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Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla.

The adrenal gland is among the organs with the highest concentration of vitamin C in the body. Interestingly, both the adrenal cortex and the medulla accumulate such high levels of ascorbate. Ascorbic acid is a cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis. Here we provide an overview on the role of vitamin C in the adrenal cortex and medulla derived from in vitro and in vivo studies. In addition, recent insights gained from an animal model with a deletion in the gene for the ascorbic acid transporter will be summarized. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die soon after birth. There is a significant decrease of tissue catecholamine levels in the adrenals. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice show depletion of catecholamine storage vesicles, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone and altered morphology of mitochondrial membranes indicate additional effects of the deficiency on adrenal cortical function. The data derived from these animal models and various cell culture studies confirm a crucial role for vitamin C for both the adrenal cortex as well as the adrenal medulla further underlining the interdependence of the two endocrine systems united in one gland.

Adrenal Cortex↗

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH.

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.

Adrenal Glands↗

Functional aspects of the effect of prolactin (PRL) on adrenal steroidogenesis and distribution of the PRL receptor in the human adrenal gland.

Hyperprolactinemia is one of the most common disorders in endocrinology. A role for PRL on the human adrenal gland has been postulated in various clinical studies. We have demonstrated for the first time the expression of the PRL receptor in the human adrenal gland and in human adrenal primary cell cultures using PCR and immunohistochemical methods. Using immunostaining, we could detect the PRL receptor in all three zones of the adrenal cortex. Only weak staining was observed in the adrenal medulla. The influence of PRL on the secretion of cortisol, aldosterone, and androgens in human primary cell cultures was investigated. After stimulation with PRL (10(-7) mol/L), we measured increased concentrations of cortisol (155 +/- 9.8%; P < 0.005%), aldosterone (122 +/- 3.7%; P < 0.005), and dehydroepiandrosterone (121 +/- 8.6%; P < 0.05) in the cell supernatant. PRL did not affect the expression of messenger ribonucleic acid of cytochrome P45017 alpha in human adrenal cell cultures. In conclusion, we found the PRL receptor in the human adrenal gland. We postulate that PRL has a direct effect on adrenal steroidogenesis, thereby regulating adrenal function, which may be of particular relevance in clinical disorders with hyperprolactinemia.

Adrenal Cortex Hormones↗

Electron paramagnetic resonance studies of cytochrome P-450 and adrenal ferredoxin in single whole rat adrenal glands. Effect of corticotropin.

Low and high spin ferric cytochrome P-450 and reduced adrenal ferredoxin (adrenodoxin) have been directly studied by EPR techniques in whole rat adrenal glands. The spectra obtained correspond closely to those obtained from sub-cellular fractions except in the case of low spin ferric cytochrome P-450, where there are differences in the shape of the g = 2.41 line. The relative magnitudes of these peaks in anaerobic and aerobic rapidly frozen adrenals from control and corticotropin stimulated hypophysectomised rats were used to investigate the control and rate limiting steps in adrenal steroid biosynthesis via cytochrome P-450. All adrenals showed a close to maximal level of reduced adrenodoxin and aerobic and anaerobic glands from control rats and aerobic glands from corticotropin stimulated rats showed similar quantities of low spin ferric cytochrome P-450. On anaerobiosis the quantity of low spin ferric cytochrome in adrenals from corticotropin stimulated rats dropped to 30--40% of the aerobic level. Treatment of the rats with cycloheximide prior to administration of corticotropin prevented these changes. Approximately 0.4% of the total cytochrome P-450 was high spin ferric in control adrenals and in aerobic stimulated adrenals this rose to approximately to 0.6%. These results demonstrate that association of substrate with cytochrome P-450 is the rate limiting step in adrenal steroidogenesis via cytochrome P-450. It is suggested on the basis of these and mitochondrial optical and EPR experiments that the limiting step being observed is cholesterol binding to cholesterol side chain cleavage cytochrome P-450, and that the rate of this association is stimulated by corticotropin.

Adrenal Glands↗

Cografts of adrenal medulla with peripheral nerve enhance the survivability of transplanted adrenal chromaffin cells and recovery of the host nigrostriatal dopaminergic system in MPTP-treated young adult mice.

