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Sympatho-adrenal medullary functions in response to intracerebroventricularly injected corticotropin-releasing factor in anesthetized rats.

Effects of intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) on adrenal sympathetic efferent nerve activity, adrenal catecholamine secretion rate and cardiovascular function (i.e. blood pressure, heart rate and renal nerve activity) were investigated in halothane-anesthetized rats. Administration (i.c.v.) of CRF resulted in a dose-dependent increase (to 140% of control, for a 6.4 nmol dose) in adrenal sympathetic nerve activity which began several minutes after injection and reached maximum values approximately 30-60 min later. This increase was significant, when tested against vehicle injected controls, for doses of 6.4 nmol and 640 pmol; however, a 64 pmol dosage did not produce significant effects. Acute hypophysectomy did not influence the response of adrenal nerve activity to i.c.v. injection of CRF. Intravenous administration of CRF (6.4 nmol) did not produce any significant increases in ongoing activity of the adrenal nerve. Following i.c.v. administration of CRF (640 pmol), epinephrine and norepinephrine secretion, as measured from adrenal venous blood samples, showed a similar response pattern to that of the adrenal nerve. Significant increases (maximum increases, from 13.2 to 31.5 ng/kg/min and from 4.1 to 8.6 ng/kg/min for epinephrine and norepinephrine secretion rates, respectively) were observed over the 90 min blood sampling period. The present study demonstrates by direct recording of adrenal sympathetic nerve activity and measurement of adrenal catecholamine secretion rate, that i.c.v. administered CRF can increase adrenal sympathetic efferent nerve activity resulting in increases in catecholamine secretion. In addition, renal nerve activity also showed dose-dependent increases after CRF i.c.v. administration (to 160% of control, for a 6.4 nmol dose) as did heart rate (increases of 35 beats/min for a 6.4 nmol dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Expression of differentiated functions in heterokaryons between skeletal myocytes, adrenal cells, fibroblasts and glial cells.

The regulation of both muscle and adrenal functions was examined in heterokaryons formed by fusing differentiated chick skeletal myocytes to Y1 mouse adrenal cells. Mouse fast skeletal myosin light chain one (LC1) synthesis was induced and acetylcholine receptor expression was maintained at muscle control levels. Steroid secretion, although reduced compared with Y1 X Y1 adrenal homokaryon control fusions, was nonetheless maintained at relatively high levels. Steroid secretion in the myocyte X adrenal heterokaryons was constitutively expressed and was not increased by exposure to either adrenocorticotrophic hormone or db-cAMP. The population of heterokaryons was thus simultaneously expressing both muscle and adrenal functions. The steroid secretion in these heterokaryons was compared to that in heterokaryons formed by fusing Y1 adrenal cells to either chick skin fibroblasts or rat C6 glial cells. Both of these sets of heterokaryons exhibited low baseline levels of steroid secretion that were inducible to control values by ACTH. These results extend previous observations showing that heterokaryons are functionally very different than cell hybrids, and exhibit a variety of phenotypic interactions. Although fibroblasts suppress muscle functions in heterokaryons, they are permissive for adrenal functions. C6 glial cells are permissive for both adrenal and muscle functions, and along with several other neurectodermal derivatives contain an inducible skeletal myosin light chain gene. Finally, myocytes and Y1 adrenal cells are mutually permissive for their differentiated functions, and Y1 adrenal cells contain an inducible myosin light chain gene.

Adrenal Cortex↗

Adrenal steroidogenesis in the guinea pig: effects of androgens.

In humans, the onset of adrenache has been found to occur with the appearance of the zona reticularis, the inner zone of the adrenal cortex. Since an increase in the volume of adrenal cortex during maturation in the guinea pig has been associated with the growth of the zona reticularis, we were interested in investigating the changes in adrenal steroidogenesis during maturation in this species. In addition, the effect of androgens on adrenal steroidogenesis was studied. We demonstrated that between 1 and 10 weeks of age, a period of maximal growth of the adrenals in the guinea pig, there is a decrease in the concentrations of adrenal pregnenolone, cortisol, dehydroepiandrosterone, testosterone, androstenedione, and 11 beta-hydroxyandrostenedione, suggesting lower steroid production by the guinea pig adrenals. In plasma, we observed that the concentration of 11 beta-hydroxyandrostenedione (the sole C19 steroid present after castration) remained unchanged during maturation, while cortisol and corticosterone were lower between 1 and 4 weeks of age. Although castration as well as the administration of the antiandrogen flutamide had no effect on adrenal steroidogenesis, dihydrotestosterone caused an inhibition of cortisol and corticosterone levels in the adrenals while the concentrations of progestins (namely, pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone) tended to increase in the adrenals, thus suggesting that dihydrotestosterone induces a blockade in the steroidogenic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Changes of adrenal catecholamines and their synthesizing enzymes during ontogenesis and aging in rats.

