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Developmental regulation of preproenkephalin (PENK) gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxemia and exogenous cortisol infusion.

Development of the fetal adrenal gland is crucial not only for maturation of several fetal organ systems and the initiation of parturition, but also for the development of the fetal response to stress. The enkephalin-related peptides are present in the chromaffin cells of the fetal adrenal medulla and are secreted in response to stress and with sympathetic stimulation. However, changes in expression of preproenkephalin (PENK) with gestation and in response to stress have not been studied in detail. Therefore we examined the developmental pattern of PENK gene expression in the adrenal gland of fetal and newborn lambs, and of adult sheep. We also determined whether levels of PENK mRNA in the fetal adrenal gland changed in response to exogenous glucocorticoids in late gestation, or in response to hypoxemia. Adrenal glands were removed from fetal sheep, lambs and adult sheep at different stages of development for measurement of PENK mRNA. Cortisol was infused (5 micrograms/min) for 12, 24 or 96 h beginning on day 124-129 of gestation. Moderate hypoxemia was induced for 48 h beginning on day 126-130, or at day 134-136 of gestation, by lowering the maternal fractional inspired oxygen. At the end of the treatment periods, the ewes and fetuses were euthanized. Adrenal PENK mRNA were measured by Northern blot analysis. PENK mRNA levels in fetal adrenals were significantly higher (P < 0.05) on days 140-141 of gestation than earlier in pregnancy, and then decreased significantly with the onset of parturition (days 142-146). After cortisol infusion to the fetus for 96 h there was a significant reduction in adrenal PENK mRNA levels. Hypoxemia resulted in a significant increase in PENK mRNA levels in fetuses at day 126-130 of gestation, but not at the later time in pregnancy when endogenous plasma cortisol concentrations were higher. We conclude that there is a decrease in levels of PENK mRNA in the fetal adrenal gland before parturition at the time of the endogenous prepartum rise in plasma cortisol. Hypoxemia led to an elevation of PENK mRNA levels in fetuses at less than 130 days, but after that time, when the basal and stimulated cortisol responses had risen, there was no significant effect of hypoxemia on PENK mRNA. Cortisol infusion to the fetus at this stage of pregnancy resulted in a decrease in adrenal PENK mRNA levels. We suggest that cortisol may play an important role in the regulation of fetal adrenal PENK mRNA levels and enkephalin synthesis by the adrenal gland of the fetal sheep.

Adrenal Glands↗

A case of unilateral adrenal hyperplasia: the diagnostic dilemma of hyperaldosteronism.

OBJECTIVE: To report the successful laparoscopic surgical management of a case of right unilateral adrenal hyperplasia. METHODS: We present a case of unilateral adrenal hyperplasia and review the pertinent literature. The effectiveness of surgical treatment of unilateral adrenal hyperplasia is evaluated. RESULTS: A 50-year-old man had a 7-year history of hypertension, which had been treated with antihypertensive medications. On initial assessment, he was taking long-acting diltiazem, 240 mg twice a day, and his blood pressure was 150/84 mm Hg. He was noted to have recurrent hypokalemia, low plasma renin activity, increased plasma aldosterone concentration, and high urinary aldosterone levels. Magnetic resonance imaging of the adrenal glands revealed a normal left adrenal gland and fullness of the right adrenal gland. Selective adrenal vein catheterization showed findings consistent with a right-sided adrenal gradient. Surgical removal of the right adrenal gland laparoscopically alleviated his symptoms and cured his hypertension and hypokalemia. Pathologic examination of the right adrenal gland revealed diffuse hyperplasia of the zona fasciculata and zona reticularis. Plasma aldosterone, renin, and potassium levels returned to normal postoperatively, and his blood pressure declined to 120/70 mm Hg. At 1-year follow-up, the patient remained normotensive without the need for antihypertensive agents. CONCLUSIONS: This rare type of hyperaldosteronism, known as unilateral adrenal hyperplasia, is difficult to categorize not only because it fails to typify a conventional subtype but also because it is difficult to confirm the pathologic diagnosis. Recognition of the variety of provocative, biochemical, and imaging results that may be seen in this disorder is important in making the correct diagnosis. Determining unilaterality of disease by selective adrenal vein sampling can result in a cure of hypertension and hypokalemia by surgical resection.

Adrenal Glands↗

Radiotherapy for adrenal gland metastasis from lung cancer: report of three cases.

