Showing papers in "Journal of Endocrinological Investigation in 1982"
TL;DR: A continuously cultured line of normal rat thyroid cells can be stimulated by immunoglobulin preparations from patients with Graves’ disease as measured by increases in intracellular cAMP levels, and cells are responsive even in the presence of such inhibitor activity.
Abstract: A continuously cultured line of normal rat thyroid (FRTL) cells can be stimulated by immunoglobulin preparations from patients with Graves’ disease as measured by increases in intracellular cAMP levels. Responsiveness is concentration-dependent but is delayed in time relative to thyrotropin. Additionally, the cells respond to Graves’ immunoglobulins which have no long-acting thyroid stimulator (LATS) activity and are negative when adenylate cyclase stimulation in human thyroid membrane preparations is assayed. No correlation exists between the stimulation activity and the ability of a Graves’ immunoglobulin preparation to inhibit thyrotropin binding; cells are responsive even in the presence of such inhibitor activity.
81 citations
TL;DR: It is concluded that, in patients receiving levothyroxine therapy, the serum T3 concentration correlates better with the clinical state than the serumT4 concentration does, and the discordance between the present and previous findings with respect toThe serum T4 concentration is ascribed to methodological errors introduced by the methods of measurement employed in earlier reports.
Abstract: It is commonly believed, as previous reports have indicated, that physiological replacement doses of oral levothyroxine in adults with hypothyroidism generally range between 0.15 and 0.20 mg daily, and that when this dose is administered, serum thyroxine (T4) concentrations are almost always within the normal range. Nonetheless, in two groups of patients receiving suppressive or replacement doses of Synthroid® or Letter®, serum T4 concentrations in more than half were above the normal range for the two different radio immunoassay (RIA) methods employed for analysis. More extensive studies in a group of 28 additional patients receiving Synthroid®, all of whom were euthyroid by clinical criteria, revealed similarly frequent elevations of serum T4 concentration, often of substantial degree. In this group, the level of the serum T4 was not significantly correlated with age, sex, dose per unit weight, or diagnosis. Comparative studies in sera from these patients, and from patients with hyperthyroidism or normal controls, revealed close concordance between values for the serum T4 concentration yielded by two RIA methods and one competitive protein-binding assay. These and other studies provided no evidence that substances other than T4 itself were contributing to the elevations of serum T4 concentration found in patients receiving levothyroxine. Mean values for the resin T3 uptake and free T4 index (FT4I) were increased. Despite elevations in serum T4 concentration and the FT4I, serum 3, 5, 3′-triiodothyronine (T3) concentrations were within the normal range, T3 /T4 concentration ratios in patients receiving Synthroid® being significantly lower than in normal controls. Serum 3, 3′, 5′-T3 (reverse T3, rT3) concentrations displayed a highly significant correlation with serum total T4 concentrations, and the mean value for the group as a whole was significantly elevated. The discordance between the present and previous findings with respect to the serum T4 concentration is ascribed to methodological errors introduced by the methods of measurement employed in earlier reports. It is concluded that, in patients receiving levothyroxine therapy, the serum T3 concentration correlates better with the clinical state than the serum T4 concentration does. Elevations of serum T4 concentration in patients receiving levothyroxine therapy do not necessarily indicate that the dosage is excessive.
42 citations
TL;DR: A newly developed sensitive and quantitative immunoradiometric assay (IRMA) for anti-thyroglobulin (anti-Tg) autoantibody is described and a good correlation was found between the antibody levels determined by the two techniques.
