Influence of naloxone on prolactin secretion in patients with acute and chronic renal failure

The influence of the opiate antagonist naloxone on chlorpromazine induced prolactin secretion was examined in 12 patients with acute renal failure (ARF), 12 patients with chronic renal failure (CRF) and in 12 healthy subjects. In all examined groups naloxone showed a suppressive effect on chlorpromazine induced prolactin secretion, which was more accentuated in normals and patients with ARF then with CRF. The results of these investigations suggest that endogenous opiates may be of importance in the regulation of prolactin secretion both in normals and uremic patients.     

Effects of Naloxone on Gonadotropin Secretion in Klinefelter Syndrome

To study the opioid control on LH and FSH secretion in Klinefelter subjects (KS), the response of gonadotropin to an opioid antagonist, naloxone, was examined in 8 KS (age range 25-35 yrs) and in 8 age matched normal men. In 6 KS with low testosterone plasma levels, naloxone infusion were also performed after treatment with testosterone enanthate, 200 mg i.m. every 3 weeks for 4 months. FSH did not show any important variation in KS and in normal men during naloxone infusion. In KS the percentage of naloxone induced LH increase was significantly lower than in controls and there was no correlation between testosterone plasma levels and LH increase after naloxone infusion. LH increases after naloxone infusion were not significantly different before and after testosterone treatment. The increases of naloxone induced LH plasma levels, before and after testosterone treatment, correlated well between themselves (r = 0.93-p less than 0.01). Plasma levels decreased in all patients after testosterone treatment, but only in two was there a return to normal range. There is a clearly positive linear correlation between the percentage of LH decrease after testosterone treatment and LH increase after naloxone infusion (r = 0.81; p less than 0.01). After testosterone therapy FSH plasma levels fall by 63 +/- 15% in all patients and did not show any important variation after naloxone infusion. In conclusion, our data are in agreement with the hypothesis that in Klinefelter's syndrome an alteration of opioid control on gonadotropin secretion may exist. This alteration does not appear to be due to androgen deficiency, but rather it may be caused by genetic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of naloxone on prolactin-secreting pituitary adenomas.

The investigators assessed the effects of the opioid antagonist naloxone on anterior pituitary hormone release in hyperprolactinemic females with pituitary microadenoma (n = 6) and macroadenoma (n = 7). In those with microadenoma, intravenous bolus injection of naloxone significantly increased serum luteinizing hormone (LH) concentrations but had no significant effect on serum prolactin (PRL), follicle-stimulating hormone, and thyroid-stimulating hormone concentrations. In patients with macroadenoma, naloxone significantly decreased serum LH and serum PRL concentrations. The response of LH to naloxone differed considerably between the two groups of patients. The results suggest that LH and PRL secretion is influenced by changes in endogenous opiates and in gonadotropin-releasing hormone and PRL inhibitory factor due to hypothalamic dysfunction.     

Long-term effects of endocrine treatment on serum pituitary hormones in advanced prostatic carcinoma patients

Peripheral serum concentrations of FSH, LH, prolactin and ACTH were measured in 22 patients with advanced prostatic carcinoma treated by castration, polyestradiol phosphate (Estradurin) administration and a combination of castration and Estradurin administration during the first 12 months of treatment. Estradurin treatment alone (80 mg i.m.l once a month) did not result in any significant changes in the circulating concentrations of FSH, LH and prolactin. Therefore, the clear-cut inhibition of testicular steroidogenesis observed under this kind of treatment does not appear to be due to an inhibition of pituitary gonadotropin secretion, and is most likely due to a direct estrogen effect on Leydig cells. Castration led to grossly elevated serum FSH and LH levels. In this group, serum FSH remained at a high level, whereas LH was close to pretreatment levels 9 months after castration, suggesting differences in pituitary capacity to secrete FSH and LH under these conditions. Concentrations of circulating FSH, and to a lesser extent LH, in the combination treatment group were between those found in the castration and estrogen-only treatment groups, suggesting that the secretion of both gonadotropins can be suppressed by estrogen. No changes in serum prolactin and ACTH concentrations were seen in the three treatment groups.     

