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Persistence of a circadian rhythmicity of glucocorticoid secretion in a patient with Cushing's syndrome: study before and after unilateral adrenalectomy.

A 47-year-old woman affected by Cushing's syndrome due to an adrenal adenoma is described. An altered but rhythmometrically apparent cortisol secretory rhythm was detected using the single-cosinor computation. In fact serum cortisol levels and urinary excretion of 17-OHCS were elevated in the PM hours, particularly between 14:00-18.00 h and 18:00-22:00 h, and normal between 02:00-10:00 h. The patient was cured by unilateral adrenalectomy and one year later the circadian rhythm of corticosteroids secretion was investigated again. A normal rhythm of cortisol secretion and of 17-OHCS urinary excretion was found. Though it may be hypothesized that factors intrinsic to the tumoral adrenal cells were responsible for the rhythmic, but phase-shifted, hormonal release, the cause of the persistent and abnormal cortisol secretory rhythm is unknown.

17-Hydroxycorticosteroids↗

Evidence for ectopic ACTH production years after bilateral adrenalectomy for Cushing's syndrome: in vivo and in vitro studies.

Three patients presented with hyperpigmentation and high plasma levels of ACTH 4-5 years after bilateral adrenalectomy for Cushing's "disease". X-rays and ct-scan of the lungs showed a small pulmonary mass in all. ACTH levels (1100-2000 pg/ml) were not suppressible by high doses hydrocortisone. A carcinoid tumor was removed in two cases and a chemodectoma in the third. Evidence for ACTH secretion by these tumors was provided by both decrease of ACTH levels after surgery and/or in vitro studies. Both carcinoid cultures showed a basal ACTH production, which was clearly increased by LVP (10(-7) M) and CRF (10(-7) M). Our findings in vitro studies suggest the presence of specific receptor sites for physiological stimuli (LVP and CRF) in tumor cell membranes.

Adrenalectomy↗

Development of autoimmune thyroid dysfunction after bilateral adrenalectomy in a patient with Carney's complex and after removal of ACTH-producing pituitary adenoma in a patient with Cushing's disease.

Although the factors that cause developments or exacerbations of autoimmune thyroid dysfunction are not known, the changes of glucocorticoids might modulate the autoimmune responses. We compared the postoperative changes in thyroid function in one patient with Carney's complex with primary adrenocortical nodular dysplasia (PAND) and 19 patients with Cushing's disease due to ACTH-producing pituitary adenoma. Thyroid dysfunction developed after surgery for glucocorticoid excess in two patients; one with Carney's complex had transient hypothyroidism after bilateral adrenalectomy for PAND, and the other had transient hyperthyroidism due to thyroiditis after removal of ACTH-producing pituitary adenoma for Cushing's disease. Both patients had no thyroid autoantibodies at the time of surgery. None of the remaining 18 patients had clinically evident thyroid disease or increased antithyroidantibody titers. Development of autoimmune thyroid dysfunction may be observed after surgery for glucocorticoid excess in the patients with any forms of Cushing's syndrome, even who do not have thyroid antibodies.

Adenoma↗

The growth hormone response to growth hormone releasing hormone in patients previously treated with bilateral adrenalectomy alone for Cushing's disease.

Human growth hormone releasing hormone (GHRH) fails to stimulate human growth hormone (GH) in hypercortisolism. In order to study whether the responsiveness to GHRH stimulation returns after cure of the hypercortisolism, the GH response to GHRH was examined in 8 patients at least 5 yr after they had undergone bilateral adrenalectomy as their sole treatment for Cushing's disease. None had current evidence of a pituitary macroadenoma. A group of 8 healthy subjects matched for age and sex formed the control group. All patients and subjects received an iv injection of GHRH 1 microgram/kg, after an overnight fast, blood samples were taken before and at 15, 30, 45, 60, 90 and 120 min. There was no statistical difference between the peak GH or area under curve (AUC) response (median, range) in the two groups studied (adrenalectomized peak GH 9.2 (4.6-32.0) vs 16.5 (7.5-63) mU/l, adrenalectomized AUC response 647.5 (344.2-1489.5) vs 1103.5 (339.7-5188.5) mU/l. Patients with Cushing's disease once cured of hypercortisolism, have a GH response to GHRH.

