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The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.

A 37-year-old woman with postoperative hypoparathyroidism had hypertension, and elevated plasma renin activity (PRA) and subsequent hyperaldosteronism during a two-month hypercalcemic period caused by vitamin D and excessive calcium supplements. The hypertension with elevated PRA, however, was resistant to the angiotensin II (AII) analog [Sar1, Ile8] ALL. PRA further increased and plasma aldosterone decreased in response to the [Sar1, Ile8] ALL. When the patient became normocalcemic, normotensive and normoreninemic, calcium gluconate (5 mg calcium/kg/h) was infused for one hour. The calcium infusion reproduced hypercalcemic hypertension mediated by an increase in total peripheral resistance. These observations suggest that the hypertension observed while taking vitamin D and excessive calcium supplements may be caused by a direct effect of calcium on peripheral blood vessels and the renin-angiotensin system may play a negligible role.

Two male patients with 'Hashitoxicosis', who revealed histologic pictures of adenomatous goiter in addition to findings of chronic thyroiditis, are described. Case 1. A 55-year-old man was admitted on May 7, 1981, for evaluation of hyperthyroidism. He had exophthalmos with positive Moebius and von Graefe's signs, and a firm, asymmetrically enlarged non tender thyroid gland with multiple cysts. The BMR was +60%, T4 26.4 micrograms/dl, free T4 7.2 ng/dl, T3 5.62 ng/ml and 24 hr radioiodine uptake 49.5%. TSH was undetectable and did not respond to TRH. 123I scan showed multiple defects in the bilateral upper poles of the thyroid gland. Antithyroglobulin and antimicrosomal antibodies were positive. He then underwent a total thyroidectomy with removal of multinodular goiter. The mutinodular goiter was associated with cystic degeneration which contained the thyroid hormone-rich fluid. Histologic examination revealed multiple adenomatous nodules and lymphocytic infiltration and degeneration in the surrounding tissues of the nodules. Case 2. A 43-year-old man was admitted on May 14, 1975, because of an 8 month history of hand tremor, weight loss (5 kg), facial and upper palpebral edema and an enlarged thyroid. He had mild exophthalmos and a firm, asymmetrically enlarged thyroid gland with multiple nodules. The BMR was +35%, T4 20.0 micrograms/dl, T3(Resomat) 0.78 ng/ml and PBI 20.0 micrograms/dl. TSH was 1.0 muU/ml and responded slightly to TRH. 24 hr radioiodine uptake was 84.4% and did not respond to T3 administration. Antithyroglobulin and antimicrosomal antibodies were positive. 123I scan showed diffusely increased uptake and no defects. Histologic examination of the biopsy specimen of the thyroid gland showed multiple adenomatous nodules in addition to typical findings of chronic thyroiditis in the surrounding tissues of the nodules. From the above observations, it is suggested that multiple adenomatous nodules accompanying chronic thyroiditis show clinical features resembling Basedow's disease rather than Plummer's disease.

Freshly isolated human monocytes ingested and killed Candida albicans, and generated O2- H2O2 and .OH efficiently. When monocytes were cultured in vitro, these cells transformed into macrophages. Cultured monocytes retained their ingestive activity but lost their candidacidal activity almost completely after day 3. The release of O2- by monocytes decreased slightly with culture and that of .OH was markedly decreased on day 3 of culture. The activity of myeloperoxidase in the monocytes decreased with culture. These results suggested that the loss of candidacidal activity is due to the decrease of .OH generation and myeloperoxidase activity in cultured monocytes.

Studies were designed to determine whether an autoregulation system exists for TSH in the rabbit. For this purpose, a species-specific RIA for rabbit TSH that does not cross-react with human (h) TSH was developed. Hypothyroid animals were studied at varying time periods up to 3 months after either surgical thyroidectomy or propylthiouracil (PTU) treatment. Highly purified hTSH was injected iv at doses of 0 (saline control), 0.1, 0.3, 1,3, and 10 micrograms into unanesthetized rabbits bearing chronically implanted Silastic catheters. Blood samples were obtained at -30, 0, 10, 20, 30, 60, 120, 180, 240, and 300 min and 24 h. Doses between 0.3 and 10 micrograms hTSH produced a prompt fall (10 min) in rabbit TSH in hypothyroid rabbits studied 8-21 days after thyroidectomy. The minimum dose of hTSH that significantly suppressed rabbit TSH was 0.3 micrograms. This dose produced a peak value of hTSH in rabbit serum of 1.3 +/- 0.1 (+/- SEM) ng/ml 10 min after injection, which translates into a bioassay potency of 2.0 microU/ml (close to the physiological level in humans). A dose-response relationship existed between the hTSH dose injected and the duration and magnitude of suppression of rabbit TSH. This response to TSH was specific; 10 micrograms hTSH produced no change in endogenous rabbit serum LH and, conversely, 10 IU hLH produced no change in rabbit serum TSH. In contrast to these striking effects in acute hypothyroid animals, hTSH produced no detectable suppression of rabbit TSH in animals that were hypothyroid for 2-3 months. The sensitivity of the autoregulatory system to the suppressive effects of exogenous hTSH decreased with increasing duration of hypothyroidism; a time-response relationship existed. We conclude that: 1) a sensitive and specific autoregulatory control system for TSH exists in the rabbit; and 2) as the duration of hypothyroidism increases, the sensitivity of the autoregulatory system to the suppressive effects of endogenous TSH changes.

Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals. The adenylate cyclase of two normal adrenals was activated only by ACTH and PGE1 among the hormones tested, while that of two hyperplastic adrenal tissues due to excessive pituitary ACTH secretion was stimulated only by ACTH. Of five ACTH-responsive adrenocortical adenomas, in contrast, three were stimulated by norepinephrine, two by epinephrine, one by thyroid-stimulating hormone, and one by luteinizing hormone in addition to ACTH, indicating the presence of multiple receptors for hormones other than ACTH and PGE1 in these four tumors. The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1. These results indicate the presence of multiple receptors for hormones other than ACTH and PGE1, the normal adrenocortical stimulants, in human adrenocortical tumors, particularly in adrenal adenomas, but not in normal and hyperplastic (of whichever an etiology) adrenocortical tissues, suggesting a functional alteration of the cellular membrane receptors in human adrenocortical tumors.

Cytolysis of leukemic cells by peripheral blood-derived macrophages was examined by means of an in vitro 111In release assay. Monocytes prepared on culture dishes lyse YK-M2. However, when monocytes were cultured in vitro and transformed into macrophages, they lost most of their lytic activity. The addition of human recombinant interleukin-2 (rIL-2) on day 5 in culture enhanced the lytic activity significantly. Similarly, treatment of macrophages with human recombinant interferon gamma (rIFN-gamma) promoted the lysis of YK-M2 and K-562, although the extent of lysis was smaller than that by rIL-2. Macrophages activated with rIL-2 and rIFN-gamma also lysed human leukemic cells. Activated macrophages lysed leukemic cells of acute myelocytic leukemia more than acute lymphocytic leukemia cells. Macrophages derived from the peripheral blood of patients with leukemia were examined for their lytic activity against YK-M2. The patient's macrophages lysed more YK-M2 than did control macrophages when they were activated with rIL-2 and rIFN-gamma. The macrophages of two patients also demonstrated autologous leukemic cell lysis.