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PubMed1989

[Hypocortisolemia with neither signs nor symptoms of cortisol deficiency: research on transcortin characteristics].

Low plasma levels of cortisol, as a result of primary or secondary adrenal hypofunction, is usually associated to findings of hypocortisolism. Low plasma cortisol levels without clinical manifestations have been observed in patients in which cortisol binding capacity (CBG) is altered. In this paper we report a clinically normal patient, with very low plasma cortisol levels. We investigated a possible CBG defect or the presence of a CBG binding substance as an explanation of the clinical findings. We found a normal CBG and no competing substance. Therefore, the presence of low cortisol levels suggests the presence in this patient of a receptor with increased sensitivity to cortisol, or another molecule that can be recognized as glucocorticoid by the cortisol receptor.

Adrenal Glands↗
PubMed2000

Ascorbate deficiency impairs the muscarinic-cholinergic and ss-adrenergic receptor signaling systems in the guinea pig submandibular salivary gland.

Ascorbic acid is preferentially concentrated in the hypothalamus, pituitary and adrenal glands. Its level in the acini of salivary glands is relatively high. We therefore hypothesized that ascorbate may have a role in salivary gland function. Ascorbate-deficient guinea pigs had lower stimulated whole salivary flow rates than well-fed, age-matched controls (P: < 0.005). Total salivary protein concentration was also markedly (P: < 0.005) reduced in the deficient guinea pigs. SDS-PAGE and densitometric quantification of protein bands confirmed significant reduction in specific salivary proteins (e.g., amylase, proline-rich proteins) in the saliva samples of malnourished guinea pigs. Some protein bands not seen in control saliva were detected in the saliva of malnourished guinea pigs. Ascorbate deficiency also produced a significant (P: < 0.005) reduction in the ss-adrenergic receptor density (subtype 1; 95 +/- 19 fmol/mg protein compared with 179 +/- 27 fmol/mg protein for the controls). No significant difference was observed between the two groups with respect to the ss-adrenergic receptor subtype 2. Additionally, ascorbate-deficient guinea pigs had significantly lower muscarinic-cholinergic receptor densities (50 +/- 5 vs. 74 +/- 8 fmol/mg protein for controls). Our data support the conclusion that diminished membrane receptors might impair the capacity of the transmembrane signaling system, resulting in salivary gland hypofunction in ascorbate-deficient guinea pigs. Without implying extrapolation of our findings in experimental animals to humans, it is perhaps relevant that many conditions often associated with salivary gland hypofunction in humans (e.g., smoking or drug ingestion) deplete cellular ascorbate.

Amylases↗
PubMed1999

Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes.

Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. In Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (< or =50 ppm) a clear dose-related increase in total proliferative lesions of the prostate (ventral and dorsolateral lesions combined) occurred (0 ppm = 21% incidence, 25 ppm = 46%, 50 ppm = 50%; trend p < .03). These lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells without stromal invasion. The lesions occurred primarily in the dorsolateral prostate with cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional cell), although few in number, showed a positive correlation with cadmium dose, as did pelvic transitional epithelial hyperplasia. Renal lesions were not associated with any cadmium-induced changes in age-related chronic nephropathy. The incidence of pheochromocytomas of the adrenal was increased by cadmium but only at the 50 ppm dose. Inflammatory lesions of the liver and spleen were common at higher doses and showed strong trends based on dose. These results indicate that oral cadmium can induce proliferative lesions in the prostate and kidney of the Noble rat. The finding of proliferative lesions of dorsolateral prostate in rats has presumed relevance to human prostate cancers.

Adrenal Gland Neoplasms↗
PubMed1994

Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency.

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

17-alpha-Hydroxyprogesterone↗
PubMed1979

Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat.

The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized. and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal alpha-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.

Adaptation, Physiological↗
PubMed2001

[Adrenal function in children with sepsis and septic shock].