Adrenal gland metastasis is often observed during the clinical course of patients with lung cancer. However, treatment of adrenal gland metastasis is seldom considered because of the systemic spread of the disease. Treatment with curative intent is very rare, but palliative treatment may sometimes be considered when symptoms such as flank pain are observed. Three cases of adrenal gland metastasis were reported. Two of them received surgery for lung cancer and developed a sole metastasis of the adrenal gland. Case 1 developed a sole left adrenal gland metastasis with left flank pain 14 months after surgery for large cell carcinoma of the lung. Curative radiotherapy after intra-arterial chemotherapy was given. A good response was obtained, and he has been alive for 2 years and 9 months. Case 2 developed a right adrenal gland metastasis after radiotherapy for brain metastasis, after having received right upper lobectomy because of SCLC. The increase in the size of the right adrenal gland led us to treat the lesion before symptoms developed. Radiotherapy was given on an outpatient basis. Case 3, who was previously treated with chemoradiotherapy for SCLC, developed brain, liver, and bilateral adrenal gland metastasis. Huge adrenal gland metastases displaced the pancreas and caused severe pain with the increase in serum amylase level. Concurrent radiotherapy with systemic chemotherapy was given and remarkable shrinkage of the adrenal gland metastases was obtained together with pain relief. Cases 2 and 3 died after 8 and 4 months, respectively. In some cases, radiotherapy for adrenal gland metastasis is a good palliative therapy even in the advanced stage patients. Radiotherapy can sometimes curatively treat adrenal metastasis from NSCLC, as in our Case 1, in which adrenalectomy appeared difficult at the time of recurrence.

Adrenal Gland Neoplasms↗

[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↗

Use of x-ray-computed tomography as an aid in localization of adrenal masses in the dog.

Four dogs with clinical evidence of hyperadrenocorticism were evaluated by use of x-ray-computed tomography (CT). Adrenal masses were identified accurately and localized. Unilateral adrenal masses were diagnosed accurately in dogs 1, 2, and 3 and were removed surgically via a paracostal retroperitoneal approach to the adrenal gland. Using CT and IV contrast medium, the adrenal mass in dog 3 also was accurately diagnosed as being highly vascular. The histopathologic diagnosis was adrenal adenoma in dogs 1, 2, and 3. In dog 4, the CT-roentgen diagnosis was asymmetric bilateral adrenal enlargement. Necropsy examination of dog 4 indicated moderate enlargement of the left adrenal gland and severe enlargement of the right adrenal gland. Results of microscopic examination indicated chronic inflammation of the left adrenal gland and adenocarcinoma of the right adrenal gland. Use of CT facilitated localization of adrenal masses and fulfilled the needs of a localizing technique. A unilateral mass can be removed surgically via a limited exposure, retroperitoneal incision on the affected side of the animal instead of removal via abdominal laparotomy, which is more invasive. Advantages of CT can reduce the needs of other imaging modalities for the localization of adrenal masses.

Adrenal Cortex Neoplasms↗

[Adrenal gland hemorrhage in neonates--radiologic aspects].

INTRODUCTION: The relatively large adrenal glands of the newborn are vulnerable to mechanical trauma during delivery. Great birth weight, difficult labor, perinatal hypoxia and prematurity are predisposing factors of adrenal haemorrhage. Minor adrenal haemorrhage may not cause symptoms. Massive adrenal haemorrhage is uncommon. Symptoms include anaemia and jaundice associated with a suprarenal mass. In cases with severe blood loss acute shock may develop. In 5 to 10 per cent of cases the haemorrhage is bilateral. Ultrasonography has replaced urography in the diagnosis of this condition demonstrating the site and size of the lesion and allowing an accurate follow-up. Within a month after haemorrhage the blood and necrotic adrenal tissue are resorbed and thin calcification appears at the periphery of the gland. Surgery is necessary if haemorrhagic pseudocyst is large and does not resorb spontaneously. MATERIAL AND METHODS: From 1992 to 1996, five patients with neonatal adrenal haemorrhage were treated at the University Children's Hospital in Belgrade. Two of them were females. All patients were born at term by vaginal delivery. Their birth weights ranged between 3200 and 4050 g. At hospitalization infants were aged from 6 hours to 18 days. The first symptom of adrenal haemorrhage was an abdominal mass in three patients. One of them had laparoschisis with guts and stomach protruding out; the surgeon discovered a mass in the right retroperitoneum during operation. Two patients had jaundice associated with anaemia, and sepsis another two. Ultrasonography was done in all patients. We punctured the haemorrhagic pseudocyst (diameter above 5 cm) in three patients and made cystography. Liquid components of pseudocysts were aspirated and sent to bacteriological and cytological analyses. RESULTS: The diagnosis of adrenal haemorrhage was confirmed by ultrasonography in all patients, demonstrating a right adrenal mass (unilateral in all patients), mostly hypoechoic, which displaced the right kidney. Calcification at the periphery of the pseudocyst appeared in one patient. The adrenal haemorrhage disappeared spontaneously in two patients after two months. An attempt to support the adrenal hemorrhagic pseudocystic regression by puncturing and aspirating its content in three patients was successful in one infant. The patient with laparoschisis died because of sepsis and thrombocytopenia. In a patient the haemorrhagic pseudocyst persisted (6 cm in diameter) and was surgically removed. DISCUSSION: Ultrasound is the method of choice in the diagnosis of adrenal haemorrhage, antenatally and neonatally. It also allows diagnosis of coexisting complications such as renal vein or inferior vena cava thrombosis and a proper follow-up. Puncture of pseudocyst and aspiration of liquid components may support involution of large haemorrhagic pseudocysts. If it is unsuccessful, surgery is necessary.