Abstract: A newly developed sensitive and quantitative immunoradiometric assay (IRMA) for anti-thyroglobulin (anti-Tg) autoantibody is described. Serum samples to be tested are added to wells of polyvinyl microtiter plates coated with human thyroglobulin. After removal of the unbound material, anti-Tg antibody is determined by adding purified 125I-anti-human immunoglobulin G antibody. Using 1.0 microliter of serum anti-Tg antibody was detected in 81.2% of patients with Hashimoto's thyroiditis or idiopathic myxedema (n = 32), in 46.4% of those with Graves' disease (n = 28), in 11.9% of subjects with other thyroid disorders (n = 42) and in 4.2% of normal controls (n = 71). Similar percentages of positive tests were observed by passive hemagglutination (PH) and a good correlation was found between the antibody levels determined by the two techniques. Using larger amounts of serum (100 microliters) detectable anti-Tg antibody by IRMA was found in the majority of patients with thyroid autoimmune disorders who had negative PH tests. Quantitative measurements of anti-Tg antibody by IRMA could be obtained by using purified anti-Tg antibody as standard reference. The minimum detectable amount of anti-Tg antibody was 0.5 ng. The present method is proposed as a simple and convenient technique for quantitative measurement of any antibody, using wells coated with the appropriate antigen.
41 citations
TL;DR: The present data indicate that methimazole treatment induces a fall of thyroid antibodies in patients with Graves’ disease, and that relapse of hyperthyroidism is associated with an increase of these antibodies.
Abstract: The changes occurring in the levels of circulating thyroid microsomal antibody (M-Ab) and antithyroglobulin antibody (Tg-Ab) during antithyroid drug therapy were studied in 32 patients receiving methimazole for Graves’ disease. M-Ab was determined by competitive binding radioassay and Tg-Ab by a sandwich radiometric method. Before treatment 25 subjects (78.1%) had abnormally elevated (≥ 75 U/ml) M-Ab levels. A more than 30% reduction of M-Ab concentration with respect to the pretreatment value was found in 16 (64.0%) of these patients within the first 3–5 months of therapy, in 23 (92.0%) within 8–11 months and in 21 (84.0%) at the end of treatment (16–18 months). No change was found in the 7 patients with initial M-Ab levels < 75 U/ml. The reduction of M-Ab was more pronounced in the patients with good control of thyrotoxicosis than in those who were still hyperthyroid or were rendered hypothyroid during treatment. Twenty-three patients were followed after completion of the course of methimazole therapy, and 13 of them showed relapse of hyperthyroidism. A significant rise of M-Ab with respect to the values observed at the end of treatment occurred in all relapsing patients who had abnormally elevated M-Ab levels before therapy. With one exception, no M-Ab increase was found in the 10 nonrelapsing patients. However, no difference between relapsing and nonrelapsing patients was observed when the M-Ab changes occurring during treatment were considered. A similar trend during and after withdrawal of therapy was noted for Tg-Ab but, because of the relatively small percentage of positive subjects (25%), the results were less conclusive. The present data indicate that methimazole treatment induces a fall of thyroid antibodies in patients with Graves’ disease, and that relapse of hyperthyroidism is associated with an increase of these antibodies. However, the antibody changes occurring during treatment showed no prognostic value in predicting the outcome of therapy.
37 citations
TL;DR: The results support the speculation that autoimmune antibodies which inhibit TSH binding to thyroid membranes are not necessarily identical to antibodies which stimulate function; that antibodies directed at the high affinity initial site of TSH interaction with a cell can behave as blocking rather than stimulating antibodies; and that a possible relationship exists between stimulating antibodies and the low affinity TSHbinding sites (gangliosides) on thyroid membranes.
