 levels are accompanied by metabolic indexes of a true hypothyroidism in COPD patients. Whether this datum supports the need to perform a replacement therapy in such a condition requires further studies.     

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.     

Effects of thyroidectomy, T4, and DITPA replacement on brain blood vessel density in adult rats

In hypothyroid patients, altered microvascular structure and function may affect mood and cognitive function. We hypothesized that adult male hypothyroid rats will have significantly lower forebrain blood vessel densities (BVD) than euthyroid rats and that treatment with 3,5-diiothyroprionic acid (DITPA) (a thyroid hormone analog) or thyroxine (T(4)) will normalize BVDs. The euthyroid group received no thyroidectomy or treatment. The other three groups received thyroidectomies and pellets. The hypothyroid group received a placebo pellet, the DITPA group received an 80-mg DITPA-containing pellet, and the T(4) group received a 5.2-mg T(4) slow-release pellet for 6 wk. Body weights, cardiac function, and body temperatures were measured. A monoclonal antiplatelet endothelial cell adhesion antibody was used to visualize blood vessels. The euthyroid group averaged body weights of 548 +/- 54 g, while the hypothyroid group averaged a body weight of 332 +/- 19 g (P value < 0.001). Relative to the euthyroid group, the DITPA-treated group was significantly lighter (P value < 0.05), while the T(4)-treated group was comparable in body weight to the euthyroid group. The same trends were seen with body temperature and cardiac function with the largest difference between the euthyroid and hypothyroid groups. BVD in the euthyroid group was 147 +/- 12 blood vessels/mm(2) and in hypothyroid group 69 +/- 5 blood vessels/mm(2) (P = 0.013) but similar among the euthyroid, DITPA, and T(4) groups. These results show that hypothyroidism decreased BVD in adult rat forebrain regions. Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD.     

Acute hypothyroidism slows the rate of left ventricular diastolic relaxation

The effect of acute thyroid hormone deficiency on left ventricular diastolic filling was studied by radionuclide ventriculography with simultaneous right heart catheterization in nine athyreotic patients without cardiovascular disease. The patients were studied when they were hypothyroid and when they were euthyroid on replacement therapy. Peak filling rate and the time to peak filling were used to characterize diastolic function. The time to peak filling was defined as the interval from end-systole on the radionuclide time-volume curve to the time of occurrence of peak filling. The peak filling rate was determined in absolute terms from the normalized radionuclide peak filling rate and from the end-diastolic volume, which was derived from the radionuclide ejection fraction and from the thermodilution stroke volume. In all patients, the values for peak filling rate were lower in the hypothyroid than in the euthyroid state (287 +/- 91 mL/s vs. 400 +/- 118 mL/s, delta = 41 +/- 13%, p less than 0.01). Peak filling always occurred during the first half of the diastolic interval. The time to peak filling was not significantly affected by the thyroid state (170 +/- 10 ms vs. 159 +/- 21 ms, delta = 7 +/- 10%). Left ventricular filling pressure as reflected by the pulmonary capillary wedge pressure and end-systolic volume were similar in both thyroid states (6 +/- 2 mmHg vs. 8 +/- 2 mmHg (1 mmHg = 133.32 Pa) and 32 +/- 11 mL vs. 32 +/- 7 mL, respectively). The data suggest that the rate of active diastolic relaxation is decreased in short-duration hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.     

Dopaminergic influence on thyrotropin secretion in primary hypothyroidism.

This study was conducted to assess the influence of dopamine on thyrotropin secretion in patients with primary hypothyroidism before and after optimized L-thyroxin replacement therapy. Thyrotropin responses to dopamine infusion (4 microg/kg/min over 3 hours) and IV metoclopramide (10 mg bolus), a dopamine receptor blocker were studied in 25 consecutive patients with primary hypothyroidism before and after achieving stable euthyroid state and compared with 15 normal age-matched controls. Thyrotropin response to both dopamine infusion (decremental) and IV metoclopramide bolus (incremental) was greater in patients with primary hypothyroidism than that in the control subjects. Thyrotropin response was greater in women than in men. The magnitude of decremental thyrotropin response to dopamine infusion and the incremental response to IV metoclopramide bolus significantly correlated with the basal T3 and T4 levels. Thyrotropin response was blunted to dopamine infusion but not to metoclopramide at follow-up after six-month replacement with L-thyroxin, and both the responses were comparable in women and men in patient group. We conclude that modulation of dopaminergic system by dopamine or by dopamine receptor blocker has a greater influence on thyrotropin secretion in patients with primary hypothyroidism than euthyroid normal subjects.