Adrenalectomy↗

Paroxystic hypertension in a long-term hemodialyzed patient. Successful adrenalectomy for a dopamine-producing pheochromocytoma.

Pheochromocytoma (Pheo) is an uncommon neoplasm producing blood pressure troubles and it may be undiagnosed in chronic dialyzed patients in whom hypertension is a common finding. The symptoms in Pheo syndrome depends on the prevalent catecholamine released, the most common being epinephrine (E) and norepinephrine (NE). Recently, a particular clinical picture has been described for dopamine (DA)-producing Pheos, in whom a normo-hypotensive status is more often observed. The authors report a case of mainly dopamine-producing Pheo in a long-term dialyzed patient, successfully treated with adrenalectomy. The main steps in diagnosis and preoperative management are described and debated also in view of the particular background produced by the end-stage renal failure. The common imaging techniques adopted for adrenal medullary neoplasms (US, CT, MIBG scintiscan) confirmed to be decisive for diagnosis; HPLC assay of plasma catecholamines is the only biochemical test available in these patients although its significance is questionable due to the poor knowledge of catecholamine metabolism in chronic renal failure. The clinical findings observed in this case seem in disagreement with those already reported in DA producing Pheos. Pheo in hemodialyzed patients is a rare event and it may be hidden by other more common causes of hypertension. However, more awareness from the medical staff allows to diagnose the neoplasm correctly by the currently available methods and to plan a safe surgical therapy also in high-risk patients.

Adrenal Gland Neoplasms↗

[Catecholamine-dependent hereditary Cushing's syndrome - follow-up after unilateral adrenalectomy].

CASE REPORT: We report on the laboratory, clinical, radiologic and histological findings of a 44-year-old male patient who was hospitalized with the clinical signs of Cushing's syndrome. The laboratory findings were suggestive of an adrenal genesis. Abdominal computed tomography revealed macronodular hyperplasia of both adrenal glands. Specific endocrinological tests demonstrated an increased secretion of cortisol during adrenergic stimulation which, however, was absent following beta-blocker medication. This would seem to point to an aberrant, beta-receptor-mediated regulation of cortisol secretion as being the cause of increased cortisol production. ACTH-independent bilateral macronodular adrenocortical hyperplasia was also noted in the patient's mother. Neither the father nor the brother were affected by the disease. Apart from one case of familial appearance involving mother and daughter previously reported in the literature, this is the second description of a familial appearance and the first case involving mother and son. The patient underwent a left-sided adrenalectomy. Quick postoperative normalization of S-cortisol day profile and excretion of free dU-cortisol were noted under supportive temporary blockade of beta-receptors. In the further course, meanwhile spanning 2 1/4 years, a low basal cortisol secretion of the right adrenal gland has been observed, together with a lack of suppressibility in the dexamethasone suppression test. CONCLUSION: In the presence of mild clinical signs of adrenocortical insufficiency, matutinal administration of 5 mg hydrocortisone has proven sufficient for the past 6 months to reestablish a physiologic S-cortisol day profile with morning peak.

Adrenal Cortex↗

[Adrenalectomy within the scope of tumor nephrectomy?].

In urology, renal cell carcinoma is the third most frequently diagnosed malignancy. Localized, non-metastatic tumors are generally cured by radical tumor nephrectomy. Since the 1960s, this procedure has routinely included removal of the kidney together with the perirenal fat, Gerota's fascia, and ipsilateral adrenal gland. In recent years, improved diagnostic methods have led to the detection of tumors at earlier stages. These methods widen the scope for organ-sparing surgical strategies and have consequently sparked controversy over adrenal gland removal. Despite this, radical tumor nephrectomy that includes adrenal gland removal is still strongly advocated. This is the only suitable surgical approach for the cure of patients with direct tumor infiltration of the adrenal gland. In the case of adrenal involvement, minimal tumor dimension and the predisposing localization of the primary tumor have to relevance. The imaging procedure for diagnosis is also difficult to assess, especially in slim patients with upper role tumors. Finally, to date, no justifiable disadvantages of adrenalectomy have been described.