Abstract: Monoclonal antibodies to the thyrotropin (TSH) receptor have been obtained from fusions of mouse myeloma cells with spleen cells immunized with solubilized thyroid membrane preparations. Two monoclonal antibodies which inhibit 125l-TSH binding and are reactive with the glycoprotein component of the bovineTSH receptor (11E8 and 13D11), are shown to inhibit basal and TSH stimulated adenylate cyclase activity in bovine thyroid membranes and human thyroid cells. Both antibodies also inhibit 125l-TSH binding in vitro, whether binding is measured at pH 6.0 in low salts and at 0–4 C or at pH 7.4 in 50 mM NaCl and at 37 C. The glycoprotein component is thus a portion of the physiologic TSH receptor in vivo and 125l-TSH binding studies apparently measure the high affinity glycoprotein component under nonphysiologic conditions and conditions more representative of the physiologic milieu. A third monoclonal antibody whose interaction with thyroid membranes is prevented by TSH is shown to stimulate adenylate cyclase activity in bovine thyroid membranes and human thyroid cells. This stimulating antibody only weakly inhibits 125l-TSH binding to thyroid membranes or to the glycoprotein component of the TSH receptor. The 22A6 antibody does, however, immunoprecipitate mixed brain gangliosides, in distinct contrast to the monoclonal antibodies to the glycoprotein receptor component, i.e., 11E8 and 13D11. The results support the speculation that autoimmune antibodies which inhibit TSH binding to thyroid membranes are not necessarily identical to antibodies which stimulate function; that antibodies directed at the high affinity initial site of TSH interaction with a cell can behave as blocking rather than stimulating antibodies and that a possible relationship exists between stimulating antibodies and the low affinity TSH binding sites (gangliosides) on thyroid membranes.
36 citations
35 citations
TL;DR: E,NE and DA concentrations in the adrenal vein were all significantly correlated to the others but not to Cortisol, suggesting that the medulla secrets E, NE and DA in rather constant ratios and that the cortex and the Medulla respond differently to surgical stress.
Abstract: Epinephrine (E), norepinephrine (NE), dopamine (DA) and Cortisol (F) were measured in samples drawn simultaneously by direct venepuncture from the brachial and the adrenal vein of 12 patients undergoing surgery for left kidney diseases. In 7 patients the influence of anesthesia on peripheral plasma levels was also assessed. Catecholamines were measured by a radioenzymatic assay and F by radioimmunoassay. Compared to basal values (mean ± SE) (E: 53.6 ± 6.2 pg/ml; NE: 209.4 ± 24.4 pg/ml; DA: 24.5 ± 3.3 pg/ml; F: 12.9 ± 1.2 μg/dl) only NE peripheral levels were significantly modified by anesthesia (NE: 343.7 ± 67.4 pg/ml p < 0.05), whereas under surgery a significant increase in the peripheral levels was found for every substance measured (mean ± SE) (E: 332.5 ± 46.6 pg/ml p < 0.001; NE: 633.6 ± 114.2 pg/ml p < 0.005; DA: 85.8 ± 15.7 pg/ml p < 0.005; F:21.3 ± 1.9 μ/dl p < 0.01). Catecholamine and F levels in adrenal vein showed a high variability suggesting an intermittent secretion. In the adrenal venous blood E levels were, in the mean, 381 times higher, NE levels 45 times, DA levels 27 times and F levels 23 times higher than in peripheral blood. E, NE and DA concentrations in the adrenal vein were all significantly correlated to the others but not to Cortisol, suggesting that the medulla secrets E, NE and DA in rather constant ratios and that the cortex and the medulla respond differently to surgical stress.
34 citations
TL;DR: It was confirmed that T4 therapy, although promptly correcting low serum T4 concentration, failed to rise serum T3levels due to lack of peripheral T4 5’-monodeiodination to T3 in these critically ill patients.
Abstract: Three consecutive cases of myxedema coma treated successfully with either nasogastric or intravenous route of administration of I-triiodothyronine, followed by oral thyroxine, are described. All were hypothermic, had biochemical evidence of advanced hypothyroidism (T4 less than 1.0 micrograms/dl, T3 less than 20 ng/dl and TSH greater than 150 microU/ml), severe hypoxemia, respiratory acidosis, hypercarbia and temporary depression of respiratory center responsiveness. In only one patient it was found significant hyponatremia (Na = 127 mEq/l). Two patients were successfully treated with the nasogastric route of administration of T3 (12.5 micrograms/6h) but in a female patient with intestinal atony (ileus) there was no absorption of the orally administered T3. Intravenously administered T3 promptly corrected the hypometabolic state in this patient. It was confirmed that T4 therapy, although promptly correcting low serum T4 concentration, failed to rise serum T3 levels due to lack of peripheral T4 5'-monodeiodination to T3 in these critically ill patients.
