Insulin receptors of erythrocytes and oral glucose tolerance test (O-GTT) were investigated in sixteen children treated with prednisolone for various diseases. Ten patients (Group 1) received low doses of prednisolone (0.2-0.5mg/kg body weight/day) and six patients (Group 2) received higher doses of prednisolone (1.5-2.0mg/kg body weight/day). Compared to the values for controls, the sums of blood glucose (Σ BS) at O-GTT in both group 1 and group 2 patients were significantly elevated.(422±75mg/dl, p<0.01 Group 1; 419±39mg/dl, p<0.01 Group 2; 338±41mg/dl controls) Significant differences were not observed in the sums of insulin concentration at O-GTT, fasting blood concentration and basal insulin levels among these two groups and the controls.There was a significant increase in the maximum insulin binding in group 2 (9.13±0.68% in group 2, 7.97±1.06% in controls, p<0.05), but not in group 1 (8.59±1.82%). There is no significant difference in binding affinity or the number of receptors between any of these two patients' groups and the controls.When patients in group 1 and group 2 were combined, Σ IRI levels were significantly elevated in the patients (p<0.05). These results suggested that prednisolone treatment with a smaller dosage as well as with the higher dosage resulted in a carbohydrate intolerance, the main cause of which is located in a postreceptor step (or steps) of insulin action.

View full abstract

A 57-year-old male, who had been suffered from hypertension and diabetes mellitus for 10 years, was admitted to the hospital because of thirst, lassitude and muscle wasting. On admission, his urinary excretion of 17-OHCS and plasma cortisol levels were elevated without diurnal variations. Plasma ACTH levels were found to be very low with repeated determinations. Dexamethasone suppression test, 2mg 4 times a day orally for 2 days, showed no changes in plasma cortisol levels and only a mild reduction in urinary 17-OHCS excretion. Estimation of urinary catecholamines showed an increase only in norepinephrine. Abdominal computerized tomography and radionuclide scanning of adrenal glands with ¹³¹I-adosterol demonstrated a well-defined adrenal mass in the left side without apparent changes in the right side. ¹³¹I-metaiodobenzylguanidine scintigraphy was negative. At surgery, his left adrenal medulla was found to be hypertrophic in addition to the cortical tumor. The left adrenal gland was also removed. After surgery, excretion of urinary catecholamines fell to nearly the normal range and he was discharged without insulin and antihypertensive drugs. Microscopically, the cortical tumor is an adenoma consisting of lipid laden cells and eosinophilic compact cells. Medullary cells were distinctly hyperplastic in appearance and many of the cells were extensively vacuolated, suggesting an active functional status. The present report describes a patient with Cushing's syndrome who showed increased urinary catecholamine excretion due to the possible coexistence of adrenal medullary hyperplasia. As far as we know, this is the first case of Cushing's syndrome with this abnormality.

View full abstract

A girl who had a nontoxic diffuse goiter with a congenital organification defect of iodide was first seen at the age of 8 years, and since then she has been followed up for a long period. The nodularity of the thyroid gland had gradually progressed, because of intermittent failure of ingestion of thyroid hormone preparation which was followed by excess TSH secretion. 18 years later, a nodular goiter developed and the patient underwent subtotal thyroidectomy.
In order to prevent the development of nodular change in the thyroid gland in this disorder, supplemental thyroid hormone medication should be started as soon as the diagnosis is confirmed, and the therapy should be carried out regularly.

View full abstract

In order to determine whether endogenous dopaminergic tone has any role in the diurnal variation in TSH secretion, the 24-h secretory pattern of TSH and the TSH response to a dopamine antagonist, metoclopramide (MCP), were evaluated in normal women (n=4) and in hyperprolactinemic-amenorrheic women with pituitary microadenoma (n=6). TSH concentrations expressed as percent deviation from the 24-h mean significantly differed with respect to time of day in normal women and hyperprolactinemic women. They were significantly higher during the night (2000-0700h) than during the daytime (0800-1900h). Whereas MCP administration induced no significant changes in serum TSH levels in normal women, it significantly increased serum TSH levels in hyperprolactinemic women. Thus, the diurnal variation in TSH secretion was demonstrated in hyperprolactinemic women with pituitary microadenoma in the face of an increased dopaminergic inhibition of TSH secretion. The present study did not provide evidence that the diurnal pattern of TSH secretion is related to the endogenous dopaminergic tone.

