[en] We studied total cell-associated A14-[¹²⁵I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity. Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[¹²⁵I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[¹²⁵I]insulin, [¹²⁵I]iodide, or [¹²⁵I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients

[en] With an antiserum against human β-endorphin (β-EP) crossreacting <2% with human β-lipotropin (β-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg β-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects β-EP ranged from <5 to 45 pg/ml. β-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, β-EP was undectectable after dexamethasone and increased after metyrapone administration and insulin-induced hypoglycemia. β-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, β-EP behaves like a hormone responding to the same stimuli as ACTH and β-LPH and blood appears to contain enzymes both generating and destroying immunoreactive β-EP

[en] Biochemical and immunological characteristics of renin secreted by two malignant renin-secreting tumors [pulmonary (PT) and paraovarian (POT)] were studied. They both contain inactive renin (IR), as renin activity of tumoral extracts was able to be increased after acid activation or trypsin treatment (10.1 to 20.8 Goldblatt units/g tissue for PT and 1.4 to 3.71 for POT). Renin activity after activation reached the value obtained by direct RIA of human renin (23 and 3.4, respectively), as both forms are recognized by renin antiserum. Both enzymatic activities could be completely inhibited by renin antiserum. Displacement curves for the two tumoral renins paralleled the MRC renin in the direct RIA. After chromatography on affigel blue, active renin was not bound to the gel, and inactive renin eluted only with 1 M NaCl. On pepstatin A Sepharose and CBL-pepstatin Sepharose (an N-modified-pepstatin), a separation of the two forms of pulmonary renin was obtained; inactive renin eluted with breakthrough proteins, whereas active renin was strongly bound to the gel. After this affinity chromatography, the molecular weights of inactive and active renin, determined on Ultrogel, were very close (46,000 and 42,500). We conclude that 1) ectopic renin in these cases is similar to the renal enzyme; 2) renin can be secreted in an inactive form, supporting the hypothesis of an inactive initial state of renin; and 3) molecular weight differences between the two forms are very slight

[en] Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status

[en] To investigate underlying ultradian periodicities in spontaneous circulating GH concentrations, blood samples were drawn from 15 normal short boys every 20 min over a 24-h period, and plasma GH concentrations were measured using an ultrasensitive immunoradiometric assay. The limit of detection for the GH assay was 0.01 μg/L. The GH time series were analyzed using the Cluster program, Ultra program, cosinor analysis, and autocorrelation analysis. Plasma GH concentrations in 1,095 samples derived from 15 normal short boys were all within the detectable range of the assay and ranged from 0.07-52.2 μg/L. Thirty-six percent of the GH values in the 1,095 samples from 15 normal short boys were below 1 μg/L, and 82% of them occurred during the diurnal awakening period. Cluster analysis disclosed a total of 176 peaks in 15 normal short boys, with a mean ± SEM number of significant GH peaks of 12.1 ± 0.5/24 h. Twelve percent of the 176 peaks were below 1 μg/L, and 95% of them occurred during the diurnal awakening period. In addition, Cluster analysis disclosed 161 interpulse intervals in total, with a mean ± SEM interval of 116.5 ± 4.3 min. The GH interpulse interval did not show a significant 24-h rhythm, whereas the GH peak height increased significantly at night. An independent discrete peak detection in program, Ultra, identified 12.6 ± 0.5 GH peaks/24 h. This result was in good agreement with that from analysis by the Cluster program (P = NS). Autocorrelation analysis revealed that GH time series were significantly autocorrelated in 9 of the 15 boys, with maximal autocorrelation coefficients at 115.5 min, on the average. The mean autocorrelation coefficient for a group of 15 normal short boys was significantly positive at a 100-min lag. These findings suggest that there could be a regularly occurring periodicity of approximately 100-120 min in the human GH time series. 18 refs., 4 figs., 1 tab

[en] Twenty men (median age, 31 yr) previously treated for unilateral testicular cancer received localized irradiation in a dose of 20 Gray in 10 fractions for carcinoma in situ of the remaining testis. Follow-up testicular biopsies performed 3 (n = 19) and 24 (n = 14) months after the treatment showed in all cases a Sertoli cell-only pattern. Hormonal evaluation was performed before as well as 3, 12, 24, and 36 months after radiation treatment. Endocrine parameters were followed for a median of 30 months (3-36 months). Baseline serum testosterone values decreased during the follow-up period from 13.3 ± 6.0 to 10.8 ± 6.4 nmol/L (mean ± SD), although the decrease was not statistically significant (P = 0.06). Serum LH values increased during the first 3 months of follow-up from 10.4 ± 5.4 to 15.6 ± 7.3 IU/L (P less than 0.0001) and then remained unchanged. Significant decreases in GnRH- and hCG-stimulated testosterone levels also indicated an impairment of Leydig cell function. FSH levels increased (P less than 0.0001) during the first 3 months of follow-up from 21.8 ± 11.1 to 33.2 ± 13.2 IU/L. The authors conclude that localized irradiation of 20 Gray eradicated carcinoma in situ germ cells. Development of a second testicular cancer has until now been prevented. Leydig cell function was partially impaired by the radiation dose given