Adrenal Gland Diseases↗

The alpha subunit of inhibin in adrenal cortical neoplasia.

We analyzed 23 adrenal adenomas and 15 adrenal cortical carcinomas by immunolabeling for the alpha subunit of inhibin, and we then compared the results with the functional status of the neoplasms. We also studied 19 pheochromocytomas, 30 renal cell carcinomas, and 5 extra-adrenal paragangliomas, tumors posing differential diagnostic problems with adrenal cortical neoplasms. Immunolabeling was performed using automated immunohistochemical methods and an antibody directed against the alpha subunit. Tumors were semiquantitatively assessed for the number of positive cells. Immunopositivity was obtained in 18 (78%) of 23 adrenal cortical adenomas, 12 (80%) of 15 adrenal cortical carcinomas, 2 (11%) of 19 pheochromocytomas, 0 of 5 extra-adrenal paragangliomas, and 0 of 30 renal cell carcinomas. Immunoreactivity was strong in 7 (78%) of 9 adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. In contrast, only 4 (14%) of 29 tumors that were clinically nonfunctioning or associated with hyperaldosteronism demonstrated strong staining (P < .001). In clinically nonfunctioning tumors, there was a tendency for increased immunopositivity in tumors from patients with elevated levels of cortisol, androgen, or their precursors, with four of six tumors having at least moderate immunopositivity. Similar reactivity was present in only one of eight tumors from patients with normal laboratory values (P=.091). Moderate or strong immunopositivity was present in 9 (60%) of 15 adrenal cortical carcinomas, whereas of the pheochromocytomas, extra-adrenal paragangliomas, and renal cell carcinomas, only 1 (1.9%) of 54 showed moderate-to-strong reactivity. We conclude that moderate or strong immunoreactivity for the alpha subunit of inhibin occurs in adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. Immunolabeling for the inhibin alpha subunit is potentially useful in the differential diagnosis of neoplasms that include adrenal cortical carcinomas.

Adenoma↗

Scintigraphy of incidentally discovered bilateral adrenal masses.

The purpose of this study was to determine the patterns of iodine-131 6 beta-iodomethylnorcholesterol (NP-59) imaging and the correlation with computed tomography (CT)-guided adrenal biopsy and follow-up in patients with bilateral adrenal masses. To this end we investigated a consecutive sample of 29 euadrenal patients with bilateral adrenal masses discovered on CT for reasons other than suspected adrenal disease. Adrenal scintigraphy was performed using 1 mCi of NP-59 injected intravenously, with gamma camera imaging 5-7 days later. In 13 of the 29 patients bilateral adrenal masses were the result of metastatic involvement from lung carcinoma (5), lymphoma (3), adrenocarcinoma of the colon (3), squamous cell carcinoma of the larynx (1), and anaplastic carcinoma of unknown primary (1). Among these cases the NP-59 scan demonstrated either bilaterally absent tracer accumulation (in eight, all with bilateral metastases proven by CT-guided biopsy or progression on follow-up CT) or marked asymmetry of adrenocortical NP-59 uptake (in five). Biopsy of the adrenal demonstrating the least NP-59 uptake documented malignant involvement of that gland in five of five patients. In two patients an adenoma was found simultaneously in one adrenal with a contralateral malignant adrenal mass. In each of these cases, the adenoma demonstrated the greatest NP-59 uptake. In 16 patients diagnosis of adenoma was made on the basis of (a) CT-guided adrenal biopsy of the gland with the greatest NP-59 uptake of the pair (n = 4), or (b) adrenalectomy (n = 2), or (c) absence of change in the size of the adrenal mass on follow-up CT scanning performed 6 months to 3 years later (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adosterol↗

Adrenal imaging with technetium-99m-labelled low density lipoproteins.

Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of 99mTc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of 99mTc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with 99mTc, can be used to evaluate adrenal cortical function by external imaging.

Adrenal Cortex Function Tests↗

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↗

Expression and localization of human dopamine D2 and D4 receptor mRNA in the adrenal gland, aldosterone-producing adenoma, and pheochromocytoma.

Aldosterone secretion is evidently regulated by a dopaminergic inhibitory mechanism. Pharmacological characterization and autoradiographic studies revealed D2-like receptors in the adrenal cortex, especially in the zona glomerulosa. However, the subtype of the dopamine receptors involving this regulation has not been elucidated. To investigate which subtype of receptors expresses in the adrenal cortex, we examined the messages of D2-like receptors, D2, D3, and D4, by RT-PCR and in situ hybridization of adrenal glands and adrenal neoplasm. Both D2 and D4 receptors were expressed in normal adrenal glands, pheochromocytoma, and aldosterone-producing adenoma. However, the D2 receptors were not universally expressed, in contrast with the D4 receptors that were detected in all cases of aldosterone-producing adenoma and adrenal remnant. No D3 receptor message was detected by RT-PCR in any adrenal sample. Both D2 and D4 receptors were expressed in significant amounts in the adrenal medulla and pheochromocytoma. In the adrenal cortex, the expression of the D2 receptors was in the zona glomerulosa and zona reticularis, with no different signal intensities between the two zones. D4 receptors were mainly localized in the zona glomerulosa and, to a lesser extent, in the zona reticularis. Both receptors were expressed at low levels in the zona fasciculata. In aldosterone-producing adenoma, the expression of D2 and D4 was especially found in nonzona fasciculata-like cells. To elucidate which dopamine receptor regulates aldosterone secretion, the effects of specific D2 and D4 antagonists, raclopride and clozapine, respectively, were examined in cultured NCI-H295 cells. Dopamine further increased angiotensin II-induced aldosterone secretion by 20%. In the presence of 1 microM dopamine and angiotensin II, 10(-5)-10(-7) M clozapine decreased aldosterone levels by 40-55%. The decrease in aldosterone secretion by clozapine was completely reversed when raclopride was added simultaneously. These data suggest that dopamine exerts dual effects on aldosterone secretion in NCI-H295 cells. Activation of D4 receptors can increase aldosterone secretion, whereas an inhibitory effect is mediated via D2 receptors. In summary, we demonstrated the existence of both D2 and D4 receptors in the human adrenal gland and adrenal neoplasm. Both receptors play significant roles in the modulation of aldosterone secretion, but in opposite directions.

Adenoma↗

[Adrenal insufficiency in children with septic shock].

OBJECTIVE: To review the criteria for diagnosing and treating adrenal insufficiency in patients with septic shock. SOURCE OF DATA: Articles published in Brazilian and foreign journals selected through these publicationś websites and Medline, as well as references cited in key articles. SUMMARY OF THE FINDINGS: The literature reports a range betwen 17 and 54% for the finding of adrenal insufficiency in patients with septic shock. There is no consensus for diagnosing adrenal insufficiency in patients suffering from critical diseases, particularly in patients with septic shock. The presence of volume-refractory and catecholamine-resistant septic shock suggests this condition, while basal cortisol under 25 micro g/dl is a diagnostic criterion indicating adrenal insufficiency. The adrenal stimulation test is a useful resource for identifying patients with relative adrenal insufficiency. Our testing option for adrenal stimulation in children is the use of corticotropin in low doses (0.5 micro g/1,73 m(2)). An increase of less than 9 micro g/dl in the value of postcorticotropin-stimulated cortisol suggests the presence of occult (relative) adrenal insufficiency. In patients with septic shock presenting adrenal insufficiency, either suspected or confirmed, the administration of hydrocortisone in shock or stress doses can be vital for a favorable clinical outcome. CONCLUSIONS: The existing data, although controversial, already provides a basis to determine when to begin hormone replacement therapy, the serum level of cortisol accepted as adequate, and the choice of corticotropin doses for performing the adrenal stimulation test and diagnosing occult or relative adrenal insufficiency in patients with septic shock.

