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PubMed1997

Maternal adrenalectomy eliminates a surge of plasma dehydroepiandrosterone in the mother and attenuates the prenatal testosterone surge in the male fetus.

Previous work has established a number of sex-related deficits in immune function, behavior, and endocrine responses to stress in the offspring of dams exposed to ethanol. To examine the potential role of maternal glucocorticoids as a mediator of these sexually dimorphic effects in the fetus, we examined the influence of prenatal alcohol exposure in the presence or absence of maternal glucocorticoids on fetal plasma corticosterone (CORT) production. An additional question to be addressed by these studies was whether maternal adrenalectomy could eliminate the known inhibition by ethanol of the prenatal surge of plasma testosterone in male fetuses. Pregnant dams were adrenalectomized (ADX) or sham-adrenalectomized on gestational day (G) 7 and placed on a liquid diet containing 35% ethanol-derived calories or pair-fed an isocaloric control diet throughout the experiment. On G18, G19, and G21, plasma levels of CORT, testosterone, and dehydroepiandrosterone (DHEA) were measured in male and female fetuses and their mothers. Ethanol administration consistently increased maternal plasma CORT levels but did not significantly alter CORT levels in the fetus. Maternal ADX resulted in compensatory increases in fetal CORT levels that were lower in fetuses of ADX dams on alcohol, suggesting a direct effect of ethanol on fetal pituitary-adrenal activity. There were no significant sex differences in fetal plasma CORT levels in response to any of these manipulations. A novel surge of maternal plasma DHEA was found on G19 that was absent in plasma from ADX dams. In spite of the absence of a surge on G19, plasma DHEA levels of ADX dams rose from very low levels at G18 to levels on G21 that were significantly higher than in Sham dams. A normal testosterone surge was observed in male fetuses on G18 and G19 from sham-adrenalectomized dams administered the pair-fed diet. However, this surge was greatly attenuated in males administered ethanol and also in male fetuses from ADX dams. These results reveal a direct inhibitory influence of ethanol on fetal CORT secretion as well as on the prenatal testosterone surge in males. Furthermore, these studies demonstrate the presence of a surge of DHEA in the pregnant rat. Overall, these data suggest that there is a critical adrenal factor in the rat that regulates the maternal surge of DHEA on G19 and the prenatal testosterone surge of male fetuses on G18-19.

Adrenalectomy↗
PubMed2001

In vivo evidence for stimulation of placental, myometrial, and endometrial prostaglandin G/H synthase 2 by fetal cortisol replacement after fetal adrenalectomy.

Fetal glucocorticoid-induced premature labor in sheep is an established model of premature labor. However, the pathways by which fetal cortisol triggers subsequent maternal endocrine changes, including enhanced PG synthesis, leading to labor are unclear. The current study was undertaken to determine whether cortisol administration to adrenalectomized fetuses to clamp fetal cortisol at levels present early in the late gestation rise, which are inadequate to produce labor, can stimulate placental, myometrial, and endometrial prostaglandin G/H synthase 2 mRNA and protein expression. At 109--13 d gestation, fetal sheep adrenals were removed (n = 8), or sham surgery was performed (n = 4). From d 6 postadrenalectomy, maternal and fetal plasma cortisol were determined daily by RIA. From d 7 postadrenalectomy, cortisol (4 micro/min) was continuously infused iv to four adrenalectomized fetuses. Endometrium, myometrium, and placentome were collected from all three groups of ewes (n = 4 for each group), and total RNA and proteins were extracted from each intrauterine tissue and analyzed by Northern and Western for prostaglandin G/H synthase 2 mRNA and protein. P45017 alpha hydroxylase mRNA was analyzed in the placentome by Northern blot. Data were analyzed by ANOVA. Plasma cortisol levels remained low in sham-operated and adrenalectomized fetus, whereas during cortisol infusion to adrenalectomized and cortisol-treated fetuses, plasma cortisol increased to the late gestation level. After adrenalectomy, prostaglandin G/H synthase 2 did not change in any tissue studied. Fetal plasma cortisol replacement to late gestation levels increased prostaglandin G/H synthase 2 to levels similar to term levels in all three tissues. PGHS1 mRNA and protein did not change in any group studied. There was a minimal increase in P45017 alpha hydroxylase mRNA in the placentome in the adrenalectomized and cortisol-treated group. Cortisol- induced labor further increased P45017 alpha hydroxylase mRNA in the placentome compared with that in adrenalectomized and cortisol-treated animals. These data provide evidence for in vivo cortisol up-regulation of prostaglandin G/H synthase 2, but not PGHS1, in late gestation in the ovine placentome, myometrium, and endometrium. As stimulation of the estrogen biosynthetic pathway was minimal in the adrenalectomized and cortisol-treated group, these data provide support for the concept that cortisol has a direct effect on prostaglandin G/H synthase 2 expression in addition to its classical indirect pathway on prostaglandin G/H synthase 2 as a result of estrogen synthesis.