Schwann cells from transected peripheral nerve segments are known to produce nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells cografted with sciatic nerve survived better than those in adrenal grafts alone; host DA fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice showed long neuronal processes which were rarely seen in the mice receiving adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic nerve promotes intrinsic host DA fiber recovery better than adrenal medulla grafts alone, and that survivability of grafted chromaffin cell may promote host DA fiber recovery. Adrenal medullary autografts have been used in patients with Parkinson's disease; we suggest that if this approach is to be used in the future, methods to increase the survivability of grafted chromaffin cells, such as co-grafting with pieces of peripheral nerve, be considered to enhance the survivability of the chromaffin cells, which might be closely related to the functional recovery of the patients by this grafting procedure. Of course, such strategies as the present cografting approach must be demonstrated to work in older animals using older donor tissue before proceeding to this next step in humans.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of dietary soy and estrous cycle on adrenal cytochrome p450 1B1 expression and DMBA metabolism in adrenal glands and livers in female Sprague-Dawley rats.

Cytochrome p450 1B1 (CYP1B1) has been shown to be important in the bioactivation of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We investigated the effects of diet and stage of estrous cycle on CYP1B1 expression in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy-containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day (PND) 21 until sacrifice at PND50+/-5. Stage of estrous at sacrifice was assessed by vaginal cytology and confirmed by histological examination of the vagina. Dietary soy at the level present in NIH-31 diet did not affect serum estrogen and progesterone levels. Immunohistochemical analysis confirmed that CYP1B1 was exclusively expressed in the zona fasciculata and zona reticularis in adrenal cortex, which are the regions vulnerable to DMBA-induced adrenal necrosis. Adrenal CYP1B1 protein expression, 3H-DMBA depletion, and formation of DMBA-3,4-, and -8,9-dihydrodiols by adrenal microsomes were greater in animals fed 5K96 diet, and the stage of the estrous cycle affected these parameters only in the soy-free 5K96 diet. In hepatic microsomes, the formation of DMBA-3,4-dihydrodiol, 7-hydroxy- and 12-hydroxy-DMBA were lower in animals fed NIH-31 diet than in those fed 5K96 diet. Thus, dietary soy and the estrous cycle appear to regulate adrenal CYP1B1 expression and DMBA metabolism by both adrenal and hepatic microsomes. The use of different basal diets containing variable levels of soy components may affect certain toxicity assessments.

9,10-Dimethyl-1,2-benzanthracene↗

Adrenal function in the Mongolian gerbil (Meriones unguiculatus): influence of confinement stress upon glucocorticosteroid, progesterone, dehydroepiandrosterone, testosterone and androstenedione plasma levels, adrenal content and in-vitro secretion.

The pattern of adrenal steroid secretion and the response to confinement stress were investigated in male Mongolian gerbils (Meriones unguiculatus). Steroid levels of glucocorticosteroids (GC), progesterone (P), dehydroepiandrosterone (DHEA), testosterone (T) and androstenedione (A) in plasma, adrenal tissue and superfusates of adrenals superfused in-vitro were measured by radioimmunoassay. The sensitivity of the assay systems and the low cross-reactivity of the antisera used allowed the determination of steroid levels in small samples (5-200 microliters), without prior chromatography. GC plasma levels were much higher than values of P, DHEA, T or A (176.7, 2.4, 3.3, 2.6 and 2.8 ng/ml, respectively). Confinement stress resulted in a significant increase of GC and DHEA plasma levels; similarly, adrenal content of GC, DHEA and P was markedly increased. In contrast, the applied stress factor had no significant effects on either plasma levels of P, T or A or on adrenal T or A content. Compared to plasma levels or adrenal content, amounts of steroids secreted from adrenals superfused in-vitro were very low (GC: 57.1, P: 2.1, DHEA: 23.0, T: 1.8, A: 3.0 pg/mg/min, respectively). Confinement stress significantly stimulated GC, P and DHEA secretion in-vitro but had no effects on T or A release. The secretion of GC, P, DHEA and T, but not of A was significantly increased by in-vitro stimulation with 0.01-10.0 mIU (1-24) ACTH. Interestingly, the amounts of GC and P, and of GC and DHEA secreted from incubated adrenal slices stimulated with (1-24) ACTH and from adrenals of controls and stressed gerbils superfused in-vitro were significantly correlated. By measuring steroid plasma levels and profiles of steroids secreted from adrenocortical and testicular tissue it now seems possible to characterize in more detail the effects of chronic intermittent stress upon the adrenalgonadal axis and the possible interrelationship between glucocorticosteroid and androgen secretion, especially in small laboratory animals from which only limited amounts of blood can be obtained repeatedly.

