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Biomedical subjects

L K Nieman

Publications and source records attributed to L K Nieman.

96 records · Page 6Linked to original sources
PubMed1985

Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486.

A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.

Adrenocorticotropic Hormone↗
PubMed1983

Effect of end-stage renal disease on responsiveness to calmodulin and thyroid hormone of calcium-ATPase in human red blood cells.

Red blood cell membrane Ca2+-ATPase, a calcium-pump-associated enzyme, has been studied in a series of 10 patients with ESRD and in a group of normal volunteers. Basal enzyme activity was significantly reduced in cells from ESRD patients (0.189 +/- 0.018 vs. controls, 0.274 +/- 0.021 mumoles of Pi per milligram of membrane protein per 90 min; P less than 0.001). Calcium efflux from intact red cells, a functional correlate of Ca2+-ATPase activity, was also decreased in ESRD patients. Normal erythrocytes have recently been shown to have membrane Ca2+-ATPase activity that can be stimulated in vitro by physiologic concentrations of thyroid hormone (10(-10) M). In the present studies, ESRD red cell membrane Ca2+-ATPase activity was found to be unresponsive to thyroid hormone. In addition, calcium efflux from intact ESRD cells, in contrast to normal red cells, could not be stimulated by thyroid hormone. ESRD membrane Ca2+-ATPase was also poorly-responsive in vitro to purified calmodulin, the activator protein of the enzyme. This reduction in activity of Ca2+-ATPase in ESRD red cells is similar to previously described alterations in sodium-potassium-ATPase, another membrane-linked cation pump.

Animals↗
PubMedDate not supplied

Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland.

Gadolinium diethylenetriamine pentaacetic acid (DTPA) enhanced magnetic resonance imaging was performed in eight patients with Cushing disease and surgically proven pituitary microadenomas. A 1.5 T scanner was used with 3 mm contiguous slices. Short repetition times (TR), short echo times (TE), and long TR, long TE sequences were obtained before and serially after intravenous administration of Gd-DTPA. Three of eight (38%) microadenomas were undetectable both without and with Gd-DTPA: one post-Gd-DTPA scan was false positive on the side opposite the adenoma. Hemihypophysectomy based on a petrosal sinus adrenocorticotropic hormone (ACTH) gradient cured all three patients. Two microadenomas (25%) were visible as hypointense foci following Gd-DTPA but not on unenhanced scans. The remaining three microadenomas (38%) were seen before and after Gd-DTPA on T1-weighted images. In this small series of ACTH-producing microadenomas, one-third were seen on unenhanced 1.5 T scans, one-third were seen only after Gd-DTPA, and one-third were not imaged even with Gd-DTPA enhancement.

Adenoma↗
PubMedDate not supplied

CT and MR imaging of massive macronodular adrenocortical disease: a rare cause of autonomous primary adrenal hypercortisolism.

We studied four patients with adrenocorticotropic hormone (ACTH)-independent hypercortisolism due to bilateral massive enlargement of the adrenal glands. The combined weight of the adrenal glands ranged from 69 to 149 g and the adrenal cortex was replaced in three of four patients by multiple nodules ranging from microscopic to 4 cm in diameter. One patient had massive diffuse enlargement. All patients had low or undetectable levels of serum ACTH, absence of petrosal sinus to peripheral gradients of ACTH in bilateral samples from the inferior petrosal sinuses before and after stimulation by corticotropin releasing hormone, and absence of an adenoma on MR imaging of the pituitary gland. The marked degree of adrenocortical enlargement and absence of ACTH dependency separates this massive macronodular disease from the more common ACTH-dependent macronodular hyperplasia encountered in older patients with pituitary-dependent Cushing disease. All patients required bilateral adrenalectomy to control hypercortisolism. We present the spectrum of nodular adrenal disease associated with hypercortisolism and a differential diagnosis based on morphologic criteria.

Adrenal Cortex Diseases↗
PubMedDate not supplied

Growth hormone receptor gene expression in the mouse uterus: modulation by gonadal steroids.

OBJECTIVES: We hypothesized that the mouse uterus expresses a growth hormone receptor (GHR) and that mouse endometrial GHR mRNA may undergo in vivo regulation by estradiol (E2) and progesterone (P). METHODS: Two weeks after bilateral ovariectomy, 35-day-old Balb/c mice were randomly assigned to receive either vehicle injections; E2 priming (300 ng/day) on days 1-6 and E2 (50 ng/day) on day 11; P (1 mg/day) on day 8-11; or E2 priming with P (days 8-11) and E2 on day 11, with or without RU 486 on day 8-11. At sacrifice 24 hours after the last injection, the uteri were processed for RNA extraction and in situ hybridization for GHR mRNA. Reverse transcriptase polymerase chain reaction amplification of uterine mRNA was performed to establish whether treatment with gonadal steroids differentially affected GHR gene expression. The GHR primers flanked a 326-bp region from the intracellular domain sharing no homology to the prolactin receptor or to the GH-binding protein. A 48-bp digoxigenin-labeled oligoprobe was used for in situ hybridization. RESULTS: Densitometry analysis of polymerase chain reaction products from total uterine mRNA revealed similar GHR mRNA expression in vehicle- and estrogen-treated animals. The addition of progesterone reduced GHR mRNA expression. In situ hybridization localized the GHR mRNA to the endometrium, glands, stroma, and myometrium. Stromal staining was reduced in the progesterone-treated mice. CONCLUSIONS: The identification of GHR message suggests that the mouse uterus is a site of action of GH. The lack of modulation of epithelial GHR by sex steroids does not support a role of GHR in this compartment.

Animals↗