Adrenal Glands↗
PubMed2002

Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy.

While the orphan nuclear receptor steroidogenic factor-1 (SF-1) has been shown to function as an induction factor to define adrenocortical cell lineage, it remains unclear whether SF-1 plays an additional role as a growth promoting agent in the adult adrenal cortex. The proliferative potential of the adrenal cortex in adult SF-1(+/-) mice was examined using the model of compensatory adrenal growth following unilateral adrenalectomy (uADX). While the right adrenal gland of wild-type (wt) mice grew significantly after uADX, the adrenal of SF-1(+/-) mice exhibited a blunted, statistically nonsignificant weight increase. Accordingly, a profound increase in the proliferation marker proliferating cell nuclear antigen could be detected only in wt mice after uADX but not in the SF-1(+/-) mice. The proposed key regulator in adrenal compensatory growth, the recently cloned adrenal secretory serine protease was up-regulated in the remaining adrenal of wt mice, whereas this increase was blunted in SF-1(+/-) mice. While no differences in preadipocyte factor-1, the presumed marker of primitive adrenocortical cells, were detectable in the adrenals of wt and SF-1(+/-) mice, an increase in the ACTH receptor as well as agouti-related protein was observed only in wt animals but not in the SF-1(+/-) mice following uADX. Taken together, these results reflect a primary inability of adrenal cortical cells of SF-1(+/-) mice to undergo compensatory adrenal growth in response to uADX.

Adrenal Glands↗
PubMed2006

Laparoscopic adrenalectomy for potentially malignant adrenal tumors greater than 5 centimeters.

PURPOSE: Laparoscopic adrenalectomy (LA) is controversial for large, potentially malignant tumors. We report a series of LA or hand-assisted LA for large (>5 cm) adrenal tumors. PATIENTS AND METHODS: Among 210 LAs performed in 6 yr, 39 patients had potentially malignant tumors greater than 5 cm in diameter. Their perioperative and follow-up data were retrospectively analyzed. RESULTS: All 39 patients had successful LAs without perioperative mortality, conversion to open surgery, or capsular disruption during dissection. The mean tumor size was 6.2 cm (range, 5-12 cm), operative time 207 min (115-315 min), and blood loss 75 ml (minimal-1400 ml). Complications included one intraoperative diaphragmatic perforation, three mild wound infections, and one pneumonia. Preoperatively there were 27 nonfunctioning tumors, seven pheochromocytomas, three cortisol-secreting tumors, and two virilizing tumors. Final pathology revealed eight malignant (four adrenocortical carcinomas and four metastatic carcinomas) and 31 benign tumors (14 cortical adenomas, eight pheochromocytomas, six myelolipomas, and three ganglioneuromas). Median follow-up was 39 months. Four patients (two adrenocortical carcinomas, one metastatic hepatoma, and one lymphoma) died 24, 10, 9, and 3 months after surgery, respectively. A hand-assisted device was used in 10 patients. Only the tumor size was larger and length of postoperative hospital stay longer for those in the hand-assisted group. CONCLUSIONS: LA is a reasonable option for selected large adrenal tumors when complete resection is technically feasible and there is no evidence of local invasion. Hand-assisted LA is a good alternative to open conversion if a difficult dissection is encountered intraoperatively.