Hormonal environment and antiandrogenic treatment in benign prostatic hypertrophy

The plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and human growth hormone (HGH) response to insulin-induced hypoglycemia in patients with benign prostatic hypertrophy and age-matched control patients were not different. Although all 6 drugs used were effective for treating these benign prostatic hypertrophy patients the 3 drugs, chlormadinone acetate, oxendrone and allylestrenol, were especially recommended.     

Testosterone Concentrations and Sirolimus in Male Renal Transplant Patients

Sirolimus damages the testes in animals; however, human data are sparse. We conducted a case-control study to obtain further insight into this issue and compared testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin concentrations in matched renal transplant patients who did or did not receive sirolimus. We found that testosterone values were lower (11.2 +/- 6.3 nmol/L vs. 15.5 +/- 7.7 nmol/L, p < 0.05), in 28 sirolimus-treated patients, compared to 28 non-sirolimus-treated controls. Furthermore, these patients more commonly had testosterone concentrations that were below our reference value for normal men. In contrast, FSH and LH concentrations were higher while prolactin levels were not different. These data are consistent with sirolimus-related testosterone suppression and suggest a need for further studies.     

Testicular Function and Prolactin Responsiveness to TRH and Cimetidine After Renal Transplantation

The hypothalamic-pituitary-testicular axis and the regulation of prolactin secretion were investigated in eleven male renal transplant recipients. Mean serum levels of testosterone and estrone were normal, whereas those of androstenedione and estradiol were low. Mean basal luteinizing hormone (LH) levels were slightly elevated, but the peak responses to 50 micrograms i.v. gonadotropin-releasing hormone (GnRH) were not dissimilar from controls. Both basal and GnRH-stimulated follicle-stimulating hormone (FSH) levels were elevated (p less than 0.02-0.05) and also positively correlated with the time spent on hemodialysis (p less than 0.005-0.002). Basal prolactin (PRL) levels were normal, in all subjects. Nine out of 11 patients had a normal PRL response to Thyrotropin-releasing Hormone (TRH). However only six out of 11 had a normal response to 200 mg i.v. Cimetidine (Cim). Three subjects normally responding to TRH failed to respond to Cim. Uremic primary hypogonadism is not fully reversed by renal transplantation: a slight defect in the pituitary LH release may persist and the impairment of the tubular testicular function is left unchanged. While uremic hyperprolactinemia is corrected, the responsiveness to PRL-stimulating agents, particularly Cim, is not restored to normal, reflecting a derangement at the pituitary as well as the hypothalamic level.     

肾移植前后妇女的性激素状态

为了解女性尿毒症及肾移植受者性激素状态,作者应用酶联免疫法检测了５０例女性患者肾移植前、后的性激素水平,并以１５例近龄健康妇女对照。结果显示肾移植受者的泌乳素（ＰＲＬ）、促卵泡素（ＦＳＨ）及促黄体素（ＬＨ）较慢性肾功能衰竭（ＣＲＦ）血液透析组明显降低,而雌二醇（Ｅ）和孕酮（Ｐ）值在正常范围。对于ＣＲＦ患者检测发现ＰＲＬ明显升高,而孕酮值显著下降,经给该组闭经患者作克罗米酚刺激试验,结果阳性,说明闭经为下丘脑性功能障碍。作者认为成功肾移植可纠正肾衰患者由于血中肌酐、尿素氮升高造成的下丘脑功能障碍,且能恢复正常月经周期及生育力。透析期间可对症治疗,但不必促排卵,而成功肾移植是最好的治疗方法。     

肾移植前后妇女的生育力和相关激素研究

本研究应用酶免疫法检测了肾移植前、后共40例女性患者的性激素水平，并以15例近龄健康妇女作对照，结果发现肾移植受者的PRL（泌乳素），FSH（促卵泡素）及LH（促黄体素）较慢性肾功能衰竭（CRF）血液透析组明显降低，而E2（雌二醇）；和P（孕酮）在正常范围。结论：认为成功肾移植后可纠正肾衰患者由于血中肌酐、尿素氮升高造成的下丘脑功能障碍，且能恢复正常月经周期及生育力。     

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.     

