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Three patients with primary aldosteronism due to adrenocortical carcinoma were studied, two with hyperaldosteronism alone and one also with hypercortisolism; in the later stages all three had hypersecretion of glucocorticoid and androgenic hormones. Although clinical presentations were similar to those of patients with benign adenoma, all had significantly higher concentrations of deoxycorticosterone and aldosterone and more profound hypokalemia. Stimulation with adrenocorticotropin in two patients showed a good cortisol response but no aldosterone response. The circadian rhythm for cortisol was normal but absent for aldosterone and deoxycorticosterone. Sequential 24-hour circadian studies in one patient showed that as the disease progressed, corticosterone and finally cortisol lost their circadian rhythms. Treatment with spironolactone, mitotane, or aminoglutethimide had transient clinical effects. The patients died 2 to 13 years later. [ABSTRACT FROM AUTHOR]

Germline mutations in p27(kip1) are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, n=252; pheochromocytomas, n=125; medullary thyroid carcinoma, n=51; and parathyroid adenomas, n=19) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (P=0.01), particularly for those with ACTH-secreting pituitary adenomas (P=0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with the sporadic counterpart of MEN2-component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27-V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.

Purpose: To assess glutamine/glutamate (Glx) and lactate (Lac) metabolism using proton magnetic resonance spectroscopic imaging (1H-MRS) in order to differentiate between adrenal gland nodules and masses (adenomas, pheochromocytomas, carcinomas, and metastases)., Materials and Methods: Institutional review board approval and informed consent were obtained. A total of 130 patients (47 men) with 132 adrenal nodules/masses were prospectively assessed (54 ± 14.8 years). A multivoxel system was used with a two-dimensional point-resolved spectroscopy/chemical-shift imaging sequence. Spectroscopic data were interpreted by visual inspection and peak amplitudes of lipids (Lip), choline (Cho), creatine (Cr), Lac, and Glx. Lac/Cr and Glx/Cr were calculated. Glx/Cr was assessed in relation to lesion size., Results: Statistically significant differences were observed in Glx/Cr results between adenomas and pheochromocytomas (P < 0.05), however, with a low positive predictive value (PPV). Glx levels were directly proportional to lesion size in carcinomas. A cutoff point of 1.44 was established for the differentiation between carcinomas larger versus smaller than 4 cm, with 75% sensitivity, 100% specificity, 100% PPV, and 80% accuracy. Lac/Cr results showed no differences across lesions. A cutoff point of -6.5 for Lac/Cr was established for carcinoma diagnosis., Conclusion: Glx levels are directly proportional to lesion size in carcinomas. A cutoff point of -6.5 Lac/Cr differentiates carcinomas from noncarcinomas.

Purpose: To prospectively determine the accuracy of in vivo proton ((1)H) magnetic resonance (MR) spectroscopy in distinguishing adrenal adenomas, pheochromocytomas, adrenocortical carcinomas, and metastases, with histologic or computed tomographic findings and follow-up data as the reference standards., Materials and Methods: This study was approved by the institutional ethics committee, and informed consent was obtained. Sixty consecutive patients (24 male and 36 female patients; mean age, 53 years) harboring adrenal tumors larger than 2 cm in diameter (mean diameter, 4.6 cm +/- 3.4 [standard deviation]) entered the study and were examined with a 1.5-T MR imaging system and point-resolved multivoxel (1)H MR spectroscopy. Thirty-eight patients had adenomas; 10, pheochromocytomas; five, carcinomas; and seven, metastases. Amplitude values for choline, creatine, lipid, and a metabolite peak at precession frequency of 4.0-4.3 ppm were measured. Metabolite ratios (choline-creatine, choline-lipid, lipid-creatine, and 4.0-4.3 ppm/creatine) and cutoff values (obtained by using receiver operating characteristic analyses) were obtained and compared for each type of adrenal mass, which was identified previously on the basis of clinical, hormonal, and pathologic evidence. Results were evaluated with chi(2) and Student t tests. Significance was inferred at P < .05., Results: Cutoff values of 1.20 for the choline-creatine ratio (92% sensitivity, 96% specificity; P < .01), 0.38 for the choline-lipid ratio (92% sensitivity, 90% specificity; P < .01), and 2.10 for the lipid-creatine ratio (45% sensitivity, 100% specificity) enabled adenomas and pheochromocytomas to be distinguished from carcinomas and metastases. A 4.0-4.3 ppm/creatine ratio greater than 1.50 enabled distinction of pheochromocytomas and carcinomas from adenomas and metastases (87% sensitivity, 98% specificity; P < .01). The best distinction was obtained by comparing choline-creatine and 4.0-4.3 ppm/creatine ratios., Conclusion: (1)H MR spectroscopy can be used to characterize adrenal masses on the basis of spectral findings for benign adenomas, carcinomas, pheochromocytomas, and metastases., ((c) RSNA, 2007.)