View full abstract

The effects of intravenous injection of synthetic human pancreatic growth hormone-releasing factor-44-NH₂ (hpGRF-44) and synthetic thyrotropin releasing hormone (TRH), or hpGRF-44 in combination with TRH on growth hormone (GH), thyrotropin (TSH), and prolactin (PRL) release in dairy female calves (6- and 12-month-old) were studied. When 0.25μg of hpGRF-44 per kg of body weight (bw) was injected in combination with TRH (1.0μg per kg of bw), the mean plasma GH concentration of the 12-month-old calves rose to a maximum level of 191.5ng/ml (P<0.001) at 15 min from the value of 6.8ng/ml before injection at 0 min. The maximum level was 3.1 and 6.1 times as high as the peak values obtained after injection of hpGRF-44 (0.25μg per kg of bw) and TRH (1.0μg per kg of bw), respectively (P<0.001). The area under the GH response curve for the 12-month-old calves for 3 hr after injection of hpGRF-44 in combination with TRH was 2.5 times as large as the sum of the areas obtained by hpGRF-44 and TRH injections. In contrast, the mean plasma GH level was unchanged in saline injected calves. The magnitudes of the first and the second plasma GH responses in the 6-month-old calves to two consecutive injections of hpGRF-44 in combination with TRH at a 3-hr interval were very similar. The peak values of plasma GH in the calves after hpGRF-44 injection were 2-4 times as high as those after TRH injection. When hpGRF-44 was given to the 12-month-old calves, no elevation of plasma TSH or PRL level was observed. These results indicate that when hpGRF-44 and TRH are administered together a synergistic effect on bovine GH release occurs and hpGRF-44 is a much more potent and specific stimulator of GH release than TRH in the bovine.

View full abstract

To elucidate the relationship between binding parameters and biopotencies of glucocorticoids, we partially purified the receptor from the liver cytosol of rats in a dexamethasone-bound and unactivated form by precipitation with protamine sulfate, gel filtration and DEAE-cellulose chromatography (approximately 100-fold) and examined the interaction of the preparation with 3 glucocorticoids of different biopotencies (dexamethasone; Dex, corticosterone; Cort and prednisolone; Pred). The partially purified receptor (PPR) was stable at -20°C for at least 2 months in the presence of bovine serum albumin, glycerol, molybdate and dithiothreitol. Treatment of the PPR with p-hyroxymercuribenzoate liberated the ligands and the treated PPR reassociated ³Hglucocorticoids efficiently following the addition of dithiothreitol. The reassociated PPR was bound to the DNA-cellulose after a brief heating. Metabolic activity on ligands and inactivation of the binding sites in the PPR were insignificant under the conditions used. K_d's were -0.9, -3 and -6 nM for Dex, Cort and Pred, respectively (at 0°C). Relative binding affinity of ligands to the PPR which was estimated by competitions was higher in the order of triamcinolone acetonide>Dex>Cort>Pred>progesterone>cortexolone. Association of Dex and Cort was relatively rapid and significantly accelerated by raising the incubation temperature, while the association of Pred was slower and effects of the temperature was moderate. The rate of dissociations was also varied with ligands. The rate of dissociation of Dex was the lowest among the 3 ligands and was elevated by raising the temperature. Because the effect of temperature was more pronounced in the dissociation than in the association, apparent K_a's decreased at higher temperature. Thermodynamic examinations of glucocorticoid binding in the PPR revealed that the binding reaction proceeds at a higher rate in the order of Dex>Cort>Pred. Because the relative biopotencies of these 3 glucocorticoids in vivo is higher in the order of Dex>Pred>Cort, from the results obtained in the present study, it appears that biopotency of glucocorticoids in vivo does not correlate with the affinity of the binding to the receptor estimated in vitro.

View full abstract

A 31-year old woman was admitted to our clinic complaining of high blood pressure, dizziness, constipation, mental irritability and weight loss. The physical examination revealed goiter in her neck. The plasma levels of norepinephrine and epinephrine were 3.45 and 0.76 ng/ml, respectively. Urinary excretion of norepinephrine was 1mg and epinephrine was 32.2μg/24-hours. The examination by radiography and radioactive isotope revealed a tumor in the left adrenal region and another in the left lower lobe of the thyroid. After the operations, pheochromocytoma and papillary adenocarcinoma of the thyroid gland were recognized pathologically. However, 17 months later, the recurrence of pheochromocytoma in the contralateral adrenal region was discoverd and removed.
Although the co-existence of bilateral pheochromocytoma and papillary adenocarcinoma of the thyroid gland is not one of multiple endocrine neoplasia, to the best of our knowledge, only 7 such cases have been reported in the published literature.