33 citations
TL;DR: The prolactinoma regression induced by Brc occurred only in patients whose serum PRL levels were markedly suppressed; however the PRL normalization was not constantly associated with tumor shrinkage, suggesting that additional mechanisms should have been operating in the Brc-induced tumor shrinkages.
Abstract: The effects of Bromocriptine (Brc) (7.5 2 - 15 mg/day for 45 days) on serum PRL levels and tumor size and morphology were investigated in 7 patients with macroprolactinomas (mean PRL ± SE = 4957 ± 920 ng/ml). Serial controls of serum PRL levels, CAT scan and visual field examination were carried out at the 5th, 10th, 20th and 45th day of Brc treatment. A rapid lowering in PRL concentrations (mean PRL ± SE = 23.1 ± 5.8 ng/ml) and a dramatic shrinkage of tumor mass were observed in 4 cases already at the 5th day of therapy. In 3 patients Brc was then withdrawn and a rapid rise of serum PRL concentration (mean PRL ± SE = 2618 ± 683 ng/ml) along with a reexpansion of the adenomas was documented within 15 days. These patients were then restarted on Brc and tumor regression was noticed again. In the remaining 3 cases no CAT scan variations occurred, though 2 of them had serum PRL in the normal range. Transsphenoidal adenomectomy was then performed in 4 patients upon Brc (1 with a marked reduction of the adenoma size and 3 with unmodified tumor mass) and tumor tissue examined. The histological picture of the 4 Brc-treated tumors was homogeneous and no relevant changes were seen in comparison with fragments of prolactinomas obtained from patients never treated with Brc. Though PRL cells appeared somewhat more closely associated, neither the tissue architecture, not the distribution of necrotic and hemorragic areas, nor the mitosis rate appeared modified by the treatment. At electron microscopy all the Brc-treated adenomas showed an increase of PRL secretory granules and a decrease of RER and Golgi apparatus. The morphometric analysis revealed in all cases a marked reduction of the cell size in comparison with the untreated tumors (73.56 μm2 ± 6.90 SE vs 148.41 μm2 ± 11.29 SE in untreated patients; p < 0.0001). In conclusion: i) the prolactinoma regression induced by Brc occurred only in patients whose serum PRL levels were markedly suppressed; however the PRL normalization was not constantly associated with tumor shrinkage; ii) all the Brc-treated adenomas showed a marked reduction in cell size and a decrease of the cytoplasmic structures responsible for PRL production; iii) cell size reduction was observed also in 3 patients who did not reduce their tumor size. This suggests that additional mechanisms should have been operating in the Brc-induced tumor shrinkage.
33 citations
TL;DR: The consistency between the responses of plasma Cortisol to exogenous ACTH and to insulin hypoglycemia was investigated in 5 patients in whom Cortisol response to insulin was absent; four of these patients showed a Cortisol responded to ACTH of variable degree.
Abstract: The hypothalamic-pituitary-adrenal function was studied in 55 patients with various pituitary disorders. In particular, the consistency between the responses of plasma Cortisol to exogenous ACTH and to insulin hypoglycemia was investigated in 5 patients in whom Cortisol response to insulin was absent; four of these patients showed a Cortisol response to ACTH of variable degree. These 4 patients had surgical or functional hypothalamus-pituitary disconnection and showed a preserved Cortisol response to lysine vasopressin. These data demonstrate the unreliability of ACTH test in assessing hypothalamic-pituitary-adrenal function in hypopituitary patients.
32 citations
TL;DR: Different forms of the Tg molecules seem to be removed at different rates, independent on the type of goiter, with a weak correlation between the weight of the removed thyroid tissue and the maximally obtained Tg concentration at the time of surgery and no correlation with the levels before operation.