[en] The acute somatomedin (SM) response to GH therapy has been examined in 21 GH-deficient children using a placental membrane radioreceptor assay (RRA) which measures a variety of SMs and a RIA specific for SM-C and insulin-like growth factor I (IGF-I). Plasma for determination of SM peptide content was obtained before initiation of therapy and 13 h after each of four daily injections of GH (0.1 U/kg). An additional SM determination was performed after 6 weeks of GH therapy (0.1 U/kg, three times per week) in seven of the subjects. RRA and RIA SM determiations were performed on the same acid-chromatographed sample and were compared to an acid chromatographed pooled plasma standard. The 4 days of GH therapy resulted in an increase in SM levels from 0.39+/- 0.24 to 1.18 +/- 0.62 (+/- SD) U/ml, determined by RIA. A single injection of GH resulted in a significant rise in plasma SM levels, measured by either RRA or RIA (P less than 0.001). Subjects who responded poorly to two injections of GH also had low SM levels after 4 days and even after 6 weeks of GH therapy. The RRA resulted in consistently higher value than the RIA. This difference was even greater when results were compared to a pure IGF-I/SM-C standard. The SM peptide contents determined by RRA and RIA were strongly correlated, not only for the group, but also among the determinations for each individual subject. However, the consistently higher values observed when the SM peptide content was measured by RRA compared to that measured by RIA and the variability in the RRA to RIA ratio among individual subjects suggest that the IGFI/SM-C RIA measures only one of a number of GH-dependent SM peptides

[en] The present report describes a RIA for 3,5-diiodothyronine (3,5T₂) which uses inner ring-labeled 3,5-[¹²⁵I]T₂ as the ligand and has a lower limit of detectability of 0.5 ng/dl. Cross-reaction was 0.14% with T₃, less than 0.001% with T₄, 1.2% with 3,3',5-triiodothyroacetic acid, and 6.1% with 3,5-diiodothyroacetic acid. No cross-reaction was detectable for iodothyronines within their physiological ranges. Intraassay variation ranged from 2.2 to 7.8%, and interassay variation ranged from 12.7 to 14%. The mean (+-SE) serum 3.5T₂ concentration in 70 normal subjects was 4.3 +- 0.2 ng/dl. The mean (+-SE) 3.5T₂ in 14 hyperthyroid patients was increased to 18.4 +- 2.3 ng/dl (P < 0.001), and all but 1 patient had an elevated level. In 10 hypothyroid patients the mean (+-SE) 3,5T₂ level was decreased to 1.4 +- 0.3 ng/dl (P < 0.001). In 4 patients, levels overlapped with the normal range. In 4 hypothyroid subjects treated with L-T₁, 3,5T₂ levels were normal, suggesting that the majority of 3,5T₂ originates from extrathyroidal conversion from T₃. Studies in fasting obese subjects demonstrated that serum 3,5T₂ (mean +- SE) levels fell from 3.4 +- 0.3 to 2.5 +- 0.7 ng/dl during fasting. This fall was significant (P < 0.001) and in parallel with the fall in T₃ levels of 182 +- 20 to 126 +- 12 ng/dl. In fasting subjects given 100 μg oral L-T₃/day T₃ levels rose from 138 +- 11 to 362 +- 26 ng/dl. 3,5T₂ levels (corrected for cross-reaction and for contamination of oral T₃ with 3,5T₂) rose from 2.2 +- 0.7 to 6.4 +- 1.0 ng/dl. In fasting subjects given 25 μg oral L-T₃/day, T₃ levels fell from 165 +- 5.1 to 139 +- 6.9 ng/dl. Corrected 3,5T₂ levels changed from 3.7 +- 0.4 to 2.5 +- 0.3 ng/dl. Neither change were significant

[en] After total thyroidectomy for medullary thyroid carcinoma, a 50-yr-old male was found to have decreased but still abnormally elevated plasma calcitonin levels. A thyroid scan with ¹³¹I revealed remaining thyroid tissue primarily in the form of a thyroglossal duct remnant. Two courses of ¹³¹I treatment of 30 and 150 mCi, respectively, produced a gradual decrease in plasma calcitonin. This study demonstrates that carefully selected patients may benefit from the use of ¹³¹I treatment as an adjunct to surgery in medullary thyroid carcinoma

[en] Dexamethasone-suppression (DS) adrenal scintigraphy localizes an aldosteronoma, but with false-negative results, i.e. 2 of 19 cases in our study. Our aim was to clarify the clinical meaningfulness of this test. Adrenal iodomethyl-norcholesterol (NP-59) uptake on the adenoma side correlated with the estimated adenoma volume (n = 15, r = 0.843, P less than 0.001). Accordingly, the uptake ratio on the adenoma side to that on the opposite side depended on the adenoma volume (r = 0.683, P less than 0.01). This explains the false-negative results (uptake ratio less than 2) in two cases with small adenomas. The NP-59 uptake correlated weakly with the plasma aldosterone level (r = 0.516, P less than 0.05). This result indicates the low correlation between NP-59 uptake and the ability to secrete aldosterone. NP-59 accumulation in the surgically removed gland was analyzed by autoradiography in six cases where DS scintigraphy was done just before surgery. The density was higher in the adenoma cells than in the adjacent cortical cells in five cases, but the difference was rather small, i.e., within a 2-fold difference in four cases. In one case, almost the same density was observed in both types of cells. Thus, the laterality of NP-59 uptake primarily depends on the adenoma volume although NP-59 uptake somewhat reflects the adenoma's ability to secrete aldosterone or the adenoma cell's activity in accumulating NP-59. Care must be taken in interpreting the findings from DS scintigraphy where the adenoma is small or adrenal uptake is low