Adrenal Glands↗

Opioids preserve the adrenal medullary response evoked by severe hemorrhage: studies on adrenal catecholamine and met-enkephalin secretion in halothane anesthetized cats.

Possible modulatory effects of mu-, delta-, and kappa-receptor agonists on the concurrent adrenal secretion of catecholamines and met-enkephalin evoked by staged hemorrhage were examined in four groups of cats (n = 5 in each group) anesthetized with halothane (1 MAC). Group I received saline, group II received the mu-agonist sufentanil (25 micrograms/kg i.v., followed by a maintenance infusion), group III received the delta/mu agonist metkephamid (3 mg/kg i.v.), and group IV the kappa agonist U50488H (3.5 mg/kg i.v.). Samples for norepinephrine, epinephrine, dopamine, and met-enkephalin were taken simultaneously from the adrenal vein, femoral vein, and femoral artery at baseline, after drug administration, and after induction of 25% and 50% hemorrhage. In cats receiving saline, 25% hemorrhage resulted in a significant decline in mean arterial blood pressure (MABP) and no change in adrenal secretion. Fifty percent hemorrhage evoked no significant further fall in MABP, but led to prominent increases in adrenal vein hormone levels (norepinephrine, 30-fold; dopamine, 14-fold; and epinephrine, ten-fold) as compared to post-saline values. During the pre-hemorrhage baseline state, administration of sufentanil evoked a significant six- to 20-fold rise in adrenal vein catecholamine and met-enkephalin levels, whereas the administration of metkephamid and U50488H produced no change in adrenal secretion and a decrease in MABP. After 25% and 50% hemorrhage, there was no difference in adrenal vein hormone levels in cats receiving the mu-, delta-, or kappa-agonists compared to those receiving saline. No differences were observed in the different treatment groups with regard to the proportional levels of catecholamines and met-enkephalin in the adrenal vein during the course of the experiment. The authors conclude that opioids are not involved in the regulation of the secretory adrenal medullary response evoked by hemorrhage, and that the systems involved in mediating these cardiovascular reflexes differ pharmacologically from those systems mediating the autonomic response evoked by pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Incidence of adrenal involvement and assessing adrenal function in patients with renal cell carcinoma: is ipsilateral adrenalectomy indispensable during radical nephrectomy?

OBJECTIVE: To determine the value of ipsilateral adrenalectomy with radical nephrectomy, by investigating the clinical aspects of adrenal involvement and adrenocortical function in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The demographic, clinical and pathological data of adrenal involvement were reviewed in 247 patients with RCC. To evaluate adrenocortical function, 14 patients (adrenalectomy in eight, adrenal-sparing in six) had a rapid adrenocorticotropic hormone (ACTH) stimulation test before and 2 weeks after surgery. RESULTS: There was adrenal involvement with RCC in seven of the 247 (2.8%) patients (a solitary adrenal metastatic tumour in four and direct extension into the adrenal gland in three). All adrenal involvement was detectable on abdominal computed tomography before surgery, and these patients had a large primary renal tumour of > pT2 and/or distant metastasis. Plasma cortisol levels declined significantly more in response to the rapid ACTH stimulation test in those treated by adrenalectomy than in those with spared adrenal glands at 2 weeks after surgery (P < 0.05), while there was no significant difference between the groups before surgery. CONCLUSIONS: These results suggest that unconditional ipsilateral adrenalectomy with radical nephrectomy for RCC should be avoidable, and thus preserve the reserve of adrenocortical function, as preoperative imaging, especially thin-slice multidetector helical computed tomography, can detect adrenal involvement with RCC in most cases. Unilateral adrenalectomy might cause an irreversible impairment of the reserve of adrenocortical function.

Adrenal Gland Neoplasms↗

Blood supply of the ovine adrenal gland and its relevance in adrenal autotransplantation.