Adrenal Glands↗

[Adrenalectomy within the scope of tumor nephrectomy--overtreatment?].

Metastatic spread to the ipsilateral adrenal gland occurs in 1.2-10% of patients with renal cell carcinoma (RCC). In the majority of these cases, the primary tumor is locally advanced with poor differentiation, venous invasion, and involvement of the regional lymph nodes. Adrenal metastases are usually detected preoperatively by CT scan or MRI. Adrenal metastases are indicators of systemic disease with poor prognosis quo ad vitam. Only 0.5-2.3% of patients with RCC and adrenal metastases are free of venous invasion or lymphatic disease. In this small subset of patients, cure is possible by surgical removal of the adrenal gland. In 97.7-99.5% of patients with RCC, ipsilateral adrenalectomy has no impact on their prognosis. We therefore conclude that this procedure should be performed only if there is radiological suspicion of an adrenal mass.

Adrenal Glands↗

Adrenalectomy attenuates nicotine-induced dopamine release and locomotor activity in rats.

Adrenalectomy (ADX) in mice can potentiate several physiological and behavioural responses to nicotine. The present experiments sought to examine this issue in this rat by characterising the influence of ADX upon the locomotor depressant, activating and dopamine-releasing properties of nicotine. Nicotine (0.8-1.2 mg/kg s.c.) dose-dependently depressed locomotor activity, an effect that was potentiated by ADX, while the locomotor activating effects of a smaller dose (0.4 mg/kg) were attenuated by ADX. In both SHAM and ADX rats chronically treated with nicotine for 5 days (daily injections of 0.4 mg/kg s.c.), the locomotor depressant effects of nicotine did not differ from saline-treated controls. Nicotine (0.4 mg/kg s.c.) increased extracellular levels of dopamine in the nucleus accumbens. This response was unaffected in rats pretreated with nicotine for 5 days (daily injections of 0.4 mg/kg s.c.). However, both ADX groups of rats showed smaller increases in dopamine following administration of nicotine. The results suggest that depletion of circulating corticosteroids can modulate sensitivity to nicotine in rats. The suppressant effects of ADX on nicotine-induced locomotor activity may be due to its effects on dopamine release in the nucleus accumbens.

Adrenalectomy↗

Stress-induced cross-sensitization to cocaine: effect of adrenalectomy and corticosterone after short- and long-term withdrawal.

We have recently shown that adrenalectomy (ADX) in rats blocks the appearance of cocaine-induced sensitization when this behavioral response is tested at early withdrawal times (1-2 days), but not after later withdrawal from cocaine (12 days). To determine if a similar phenomenon occurred with stress-induced sensitization, male Sprague-Dawley rats were given a sham ADX, ADX surgery, or ADX plus s.c. implanted corticosterone (CORT) pellets (CORT 12.5% pellets or CORT 50% pellets). A fifth group was given ADX surgery, but CORT 50% pellets were implanted after repeated stress treatment. One week after surgery, each group was divided into two additional groups, naive and stress. Naive animals remained unhandled, while stress rats were given a variety of daily stressors administered twice per day for 6 consecutive days. One day after the last stress, rats were given a saline injection followed by a cocaine injection (15 mg/kg, i.p.) the next day, and locomotor activity was monitored (early withdrawal). Two weeks after the last stress, the locomotor responses to an additional saline and cocaine injection were monitored (late withdrawal). At early withdrawal, no significant sensitization occurred for horizontal activity, but cross-sensitization was demonstrated for vertical activity. At late withdrawal, sham controls showed a stress-induced elevation in horizontal activity, with only a trend toward increased vertical activity. Animals given ADX surgery or ADX and CORT 12.5% pellets did not demonstrate sensitization to repeated stress, while CORT 50% pellets in ADX rats restored the sensitized horizontal response to cocaine challenge at late withdrawal. In contrast, stress-pretreated rats which were given CORT 50% pellets during the 2-week withdrawal period after the stress showed a marked decrease in horizontal activity in response to cocaine challenge at late withdrawal. The results provide evidence for a necessary role for adrenal hormones in long term, but not short-term, stress-induced cross-sensitization. Together with our previous study on the role of CORT in cocaine-induced sensitization, the results indicate that CORT is not the common factor mediating the long-term sensitization to cocaine and stress.