Purpose: To understand the advances that were made in the management of pheochromocytoma since laparoscopy was initiated at our institution., Materials and Methods: Data for all patients who underwent surgical procedure for adrenal diseases had been recorded prospectively since September 2000, when laparoscopy was routinely initiated at our institution; all patients with a diagnosis of pheochromocytoma up to December 2005 had their data assessed (group 1). Charts for all patients with a diagnosis of pheochromocytoma who underwent surgery at our institution from 1990 to 1995 (group 2) were reviewed, and the data were compared with data from patients in group 1., Results: In group 1, 24 patients with pheochromocytoma underwent 26 procedures at our institution, including five patients with extra-adrenal tumor and one patient with bilateral tumor; 18 adrenalectomies (one bilateral) were performed, and two extra-adrenal tumors were removed using a laparoscopic approach. In group 2, ten open adrenalectomies were performed in 9 patients (1 bilateral). The patients who underwent laparoscopy for either adrenal or extra-adrenal tumor had shorter operative times and hospital stay and less bleeding., Conclusions: Pheochromocytoma is a complex disease with potentially severe complications. Laparoscopic adrenalectomy can be safely performed for removal of either adrenal or extra-adrenal tumors. Patients spend a shorter time in the critical care unit after the procedure.

Objective: To evaluate the frequency of autoantibodies (Ab) against 21 hydroxylase (21OH), side-chain cleavage (SCC) and 17alpha-hydroxylase (17OH), in Addison's disease (AD) and autoimmune polyendocrine syndrome type III (APSIII)., Design and Methods: We used radiobinding assays and in vitro translated recombinant human (35)S-21OH, (35)S-SCC or (35)S-17OH and studied serum samples from 29 AD (18 idiopathic, 11 granulomatous) and 18 APSIII (autoimmune thyroid disease plus type 1 diabetes mellitus, without AD) patients. Results were compared with those of adrenocortical autoantibodies obtained with indirect immunofluorescence (ACA-IIF)., Results: ACA-IIF were detected in 15/18 (83%) idiopathic and in 1/11 (9%) granulomatous AD subjects. 21OHAb were found in 14/18 (78%) idiopathic and in the same (9%) granulomatous AD subject. A significant positive correlation was shown between ACA-IIF and 21OHAb levels (r(2)=0.56, P<0.02). The concordance rate between the two assays was 83% (24/29) in AD patients. SCCAb were found in 5/18 (28%) idiopathic (4 of whom were also positive for 21OHAb) and in the same (9%) granulomatous AD subject. 17OHAb were found in only 2/18 (11%) idiopathic and none of the granulomatous AD patients. Two APSIII patients were positive for ACA-IIF, but only one was positive for 21OHAb and SCCAb. 17OHAb were found in another two APSIII patients., Conclusions: Measurement of 21OHAb should be the first step in immune assessment of patients with AD and individuals at risk for adrenal autoimmunity, in addition to ACA-IIF. Due to their low prevalence in AD, measurement of SCCAb and 17OHAb should be indicated only for 21OHAb negative patients and/or for those with premature ovarian failure, regardless of ACA-IIF results.