Adrenal Cortex Function Tests↗

Dynamic evaluation of adrenal hypofunction.

The diagnosis of adrenal hypofunction is suggested by clinical features and confirmed by biochemical testing. The characteristic features of acute primary adrenal insufficiency include orthostatic hypotension, fever, and hypoglycemia. By contrast, patients with chronic primary adrenal insufficiency have a longer history of malaise, as well as fatigue, anorexia, diarrhea, weight loss, joint and back pain, and darkening of the skin. While the clinical presentation of secondary adrenal insufficiency is similar to that of primary adrenal insufficiency, there is no hyperpigmentation, and hypotension and orthostasis are less pronounced. As a result, patients often present with vague, non-specific symptoms and the diagnosis may not be entertained. There is considerable debate regarding the best dynamic test for the diagnosis of adrenal hypofunction. Optimally, a screening test would be economic, convenient and safe. It would have high sensitivity and specificity based on consensus criteria for interpretation. Unfortunately, to date no test meets all of these criteria. Measurement of basal cortisol is an inexpensive and convenient screening test that can include (< 3 microg/dl; 83 nmol/l) or exclude (> 19 microg/dl; 524 nmol/l) adrenal insufficiency. However, most patients will have intermediate values and will require dynamic testing. This review discusses the use of metyrapone, insulin, CRH and synthetic ACTH 1-24 as provocative agents for cortisol secretion. Although the insulin and metyrapone stimulation tests have the advantage of testing the entire hypothalamic-pituitary-adrenal axis, they are cumbersome and carry more risk than the other tests. The 250 microg ACTH test works well to identify primary adrenal hypofunction, but can only detect secondary adrenal hypofunction when there is sufficient time for the glands to atrophy because of reduced endogenous ACTH stimulation. The 1 microg ACTH test has been advocated in the setting of possible secondary adrenal insufficiency, but its widespread use has been mitigated by the lack of a commercial preparation of this small dose and controversy regarding diagnostic criteria. Ultimately, the choice of test should be individualized for each patient, with knowledge of the available reference assays and the vagaries of each test.

Adrenal Cortex Function Tests↗

[Non-functioning adrenal tumor: clinical analysis of 29 cases].

29 patients with adrenal tumors were admitted to our hospital from June 1985 to July 1994. The diagnosis was made preoperatively in 7 patients (5 adrenal cyst, 2 adrenal myelolipoma) by B-US, CT or MRI. Of the 22 patients whose diagnosis was not made before operation, 8 (tumor diameter: < 3cm) had adrenal cortical adenomas, 6 (tumor diameter: 3-6cm) adrenal medullary tumor, 8 (tumor diameter: > 6cm) adrenocortical cancer (2), adrenal neuroblastoma (1), metastatic cancer (2), adrenal pheochromocytoma (1) and adrenal lymphatic hyperplasia (1) respectively. All non-functioning adrenal tumors should be treated operatively except for adrenal cyst smaller than 3 cm or adrenal myelolipoma.

Adrenal Cortex Neoplasms↗

Calcified adrenal masses.

We reviewed 106 cases of adrenal masses of all types in all age groups. Thirty-three contained calcium visible on radiographs, sonography, or computed tomography (CT). Neuroblastoma was the most common calcified adrenal mass (10 cases), and occurred only in children. Adrenal cyst (6 cases) was the most common calcified adrenal mass in adults. Other calcified adrenal masses included 5 cortical adenomas, 4 adrenal carcinomas, 3 cases of adrenal hemorrhage, 2 adrenal metastases, 2 pheochromocytomas, and 1 histoplasmoma. Calcification within an adrenal mass is therefore nonspecific. All the adrenal cysts had a characteristic radiographic pattern, showing only peripheral curvilinear calcification. The presence and pattern of calcium in an adrenal mass must be correlated with other imaging features (e.g., size, homogeneity, enhancement pattern, margination) to allow correct differential diagnosis. This can best be done by CT.

Adenoma↗

Retroperitoneal hemorrhage due to bilateral adrenal metastases from lung adenocarcinoma.