Adrenalectomy↗

Effects of adrenalectomy on 8-OH-DPAT induced hypothermia in mice.

Complex interactions exist between the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system, and it has been suggested that these interactions may be fundamental to the pathophysiology and treatment of depressive illnesses. It has previously been found that chronic administration of corticosterone leads to adrenal suppression and an attenuation of somatodendritic 5-HT1A receptor function. Adrenalectomy (ADX) has been shown to cause an increase in postsynaptic 5-HT1A receptor numbers and possibly function. However, other reports have suggested that ADX does not alter somatodendritic 5-HT1A receptor mRNA or binding, though little is known of the effect of ADX on the function of somatodendritic 5-HT1A receptors. This study investigated the effect of markedly reducing corticosterone levels by ADX on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)-induced hypothermia in mice, an in vivo model of somatodendritic 5-HT1A receptor function. The degree of 8-OH-DPAT-induced hypothermia did not differ between control, sham, and ADX animals 14 days post operatively. Although repeated administration of corticosterone attenuates somatodendritic 5-HT1A receptor function, these data demonstrate that lowering of corticosteroid levels by ADX have no effect. This suggests that the effects of repeated corticosterone administration is not mediated by a secondary adrenal suppression. The difference in the effects of ADX on somatodendritic as opposed to postsynaptic 5-HT1A receptors may reflect the differential expression of corticosteroid receptor subtypes at postsynaptic and somatodendritic sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Long-term follow-up after adrenalectomy for primary aldosteronism.

The objective of this study was to assess the long-term effects of adrenalectomy on the blood pressure and antihypertensive medication in patients with primary aldosteronism (PA). Twenty-four patients (15 female and 9 male) with a mean age of 48.3 +/- 10.8 years underwent surgery for PA in our institution between 1988 and 2001. All subjects were re-examined with a complete clinical work-up after a mean follow-up period of 86 +/- 48 months, including blood pressure readings (<140/90 mmHg defined as normal), endocrine adrenal function, and specific medication. All patients suffered from hypertension (onset 8.5 +/- 5.5 years prior to surgery). In 92% of the patients, hypokalemia was present (onset 2.0 +/- 2.6 years prior to surgery). The histopathologic examinations revealed unilateral adenomas in 23 patients and a bilateral hyperplasia in one patient. At follow-up, 33% (8) of the patients were completely cured (normal blood pressure and no antihypertensive treatment), with seven of these eight patients being under 50 years of age at the time of surgery. One patient revealed a contralateral aldosterone-secreting adrenal adenoma during the subsequent endocrine and imaging examination 44 months after the first operation. Despite normalized plasma-aldosterone concentration (PAC), plasma-renin-activity (PRA) and serum potassium levels, a long-lasting insufficiently treated hypertension due to the delayed diagnosis in patients with PA may explain the persistent blood pressure elevation, indicating the necessity of a life-long, regular control of the blood pressure and antihypertensive medication.

Adenoma↗

Laparoscopic adrenalectomy.

Using the transperitoneal, laparoscopic approach, we performed 67 successful adrenalectomies between June 1993 and July 1995 at Greenslopes Hospital, Brisbane. There were 30 women and 37 men. Syndromes of primary adrenal hormone overproduction--primary aldosteronism (n = 52), pheochromocytoma (n = 6), and hypercortisolism (n = 1)--were present in 59 patients and apparently nonfunctioning adrenal tumors (of which one was malignant) in 8 patients. There was a significant difference in the time of operation between patients weighing < 80 kg and those weighing > 80 kg. Operations on males were slower than those on females, possibly explained by males being significantly heavier. Left-sided tumors outnumbered right-sided tumors; removal of right-sided adrenals took, on average, longer, but this difference was not significant.

Adrenal Gland Neoplasms↗

Subtotal adrenalectomy by the posterior retroperitoneoscopic approach.

