Our data showed that Sal-T is a reliable marker of testosterone bioavailability. The results support the inclusion of this biomarker as a noninvasive approach in the diagnosis of male androgen deficiency.
To more conveniently assess dynamic changes in the biologically active fraction of cortisol, we measured cortisol in 1-h urine samples obtained from 0700-0800 and from 2200-2300 h. In 20 normal subjects, morning 1-h urinary cortisol levels were 78 +/- 36 ng/mg creatinine (mean +/- SD), whereas levels from 2200-2300 h were 22 +/- 12 ng/mg creatinine, demonstrating diurnal variability. In 14 patients with Cushing's syndrome, mean morning urinary cortisol was elevated (207 +/- 176 ng/mg creatinine), but there was overlap with values in normal subjects. In contrast, evening values in Cushing's syndrome (248 +/- 208 ng/mg creatinine) were elevated in each patient; there was no diurnal variation and no overlap with normal subjects. Similarly, the morning urinary cortisol response to dexamethasone (1 mg, orally, at 2300 h) clearly separated normal subjects from those with Cushing's syndrome (5 +/- 6 vs. 169 +/- 149 ng/mg creatinine, respectively). In 10 patients with secondary hypoadrenalism, urinary cortisol levels were less than 2 ng/mg creatinine in both morning and evening 1-h samples. Thus, the determination of cortisol in 1-h samples is a practical and simple method of assessing cortisol secretion and allows multiple sampling without hospitalization. It is effective in assessing dynamic cortisol responses, such as diurnal variation and responsiveness to suppression, and it is an effective screening test for Cushing's syndrome and hypoadrenalism.
The effect of chronic administration of CRF on rat pituitary morphology was studied. Experimental animals received CRF (10 micrograms/day) over a period of 52 days by means of sc osmotic pumps changed at 10- to 14-day intervals. The average 0800 h plasma corticosterone levels in the treated animals were significantly greater than control values [7.52 +/- 0.99 (+/- SE) vs. 1.14 +/- 0.5 micrograms/dl; P less than 0.001]. The CRF-treated animals also had a significantly greater adrenal weight (16.44 +/- 1.38 vs. 12.24 +/- 0.85 mg; P less than 0.05) and lower thymus weight (164 +/- 12 vs. 248 +/- 27 mg; P less than 0.005). There was a marked increase in the number of ACTH-producing cells in the anterior pituitaries of the rats that received CRF (13.3 +/- 0.8% vs. 4.5 +/- 0.3% ACTH-producing cells; P less than 0.001), as determined by immunocytochemical methods. Corticotrophs of rats treated with CRF manifested a significant increase in nuclear area (24.0 +/- 0.7 vs. 21.4 +/- 0.4 micron 2; P less than 0.001) and an increased diameter of forming and storage granules (191.1 +/- 1.1 vs. 158.6 +/- 3.5 nm and 196.1 +/- 1.2 vs. 170.1 +/- 3.7 nm, respectively; P less than 0.001). There was no demonstrable increase in ACTH cell area. These data indicate that long term administration of CRF is capable of increasing the number of pituitary corticotrophs. It also supports the view that the corticotroph hyperplasia occurring after adrenalectomy, in unusual cases of ectopic CRF production, and in rare instances of Cushing's disease is a proliferative response to CRF.
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