[Case of XY gonadal dysgenesis associated with skeletal anomalies around the foramen magnum].
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Biomedical subjects
Publications and source records attributed to I Morimoto.
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We report here on a patient who was unilaterally adrenalectomized for Cushing's syndrome, and who developed antibodies to 1-24 ACTH. A 49-year-old nurse had undergone right adrenalectomy for adrenal adenoma. After surgery, she was treated with 0.5 mg of 1-24 ACTH-Z together with glucocorticoid replacement therapy for 40 days. Thereafter she was given 0.25-0.5 mg of ACTH-Z every other day for 4 months. ACTH-Z was then stopped for a year but glucocorticoid therapy was continued. About one year prior to this admission, 1 mg of ACTH-Z was again initiated 1 to 2 times a week. Glucocorticoid therapy was not withdrawn during the four years after adrenalectomy. She was admitted for the purpose of withdrawal of glucocorticoids. Her serum was found to bind labeled ACTH. This labeled ACTH was competitively displaced from binding by unlabeled hormones. Finally, reaction with specific antihuman Ig demonstrated an antibody of the IgG class. The titer of the antibodies gradually decreased after the discontinuation of ACTH-Z, but it is still present in measurable quantity in her serum. The clinical significance of the circulating anti-ACTH antibody in her serum is discussed.
This paper describes the screening studies of 104 commercial crude drugs for mutagenicity by the rec-assay with Bacillus subtilis as well as the reversion assay with Ames strains TA98 and TA100 of Salmonella typhimurium. The rec-assays showed that 13 water extracts and 27 methanol extracts of the crude drugs were positive. The Ames assays with or without metabolic activation showed that 24 water extracts and 16 methanol extracts were mutagenic. In total, mutagenic activities were found in 45 samples among the 104 crude drugs tested.
The case to be reported is that of a 72-year-old woman with isolated adrenocorticotropic hormone (ACTH) deficiency, who complained of anorexia and generalized malaise. The secretions of human growth hormone (HGH), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were all within normal limit. In spite of the extremely low level of cortisol, the plasma level of ACTH would not rise sufficiently, but a marked response of cortisol to ACTH stimulation was recognized. The postmortem examination revealed a decrease in basophilic or PAS-positive cells of the anterior pituitary gland which also showed a selective loss of ACTH-secreting cells over immunohistochemical study. Electron microscope could easily visualize somatotroph, mammotroph, thyrotroph, FSH- and LH-gonadtroph, but corticotroph was difficult to be discerned. Adrenocortical cells demonstrated atrophy and degeneration, for which the zona fasciculata and zona reticularis were narrowed. The zona glomerulosa was slightly enlarged in width.
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The in vivo origin of androstanediol (3 alpha diol) and its glucuronide was studied in six young and five elderly men undergoing cardiac catheterization. Constant infusions of [14C]testosterone and [3H]3 alpha diol were given, and blood was obtained from the aorta and hepatic vein in order to measure metabolic clearance, splanchnic extraction, and the possibility of splanchnic production of both 3 alpha diol and its glucuronide. In young elderly men, the concentrations of labeled and unlabeled testosterone, dihydrotestosterone, and 3 alpha diol were lower in the hepatic vein than in the aorta. The specific activities of dihydrotestosterone and 3 alpha diol were the same in blood entering and leaving the splanchnic compartment. The plasma concentration of 3 alpha diol was 18 +/- 2 in the young men and 15 +/- 4 ng/dl in the elderly group. However, the blood production rate of 3 alpha diol determined from the metabolic clearance and morning plasma concentration was reduced (324 vs. 199 micrograms/day) as a result of lower clearance in the elderly men. Plasma 3 alpha diol glucuronide concentrations were 197 +/- 68 and 96 +/- 35 ng/dl in the two groups. No difference in the concentration of 3 alpha diol glucuronide was observed across the splanchnic tissues by mass, radioactive levels, specific activity, or 14C to 3H ratios. The 14C to 3H ratio for 3 alpha diol glucuronide was 10 times higher than for the free steroid, indicating that more than 90% of the glucuronide originates from a pool separate from blood 3 alpha diol. Both the splanchnic extraction of 3 alpha diol and the metabolic clearance were reduced in elderly men. These studies indicate that both 3 alpha diol and its glucuronide in blood result from extrasplanchnic events. A major reduction in the plasma concentration of 3 alpha diol glucuronide occurs in the aging male, although no difference is seen in the levels of the unconjugated 3 alpha diol. 3 alpha diol and its glucuronide are derived principally by extrahepatic (target) tissue events.
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In vivo androgen kinetics were determined in six young (21--49 yr) and elderly men (62-77 yr) with prostatge hyperplasia (BPH). Steady-state infusions of [14C]testosterone and [3H]androstanediol (3 alpha diol) were given, which allowed determination of the conversions testosterone leads to dihydrotesterone (DHT) in equilibrium or formed from 3 alpha diol. These infusions also yield metabolic clearance data which, together with meaurement of nonisotopic steroid levels, yield estimations of blood production rates. The production rate for testosterone was 6.04 +/- 1.66 vs. 3.69 +/- 0.62 mg/d, whereas the production rate for 3 alpha diol was 319 +/- 57 and 193 +/- 34 micrograms/d (P < 0.05 both groups). The irreversible conversion rate of testosterone to DHT was 3.1 +/- 0.4 and 3.5 +/- 0.9% (NS). The back conversion of 3 alpha diol to dHT was high (68 +/- 25 vs. 81 +/- 17, NS) indicating that 3 alpha diol might cause BPH as a result of conversion to DHT in vivo. The conversion of DHT to 3 alpha diol is reduced in the elderly group (15.8 +/- 2.6 and 6.3 +/- 1.4, P < 0.001). Since DHT formation in the prostate is a key event in the development of BPH and blood DHT appears to be a measure of extrasplanchnic sexual target tissue activity, our in vivo studies suggest that the tissue increase in DHT may result from reduced metabolism and the activity of 3 alpha-oxidoreduction favors the oxidative pathway in elderly men.
A 35-yr-old woman with Nelson's syndrome presented with amenorrhea and virilization. Serum testosterone (T) concentration was 605 ng/dl and fell to 33 ng/dl when dexamethasone was administered. The MCR of T fell from 1383 to 991 liters/day and the T production rate decreased by 96%. With administration of synthetic ACTH, T concentration rose to 338 ng/dl. Plasma ACTH concentration paralleled T during repeated suppression testing, suggesting that T secretion was dependent on ACTH hypersecretion. Preoperative and intraoperative ovarian vein catheterization suggested that the predominant source of androgen production was from the right ovarian vein. Laporatomy revealed multiple paraovarian tumors in the right mesosalpinyx and mesovarium. Incubation of tumor slices and ovarian tissue with [3H]pregnenolone and [14C]17-hydroxyprogesterone demonstrated conversion of both precursors to T by the tumor and confirmed that the tumors were the source of androgen excess. The microscopic appearance of the tumors closely resembled the morphology of testicular and paratesticular tumors of men with congenital adrenal hyperplasia and Nelson's syndrome. The analogous dependency of the tumors on ACTH hypersecretion in men with paratesticular tumors and in this woman with paraovarian tumors suggests that the tumors may arise in both males and females from a common steroid-secreting cell of adrenogenital origin.
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