The retroperitoneoscopic approach offers an established operative procedure for primary adrenal gland tumors. It allows a detailed view of the adrenal gland and its surrounding region. Therefore clear differentiation between normal and neoplastic adrenal tissue is sometimes possible, permitting a planned, unilateral, subtotal resection of the gland. Between July 1994 and August 1997 primary benign adrenal gland tumors (11 Conn adenomas, 4 phenochromocytomas, 4 Cushing adenomas, 3 hormonally inactive tumors; 2.4 +/- 1.2 cm in size; 8 on the right, 14 on the left) were removed from 22 patients by the posterior retroperitoneoscopic approach maintaining tumor-free portions of the ipsilateral adrenal gland. Two patients suffered from bilateral pheochromocytomas associated with multiple endocrine neoplasia (MEN-IIa) syndrome and had previously undergone complete adrenalectomy of the contralateral gland. Following subtotal resection the operating time and blood loss did not differ significantly (p > 0.05) from that seen with complete extirpation (46 patients operated during the same period). All patients with Conn adenomas and pheochromocytomas were biochemically and clinically cured (follow-up 11 months; range 1-31 months). The four patients with Cushing adenoma currently require decreasing cortisol substitution. In the two MEN-II patients adrenal gland cortical function could be maintained; one patient is on low-dose steroid supplementation and the other on none. No local recurrence of tumors has been observed. In selected cases the retroperitoneoscopically performed subtotal adrenal gland resection is a safe procedure that can potentially maintain the function of the adrenal gland cortex.

Adolescent↗

Helium and carbon dioxide pneumoperitoneum in patients with pheochromocytoma undergoing laparoscopic adrenalectomy.

Insufflation with helium is used to prevent respiratory acidosis, hypercapnia, and cardiovascular instability associated with carbon dioxide (CO2) pneumoperitoneum. The aim of this prospective study was to compare CO2 with helium pneumoperitoneum with special reference to respiratory and hemodynamic changes at different times during the operation. Altogether 22 pheochromocytoma patients undergoing laparoscopic adrenalectomy (LpA) were included using CO2 in 11 patients (CO2LpA) and helium in 11 patients (HeLpA). The insufflation pressure was 12 mmHg. The two groups were comparable with regard to demographic data and preoperative management. CO2 and helium insufflation were associated with similar catecholamine increase. The most striking significant increase compared with the baseline was observed during tumor isolation: The mean plasma epinephrine (EPI) and norepinephrine (NE) levels increased 32.86-fold and 25.92-fold, respectively, in the CO2LpA patients and 27.43-fold and 18.46-fold, respectively, in the HeLpA patients. HeLpA did not result in significant hypercarbia or acidosis at any measured intraoperative point; this was without any alteration in minute ventilation to maintain these normal PaCO2, excess base (EB), and pH values. Significant increases of mean arterial pressure, pulmonary arterial pressure, pulmonary vascular resistance index, PaCO2, EB, and acidosis were seen in the CO2LpA patients at the time of tumor isolation and tumor removal compared with those in HeLpA patients. No patient required conversion to open surgery. There were no significant differences between CO2LpA and HeLpA regarding mean operative time (117.50 +/- 93.68 vs. 106.87 +/- 16.60 minutes), mean blood loss (168.54 +/- 78.63 vs. 142.02 +/- 109.26 ml), hospital stay (4 days), the need for analgesics, or mean time required to return to normal activity (12 days). There was one wound infection in the HeLpA group and one wound hematoma and one case of atelectasis in the CO2LpA group. Helium may be the agent of choice for abdominal insufflation in patients undergoing LpA for pheochromocytoma, eliminating the adverse hemodynamic and respiratory changes associated with CO2 insufflation.

Adrenal Gland Neoplasms↗

Laparoscopic transperitoneal adrenalectomy.