Male Wistar specific-pathogen-free rats aged 2, 7, 17, 30, 60, 120, 200, 360 and 600 days, all killed in experiment on the same day, were examined. The body weight significantly increased until the 200th day, the weight of adrenals until the 120th day and the adrenal protein content until the 30th day of life. The adrenaline content of the adrenals increased continuously during the 600 days studied. Adrenal noradrenaline content increased rapidly over the first 17 days, remained at a stable level until the 120th day, and rose to a higher level after 200 days. The activity of adrenal catecholamine-synthesizing enzymes also increased with age: tyrosine hydroxylase gradually increased until the 360th day, dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase until the 200th day. Our results demonstrate that, in the rat, during development there is a gradual increase of adrenal weight, adrenaline content, tyrosine hydroxylase and phenylethanolamine-N-methyl transferase activity until maturation (120th day), whereas the adrenal noradrenaline content reaches the adult values earlier, around the 17th day. During aging, adrenal catecholamines significantly increase when compared to young-adult rats (120-day-old), probably due to the elevated activity of the adrenal catecholamine-synthesizing enzymes. The increased adrenal catecholamine levels in old animals might be connected with a higher incidence of cardiovascular diseases in aged.

Adrenal Glands↗

Biochemical, autoradiographic and functional studies on a unique glutamate binding site in adrenal gland.

L-Glutamate is known to function as a major excitatory neurotransmitter in the mammalian central nervous system, and recent reports suggest the existence of receptors for glutamate in several peripheral tissues. In the present study, the characteristics of the binding of [3H]L-glutamate to sections of bovine adrenal gland were studied, and the localisation of this binding was investigated in adrenal glands from cow, dog, rat and guinea pig. In addition, the effects of glutamate on catecholamine release from the perfused isolated bovine adrenal gland were investigated. Binding of [3H]L-glutamate to slide-mounted sections of bovine adrenal gland was of high affinity (Kd 0.4 microM), rapid, saturable, reversible, stereospecific and to a single population of sites. The pharmacological profile of this binding site appeared to be unique, and did not correspond to any of the central receptor subtypes for glutamate so far identified. In the adrenal gland of the cow, rat and guinea pig, the binding density of [3H]L-glutamate was higher in cortex than medulla, while this pattern was reversed in the canine adrenal gland. Glutamate had no effect on the basal secretion of noradrenaline or adrenaline from the perfused isolated bovine adrenal gland, and neither glutamate nor the glutamate receptor antagonist kynurenate altered the nicotine-stimulated release of these catecholamines. These results suggest the existence of a novel peripheral binding site for glutamate in the adrenal gland. The differential autoradiographic localisation of this binding site in the adrenal glands of the various species studied may reflect different functional properties of glutamate in these species, and suggests possible roles for glutamate in the modulation of adrenal function.

Adrenal Glands↗

Sex- and age-related changes in catecholamine metabolism and release of rat adrenal gland.

To examine the possible existence of changes in the adrenal catecholaminergic activity during aging, we analyzed the adrenal content of catecholamines (CA) and the activities of selected enzymes involved in their metabolism as well as the basal and the K+-stimulated release of these CA in incubated adrenal tissue of aged (greater than 22 months) and young (2 months) rats of both sexes. Adrenal contents of norepinephrine (NE) and epinephrine (E) of male rats were unaltered in aging, although aged males showed an increased activity of tyrosine hydroxylase (TH) and a decrease in phenylethanolamine-N-methyl transferase (PNMT) activity. In addition, the in vitro release of both CA as well as their content in the incubated adrenal tissue were higher in aged males than in young animals. However, the response of the adrenal of aged males to incubation with stimulatory concentrations of K+ was significantly lower than that observed in young males. Aged females showed increases in the adrenal content of E, although the activities of TH and PNMT were unaltered. As in aged males, the in vitro release of CA from incubated adrenal tissue was higher in aged females than in young rats, but the CA amounts measured in the incubated tissues were similar. Moreover, the response to stimulatory concentrations of K+ was lower in aged females than in young animals. In summary, these results clearly indicate that adrenal catecholaminergic activity is enhanced during aging, which could have important consequences for physiological functions regulated by the adrenal secretion. Also, some differences in the effects of aging could be observed between males and females.