Adenoma↗
PubMed1997

Primary pigmented nodular adrenocortical disease: reevaluation of a patient with carney complex 27 years after unilateral adrenalectomy.

A 45-yr-old man with primary pigmented nodular adrenocortical disease (PPNAD) is described. This patient underwent unilateral adrenalectomy for ACTH-independent Cushing's syndrome (CS) in 1969. Although his daily urinary free cortisol (UFC) excretion rate normalized, and the major clinical manifestations of CS subsided, loss of a circadian cortisol rhythm persisted after surgery. Twenty-seven years later, the patient presented again with short stature, severe osteopenia, skeletal deformities, thinning of the skin, and myopathy.

Adrenal Cortex Diseases↗
PubMed2001

Fertility and body composition after laparoscopic bilateral adrenalectomy in a 30-year-old female with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by an inborn defect in the 21-hydroxylase gene (CYP21), leading to virilization of female patients and causing ambiguous genitals in the majority of female infants. Adult women may suffer from loss of libido, irregular or absent cycles, and reduced fertility, despite intensive medical treatment. These problems have stimulated the search for alternative treatment modalities. We present an adult female patient, who was difficult to treat medically and whose clinical situation markedly improved after laparoscopic bilateral adrenalectomy. The procedure was well tolerated and without side effects. Postoperatively the elevated serum progesterone and 17-hydroxyprogesterone levels, as well as the undetectable LH levels, normalized. The procedure resulted in marked clinical improvement. Within 12 months after surgery she lost 11 kg in weight. This weight loss consisted mainly of adipose tissue. Acne disappeared, and she had a regular 4-week menstrual cycle, with progesterone levels that are compatible with a luteal phase. The introduction of laparoscopic techniques may give an impulse to the application of surgical therapy at a larger scale in patients with 21-hydroxylase deficiency who are difficult to treat with adrenal suppression therapy.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Type I and type II corticosteroid receptor gene expression in the rat: effect of adrenalectomy and dexamethasone administration.

We have used 32P-labeled cRNA probes directed against Type I (mineralocorticoid, high affinity glucocorticoid) and Type II (classical glucocorticoid) receptor mRNA to screen various tissues, and have investigated the effect of adrenalectomy (ADX) and dexamethasone (DM) administration on their levels in hippocampus. Both Northern blot and S1 nuclease analysis showed Type I mRNA to be high in hippocampus, colon, and heart; low in liver; and undetectable in thymus. Type II mRNA was high in liver, thymus, and brain; and low in testis and parotid. A transient increase in both hippocampal Type I and Type II mRNA was noted at 1-3 days post ADX. DM similarly elicited a rise in hippocampal Type I mRNA at 2-4 days after ADX, but prevented the ADX-induced increment in Type II mRNA. In contrast to the transient increase in Type I receptor mRNA levels, hippocampal levels of Type I receptors measured by [3H]aldosterone binding were constant 1-16 days post ADX. DM administration caused a doubling in Type I receptor levels over 4 days, with plateau levels at 4-16 days; previously, DM has been shown to lower Type II receptor levels in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1979

The mechanism of aggravation of indomethacin-induced gastric ulcers by adrenalectomy in the rat.

Bilateral adrenalectomy markedly aggravated gastric ulcers in rats induced by 5 or 20 mg/kg of indomethacin. The degree of aggravation was much the same in experiments done 1 and 14 days after operation. Pretreatment with prednisolone 10 mg/kg or cortisone acetate 10 mg/kg given subcutaneously significantly suppressed the aggravated ulceration in response to 20 mg/kg of indomethacin in these adrenalectomized rats. Desoxycorticosterone acetate 10 mg/kg, however, had no effect on the aggravation of indomethacin-induced ulcers. Epinephrine 0.1 or 1 mg/kg given subcutaneously markedly suppressed the indomethacin-induced ulcers in adrenalectomized rats. Removal of the adrenal medulla alone did not appreciably influence the development of indomethacin-induced ulcers. These results indicate that the adrenal cortex, particularly the area containing glucocorticoids, plays an important role in suppression of the noxious effect of indomethacin on the rat gastric mucosa.