The arterial supply and venous drainage of 62 left and 5 right ovine adrenal glands is described, and the contribution of individual arteries to successful adrenal gland autotransplantation was evaluated. Arterial flow was measured by direct collection from the draining adrenal vein. Assessment of function of the transplanted adrenal gland was made from survival of the sheep and by the cortisol response to infusion of ACTH and the aldosterone secretory response to infusion of angiotensin II or potassium. For the left adrenal, the principal arterial supply was from the renal artery in 21 (34%), a lumbar artery in 32 (52%), and the anterior mesenteric artery in 3. The total blood flow was 5.0 +/- SEM 0.4 mL/min, the flow from the renal branch 2.3 +/- 0.3 mL/min, and the principal lumbar branch 2.6 +/- 0.3 mL/min. Venous drainage from the left adrenal was via a major adrenal vein to the left renal vein, but additional tributaries to the renal vein were present in 26%. The arterial supply to the adrenal is regional and omission of a branch at transplantation could result in infarction of portion of the gland. By defining arterial supply and measuring blood flow, selection of the appropriate artery or multiple arteries can achieve an adrenal gland autotransplant survival of 90%.

Adrenal Glands↗

Adrenal mitochondrial and serum corticosteroid studies in rats resistant to adrenal-regeneration hypertension (ARH).

Female rats of the Wistar-Furth (W/Fu) strain appear to be resistant to the development of adrenal regeneration hypertension. At a time period, after adrenal enucleation, when Holtzman female rats had elevated serum 11-deoxycorticosterone levels and were hypertensive, none of the W/Fu rats became hypertensive. In vitro adrenal studies after quiescent kills of W/Fu rats indicated that cholesterol side chain cleavage activity was greater in mitochondria from regenerating adrenals than from controls. Both serum deoxycorticosterone and corticosterone levels were significantly greater in the adrenal-enucleated group. These studies were repeated in animals which were given a standard ether anesthetic stress. Ether stress increased cholesterol side chain cleavage activity comparably in control and adrenal-enucleated rats and also increased their serum deoxycorticosterone and corticosterone levels. Adrenal-enucleated Wistar-Furth rats had higher serum deoxycorticosterone levels than controls, whereas controls had higher serum corticosterone levels than the adrenal-enucleated group after the ether stress. These results indicate that although the adrenal-enucleated W/Fu rats have increased serum deoxycorticosterone levels, none of these rats develop frank hypertension. This suggests a resistance to deoxycorticosterone-induced hypertension in this strain of rat.

Adrenal Glands↗

Adrenal insufficiency attributable to adrenal hemorrhage: long-term follow-up with reference to glucocorticoid and mineralocorticoid function and replacement.

OBJECTIVE: To describe the long-term follow-up of acute adrenal insufficiency attributable to bilateral adrenal hemorrhage. METHODS: We performed a retrospective review of medical records of four patients who underwent follow-up for 6(1/2) to 19 years. RESULTS: Despite published reports of more than 500 patients with bilateral massive adrenal hemorrhage through 2001, no long-term data assessing the continuing requirements for glucocorticoid and mineralocorticoid replacement are available. After follow-up of four patients with acute bilateral adrenal hemorrhage and glucocorticoid insufficiency for 6(1/2) to 19 years, we document the absence of need for long-term mineralocorticoid replacement on the basis of no occurrence of postural hypotension, normal electrolytes, normal baseline or cosyntropin-stimulated serum aldosterone levels, and generally, though not invariably, normal plasma renin activity levels. We further document the improvement in either or both baseline and cosyntropin-stimulated serum cortisol levels in three of the four patients and the ability of one patient to function normally without cortisol replacement for 4 years. Adrenal histologic findings in this last-mentioned patient revealed previously undescribed changes consistent with regeneration and myelolipoma. Finally, we confirm bilateral atrophic adrenal glands by computed tomography 5(1/2) to 11(1/2) years after bilateral adrenal hemorrhage in three of the four patients. CONCLUSION: Long-term follow-up of patients with acute adrenal insufficiency attributable to adrenal hemorrhage demonstrates, for the first time, absence of need for prolonged mineralocorticoid replacement and some improvement in endogenous glucocorticoid function in at least some of these patients.

Adrenal Insufficiency↗

Adrenal regeneration hypertension prevented by thyroidectomy: a quantitative ultrastructural study of the regenerating adrenal cortex.