Adrenal Glands↗

The relationship between adrenal vascular events and steroid secretion: the role of mast cells and endothelin.

The actions of ACTH on the adrenal cortex are known to be 2-fold. In addition to increased steroidogenesis, ACTH also causes marked vasodilation, reflected by an increased rate of blood flow through the gland. Our studies, using the in situ isolated perfused rat adrenal preparation, have shown that zona fasciculata function and corticosterone secretion are closely related to vascular events, with an increase in perfusion medium flow rate causing an increase in corticosterone secretion, in the absence of any known stimulant. These observations give rise to two important questions: how does ACTH stimulate blood flow; and how does increased blood (or perfusion medium) flow stimulate steroidogenesis? Addressing the first question, we have recently identified mast cells in the adrenal capsule, and shown that Compound 48/80, a mast cell degranulator, mimics the actions of ACTH on adrenal blood flow and corticosterone secretion. We have also demonstrated an inhibition of the adrenal vascular response to ACTH in the presence of disodium cromoglycate, which prevents mast cell degranulation. We conclude, therefore, that ACTH stimulates adrenal blood flow by its actions on mast cells in the adrenal capsule. Addressing the second question, we looked at the role of endothelin in the rat adrenal cortex. Endothelin 1, 2 and 3 caused significant stimulation of steroid secretion by collagenase dispersed cells from both the zona glomerulosa and the zona fasciculata. A sensitive response was seen, with significant stimulation at an endothelin concentration of 10(-13) mol/l or lower. Endothelin secretion by the in situ isolated perfused rat adrenal gland was measured using the Amersham assay kit. Administration of ACTH (300 fmol) caused an increase in the rate of immunoreactive endothelin secretion, from an average of 28.7 +/- 2.6 to 52.6 +/- 6 fmol/10 min (P less than 0.01, n = 5). An increase in immunoreactive endothelin secretion was also seen in response to histamine, an adrenal vasodilator, which stimulates corticosterone secretion in the intact gland, but has no effect on collagenase-dispersed cells. From these data we conclude that endothelin may mediate the effects of vasodilation on corticosterone secretion, and this mechanism may explain some of the differences in response characteristics between the intact gland and dispersed cells.

Adrenal Cortex↗

Down-regulation of adrenal neuronal nitric oxide synthase mRNAs and proteins after deoxycorticosterone acetate-salt treatment in rats.

The aim of this study was to evaluate the possible changes of adrenal neuronal nitrite oxide synthase (nNOS) messenger RNA (mRNA) and protein of rats after deoxycorticosterone acetate (DOCA)-salt treatment. We determined adrenal nNOS expression in 12 vehicle-treated and 13 DOCA-salt-treated rats by in situ hybridization, immunohistochemistry, and multiplex RT-PCR methods. Adrenal nNOS was also detected by Western blot in five vehicle-treated and five DOCA-salt-treated rats. The results showed that adrenal nNOS mRNA and nNOS immunoreactivities were mainly localized in the medulla and some in the regions of zona glomerulosa. DOCA-salt treatment inactivated nNOS mRNA and peptide expression prominent in the adrenal medulla and slight in the zona glomerulosa. The relative quantities of nNOS mRNA in the adrenals of the DOCA-salt-treated group was 8.8-fold decreased. At the same time, the relative quantities of steroid acute regulatory protein mRNA and phenylethanolamine N-methyltransferase mRNA in the adrenals of the DOCA-salt-treated group were significantly decreased. Western blots showed that total adrenal nNOS were 3.7-fold down-regulated after DOCA-salt treatment. Our results indicated that the down-regulation of adrenal nNOS synthesis might be associated with the inactivation of adrenal function in face of volume expansion.

Adrenal Glands↗

Adrenal autoantibodies and Addison disease in insulin-dependent diabetes mellitus.