View full abstract

A simplified method for the determination of natriuretic factor in the urine as measured by digoxin-like substance was studied. Digoxin-like substance in the urine was estimated by RIA using anti-digoxin antibody after being extracted by reversed phase cartridge column but without gel filtration. The values found by radioimmunossay (RIA) yielded a significant correlation with those of the inhibitory effect of Na-K-ATPase activity which was measured by biochemical assay as described by Hamlyn et al.
Using this RIA method, the effect of salt intake on natriuretic factor in urine was studied in patients with essential hypertention. The natriuretic factor on a high sodium diet (NaCl 20g/day for three days) increased approximately 1.5 times, as compared to those on a low sodium diet (NaCl 3g/day)(p<0.05). The Natriuretic factor showed a positive correlation with urinary Na excretion (P<0.050) when the patients were placed on adlib. sodium diet. From these results, it is suggested that secretion of natriuretic factor in the urine might be regulated in part by salt intake.

View full abstract

It has been reported that vasopressin (AVP)-sensitive renal epithelial cell line (MDCK) forms morphologically polarized monolayers when cultured on plates. We studied whether the AVP-responsive cAMP production system would be located solely on the basolateral surface of these cells as has already been shown on the renal tubules. We used two methods to overcome the inaccessibility to the basolateral surface of the cultured cell layer and to study the apical and basolateral surfaces separately. One was culture on collagen sheet and the other was on Millipore filters. Our experiments showed that MDCK cell increased adenosine 3': 5'-cyclic monophosphate (cAMP) content prominently only when vasopressin was accessible to the basolateral surface.
Accordingly, MDCK cells were shown to have the AVP-responsive cAMP production system predominantly on the basolateral surface of the cell membrane.

View full abstract

In order to obtain a good separation line between patients with primary hyperparathyroidism (1°HPT) and those with non-parathyroidal hypercalcemia (NPHC), serum chloride (Cl) and phosphate (P) concentrations were analyzed. Ninety-nine per cent of the patients with 1°HPT had a Cl/P ratio greater than or equal to 33, but 29% of patients with NPHC were also included in this range. When the (Cl-90)/P ratio was used to separate into two groups, 98% of the patients with 1°HPT had a ratio greater than or equal to 5.0, and 94% of the patients with NPHC had a ratio less than 5.0. From these results, while high sensitivity was achieved both with the Cl/P and (Cl-90)/P ratios, the (Cl-90)/P ratio provided higher specificity. Therefore we concluded that the (Cl-90)/P ratio was excellent in distinguishing 1°HPT from other types of hypercalcemia.

View full abstract

We encountered a 65-year-old man with gamma heavy chain disease associated with extramedullary plasmacytoma of the thyroid gland. Serum electrophoresis revealed an abnormal fast gamma band that cross-reacted with anti-IgG (Fcγ) sera immunoelectrophoretically. Intracytoplasmic monoclonal immunoglobulin, IgG (Fcγ), was demonstrated in thyroid tissue sections using an indirect immunofluorescence method. After surgery, the serum abnormal fast gamma band disappeared.
At the time of writing, the patient has survived 18 months post-surgery.

View full abstract

We have recently encountered a patient with rapidly enlarging thyroid masses histologically diagnosed as diffuse histiocytic lymphoma which developed in the active course of Graves' disease. The primary thyroid lymphoma has been in complete remission after local radiation therapy. The association of Hashimoto's thyroiditis and thyroid lymphoma has well been recognized. Meanwhile, data have accumulated to demonstrate that Hashimoto's thyroiditis and Graves' disease share possible similar causal immunological abnormalities and are closely related entities. However, the association of Graves' disease and primary thyroid lymphoma has never been reported, as far as we know. Therefore, this case may be the first one that supports the natural concept that thyroid lymphoma develops from pre-existing Graves' disease secondary to the similar immunological abnormalities in Hashimoto's thyroiditis.

View full abstract

In a perifusion system in the presence of 3-isobutyl-1-methylxanthine, forskolin stimulated secretion of not only cAMP but also 3, 5, 3'-triiodothyronine (T₃) from rat thyroid glands. The increases in both cAMP and T₃ were dose-dependent at forskolin concentrations of 2.0×10^-7M to 2.0×10^-5M. After perifusion for 4 h, tissue concentrations of cAMP also increased as a result of forskolin treatment. Since forskolin is regarded as a specific activator of the cAMP generating system, this observed forskolin stimulation of T₃ secretion from perifused rat thyroid glands indicates that cAMP is involved in regulating thyroid hormone secretion.

View full abstract