Thyroparathyroidectomy (TPX) prevents adrenal regeneration hypertension (ARH) in female rats and concomitantly inhibits regeneration of the adrenal cortex. Removal of the thyroid gland plays the major role in preventing ARH inasmuch as parathyroidectomized adrenal-enucleated (PX-AE) rats became hypertensive, whereas thyroparathyroidectomized adrenal-enucleated rats (TPX-AE + PT) did not. Inhibition of adrenocortical regneration by TPX is reflected by a significant decrease in adrenal weight, volume of cortical parenchymal tissue per gland, and average cell volume at three weeks, compared with the regenerating adrenal gland in adrenal-enucleated thyroid-parathyroid-intact (AE) rats. Mitochondria in TPX-AE rats resembled closely those from zona fasciculata cells of a normal adrenal gland; stereologic techniques for electron microscopic examination confirmed that mitochondrial volume/cell and surface area of total mitochondrial membranes/cell (outer/inner membranes plus cristae) of adrenocortical cells from TPX-AE rats did not differ significantly from those of AE animals. The surface area of mitochondrial cristae of TPX-AE rats, however, was significantly greater than that of AE rats, whereas the surface area of the inner/outer mitochondrial membrane of the TPX-AE group was decreased significantly as compared with that of the AE group. The diameter of mitochondria in TPX-AE rats was larger than in the AE group, although the number of mitochondria/cell was significantly less in TPX-AE rats than in AE rats. Although TPX had no significant effect on the levels of DOC or corticosterone in the serum of quiescent AE rats as compared with TPX-AE rats, the rise in DOC in the serum after ether stress was blunted in the TPX-AE group as compared with that in the AE group. The rise in corticosterone in the TPX-AE group was comparable to that of the AE animals. Thus, partial inhibition of adrenal regeneration in TPX-AE rats in combination with a blunted rise in DOC levels in response to stress may well contribute to the prevention of ARH.

Adrenal Cortex↗

Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability.

Previous investigations have demonstrated that adrenal chromaffin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striatum. However, chromaffin cells isolated from the nonchromaffin constituents of the adrenal medulla (fibroblasts and endothelial cells) have recently been demonstrated to survive grafting into a number of CNS sites. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We compared the survival of intrastriatally grafted isolated bovine chromaffin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell types or isolated chromaffin cells that were then reseeded with autologous fibroblasts and endothelial cells. Implants of perfused adrenal medullary cells survived poorly and most graft sites were infiltrated with macrophages. The chromaffin cells in this group that did survive appeared to be in the process of degeneration. In contrast, large numbers of isolated chromaffin cells survived for up to 2 months following transplantation. These cells maintained their endocrine phenotype and stained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cells seen in situ and the perigraft region was essentially devoid of macrophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host-derived sprouting response of tyrosine hydroxylase-immunoreactive fibers. These data demonstrate that large numbers of adrenal chromaffin cells can survive intrastriatal implantation in the absence of exposure to exogenous NGF. Rather, the nonchromaffin cells of the adrenal medulla (fibroblasts and endothelial cells) appear to compromise the viability of grafted chromaffin cells. Once they are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are still to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viability.

Adrenal Medulla↗

Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients.

BACKGROUND: Primary aldosteronism (PA) is caused by an adrenal aldosterone-producing tumor (A-APT) or adrenal hyperplasia. An extra-adrenal APT (E-APT) as a cause of PA has been reported in 5 cases. Autopsy studies show a high incidence of ectopic adrenocortical tissue. We did a prospective study of the prevalence of A-APTs and E-APTs and the biochemical features of E-APTs in patients with PA. METHODS: Hypertensive patients (N = 3900) referred to our unit were screened for PA by measuring renin activity, urinary aldosterone-18-glucuronide, tetrahydroaldosterone, and 18-hydroxycorticosterone (18-OH-B). Primary aldosteronism was found in 257 cases. The differentiation between A-APTs and adrenal hyperplasia was based on the results of postural response of renin, plasma aldosterone, 18-OH-B, computed tomography, isotope scanning, or adrenal venous aldosterone. Ultrasound examination of the abdomen was used to screen for E-APT. RESULTS: The cause of PA was bilateral adrenal hyperplasia in 101 cases, unilateral adrenal hyperplasia in 2, an A-APT in 146, and an E-APT in 1. The site of aldosterone production was uncertain in 7 patients who had normal adrenal glands on computed tomography but refused to undergo isotopic scanning and adrenal venous catheterization. Ultrasound examination disclosed normal retroperitoneum in 4 of the 7 cases but could not rule out E-APT in 3 cases. The biochemical features of the patient with the E-APT were similar to classic A-APT, with low renin, high aldosterone, and high 18-OH-B values without appropriate response to posture or to short-term volume expansion. The excision of the E-APT in the right kidney resulted in normalization of blood pressure and renin, aldosterone, and 18-OH-B levels. CONCLUSION: Although E-APT is rare, it should be considered in the interests of specific therapy for PA because aldosterone-secreting malignant ovarian tumors also have been reported.