Stored sera from 466 patients with insulin-dependent diabetes mellitus and from 144 controls were examined for organ-specific antibodies to human adrenal cortex. Adrenal antibodies were found in seven of the patients with IDDM (1.5%) and in one control (0.7%). None of 91 black patients with IDDM had adrenal antibodies. All of the seven patients with adrenal antibodies had other organ-specific antibodies. Three had clinical hypothyroidism and one was thyrotoxic. All of these seven patients had a HLA-B8-bearing haplotype, suggesting that the B8-bearing haplotype confers an extremely high "relative risk" for adrenal autoimmunity in IDDM. Organ-specific autoimmune disease and/or organ-specific antibodies were found in 30% of the first-degree relatives of these eight probands with the adrenal antibodies (seven with IDDM and one control). We conclude that screening patients with IDDM for adrenal antibodies of low yield (1.9% among white patients). Further, adrenal antibodies may be present for at least two years without the development of Addison disease. Antibodies reactive only to the zona glomerulosa of the adrenal cortex may be benign. Patients with IDDM and thyroid microsomal antibodies are more likely to have adrenal antibodies (6.5%), as are patients with IDDM and a B8-bearing haplotype and those with IDDM and family histories of organ-specific autoimmunity.

Addison Disease↗

[Contribution of the scintigraphy with iodocholesterol (I-COL) to the diagnosis and characterization of silent adrenal masses].

OBJECTIVE: To assess the role of the adrenal cortical scintigraphy with 131-I Norcholesterol (I-COL) in the diagnosis and characterization of silent adrenal masses. METHODS: We selected 57 patients who underwent an adrenal scintigraphy with I-COL, 36 women and 21 men (mean aged: 62.5 years), and who were classified into two groups: Group I or Incidentalomas, 39 patients without signs or symptoms of adrenal disease in whom an adrenal mass is incidentally discovered during a CT or ultrasound scan; and a second group or Group II, 18 patients with history of cancer in whom an adrenal mass is discovered. We defined the following Scintigraphic patterns in relationship with the CT: Normal, concordant unilateral (CU) or exclusive; discordant unilateral (DU); concordant asymmetrical (CA) or prevalent; discordant asymmetrical (DA) and nonvisualization (NV). The final diagnosis was obtained with clinical, analytical, and radiological evaluation and in some cases surgery. RESULTS: In Group I, the diagnoses were: 17 adrenal masses without criteria of malignancy or hormonal overproduction (the Scintigraphic patterns were 10 CA, 5 normal and 2 CU), 9 Subclinical Cushing's syndrome (4 CU, 4 CA and 1 normal), 5 adenomas (all CU), 3 adrenal primary carcinomas, with no uptake in the scintigraphy, and 5 were other diagnoses. In group II, 14 patients had benign masses (all patterns were normal or concordant) and 4 patients metastases (3 discordant and 1 NV patterns). The follow-up time was at least one year. CONCLUSIONS: The adrenal cortical scintigraphy with I-COL provides us information on the functional status of silent adrenal masses and it is an useful tool to distinguish benign from malignant lesions; for this reason we considered that it must be integrated in the diagnostic algorithm as a complement to other techniques.

19-Iodocholesterol↗

The involvement of prolactin in the regulation of adrenal cortex function in pigs.

We investigated the in vivo and in vitro effect of prolactin (PRL) on porcine adrenal cortex function. The in vivo study was performed on 10 multiparous sows. Blood was sampled every 4 h beginning on the 17th day of the estrous cycle and continuing for 6 subsequent days. Plasma was stored at -20 degrees C until steroid hormones analysis was completed. PRL or saline were administered iv for 48 h in 2 h intervals. Injections of PRL began 4-20 h after the preovulatory LH surge. At the end of the sampling period sows were slaughtered and adrenals were immediately dissected. Adrenals were frozen at -70 degrees C for determination of adrenal cortex steroid hormones content. At the end of PRL treatment period mean plasma level of cortisol in control sows was significantly lower than that of PRL-treated sows. Moreover, the area under the mean plasma cortisol concentration curve was significantly higher in PRL-treated sows in comparison to controls. The mean cortisol adrenal content was significantly higher in adrenal cortex of PRL-treated sows than that of controls. PRL did not affect adrenal cortex concentration of androstenedione (A(4)), testosterone (T), dehydroepiandrosterone (DHEA) and estradiol (E(2)). Dehydroepiandrosterone sulfate (DHEAS) was not found in porcine adrenal cortex. In the in vitro experiment adrenal glands were removed immediately after slaughter of 6 crossbred gilts. Dispersed adrenocortical cells were incubated for 8 h with or without porcine PRL. Prolactin stimulated cortisol secretion in a dose-dependent manner. These results suggest that PRL is one of the key factors involved in the regulation of adrenal cortex function in pigs.