Adrenal Glands↗
PubMed1997

Long-term survival after bilateral adrenalectomy for metastatic lung cancer: a case report.

Selected patients with solitary metastases from non-small cell lung cancer can benefit from an aggressive treatment approach that includes resection of the metastases. This approach has been used for solitary adrenal metastases, but successful long-term treatment of bilateral adrenal metastases has not been previously reported. This is the report of a patient with bilateral adrenal metastases from lung cancer who is disease-free 9 years after bilateral adrenalectomy and chemotherapy. From this evidence, one may hypothesize that adrenal metastases are occasionally lymphatic in origin and that metastases with this route of spread are more amenable to aggressive curative treatment than adrenal metastases of hematogenous origin.

Adrenal Gland Neoplasms↗
PubMed1999

Effects of adrenalectomy on the stress-induced changes in ovarian sympathetic tone in the rat.

A 3-wk period of stress promotes the development of ovarian cysts in rats apparently mediated by increased sympathetic nerve activity and ovarian steroid secretion. After 11 wk of stress, these parameters are indistinguishable from nonstressed control rats. To study adrenal contribution, we adrenalectomized rats and studied the effect of 3-wk of cold/restraint stress (1.5 h/d) on them compared to intact animals. Adrenalectomy (ADX) increased ovarian norepinephrine (NE) release, the content of beta-adrenergic receptors (betaAR) and basal, but not isoproterenol (Iso)-induced, androgen secretion. Stress to intact animals increased NE release, decreased betaAR content, and Iso-induced, but not basal, androgen secretion from the ovary. ADX did not modify the response to stress. We propose a tonic inhibition by the adrenal gland on nerve activity of ovarian nerves. Stress overrides this inhibitory effect, and nerve activity downregulates betaAR, decreasing ovarian steroid secretion.

Adrenal Glands↗
PubMed2005

Induction of uterine prostaglandin H synthase 2 by estradiol following fetal adrenalectomy.

In sheep, fetal cortisol stimulates the conversion of progesterone to estradiol in late gestation initiating labor. It is unclear whether an intact fetal hypothalamic-pituitary-adrenal (HPA) axis is required to induce the estradiol-triggered subsequent endocrine changes including enhanced intrauterine prostaglandin (PG) synthesis associated with the onset of labor. We have shown that maternal estradiol administration stimulates PG H synthase (PGHS)-2 expressions in pregnant ovine intra-uterine tissues. The current study was undertaken to determine whether the fetal adrenal mediates estradiol's stimulation of the intrauterine PGHS-2 in pregnant sheep. Placenta, myometrium, and endometrium were collected from two groups of ewes at 123-127 d of gestational age (dGA) after fetal adrenalectomy and vehicle treatment (ADX; n = 5); or fetal ADX and maternal estradiol administration (5 mg twice a day for 2 d, ADX+E2, n = 5). PGHS-2 mRNA and protein were analyzed by Northern and Western Blot analyses in both groups and presented as the ratios to beta actin mRNA for Northern and G protein beta subunit for Western blot analysis. Fetal plasma cortisol was measured by radioimmunoassay. Data were analyzed by Student's t test. Fetal plasma cortisol levels were low in ADX and ADX+ E2 groups (<6 ng/mL). The cervix of all ADX+E2 treated ewes was dilated at necropsy. Three out of five ADX+ E2-treated ewes delivered within 48 h. The cervix was closed in all fetal ADX ewes at necropsy. PGHS-2 mRNA and protein increased (p < 0.05) in myometrium and endometrium, but not placenta in ADX+E2-treated ewes compared with ADX group. These data provide the first in vivo evidence for estradiol upregulation of intrauterine PGHS-2 in late gestation in the absence of an intact fetal HPA axis. Thus, the fetal adrenal is not required to mediate estradiol's stimulation of uterine PGHS-2 expression associated with the onset of labor.