Abstract: Twenty-five patients with nontoxic nodular goiters and six with toxic goiter were studied prior to subtotal thyroidectomy, with closely spaced blood sampling up to three weeks after surgery, and approximately one year after surgery Serum thyroglobulin (Tg) was measured by a previously described radioimmunological method The mean serum Tg was elevated in patients with nontoxic nodular and toxic goiters compared to sex and age matched control groups with pronounced increases during surgery The disappearance curves of Tg in both groups had two exponentials, an initial steep slope with a half-life of 40 ± 18 (SD) h in nontoxic goiter and 45 ± 32 h in toxic goiter This was followed by a more shallow slope with a half-life of 36 ± 11 days in nontoxic goiter and 34 ± 08 h in toxic goiter, the breaking point between the slopes lying approximately at 48–72 h There was no significant difference between the half-life of Tg in patients with toxic or nontoxic goiters, respectively There was a weak correlation between the weight of the removed thyroid tissue and the maximally obtained Tg concentration at the time of surgery, but no correlation with the levels before operation Serum Tg was significantly lower three weeks after operation and approximately one year after surgery In conclusion, different forms of the Tg molecules seem to be removed at different rates, independent on the type of goiter
TL;DR: There was a clear difference between the sexes in the hepatic alcohol metabolizing enzymes with higher enzymic activities of the microsomal ethanol oxidizing system and catalase in male than in female rats, whereas the opposite constellation was found for alcohol dehydrogenase activity.
Abstract: In mature female rats the administration of testosterone led to a striking reduction of hepatic alcohol dehydrogenase activity, whereas the hepatic microsomal ethanol oxidizing system as well as catalase were both increased in activity under these experimental conditions. Conversely, estradiol left the activities of all hepatic alcohol metabolizing enzymes virtually unchanged. Ovariectomy also had little if any influence on the activity levels of the enzymes. There was a clear difference between the sexes in the hepatic alcohol metabolizing enzymes with higher enzymic activities of the microsomal ethanol oxidizing system and catalase in male than in female rats, whereas the opposite constellation was found for alcohol dehydrogenase activity. These data therefore indicate the sex-dependent nature of alcohol dehydrogenase, the hepatic microsomal ethanol oxidizing system and catalase activities in rat liver.
TL;DR: An association of granulocytopenia, eosinophilia, skin reaction and hepatitis during propylthiouracil (PTU) therapy for thyrotoxicosis in a 47 year old black female is reported.
Abstract: An association of granulocytopenia, eosinophilia, skin reaction and hepatitis during propylthiouracil (PTU) therapy for thyrotoxicosis in a 47 year old black female is reported. Clinical and biochemical abnormalities disappeared soon after discontinuation of PTU. That the drug was directly responsible for the observed complications is suggested by the clinical course and by in vitro lymphocyte transformation studies. The latter revealed sensitization to PTU during the acute phase of the disease, which was greatly reduced 5 weeks after discontinuation of the drug and was completely absent after 5 months.
TL;DR: The study of the effect of an infusion of 5HT in 14 normal subjects suggests that 5HT may influence aldosterone secretion also in man.
Abstract: Serotonin (5HT) is known to be one of the most active aldosterone-stimulating substances in rat adrenal tissue, but its effect in vivo has been scarcely investigated, especially in man. We have studied the effect of an infusion of 5HT in 14 normal subjects. Plasma aldosterone significantly increased during 5HT infusion, while Cortisol and plasma renin activity were not modified. No changes in serum K, blood pressure or heart rate were noticed. These data suggest that 5HT may influence aldosterone secretion also in man.
TL;DR: After one year treatment and five days withdrawal of Cortisol administration, the insulin-induced hypoglycemia still failed to elicit secretory responses of ACTH and Cortisol, despite the normalization of thyroid hormone levels.
Abstract: A 50 year old man is described in whom primary hypothyroidism and isolated ACTH deficiency leading to adrenocortical insufficiency occurred simultaneously. Low thyroid hormone levels, elevated serum TSH values and high titers of antithyroid antibodies (ATA) were consistent with primary hypothyroidism. The diagnosis of secondary adrenocortical insufficiency was based on low cortisol and ACTH morning levels, low urinary steroids, a significant increase of cortisol levels after 0.25 mg tetracosactide iv, an absence of ACTH and cortisol release after insulin-induced hypoglycemia and a similar absence of ACTH and 11-deoxycortisol increase after metyrapone administration. After one year treatment and five days withdrawal of cortisol administration, the insulin-induced hypoglycemia still failed to elicit secretory responses of ACTH and cortisol, despite the normalization of thyroid hormone levels. The etiopathogenesis of these two coexisting endocrine deficiencies is discussed.
