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Biomedical subjects

D T Krieger

Publications and source records attributed to D T Krieger.

At least 127 records · Page 7Linked to original sources
PubMed1976

Absence of nocturnal elevation of plasma prolactin concentrations in Cushing's disease.

The mean prolactin concentration during sleep and the per cent change (increase) and increment in the nocturnal elevation of plasma prolactin concentrations were significantly reduced (P less than .01, less than .01, and less than .001, respectively) in 6 untreated patients with clinically active Cushing's disease, compared with concentrations seen in normal subjects. There was no significant difference between mean-awake and mean-sleep plasma prolactin concentration in these patients, in contrast to that seen in normal subjects. In contrast, patients with hypercorticism secondary to adrenal adenoma (n = 2) or receiving long-term, high-dose corticosteroid therapy (n = 6) did not differ significantly from normal subjects in the percentage change seen in the nocturnal elevation of their plasma prolactin concentrations. Although mean prolactin concentration during sleep was reduced in these two categories of hypercorticism, a significant difference was still present between mean-awake and mean-sleep plasma prolactin concentration. (The nocturnal increment in plasma prolactin concentrations in these patients with hypercorticism compared with that of normal subjects was reduced, P less than .02). The difference between the percentage change and nocturnal increment observed in patients with Cushing's disease versus that seen in these two categories of hypercorticism was significant at P less than .02 and P less than .01, respectively. Four untreated patients with localized hypothalamic tumors also showed a significant reduction in the percentage change and increment in the nocturnal elevation of plasma prolactin concentrations (P less than .05 and P less than .02). In contrast to these findings, the prolactin responses to thyrotropin-releasing hormone (indicative of pituitary responsiveness) in patients with Cushing's disease, patients with adrenal adenoma, or those receiving chronic corticosteroid therapy, were all within the normal range seen in sex-matched control subjects. These findings provide additional evidence for the suggestion that there is altered hypothalamic function in patients with Cushing's disease.

Adrenal Cortex Hormones↗
PubMed1976

Effectiveness of cyproheptadine in decreasing plasma ACTH concentrations in Nelson's syndrome.

Cyproheptadine (24 mg q.d.) was administered to four patients with Nelson's Syndrome for a 3-5 month period. This resulted in a significant reduction in plasma ACTH and prolactin concentrations in 3 of these subjects. A rise in plasma ACTH concentrations occurred following discontinuance of medication in one patient. The results suggest that pituitary ACTH secretion in some patients with Nelson's Syndrome is under Central Nervous System control.

Adrenocorticotropic Hormone↗
PubMed1976

Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities.

A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.

Adrenocorticotropic Hormone↗
PubMed1975

Cyproheptadine-induced remission of Cushing's disease.

Experimental evidence suggests a central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release. The efficacy of cyproheptadine therapy, therefore, was studied in three patients with such disease. Administration of 24 mg daily over a period of three to six months was associated with prompt and sustained clinical and laboratory remission. Lessening of the physical manifestations of hypercorticism occurred, together with marked improvement in muscular weakness. Urinary corticosteroid excretion and cortisol secretory rate returned to normal. The urinary corticosteroid response to dexamethasone (2 mg per day) became normal; a paradoxical increase followed 8 mg per day. Abnormal circadian periodicity of plasma cortisol concentrations persisted. Return of normal amounts of Stage III to IV sleep occurred in the one patient so studied, who previously had markedly decreased periods of these stages. Discontinuance of therapy in one patient was associated with return of laboratory evidence of hypercorticism.

Adrenal Cortex Hormones↗
PubMed1975

Effect of intraventricular neonatal 6-OH dopamine or 5,6-dihydroxytryptamine adminisration on the circadian periodicity of plasma corticosteroid levels in the rat.

The extent of circadian variation in plasma corticosteroid levels at 30 days of age was normal in rats who received either intraventricular 6-OH dopamine or 5,6-dihydroxytryptamine on day 3 of life. A 4-h advance in the time of peaking was present in this latter group. At the time of study the depletion of 8.00 a.m. and 8.00 p.m. levels of norepinephrine was significant in the cortex (--49%), hypothalamus (--58%), hippocampus (--65%), and amygdala (--44%) of the 6-OH dopamine-treated animals, as was a similar depletion of serotonin in these areas in the 5,6-dihydroxytryptamine-treated animals. There was no difference between 8.00 a.m. and 8.00 p.m. levels of either amine in any of these areas, in contrast to the variation seen in uninjected animals in whom 8.00 a.m. levels of both amines were higher in all areas than 8.00 p.m. levels. The female 6-hydroxydopamine-treated animals had significantly increased adrenal weights. No other significant changes were noted in the adrenals or gonads of either treated group. Body weights were not significantly altered in any of the animals. These data demonstrate that the circadian variation in plasma corticosteroid levels can develop in the presence of either marked norepinephrine or serotonin depletion in CNS areas that have been implicated in the regulation of such periodicity.

Adrenal Cortex Hormones↗
PubMed1975

A sensitive bioassay for the determination of human plasma ACTH levels.