Adrenal Cortex↗

Factors influencing adrenal metastasis in renal cell carcinoma.

OBJECTIVES: We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. MATERIAL AND METHODS: From 1993 to 1999, 210 patients with renal cell carcinoma (RCC), (139 men and 71 women, mean age 60.8 years, range 12-96) underwent radical nephrectomy with associated adrenalectomy. Patients were divided into two subgroups of 106 with localized (stage T1-2 tumor, groupl) and 104 with advanced (stage T3-4N01M01, group2) renal cell carcinoma. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological results to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS: Of the 210 patients, 15 (7.1%) had adrenal involvement. Tumor stage correlated with probability of adrenal spread, with T3-4 and T1-2 accounting for 13.4% and 0.9% of cases, respectively (p < 0.001). Upper pole intrarenal RCC most likely to spread was local extension to the adrenal gland, representing 53.3% of adrenal involvement. In contrast, multifocal, lower pole and mid region RCC tumors metastasized hematogenously, representing 21.4%, 7%, and 14% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 7.8 cm, range 4 to 21) and adrenal involvement was not statistically significant. Preoperative CT demonstrated 97.7% specificity, 98.4% negative predictive value, 87% sensitivity and 80% positive value for adrenal involvement by RCC. CONCLUSIONS: Ipsilateral adrenalectomy should only be performed if a lesion is seen preoperatively on CT scan or if gross disease is seen at the time of nephrectomy. The prognosis is poor for RCC with ipsilateral involvement even with complete removal. Because of this poor prognosis we believe that adrenal involvement should constitute a separate stage category.

Adolescent↗

A critical examination of adrenal tuberculosis and a 28-year autopsy experience of active tuberculosis.

OBJECTIVE: Tuberculosis is potentially fatal and adrenal gland involvement is uncommonly reported. The aims of the current study were to define the characteristics of tuberculosis in hospitalized patients and to analyse the features of adrenal tuberculosis. DESIGN: Retrospective analysis of autopsies and adrenalectomies. PATIENTS: 13,762 patients (13492 at autopsies and 270 at adrenalectomy). MEASUREMENTS: The presence of active tuberculosis, the predisposing factors, the pathological features and organs of involvement were examined. RESULTS: Active tuberculosis was present in 871 patients (6.5% of all 13492 autopsies). It was first diagnosed in 70% of these patients during autopsy. Cancers and a history of recent major operations were the 2 main concomitant factors in the patients with tuberculosis. Extra-pulmonary tuberculosis was seen in 261 patients (30%). The five most common extra-pulmonary sites of tuberculosis were the liver, spleen, kidney, bone and adrenal gland. Adrenal tuberculosis was seen in 52 of the 871 patients (6%) with active tuberculosis at autopsy and in 3 patients at adrenalectomy. The adrenal gland was the only organ involved by active tuberculosis in 14 of these 55 patients (25%; 35 men, 20 women). Tuberculosis was evident on macroscopic examination of the adrenal glands in 46% of the patients. On histological examination, caseous necrosis and granulomatous inflammation with Langhan's giant cells were seen in 71% and 40% of patients, respectively. Seven patients presented with signs and symptoms of Addison's disease due to bilateral adrenal involvement. Langhan's giant cells were frequently seen in histological sections and bilateral enlargement of the adrenal glands was often noted. Fine needle aspiration cytology was not useful for diagnosing adrenal tuberculosis. CONCLUSION: Unexpected and extra-pulmonary tuberculosis such as adrenal tuberculosis has been a common problem. A high index of suspicion, correct diagnosis and proper treatment are essential for the management of tuberculosis.

Addison Disease↗

Fetal adrenal and middle cerebral artery Doppler velocimetry in high-risk pregnancy.