Endocrinological evaluation of sellar and suprasellar tumor cases (the 2nd report);--on postoperative pituitary function (author's transl)]

Fifty-six cases of sellar and suprasellar tumors were examined endocrinologically before and 3 weeks after surgery. 1) Hyporeactive cases of GH & ACTH were more frequently found in pituitary adenoma (100% and 23% respectively than in craniopharyngioma (86% and 14% respectively) before surgery. 2) GH secretion was impaired 3 weeks after surgery in all the cases. 3) ACTH secretion impaired preoperatively in 5 cases of pituitary adenoma improved in 3 cases 3 weeks after surgery. 4) Hyporeactivity of LH, FSH and TSH was found more frequently after surgery than before. 5) Almost all the cases of tuberculum sellae meningioma were endocrinologically normal before surgery. 6) ACTH, LH, FSH and prolactin secretion in cases of tuberculum sellae meningioma was not impaired after surgery, but TSH secretion in these cases became hyporeative in 4 of 5 cases after surgery.     

Abnormal Gonadothrophin Secretion in Children with Chronic Renal Failure

LH and FSH response to intravenous injection of GnRH was evaluated in a group of patients with chronic renal failure on intermittent haemodialysis and in two children with successful renal transplant. Basal plasma LH was elevated in children with chronic renal failure as compared to control, and significantly increased following GnRH injection in most of the children. Basal plasma FSH was higher than in the control group, and slightly increased after GnRH. These data suggest an abnormal response to GnRH in chronic renal failure and an involvement of hypothalamus and pituitary in chronic renal disease. The role of abnormal gonadotrophin secretion in growth retardation and pubertal delay of these children is still not well understood.     

Effects of different calcineurin inhibitors on sex hormone levels in transplanted male patients

Hormonal abnormalities in male patients with end-stage renal diseases are primarily organic and related to uremia as well as the other comorbid factors that frequently contribute to chronic renal failure and concomitant drug administration. The restoration of hormonal profiles after successful renal transplantation is still controversial. Immunosuppressive drugs may influence hormonal profiles. Our cross-sectional study of 37 male kidney transplant recipients investigated two groups according to their calcineurin inhibitor therapy, namely 21 cyclosporine versus 16 tacrolimus patients. The two groups were matched for age, graft function, mean duration of dialysis before transplantation, and duration of follow-up after transplantation. There was no statistical significant difference in baseline circulating levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TTE), and prolactin (PRL) between the two groups. We found that calcineurin inhibitors have favorable effects on sexual hormone levels of male renal transplant patients and that there is no difference in baseline hormone levels between cyclosporine- and tacrolimus-treated male patients.     

Pathogenesis of refractory secondary hyperparathyroidism

Calcitriol is currently used to reduce parathyroid hormone (PTH) levels in uremic patients. However, a significant number of patients fail to respond to calcitriol therapy. The data suggest that a poor response to calcitriol can be anticipated in patients with severe hyperparathyroidism (with a high basal PTH levels) and uncontrolled serum phosphate. The abnormal parathyroid response to calcitriol in uremic patients with severe parathyroid hyperplasia may be attributed, to a large extent, to the development of nodular hyperplasia as a result of clonal transformation from a diffuse polyclonal hyperplasia. The factors involved in the development of polyclonal parathyroid hyperplasia, at earlier stages of secondary hyperparathyroidism, appear to be the same factors that stimulate PTH secretion and synthesis: hypocalcemia, hyperphosphatemia and low serum calcitriol levels. Studies performed in vitro using parathyroid tissue from uremic patients who required parathyroidectomy demonstrate that in nodular hyperplasia there is an abnormal response to calcium and calcitriol, which suggests that there are factors intrinsic to the hyperplastic cell (such as decrease in calcium sensor receptors and vitamin D receptors) responsible for an abnormal regulation of parathyroid function. Accumulation of phosphate is a key factor in the pathogenesis of secondary hyperparathyroidism and a poor response to calcitriol treatment is associated with the failure to control the serum phosphorus. High phosphate stimulates PTH secretion as demonstrated by in vivo and in vitro studies. In addition, animal studies strongly suggest that phosphate increases parathyroid cell proliferation. There are growth-related genes potentially involved in uremic hyperparathyroidism; however, changes in the expression of these genes may be the consequence rather than the cause of parathyroid hyperplasia.     