OBJECTIVES: To assess adrenal function in children with sepsis and septic shock with petechiae and to investigate the possible relationship between adrenal hypofunction, sonographic diagnosis of massive bilateral adrenal hemorrhage, and other factors available early in this disturbance. PATIENTS AND METHODS: Prospective observational study of 24 patients (14 boys, 10 girls), aged 2.9.24 years, admitted to the pediatric intensive care unit with sepsis and septic shock with petechiae during a 1.5-year period. The control group included 26 healthy children (13 boys, 13 girls), aged 8.8.6.4.2 years. Plasma cortisol and adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay and adrenal ultrasonography was performed. RESULTS: Plasma cortisol and ACTH levels were 243.7 ng/ml and 135.0 pg/ml in the patient group and 145.4 ng/ml and 21.1 pg/ml in the control group (p<0.01 in both). Adrenal insufficiency was found in four patients. Children with insufficiency more frequently required noradrenaline than did those with normal adrenal function (4/4 vs 2/20). Necrotic purpura (2/4 vs 2/20), massive adrenal hemorrhage (2/3 vs 1/20), lower platelet count (69.500 vs 212.895/l), lower prothrombin activity (19.0 vs 49.2%), lower fibrinogenemia (51.2 vs 304,4 mg/dl), higher pediatric risk of mortality III (PRISM III) scores (11.7 vs 2.7) and higher mortality rate (3/4 vs 1/20) were found in children with adrenal insufficiency than in those with normal adrenal function. CONCLUSIONS: Plasma cortisol and ACTH levels were increased in children with sepsis and septic shock. Adrenal insufficiency was uncommon. Adrenal insufficiency was associated with severe hemodynamic failure, necrotic purpura, disseminated intravascular coagulopathy, massive bilateral adrenal hemorrhage and high mortality rate.

Adrenal Gland Diseases↗
PubMed1998

Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo-pituitary-adrenal axis responsiveness to restraint stress after long-term social isolation.

We have studied the effects of long-term social isolation of male Wistar rats, after early weaning (16 days), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis. In addition to studying basal HPA activity, the response of the HPA axis to 15 min of immobilization stress was examined. Plasma corticosterone concentrations were measured, and the relative weights of adrenal glands, thymus, and testes were obtained, the latter to check whether gonadal function was affected by the isolation paradigm. Moreover, we carried out a quantitative immunohistochemical study of pituitary ACTH and its hypothalamic secretagogues: CRF, arginine vasopressin (AVP), and oxytocin (OT), both at the level of the synthesizing cell bodies in the hypothalamic paraventricular nucleus and of the releasing fibers in the median eminence (ME). Body weight and daily consumption of food and water were not altered, but social isolation caused a reduction in plasma corticosterone levels, both under basal and stress-stimulated conditions; this was correlated with an increased thymus weight, without affecting adrenal or testicular weights. The immunohistochemical study revealed that isolation caused a smaller increase in the number of ACTH-immunoreactive cells in the pars distalis of the anterior pituitary after exposure to restraint stress, as compared with control animals. This result indicates that fewer corticotrophs were activated by restraint stress in isolated animals, such cells being smaller and exhibiting a smaller ACTH-immunoreactive area than in control animals. Isolated animals also showed an increase in the content of CRF-ir fibers in the ME and a smaller decrease in the neuropeptide immunoreactivity after stress than that observed in control animals. This result could indicate a reduced release of CRF into the portal vasculature in response to acute stress and may partially explain the reduced activation of corticotrophs observed in the pituitary of isolated animals. However, no changes were found in the content of CRF, AVP, or OT within the paraventricular nucleus, nor of the AVP or OT content in the ME. The results of this study show that long-term social isolation after early weaning caused a hypofunction of the HPA axis in the adult rat. This hypofunction was particularly evident after exposure to an acute stressor, suggesting a desensitization of this axis to stressful stimuli.

Animals↗
PubMed1975

Effects of gentamicin on the thyroid function of rats.

The effect of gentamicin (GM) on the thyroid function was investigated in relation with its stimulating action to the growth of rats at a very small dose level. The results may be summarized as follows: (1) Changes in 131-I-uptake of the thyroid after administration of GM were unremarkable. The change in wet weight of the thyroid was also unremarkable. Therefore, GM may not affect the thyroid itself. (2) GM-treated rats clearly showed a decrease in 131-I-triiodothyronine resine sponge uptake (trisorb test) as compared with the control animals, viz.,GM-treated rats indicated hypofunction of the thyroid. (3) Thyroxin (t4) levels in theserum, determined by 125-I-T4 resine sponge uptake (tetrasorb test), were apparentlylower in the GM-treated rats than in the control. (4) The thyroid function test for synthesis of the hormones revealed an increase in diiodotyrosine (DIT) value and decreases in 3, 5, 3'-triiodothyronine (T3) and T4 values in the GM-treated groups as compared with the values in the control. (5) In view of the above results iit was obvious that GM does not cause abnormalities on iodine-uptake, iodine oxidation, organic conversion to iodinated tyrosines, deiodination and thyroglobulin. In contrast, GM may induce abnormality on coupling reaction from DIT to T3 and T4 because the increase in DIT value and decreases in T3 and T4 values are seen following administration of GM. The whole of these facts seems to play an important role in stimulation to growth of rats after administration of the drug.