Adrenal Glands↗
PubMed1993

[The prediction of blood pressure after adrenalectomy in primary aldosteronism].

In 30-40% of patients with primary aldosteronism owing to adenoma, hypertension is not relieved even though a hyper-functioning adenoma has been completely removed. The purpose of this study is to determine whether the prognosis of hypertension can be evaluated pre-operatively in patients with primary aldosteronism. Thirteen patients (6 men, 7 women; 47 +/- 9 years old) with primary aldosteronism were studied and adrenalectomy was performed in all cases. The success of the operation was confirmed by the normalization of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and serum potassium. Eight patients, 3 men and 5 women, whose blood pressure (BP) was reduced to below 140mmHg systolic and 90mmHg diastolic at one year after the operation were classified as "group N" and the other 5 cases, 3 men and 2 women, remained hypertensive and were classified as "group H". There were no significant differences in the age of the patients, duration of hypertension, pretreatment mean BP and severity of hypertension between the two groups. Thus, it is doubtful that the lack of improvement of hypertension is due to the irreversible damage of the small arteries. Although pretreatment BP was similar in the two groups, systolic BP after the administration of 200mg per day of spironolactone for one week was significantly reduced in group N, but not in group H. Moreover, a significant correlation was found between mean BP after treatment with spironolactone and post-operative mean BP in all subjects. Pretreatment PRA was significantly lower in group H.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1993

[An incidentally found asymptomatic pheochromocytoma: a case report--successful removal laparoscopic adrenalectomy].

A 31-year-old male was admitted to our hospital for further examination of a right adrenal mass, which was incidentally discovered by abdominal ultra-sonography in another hospital. The adrenaline and noradrenaline in the plasma and the adrenaline and VMA in the urine were slightly elevated, and catecholamines in the blood from the right adrenal vein were markedly increased. Glucose tolerance test showed a borderline case. Otherwise, there was no clinical sign. Asymptomatic pheochromocytoma originating from the right adrenal gland was suspected in the preoperative diagnosis. Laparoscopic right adrenalectomy was performed. Although the blood pressure was stable preoperatively, paroxysmal hypertension was observed during the tumor manipulation. Blood pressure was well controlled during the operation with ATP, nitroglycerin and phentolamine. Blood loss was less than 150ml, and there was no surgical complication. The resected tumor specimen was 32[28[33mm in size, weighed 14g, and histological examination showed typical pheochromocytoma. The post-operative course was unremarkable and glucose tolerance test was normalized after the operation. This is the first case of the successful removal of pheochromocytoma using the laparoscopic procedure.

Adrenal Gland Neoplasms↗
PubMed1994

A case of ectopic ACTH syndrome associated with Zollinger-Ellison syndrome: long-term survival with chemical adrenalectomy.

The female patient in this report was suffering from a pancreatic islet cell tumor which exhibited ectopic ACTH syndrome associated with Zollinger-Ellison syndrome. When this combined syndrome was diagnosed, there were already multiple metastasis to the liver. Zollinger-Ellison syndrome was treated with a histamine-H2-receptor blocker, and ectopic ACTH syndrome was controlled with trilostane, metyrapone and o,p'-DDD. She survived more than 6 years after the diagnosis, mostly as an outpatient. During treatment she became cachexic. After she died, an autopsy was done. Immunohistochemical staining established that tumor cells contained ACTH- and gastrin-like immunoreactivity. Our treatment suggested the efficacy of chemical adrenalectomy in managing ectopic ACTH syndrome associated with Zollinger-Ellison syndrome.

ACTH Syndrome, Ectopic↗
PubMed1994

Acute adrenal insufficiency after unilateral adrenalectomy in Cushing's syndrome: precipitation by lithium-induced thyrotoxicosis during cortisol replacement.