Adrenal Cortex Neoplasms↗

Delineation of adrenal in controls and nontumorous adrenal disorders by real-time ultrasonic-scanner.

In 90 control subjects, 90% of the right adrenal and 38% of the left were delineated by sector US scanner. A longitudinal scan from an intercostal space in the mid-axillary line and a right-anterior-transverse scan from the intercostal space were useful in displaying the right adrenal, and an anterior-transverse scan from the epigastrium was also useful in showing the left adrenal. The latter was not as clear as the right. Moreover, a transverse scan from the left flank did not fully display the whole image of the left adrenal. The sizes of both adrenal images were somewhat smaller than those made by computerized tomography (CT), as shown in our previous study. Although the left adrenal in one case of congenital adrenogenital syndrome and those in three cases of Cushing's disease could not be delineated, all of the enlarged right adrenals in these cases were demonstrated by ultrasonic scanning (US). These results suggest the clinical usefulness of US for the detection of affected, nontumorous right adrenals.

Adolescent↗

Dependence of fetal hairs and sebaceous glands on fetal adrenal cortex and possible control from adrenal medulla.

Human fetal adrenal development is characterized by rapid growth, high steroidogenic activity, and a distinct morphology, including a unique cortical compartment known as the fetal zone. For most of gestation, the predominant fetal zone accounts for 80-90% of the cortical volume and is the primary site of growth and steroidogenesis, producing 100-200 mg/day of the androgenic steroid, dehydroepiandrosterone sulfate (DHEA-S). The physiological role of this zone during intrauterine life is not well understood. While the glands appear to be capable of DHEA-S synthesis early in gestation (8-10 weeks), we noticed that this event precedes the differentiation of hairs and sebaceous glands. Hairs begin to develop between 9 and 12 weeks and sebaceous glands between 13 and 15 weeks of gestation. Sebaceous glands form an oily secretion - sebum that mixes with desquamated epidermal cells to form vernix caseosa. Vernix caseosa protects the developing skin from constant exposure to amniotic fluid, and hairs helps to hold the vernix caseosa on the skin. We suggest therefore that the human fetal adrenal cortex produces DHEA-S beginning at around 8-10 weeks of gestation in sufficient quantities to influence the growth of hairs and sebaceous glands. Soon after birth, the fetal zone atrophies, and adrenal androgen production decreases to minimal levels. As a consequence, in concordance with the rapid decrease in adrenal androgen levels and in consistent with our hypothesis, fetal hairs are shed and sebaceous glands shrink to small structures. The mechanism that regulates fetal adrenal androgen production is a key unanswered problem in human adrenal biology. Since there exists a close relationship between epinephrine and DHEA-S levels during adrenarche which shows modulatory interactions between adrenal androgen production and adrenomedullary function, we suggest again that adrenomedullary function might play a role in the control of fetal adrenal androgen secretion.

Adrenal Cortex↗

[Heparin-induced thrombocytopenia complicated by hematoma of the adrenal glands and acute adrenal insufficiency].

Three cases of acute adrenal haemorrhage complicating heparin induced thrombocytopaenia are described. The patients were 2 men and 1 woman, respectively 62, 74 and 76-year old. They all had orthopaedic problems requiring a treatment by subcutaneous calcium heparinate. Thrombocytopaenia occurred 7 to 10 days after the beginning of treatment, with a progressive return to normal of platelet count on stopping heparin. A syndrome suggestive of adrenal failure appeared on the 10 th to 12 th day consisting of abdominal pain, hyperpyrexia, arterial hypotension, asthenia, altered consciousness. Adrenal hormone levels were decreased. Abdominal scanography demonstrated adrenal haemorrhage in 2 patients. The third patient died before further investigations could be carried out. Hormonal replacement therapy brought things back to normal. Six other similar cases have already been published. The heparin induced thrombocytopaenia probably explains the two paradoxes of adrenal haemorrhage complicating heparin therapy: its occurrence in the absence of excessive anticoagulation, and adrenal venous thrombosis. The presence of abdominal pain, fever, collapse, or hyponatraemia with heparin induced thrombocytopaenia should suggest a possible adrenal haemorrhage. Adrenal CT scans should be carried out rapidly, so that hormone treatment can be initiated without delay.

Acute Disease↗