OBJECTIVES: Animal studies have shown that hypoxic fetuses redistribute their blood flow, giving preferential supply to the brain, heart and adrenal glands. The aim of this study was to establish whether blood velocity waveforms in the human fetal adrenal artery and middle cerebral artery showed signs of redistribution of fetal circulation in high-risk pregnancy, and to analyze the relationship between signs of such redistribution and the outcome of pregnancy. METHODS: Fetal middle adrenal artery and middle cerebral artery waveforms were recorded between 27 and 41 weeks of gestation in 102 pregnancies complicated by pregnancy-induced hypertension. Signs of fetal adrenal-sparing were deemed present when the pulsatility index (PI) fell below the fifth percentile of the normal range. Signs of fetal brain-sparing were deemed present when the cerebral artery PI was below the mean -2 SD of the normal range and the cerebroplacental PI ratio was < 1.08. RESULTS: Signs of adrenal sparing were found in 64 cases and brain sparing in 32 cases. Fetal adrenal sparing was strongly associated with adverse perinatal outcome; all perinatal mortality cases showed signs of adrenal sparing. There was a significant positive correlation between the fetal adrenal artery PI and umbilical arterial and venous pH. CONCLUSIONS: Signs of adrenal sparing are frequent in high-risk pregnancies. Adrenal artery velocimetry may be a useful procedure for fetuses at risk for hypoxemia.

Adrenal Glands↗

Identification of virilizing adrenal tumors in hirsute women.

BACKGROUND: Hirsutism in women is usually caused by benign adrenal or ovarian disorders, but it can also be caused by adrenal carcinoma. The most effective way to identify such carcinomas is not known. METHODS: We measured serum and urinary steroids before and after the administration of 3 mg of dexamethasone per day for five days in 14 hirsute women with histologically proved adrenal tumors (12 adrenal carcinomas and 2 adrenal adenomas) and in 73 women with hirsutism of non-neoplastic origin. RESULTS: All the women with adrenal tumors had elevated basal serum concentrations of testosterone or dehydroepiandrosterone sulfate, as compared with 36 of the 73 women with non-neoplastic hirsutism (sensitivity, 100 percent; 95 percent confidence interval, 77 to 100; specificity, 50 percent; 95 percent confidence interval, 38 to 62). After the administration of dexamethasone, serum dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid excretion decreased to values similar to those in normal women in all the women with non-neoplastic hirsutism, but in none of the 12 with adrenal tumors who were tested. All the women who did not have adrenal tumors had serum cortisol concentrations below 3.3 micrograms per deciliter (90 nmol per liter) after dexamethasone administration, whereas in all 12 patients tested who had tumors the values were higher. The suppression of serum dehydroepiandrosterone sulfate and cortisol and urinary 17-ketosteroid excretion excluded the likelihood of adrenal tumors with a sensitivity of 100 percent (95 percent confidence interval, 74 to 100) and a specificity of 100 percent (95 percent confidence interval, 89 to 100). CONCLUSIONS: Among women with hirsutism, an adrenal tumor is unlikely if the patient has normal basal serum concentrations of testosterone and dehydroepiandrosterone sulfate. In women in whom these concentrations are elevated, a tumor is unlikely if the serum concentration of dehydroepiandrosterone sulfate and urinary 17-ketosteroid excretion are in the normal basal range and the serum cortisol concentration is less than 3.3 micrograms per deciliter after the administration of dexamethasone.

17-Ketosteroids↗

Limitations of size as a criterion in the evaluation of adrenal tumors.

BACKGROUND: Size has been considered to be the single best predictor of malignancy in adrenal neoplasms that have been identified incidentally. However, small adrenal cortical cancers have been reported from multiple centers. METHODS: We retrospectively evaluated the value of tumor size and other clinical parameters in the prediction of the presence of adrenal malignancy. RESULTS: The records of 117 patients who underwent evaluation for tumors of the adrenal gland were reviewed. The median tumor size of the adrenal cortical carcinomas (n = 38 carcinomas) was 9.2 cm (range, 1.7-30 cm); 5 cancers (13.5%) were smaller than 5.0 cm. The median overall size of the benign tumors, excluding pheochromocytomas, was 4.0 cm (n = 38 carcinomas); 10 benign tumors (26%) were larger than 5.0 cm. The imaging features of 4 of 5 small adrenal cancers predicted malignancy; the remaining patients had hormonally functioning tumors. The imaging features of 7 of 10 large benign adrenal tumors predicted benign histologic features, including 5 of 5 myelolipomas. CONCLUSIONS: Although size remains a good predictor of the histologic features and clinical behavior of adrenal neoplasms, both small adrenal cortical cancers and large benign tumors occur with measurable frequency. High-quality imaging studies may be helpful in the identification of relatively small adrenal cancers and of characteristic benign lesions that may be selectively followed.