Influence of lisuride, a dopaminergic agonist, on the sexual function of male patients with chronic renal failure

The effects of Lisuride, a dopaminergic agonist, on the levels of plasma prolactin (PRL), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and on the variations of libido and coital frequency of patients with chronic renal failure (CRF) have been investigated in a group of 20 male patients (ten normoprolactinemic and ten hyperprolactinemic). Ten patients were included in a hemodialysis program and another ten received conservation therapy (all had creatinine clearance rates below 15 mL/min). The response of PRL to TRH administration and that of LH and FSH to LH-RH administration have also been studied. Low levels of plasma testosterone found initially in all the patients, increased in both normoprolactinemic (P less than 0.05) and hyperprolactinemic patients (P less than 0.01) during Lisuride administration. PRL decreased (P less than 0.01) in both groups during therapy. The increase of plasma testosterone was greater in hyperprolactinemic patients (86% v 15% in normoprolactinemic) and was accompanied by a clear improvement in the studied parameters of sexual behaviors. The response of PRL to TRH was modified in hyperprolactinemic patients while that of LH and FSH to LH-RH was not modified, although Lisuride induced an increase of the basal value of LH (P less than 0.01) in the hyperprolactinemic group. The drug was fairly well tolerated, did not induce hypotension, and the overall incidence of side effects decreased along the study. These results stress the need for further studies with this agent in patients with chronic renal failure and sexual dysfunction.     

Effects of long-term testosterone administration on pituitary-testicular axis in end-stage renal failure

The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p less than 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.     

Influence of total pancreatectomy on the secretion of human growth hormone and the endocrine pancreas

To evaluate the effect of total pancreatectomy on the secretion of human growth hormone, twenty-six patients undergoing total pancreatectomy and twelve healthy subjects (controls) were investigated. Blood glucose (BG), plasma insulin (IRI), C-peptide (CPR), immunoreactive glucagon (IRG) and human growth hormone (HGH) levels were determined. In the glucose tolerance test, the mean basal blood glucose level in the patients before operation was significantly higher than the level in the controls. The basal blood glucose level in the patients after operation was still higher than the level before operation. The responses of IRI, CPR, and IRG secretion after arginine infusion in the patients before operation were less than those in the controls. After operation, arginine infusion did not alter the levels of IRI, CPR and IRG. The mean basal HGH levels were not significantly different between the controls and the patients before and after operation. However, a statistically significant correlation was shown between the basal values of plasma HGH and those of plasma IRI in the patients after operation. Thus, it suggested that the basal secretion of HGH is closely related to the exogenous plasma insulin levels in the pancreatectomized patients. After arginine infusion, the HGH levels in the patients before operation were lower than the those in the controls, but insignificant. After operation, mean HGH levels were significantly lower than those before operation. These findings suggested the absence of pancreatic endocrine function caused by total pancreatectomy resulted in decreased responses of HGH secretion after arginine infusion.     

A prospective analysis of testicular androgenic function in recipients of a renal allograft

Eighteen adult males with end stage renal disease (ESRD) were studied to determine the serum levels of gonadotropins (LH and FSH), prolactin (PRL) and testosterone. All of the patients were studied longitudinally while undergoing maintenance hemodialysis (HD) and six months after renal transplantation. Prior to transplantation, significantly high levels of gonadotropins and PRL were observed. During HD the serum testosterone levels tended to be subnormal in most of the uremic patients and low normal in some of the subjects. Renal transplantation led to a significant improvement (P < 0.05) in serum testosterone. Elevated gonadotropin and PRL levels observed in patients on HD returned to the normal range in most of the patients after successful renal transplantation.     

Male hypogonadism of uremic patients on hemodialysis

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.     

Carbohydrate metabolism in uremia

Abnormalities of insulin and glucose metabolism, namely glucose intolerance, inhibition of insulin secretion and insulin resistance, are present in children with chronic renal failure. Insulin resistance is universal among children with end-stage renal disease and may be caused by uremic toxins accumulated because of reduced renal function. The normal response of the beta cell is to enhance insulin secretion to overcome the insulin resistance. In patients with secondary hyperparathyroidism, this increase in insulin secretion is inhibited, resulting in glucose intolerance. Presence of glucose intolerance may be responsive for the growth retardation in uremic children. Improvements in glucose tolerance correlate with improvements in linear growth in uremic children. Further research should be directed towards investigation of the mechanisms by which abnormal energy utilization may affect growth in uremia and development of indices of glucose metabolism as predictors of growth in aremia.