TL;DR: In vitro studies using isolated perfused rat zona glomerulosa cells suspended in Biogel suggest that the inhibitory effect of somatostatin on aldosterone production is not cAMP-dependent, since ACTH maintains its stimulatory capacity.
Abstract: It has been demonstrated that somatostatin (SRIF) can suppress hypophyseal and extrahypophyseal hormones; moreover, many studies have shown that SRIF inhibits frusemide-induced hyperreninemia in normal man, and renin and aldosterone in renovascular hypertension, possibly through a beta-adrenergic block. To further investigate the possible aldosterone-inhibiting effect of somatostatin, we have carried out in vitro studies using isolated perfused rat zona glomerulosa cells suspended in Biogel. Paired columns were set up and the cells stimulated using either angiotensin II, ACTH, serotonin or potassium. One column was perfused with somatostatin (3–4 ng/ml) and the other was used as a control. Aldosterone was measured by highly specific direct radioimmunoassay. Somatostatin significantly blocked the aldosterone response to angiotensin II but not to ACTH, serotonin or potassium. The inhibitory effect of somatostatin persisted as long as it was added to the medium; the aldosterone response to angiotensin II was progressively restored after discontinuation of the SRIF infusion. From these data it might be suggested that the inhibitory effect of somatostatin on aldosterone production is not cAMP-dependent, since ACTH maintains its stimulatory capacity. The recent demonstration of the presence of specific somatostatin receptors on the rat adrenal cells suggests that its inhibitory effect could be mediated by the second messenger system rather than the interaction with angiotensin II receptors.
TL;DR: Dynamic exploration of the endocrine functions suggests the presence of an autonomous pituitary adenoma as the cause of the abnormal hormonal findings in Mc Cune-Albright syndrome.
Abstract: A case of Mc Cune-Albright syndrome is presented with the unusual combination of gigantism and hyperprolactinemia. Dynamic exploration of the endocrine functions suggests the presence of an autonomous pituitary adenoma as the cause of the abnormal hormonal findings. These were successfully normalized by radiotherapy to the pituitary gland.
TL;DR: The results suggest that both steroid and plasmapheresis treatment are useful for lowering abnormal antibody titers in sera of patients with Graves’ disease, and that plasmAPheresis can be of some value in the treatment of pretibial myxedema.
Abstract: The effect of prednisone treatment and plasmapheresis was studied in two patients with Graves' disease complicated by severe exophthalmos and/or pretibial myxedema. Titers of Thyrotropin Binding Inhibitory Immunoglobulins (TBII), Long Acting Thyroid Stimulator (LATS), antithyroid antibodies, and serum gammaglobulin concentrations, as well as clinical changes in exophthalmos and pretibial myxedema, were observed during the course of treatment. Steroid treatment lowered all of the abnormal antibody titers. Plasmapheresis did not change the TBII activity when determined using a fixed amount of immunoglobulin G fraction. However, serum gammaglobulin concentration was reduced by plasmapheresis, and therefore, total TBII activity in a unit of serum was reduced. Plasmapheresis also partially and temporarily resolved the pretibial myxedema, whereas no significant change in exophthalmos was observed. These results suggest that both steroid and plasmapheresis treatment are useful for lowering abnormal antibody titers in sera of patients with Graves' disease, and that plasmapheresis can be of some value in the treatment of pretibial myxedema.
TL;DR: Tumor extract, assayed under conditions designed to prevent artefactual generation of peptides, was found to contain a wide variety of immunoreactive hormones including ACTH, α-MSH, CLIP, β-endorphin and met-enkephalin.