A sensitive bioassay for the measurement of plasma ACTH is presented. The use of silicic acid adsorption of plasma, with a subsequent acid wash and aqueous acetone desorption, was successful in removing those substances which had interfered with the steroidogenic response of dispersed adrenal cells when unextracted plasma was employed. This extraction procedure extracted 72-76% of ACTH present in plasma. Two pg ACTH1-39 could be consistently detected. Alpha-hACTH1-39 and alpha-pACTH1-39 exhibited equal potencies. Beta-MSH was ineffective at dosage levels up to 2 x 10(8) pg. One x 10(8) pg of ACTH1-10, ACTH4-10, or alpha-MSH had a steroidogenic effect equivalent to that of 40 pg ACTH1-39. ACTH 17-39 and ACTH 11-24 were incapable of stimulating steroid production at doses of 1 x 10(8) pg. Excesses of the latter, but not of the former appeared to be able to antagonize the steroidogenic effect of ACTH1-39. Plasma from normal subjects, bioassayed by this extraction procedure, contained 12-186 pg/ml ACTH at 0400-0800: 14-93 pg/ml ACTH at 1000-1300, and less than 10-34 pg/ml ACTH at 1600-2200. Hypoglycemia and vasopressin administration were followed by increases in plasma ACTH concentratrations. Plasma ACTH concentrations in untreated patients with Cushing's disease (sampled over the period 0900-1300) ranged from 65-220 pg/ml. Three patients with Addison's disease (untreated or 12 h following replacement steroid withdrawal) had ACTH concentrations of 223, 370 and 1226 pg/ml. Markedly elevated ACTH concentrations were observed in a patient with Nelson's syndrome (391 and 835 pg/ml). Bioassayable ACTH was not detected in 2 patients with panhypopituitarism.

Acetone↗
PubMed1975

Relationship of bioassayable and immunoassayable plasma ACTH and cortisol concentrations in normal subjects and in patients with Cushing's disease.

Plasma ACTH and cortisol concentrations were determined at 5-min intervals over a 3- or 4-h sampling period in 2 normal subjects. Time spans studied were 10:00 AM-1:00 PM, 4:00 PM-8:00 PM, 8:00 PM-11:00 PM, and 4:00 AM-8:00 AM. Similar sampling for 3 h, (onset 9:00-9:30 AM) was performed on 4 patients with Cushing's disease, 3 untreated and 1 in remission following pituitary irradiation. Two of these patients were studied on 2 separate occasions. Plasma ACTH was determined by both immunoassay (I) and bioassay (B). Although in general, these studies demonstrated significant correlation between I-ACTH or B-ACTH concentrations and those of plasma cortisol, a striking finding in both subject categories was the presence of 30- to 50-min episodes during which marked rises in both I- and B-ACTH concentrations occurred without concomittant, or markedly diminished, increments in plasma cortisol concentrations. This could not be explained by biological inactivity of the ACTH, since a highly significant correlation was present between I- and B-ACTH concentrations at all times; r values ranged between 0.86 and 0.98 for normal subjects, and 0.76 and 0.96 for patients with Cushing's disease. The lack of correlation in these episodes also does not appear to be secondary to an 11-beta-hydroxylase block, differences in the rate of change of plasma ACTH concentrations, lack of adrenal "priming" by prior ACTH or incapacity of the adrenal gland to further increase secretion. I/B ACTH ratios were similar in the normal subjects (1.42-1.64) and in the patients with Cushing's disease (1.27-1.47). "Apparent" ACTH half lives calculated from "peaks" of ACTH secretion were 7-12 min for I-ACTH and 3-9 min for B-ACTH in the normal subjects; and 9-13 min and 7-9 min respectively, in the patients with Cushing's disease. Mean plasma ACTH I-and B-concentrations at comparable time periods were higher in patients with active Cushing's disease than in normal subjects. These studies also indicate that in Cushing's disease, the abnormality present resides in ACTH regulatory mechanisms, not in the nature of the ACTH secreted. Approximation of the total amount of immunoassayable ACTH secreted in one normal subject over a 24-h period yielded a value of 73 mug. Total mug/h secreted in the 2 normal subjects were highest in the hour preceding awakening (6:30-7:30 AM; 12.9 and 12.2 mug/h); were 5.3 and 4.0 mug/h between 10:00-11:00 AM, and 1.4 and 1.7 mug/h between 9:00-10:00 PM. In the 3 patients with clinically active Cushing's disease, apparent ACTH secretion between 10:00-11:00 AM varied from 19.2-34.3 mug/h, the magnitude of such secretion being positively correlated with the extent of increased adrenal cortical activity present.

Adrenocorticotropic Hormone↗
PubMed1975

Endocrine disturbances in patients with congenital aqueductal stenosis.

Congenital stenosis of the aqueduct of Sylvius is reported to be associated with sella turcia enlargement and clinical and laboratory abnormalities of the hypothalamic-pituitary-target-organ axis. It is a surgically reversible lesion. In the present report, 3 female patients with this lesion were studied with tests of basal endocrine function, as well as insulin tolerance tests, response to metyrapone and determination of circadian periodicity of plasma cortisol levels. In one patient all testing was normal and no surgery was performed. In 2 other patients the insulin tolerance test revealed either abnormal cortisol or growth hormone responses and in one patient urinary gonadotrophins were absent. All tests became normal post-operatively although in one instance not completely so until 5 years after surgery.

17-Hydroxycorticosteroids↗