A 56-yr-old man was admitted to our university hospital for severe back pain one month after a resection for lung adenocarcinoma (stage IIIA) without evidence of the adrenal mass. Computed tomography (CT) of the abdomen showed bilateral bleeding of adrenal tumors. Endocrinological laboratory studies showed high plasma ACTH and normal serum cortisol levels with the loss of circadian rhythm. Although plasma ACTH levels increased, there was no cortisol response to administration of human corticotropichormone (hCRH). Core-needle biopsy was performed on the right adrenal tumor and revealed adenocarcinoma cells mimicking a primary lung tumor previously examined. We diagnosed retroperitoneal hemorrhage due to bilateral adrenal gland metastasis from lung adenocarcinoma with adrenal insufficiency. Adrenal metastases most commonly originate from a primary lung tumor, followed by stomach, esophagus and liver/bile ducts. Bilateral adrenal metastases were noted in approximately half of all adrenal metastases patients. Clinically significant adrenal hemorrhage by metastasis is exceedingly rare and non-specific symptoms, such as abdominal, chest or back pain, nausea and vomiting, confusion, weakness, hypotension, shock and high fever, are often observed in these patients. We present a case of massive retroperitoneal hemorrhage and adrenal insufficiency due to adrenal gland metastasis from adenocarcinoma of lung.

Adenocarcinoma↗

Preproenkephalin mRNA and enkephalin in normal and denervated adrenals in the Syrian hamster: comparison with central nervous system tissues.

The distribution and characteristics of preproenkephalin (PPenk) mRNA and enkephalin-containing (EC) peptides are compared in CNS and adrenal tissues from Syrian hamsters and Sprague-Dawley rats. Total cellular RNA extracts from both rat and hamster tissues produce a single hybridization band of PPenk mRNA of approximately 1500 bases when analyzed by Northern blot hybridization. Quantitation by solution hybridization reveals that in the hamster the highest levels of PPenk mRNA are found in adrenal (16.3 +/- 1.4 pg equivalents/micrograms RNA (mean +/- S.E.M.)) and striatum (13.3 +/- 0.7), followed by hypothalamus (0.8 +/- 0.2), and hippocampus (0.4 +/- 0.2). In the rat the highest levels of PPenk mRNA are in the striatum (35 +/- 2 pg/micrograms RNA) followed by the hypothalamus (3.0 +/- 0.5), hippocampus (0.3 +/- 0.1) and adrenal (0.18 +/- 0.04). Thus, the rank order of abundance of PPenk mRNA is similar in these CNS tissues for rat and hamster. The hamster adrenal levels are more than 90-fold greater than those of the rat. The abundance of EC peptides in both hamster and rat tissues mirror the rank order found with PPenk mRNA. Hamster adrenal contains the highest level of EC peptides (441 +/- 37 pmol/mg protein (mean +/- S.E.M.)) which is more than 400-fold greater than that of the rat adrenal and 8- to 12-fold greater than that found in rat and hamster striatum or hypothalamus. Both size exclusion chromatography and Western blot analysis indicate that EC peptides in hamster adrenal are predominantly large proenkephalin-like peptides with approximately 6 copies of Met- and 1 copy of Leu-enkephalin and that included in their number is a prominent EC peptide with a molecular weight of 34 kDa. Unilateral denervation of the hamster adrenal results in a time-dependent ipsilateral decrease in EC peptide and PPenk mRNA levels. Thus, by day 8 postsurgery, PPenk mRNA levels have declined by an average of 80% while EC peptides are reduced by 68% when compared to the innervated contralateral adrenal. These results demonstrate the great abundance of PPenk mRNA and EC peptides in the hamster adrenal. They also demonstrate the apparent need for transsynaptic impulse activity to maintain the high steady-state levels of PPenk and EC peptides. These characteristics of the hamster adrenal system provide opportunities for physiological and pharmacological investigations of the regulation of proenkephalin gene expression.

Adrenal Glands↗

Effects of endocrine-disrupting chemicals on adrenal function.

Considering the wide range of chemicals known to disrupt adrenal function and the physiological importance of the adrenal cortex, it is surprising that endocrine disruption of the adrenal gland has not been more widely researched. The chemical nature of adrenal disruptors is highly varied, and there are features of the adrenal structure and function, which render it particularly vulnerable to toxic attack. However, the homeostatic mechanisms inherent in the hypothalamo-pituitary-adrenal axis mean that only the most catastrophic effects are recognized as adrenal disruption, such as in the case of etomidate. In order to detect potentially significant but milder forms of toxic disruption of adrenal function a new approach is needed; this requires the use of more sophisticated approaches than simply measuring one hormone at one time point. New methodologies are also needed, such as the use of human adrenal cell lines for the screening of toxins and for mechanistic investigation of adrenal disruptors. This review focuses on mechanisms of adrenal toxicity and on the challenges facing researchers in this important field.

Adrenal Glands↗