Abstract: A 51-year old man presented with the classical features of Cushing's syndrome which had evolved over the previous 5 yr, and was found to have ACTH secretion from an atypical thymic carcinoid tumor. Tumor extract, assayed under conditions designed to prevent artefactual generation of peptides, was found to contain a wide variety of immunoreactive hormones including ACTH, alpha-MSH, CLIP, beta-endorphin and met-enkephalin. The ACTH-related peptides were probably derived from a common precursor, pro-opiocortin, but the presence of met-enkephalin suggests the production of a separate type of precursor molecule. The tumor was locally invasive and, depsite subtotal excision and radiotherapy, continued to secrete large amounts of ACTH. Hypercortisolism was controlled longterm with pharmacological adrenal blockade and steroid replacement.
TL;DR: Blood polyamine levels have been determined in 161 healthy subjects from newborn to adult age and may suggest that also in humans these substances play a role in the process of cellular proliferation.
Abstract: Blood polyamine levels have been determined in 161 healthy subjects from newborn to adult age. During the growth period spermidine concentrations are always higher than in adulthood. In the first days of life a typical pattern for spermidine and spermine appeared with an early increase in the first hours after birth and a maximum at 24 h; afterwards the levels of both amines gradually and progressively decreased. The levels reached by 10 days of life were maintained until adulthood, at which time a further decrease was evident. The high levels of polyamines during the period of body growth may suggest that also in humans these substances play a role in the process of cellular proliferation.
TL;DR: GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog, and the most likely inhibitory mechanism seems to be a decrease of the vagal activity.
Abstract: The effects of GnRH on gastric secretion and gastrin release from dogs provided with gastric fistulae and Heidenhain pouches have been investigated. A transient yet significant inhibition of pentagastrin-stimulated secretion from gastric fistulae was observed, while secretion from Heidenhain pouches was unchanged. The maximal inhibitory effect of GnRH on both acid and pepsin secretion stimulated by 2-deoxy-D-glucose was obtained from gastric fistulae. On the contrary, GnRH failed to affect either acid secretion stimulated by bethanechol or acid secretion and gastrin release induced by bombesin. The present results indicate that GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog. The most likely inhibitory mechanism seems to be represented by a decrease of the vagal activity.
TL;DR: The intrathyroidal stable iodine (ITI) was determined in 776 patients chosen at random: an acrophase was found in April/May, a nadir in Semptember/October, as well as a possible relationship with variation in chronic TSH stimulation related to ambient temperature.
Abstract: The intrathyroidal stable iodine (ITI) determined in 776 patients chosen at random. Ninety % of these patients presented with nontoxic goiter. Curve-filtering analysis techniques showed a seasonal variation in ITI: an acrophase was found in April/May, a nadir in September/October. The possible relationship of this seasonal variation with the intake of iodine or alimentary antithyroid substances are discussed, as well as possible relationship with variation in chronic TSH stimulation related to ambient temperature.
TL;DR: A micromethod for measuring 17a-hydroxyprogesterone in blo’od collected on filter paper has been developed and has the specificity, accuracy and precisoin of the radioimmunoassay in whole blood.
Abstract: A micromethod for measuring 17a-hydroxyprogesterone in blo’od collected on filter paper has been developed. Our method is rapid, easy and has the specificity, accuracy and precisoin of the radioimmunoassay in whole blood. The method has been applied for screening patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Fifty samples collected on filter paper were assayed by our method, using 1251 as tracer, and results were compared with those obtained for the same samples using a tritium tracer. The agreement between the two methods was particularly good in the area ranging from 15 to 100 pg/disc. In one neonate the diagnosis of CAH was made utilizing the microfilter paper method. Our method is a promising screening test for CAH. An indication of the advantages or disadvantages of this type of screening will become available when an adequate number of infants has been examined.
TL;DR: The antiarrhythmic agent amiodarone was found to inhibit the stimulatory effects of L-triiodothyronine on [3H ] thymidine incorporation into GH3 rat pituitary tumor cells, suggesting that amiodrone acted as a non-competitive antagonist.