Adrenal Glands↗
PubMed2002

Imaging of adrenal masses.

Adrenal pathology may be discussed based on hormonal functionality of the adrenals, appearances on imaging modality, or pathological determination. There are three main categories of adrenal function. Hyperfunctional states include Conn's or Cushing's syndrome. Lesions with normal function may be detected incidentally. Hypofunctional states may occur from idiopathic Addison's disease or some bilateral adrenal pathology. The most common modalities for characterization of adrenal pathology are non-enhanced CT, often followed by contrast CT or chemical shift MRI. The common appearance on non-enhanced CT is a well-defined homogeneous lesion with low-density due to the microscopic fat present and adrenal adenomas. When density criteria are not met, many of these may be characterized as adenomas by washed out of contrast or signal decrease using in phase and out-of-phase MRI sequences. Other non-invasive modalities may incidentally discover adrenal lesions, but are not typically used in the work-up. NP-59 is an uncommonly used nuclear medicine technique which is very specific for adenoma when correlated with pathology on other imaging studies. In the rare cases where non-invasive imaging is non-specific, fine needle aspiration or core biopsies may be necessary. However, biopsies have associated risks including infection and hemorrhage. The imaging appearance of an adrenal lesion is often specific such that further imaging is not necessary. These lesions include adrenal adenoma, pheochromocytoma, myelolipoma, adrenal cyst, and some large adrenocortical carcinomas. However, the findings in lesions such as metastasis, smaller primary adrenal carcinomas, lymphoma, granulomatous disease, and many adenomas are not as specific. In the proper clinical situation, follow-up imaging may be necessary, or biopsy may be warranted.

Adenoma↗
PubMed1978

Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol.

Previous studies have indicated that a significant reduction in plasma cortisol levels occurs during nonpulsatile cardiopulmonary bypass as a result of adrenocorticol hypofunction. The Stöckert pulsatile pump system described in Part I has been employed in a comparative study of plasma cortisol levels in 20 patients subjected to pulsatile or nonpulsatile perfusion during open-heart surgery. The plasma cortisol response pattern in the nonpulsatile group was identical to the pattern previously described, with no significant rise in cortisol levels during the period of perfusion. In the pulsatile group, however, plasma cortisol levels rose significantly during perfusion, reaching a mean level at the end of perfusion which was highly significantly greater than that in the nonpulsatile group (p less than 0.001). Correction of the plasma cortisol values for the effect of hemodilution was performed and, again, corrected cortisol values indicated a highly significant increase in end-bypass levels in the pulsatile groups (p less than 0.001). These results clearly indicate that the reduction in cortisol secretion during nonpulsatile bypass may be prevented by the use of pulsatile perfusion.

Adrenal Glands↗
PubMed1999

Decreased expression of the mRNA for somatostatin in the periventricular nucleus of depression-model rats.

Expression of the mRNA for somatostatin (SRIF) in the periventricular nucleus (PeN), the level of SRIF in the stalk-median eminence (SME) and the concentration of growth hormone (GH) in the plasma were examined in depression-model rats in an attempt to confirm the hypothesis that SRIF neurons in the hypothalamus are hypofunctional in this model. We exposed male Wistar rats to intermittent walking stress for two weeks and then we measured their spontaneous running activity for 12 days. We divided the rats into a depression-model group and a partial-recovery group according to the spontaneous running activity of each rat after the termination of exposure to stress. Expression of SRIF mRNA in the PeN of the hypothalamus was monitored by in situ hybridization and relative levels were determined with an image analysis system. The relative level of expression of SRIF mRNA in the PeN was lower in rats in the depression-model group than in the control group and the partial-recovery group. The level of SRIF in the SME was lower and the plasma concentration of GH was higher in the depression-model group than in the other groups. Our findings suggest that reduced expression of mRNA for SRIF in the PeN might be associated with the pathophysiology of rats with this particular model of depression.

Adrenal Glands↗
PubMed2000

Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency.