BACKGROUND: From November 1993 to May 2002 a total of 172 laparoscopic adrenalectomies were attempted in 152 patients in centers throughout the United Kingdom. RESULTS: The median age was 52 years (18-77 years). Sixty-three percent were female. Indications for resection were Conn's syndrome (60), pheochromocytoma (35), Cushing's disease (24), Cushing's adenoma (8), cortisol-secreting carcinoma (1), other secreting tumor (2), nonfunctioning adenoma (17), congenital adrenal hyperplasia (4), metastatic disease (7), nonsecreting adrenal carcinoma (2), others (12). Median size of the lesions was 3.0 cm (0.5-20 cm). Median operating time was 65 min (30-170 min). Conversion to an open procedure was necessary in 10 patients (7%). Minor morbidity occurred in nine patients (5%). Major morbidity occurred in two patients (pancreatitis, peritonitis). Median hospital stay was 3 days (1-16 days). At median follow-up of 36 months (1-105 months) five patients (4%) had persistent hypertension. No patient had evidence of recurrent hormonal excess. CONCLUSIONS: Laparoscopic removal of the adrenal gland should be considered the surgical procedure of choice in experienced minimally invasive centers.

Adrenal Gland Diseases↗

Laparoscopic adrenalectomy: ascending the learning curve.

BACKGROUND: Soon after its introduction, laparoscopic adrenalectomy (LA) became the procedure of choice in the surgical management of most adrenal tumors. The aim of this study was to assess the outcome and learning curve of the first 100 cases operated by the same surgical team. METHODS: Retrospective analysis of prospectively collected data of 100 consecutive LAs was performed. The parameters studied were indication for surgery, side and length of operation, intra- and postoperative complications, size of tumor, conversion to open surgery, final diagnosis, and length of stay. RESULTS: Between 1996 and 2002, 100 LAs were performed in 90 patients. The procedures included 45 left, 35 right, and 10 bilateral resections for pheochromocytoma (29), Cushings syndrome (27), Conns syndrome (16), nonfunctioning adenoma (13), and others (5). Mean tumor size was 4.16 cm (range, 0.3-11). Overall major morbidity occurred in eight patients (9%); there was one mortality due to cerebrovascular accident in an elderly patient. Five cases (5%) were converted to open surgery. The mean length of stay for the whole group was 4.7 days (range, 2-25). In order to assess the learning curve, procedures were divided into three, equal consecutive groups (n = 33, 33, and 34). Intraoperative complications in the intermediate and late groups were significantly less compared to those in the early group (2/33, 2/34, and 7/33, respectively; (p < 0.05). Similarly, the mean operating time was significantly reduced between the early (169 min) and both intermediate (116 min) and late (127 min) groups (p < 0.005). The conversion rate was reduced between the three groups (3/33, 2/33, and 0/34), but this was not significant (p = 0.06). CONCLUSIONS: As expected, the outcome of LA is associated with a steep learning curve. According to this study, it seems that performance of approximately 30 cases by an experienced laparoscopic surgeon is required to master the procedure.

Adolescent↗

Laparoscopic adrenalectomy: 100 resections with clinical long-term follow-up.

BACKGROUND: The operative results of 100 laparoscopic adrenal resections in 94 patients and the subsequent impact on postoperative antihypertensive therapy are presented. METHODS: Clinical and follow-up data for resections performed between 1995 and 2003 were obtained from medical records, patient questionnaires, and telephone interviews. RESULTS: The diseases included Conn's syndrome (27 patients), Cushing's syndrome (30 patients), pheochromocytoma (11 patients), and Other tumors (26 patients). Antihypertensive therapy was eliminated or reduced for Conn's syndrome (75%), Cushing's syndrome (27%), pheochromocytoma (88%) and patients with Other tumors (54%). Clinical improvement was observed by 12 months for pheochromocytoma patients as compared with 35 to 45 months for the other groups (p < 0.05). Multivariate analysis showed that pheochromocytoma patients were more likely to experience improvement or cure than the Other tumor group (hazard ratio, 4.87; 95% confidence interval, 1.61-14.7). CONCLUSIONS: Laparoscopic adrenalectomy continues to be safe and efficacious for benign adrenal diseases. Although patients with functional tumors can expect improvement or cure, the time until improvement may be longer than previously recognized.

Adrenal Gland Diseases↗