Abstract: The antiarrhythmic agent amiodarone was found to inhibit the stimulatory effects of L-triiodothyronine on [3H ] thymidine incorporation into GH3 rat pituitary tumor cells. This inhibitory effect of amiodarone was detected at concentrations as low as 0.5 μM; at 2 μM greater than 50% of the stimulatory effect of L-triiodothyronine was inhibited. The effect of amiodarone was present at all concentrations of L-triiodothyronine tested (50 pM to 10 nM), suggesting that amiodarone acted as a non-competitive antagonist. These studies raise the possibility, therefore, that the effect of amiodarone on thyroid hormone metabolism may be mediated in part by an inhibition of thyroid hormone action at the cellular level.
TL;DR: A patient with Cushing’s disease is described in whom an acute inhibition of ACTH and cortisol was demonstrated following bromocriptine and in whom the long term administration of bromoriptine as the sole therapy produced a transient beneficial response.
Abstract: Recently, bromocriptine has been successfully introduced as medical therapy for the pituitary hypersecreting syndromes of hyperprolactinemia and acromegaly. Subsequently, an inhibitory effect on ACTH secretion was reported using bromocriptine in Cushing’s disease. While most studies have focused on the acute response to bromocriptine, few have investigated the response to chronic therapy with this agent. In this report, we describe a patient with Cushing’s disease in whom an acute inhibition of ACTH and cortisol was demonstrated following bromocriptine and in whom the long term administration of bromocriptine as the sole therapy produced a transient beneficial response. Further pharmacologic testing suggested this inhibitory effect on the hypothalamic-pituitary-adrenal axis was mediated through dopaminergic stimulation.
TL;DR: Postmenopausal women are particularly important in this context, not only because of the increased incidence of breast and endometrial cancer at and around the menopause, but because it is at this time that major changes occur in the endocrine milieu which may relate directly to the risk of developing cancer.
Abstract: The role which steroid hormones play in the development and maintenance of human cancer is a problem which has attracted the attention of research investigators for many years. Oestrogens have come under particular scrutiny, since there is a good deal of indirect evidence that altered oestrogen production may be protective in some situations (e.g. the diminished risk of female breast cancer conferred by earlier castration) and disadvantageous in others (e,g, the enhanced risk of endometrial cancer attributable to increased oestrogen exposure in women bearing oestrogen-secreting tumours). Furthermore, in the last decade or so, studies of cellular receptors have clearly delineated the importance of oestrogens amongst other hormones in the maintenance of tumour growth. It is therefore entirely logical to investigate oestrogen metabolism in detail in the hope and expectation that some metabolic abnormality exists in women who are predisposed to these types of endocrine cancer, which may be revealed by careful biochemical examination. As a group, postmenopausal women are particularly important in this context, not only because of the increased incidence of breast and endometrial cancer at and around the menopause, but because it is at this time that major changes occur in the endocrine milieu which may relate directly to the risk of developing cancer.
TL;DR: The data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations, and that the influence of total calories is perhaps as pronounced as that of CHO when a “permissive” amount of CHO is ingested.
Abstract: The effect of different hypocaloric carbohydrate (CHO) intakes was evaluated in 8 groups of obese patients in order to assess the role of the CHO and the other dietary sources in modulating the peripheral thyroid hormone metabolism. These changes were independent of those of bw. Serum T3 concentrations appear to be more easily affected than those of reverse T3 by dietary manipulation and CHO content of the diet. A fall in T3 levels during the entire period of study with respect to the basal levels occurred only when the CHO of the diet was 120 g/day or less, independent of caloric intake (360, 645 or 1200 calories). Moreover, reverse T3 concentrations were found increased during the entire period of study when total CHO were very low (40 to 50 g/day) while they demonstrated only a transient increase when CHO were at least 105 g/day (with 645 or more total calories). Indeed, our data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations. From these results it appears that the CHO content of the diet is more important than non-CHO sources in modulating peripheral thyroid hormone metabolism and that the influence of total calories is perhaps as pronounced as that of CHO when a "permissive" amount of CHO is ingested.