We present a patient with Cushing's syndrome due to adrenocortical adenoma who developed acute adrenal insufficiency one month after unilateral adrenalectomy. She had received lithium carbonate for five years for manic-depressive psychosis. Drug administration was interrupted for 2 weeks postoperatively and was resumed thereafter. At the adrenal crisis, her serum free T4 and T3 levels were both high and serum TSH was subnormal. The thyrotoxicosis subsided spontaneously within 2 weeks. Serum thyroglobulin was markedly increased during the thyrotoxic state. Tests for antimicrosomal antibodies and antithyroglobulin antibodies remained negative. Examination of an open-biopsy specimen of the thyroid gland showed no evidence of thyroiditis. We considered the transient thyrotoxicosis to be due to lithium-induced thyrotoxicosis. Caution should therefore be exercised in administering lithium carbonate, especially when the patient's adrenal reserve is low, since even a mild degree of thyrotoxicosis can precipitate an acute adrenal crisis.

Acute Disease↗
PubMed2006

Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy.

A pregnant 26-year-old woman was referred for evaluation and management of progressive hypertension and hypokalemia at 14 weeks of gestation. Her plasma aldosterone level was markedly elevated and magnetic resonance imaging showed a right adrenal tumor. Primary aldosteronism due to an aldosterone producing-adenoma was diagnosed. Because of progressive severe hypertension, a laparoscopic adrenalectomy was performed at 17 weeks of gestation. The procedure was completed without complication, and plasma aldosterone and potassium levels rapidly improved post-operatively. However, her hypertension persisted and the growth retardation of the fetus was found. Regrettably, intrauterine fetal death was confirmed at 26 weeks of gestation. Histological examination of the placenta revealed that the placental artery had very thick walls which had apparently caused a critical failure in fetal blood flow. The optimal timing of laparoscopic surgery during pregnancy and perioperative management were subsequently discussed.

Adenoma↗
PubMed1984

Transient thyrotoxicosis after unilateral adrenalectomy in two patients with Cushing's syndrome.

We found transient hyperthyroidism in the course of hydrocortisone withdrawal in two patients who had undergone unilateral adrenalectomy to resect cortisol-hypersecreting adenoma. A 38-yr-old woman showed clinical thyrotoxicosis 3 months after the operation. Serum T4, T3 and TBG levels were 11.9 micrograms/dl, 310 ng/dl and 16.5 micrograms/ml, respectively. She was given methimazole (MMI) 15 mg/day for 4 weeks. After the cessation of MMI treatment, she eventually recovered to the euthyroid state. The other patient, a 34-yr-old man showed very mild clinical symptoms of hyperthyroidism 2 months after the operation. Serum T4, T3 and TBG levels were 10.4 micrograms/dl, 240 ng/dl and 14.5 micrograms/ml, respectively. In this case, no antithyroid drug was given. Two to three months after the onset of hyperthyroidism, he returned to the euthyroid state spontaneously. We carefully eliminated the possibility of factitious thyrotoxicosis in both cases. They had neither neck pain nor fever. Both had low radioactive iodine uptake by the thyroid. Therefore, we diagnosed them as painless thyroiditis induced after the resection of hypersecreting adrenal adenoma.

Adrenalectomy↗
PubMed1977

Insulin stimulation tests in pituitary dependent Cushing's syndrome after complete adrenalectomy.

The present study shows that in a group of 6 euadrenal patients, previously treated by complete adrenalectomy for pituitary dependent Cushing's syndrome, the stress stimulus of insulin induced hypoglycaemia is followed by a plasma ACTH response which is of similar magnitude as the response obtained with lysin-vasopressin. Both observations indicate that the central nervous system-pituitary axis is basically normal in pituitary dependent Cushing's syndrome as assessed by insulin induced hypoglycaemia. It is concluded that non-responsiveness of the pituitary-adrenocortical system to insulin induced hypoglycaemia in untreated patients with pituitary dependent Cushing's syndrome does not represent a fundamental defect of the stress mechanism, but is due to hypercorticism per se.

Adrenalectomy↗