Adolescent↗

Role of pituitary POMC-peptides and insulin-like growth factor II in the developmental biology of the adrenal gland.

During fetal life, it is critical that there is coordinate regulation of the growth, zonation and differentiation of the fetal adrenal cortex to ensure that cells in key tissues and organs are exposed in a programmed temporal sequence to the actions of glucocorticoids. Glucocorticoids are essential for maturation of key target organs before birth, including the lung, brain, liver, gut, kidney and adrenal, and the prepartum increase in glucocorticoid synthesis and secretion by the fetal adrenal gland is critical for the successful transition to postnatal life. It is also evident that premature or abnormal exposure of embryonic or fetal tissues to glucocorticoids during critical windows of development can irreversibly alter the programmed development of organ systems. Premature or abnormal exposure of the fetus to excess glucocorticoids may occur either as a consequence of endogenous stimulation of the fetal hypothalamo-pituitary-adrenal axis (HPAA) or as a consequence of exposure to exogenous glucocorticoids in a therapeutic context. Administration of synthetic glucocorticoids to women at risk of preterm labour, for example, is a routine clinical practice designed to improve respiratory function and neonatal outcome. It is clearly important to understand what endogenous factors regulate the growth and functional maturation of the adrenal cortex during development and the consequent likelihood of exposure of developing tissues to excess corticosteroids. To date, investigations have centred on the role of ACTH 1-39 in the stimulation of adrenal growth and steroidogenesis in long gestation species, such as the primate and sheep, where maturation and differentiation of organ systems occurs predominantly before birth. In this review, we will focus on the evidence that in addition to ACTH 1-39, other pro-opio-melanocortin (POMC) derived peptides, which are synthesized, processed and secreted by the fetal pituitary, play a role in the coordinate regulation of the specific phases of growth and functional development of the fetal adrenal gland in vivo. We will discuss our recent findings on the direct in vivo actions of N-POMC 1-77 and separately, insulin like growth factor II (IGF-II), as adrenal growth factors. These studies provide an understanding of the separate regulatory mechanisms which control activation of adrenal growth and stimulation of adrenal steroidogenesis in the late gestation fetus.

Adrenal Glands↗

Acute and chronic interstitial cryotherapy of the adrenal gland as a treatment modality.

BACKGROUND AND OBJECTIVES: Adrenalectomy is indicated for patients with large adrenal lesions or functional tumors. Cryoablation is currently used as a surgical alternative for the treatment of prostate, lung, brain, pharynx, and liver tumors. The purpose of this study was to determine if cryosurgery could be delivered to small areas in the adrenal gland in a controllable and reproducible manner, so that tissue could heal in a nonpathological way. MATERIALS AND METHODS: Fourteen female mongrel dogs underwent acute (N = 8) or chronic (4 weeks) (N = 6) cryoablation using the Cryounit. In the acute study, using an open transabdominal approach, a 2-mm cryoprobe was placed interstitially into the adrenal tissue, while 0.032-inch thermocouples were cannulated into the ipsilateral adrenal artery and vein. Adrenal parenchymal temperature changes were measured using thermocouples placed at 0.4- and 0.8-cm intervals from the cryoprobe. In the chronic study, cryoablation was achieved by transperitoneal laparoscopic access using standard laparoscopic technique. RESULTS: Interstitial cryoprobe temperatures decreased from 33.1 +/- 1.9 degrees C to -148 +/- 1.2 degrees C following 15 minutes of freezing in the acute study. Cryoablation of adrenal tissue achieved temperatures of -41.8 +/- 5.7 degrees C and -21.8 +/- 1 degrees C at distances of 0.4 and 0.8 cm from the cryoprobe, respectively. There were no significant changes in adrenal artery or vein temperatures during cryoablation. Histologically, there was a clear demarcation between viable and nonviable tissue, the latter being characterized by areas of multifocal hemorrhage and pyknosis. After 4 weeks of healing, there was a well-defined line between necrotic and viable tissue. CONCLUSION: Cryoablation of the adrenal gland can be obtained in an effective, controllable, and reproducible manner. This controllable energy form may provide new modality for tissue destruction where adrenal gland preservation is necessary and can be delivered by the laparoscopic approach. Understanding the effect of adrenal cryoablation may allow us to treat selected patients with small tumors in whom organ preservation is necessary.

Adrenal Glands↗