BACKGROUND: Glucocorticoids are essential for the normal development and functioning of the adrenal medulla. Whether adrenomedullary structure and function are normal in patients with congenital adrenal hyperplasia is not known. METHODS: We measured plasma and urinary catecholamines and plasma metanephrines in 38 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (25 children with the salt-wasting form and 13 with the simple virilizing form), 39 age-matched normal subjects, and 20 patients who had undergone bilateral adrenalectomy. Adrenal specimens obtained from three other patients with 21-hydroxylase deficiency who had undergone bilateral adrenalectomy and specimens obtained at autopsy from eight other patients were examined histologically. RESULTS: Plasma epinephrine and metanephrine concentrations and urinary epinephrine excretion were 40 to 80 percent lower in the patients with congenital adrenal hyperplasia than in the normal subjects (P<0.05), and the values were lowest in the patients with the most severe deficits in cortisol production. Urinary epinephrine excretion and plasma epinephrine concentrations were at or below the limit of detection of the assay in 8 (21 percent) of the patients with congenital adrenal hyperplasia and in 19 (95 percent) of the patients who had undergone adrenalectomy. In the group of patients with congenital adrenal hyperplasia, plasma epinephrine and metanephrine concentrations and urinary epinephrine excretion were approximately 50 percent lower in those who had been hospitalized for adrenal crises than in those who had not. In three patients with congenital adrenal hyperplasia who had undergone bilateral adrenalectomy, the formation of the adrenal medulla was incomplete, and electron-microscopical studies revealed a depletion of secretory vesicles in chromaffin cells. CONCLUSIONS: Congenital adrenal hyperplasia compromises both the development and the functioning of the adrenomedullary system.

Adolescent↗
PubMed2001

[Hypothalamo-hypophyseal-adrenal hypofunction caused by the use of bleaching cosmetics in Senegal].

Cosmetic use of bleaching agents to clear skin is widespread among black West African women. In Dakar, most products used for whole body applications contain highly potent corticosteroids. Whereas cutaneous adverse effects are well described, little is known about possible systemic consequences. In order to assess transcutaneous absorption of glucocorticoids, hypothalamo-pituitary-adrenal axis functionality can be tested. We measured plasma cortisol concentration at 8 h and 1 h after intramuscular injection of 250 micrograms of cosyntropin (Synacthen) in 12 women with a more than 10 years use of bleaching agents. Cortisol at 8 H was also measured in 9 non exposed women without disease or treatment able to disturb glucocorticoids metabolism. All controls had 8 H cortisol concentration (mean = 521 +/- 113 nmol/l) above the minimal normal level considered by our laboratory. The 8 H cortisol concentrations were under the minimal normal level in 9 exposed women and the overall mean value was significantly lower than the one observed in controls (264 +/- 81 nmol/l; p < 0.001). After cosyntropin, cortisol concentrations were elevated among all exposed women (469 +/- 196 nmol/l), and less so in 3 of them. Most of the bleaching agents users present a functional inertia of hypothalamo-pituitary adrenal axis. While there is no absolute evidence for risk of stress-induced adrenal insufficiency, our results show conclusively that an excessive corticosteroids charge among users who could be exposed to systemic adverse effects.

Absorption↗
PubMed1999

A simple method of predicting hormonal outcome in children with intracranial germinoma.

Even a small intracranial germinoma (GE) frequently provokes pituitary hypofunction. We evaluated the relationships between preoperative hormonal status and hormonal outcome and between size of suprasellar mass and hormonal outcome in 22 children with intracranial pure GE to determine whether or not these can reflect the degree of hypothalamo-pituitary axis destruction. Preoperative hormonal status was graded from I to IV according to the serum prolactin level (s-PRL) and thyroid function (TF). The hormonal outcome was estimated by the type and the number of hormonal replacement medications taken on the basis of the triple load test and endocrinological examinations at the time of the last follow-up (median period: 43 months). Fifteen of the 22 patients had suprasellar lesions. All 13 patients who had diabetes insipidus (DI) at presentation needed desmopressin acetate (DDAVP) during the follow-up period. The correlation between increment of preoperative grade and the increment in the number of hormones to be replaced was statistically significant (P<0.05). This preoperative grading was a more reliable predictor than the size of suprasellar tumor. In conclusion, preoperative grading by s-PRL and TF test is useful for the prediction of posttreatment hormonal replacement in children with intracranial pure GE.

Adolescent↗