Adrenocortical autoantibodies (ACA), present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF) on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA) technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13) and granulomatous (N = 9). ACA-PLPA were detected in 10/22 (45%) patients: 9/13 (69%) with the idiopathic form and 1/9 (11%) with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%): 10/13 (77%) with the idiopathic form and 1/9 (11%) with the granulomatous form. Twelve of the 13 idiopathic addisonians (92%) were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time). However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.

All levels of the growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor (IGF) and IGF binding protein (IGFBP) axis are influenced by chronic hypercortisolism. Thus, there is a blunted response to GHRH alone or together with other stimuli associated with a marked suppression of endogenous GH secretion but accompanied by normal GHBP, normal to low IGF-1 and GHBPs 1 and 3 with the correspondent 41.5 and 38.5-kD molecular forms of the latter presenting values similar to normal. These findings may suggest enhanced GH sensitivity with normal or increased IGF-1 bioavailability to the correspondent tissue receptors. In conclusion, the glucocorticoid (GC)-induced target tissue resistance can neither be attributed to the suppression of the GH axis nor to changes in circulating GHBPs 1 and 3. However, it may be related either to the described 12-to-20-kD inhibitor(s) which antagonizes postbinding IGF-1 bioactivity (gene expression) and/or by the downmodulation of activator protein-1 (Fos/Jun) activity by the GC-GC receptor complex.

Ten-20% of patients with AIDS may present clinical evidence of primary or secondary adrenal insufficiency. PURPOSE--To evaluate the hypothalamic-pituitary-adrenocortical axis (HPAA) with CRH in patients with AIDS. METHODS--We studied 20 patients with AIDS and 17 normal subjects (NS) with exogenous ACTH (cosyntropin, 250 micrograms IV bolus) followed one week later by ovine corticotropin releasing hormone (oCRH 1 microgram/kg BW IV bolus). Basal and 60' cortisol (micrograms/dL) were determined in the former whereas ACTH (pg/mL) and cortisol were measured every 15-30' for 2 hours in the latter. RESULTS--Basal and peak values (mean +/- SD) of ACTH and cortisol for both tests were: cosyntropin test (AIDS x NS): basal cortisol 22.5 +/- 7.1 x 10.6 +/- 3.6 (p < 0.01), peak 36.0 +/- 12.8 x 28.3 +/- 7.6 (p < 0.05); oCRH test: basal ACTH 42.2 +/- 33.5 x 28.9 +/- 12.7 (NS), peak 104.7 +/- 62.2 x 59.3 +/- 17.6 (p < 0.05); basal cortisol 19.7 +/- 9.0 x 10.1 +/- 3.4 (p < 0.01), peak 27.5 +/- 8.9 x 18.3 +/- 5.1 (p < 0.05). CONCLUSION--AIDS patients had elevated basal and CRH stimulated ACTH levels and an intact glucocorticoid pathway with elevated basal and peak cortisol levels to both stimulation tests. This situation is probably due to the stressful disease condition, where lymphokines may play a role activating the hypothalamic-pituitary axis.

Limited cortisol response to ACTH stimulation has been documented in 22 to 48% of patients with paracoccidioidomycosis (PM). Different approaches to interpret the test and inadequate selection of patients preclude an accurate appraisal of the actual incidence of adrenal insufficiency in PM. Rapid cosyntropin (ACTH) stimulation tests were performed in 38 consecutive patients (9 with the localized and 29 with the disseminated form of PM) and 40 normal controls. Subnormal cortisol responses to ACTH (60 minutes post-ACTH values below 455 nmol/l, 95% confidence limits) were found in only 4 patients (14%) with disseminated PM. If a retrospective sample of 6 patients studied previously (in whom tests were indicated due to clinical suspicion of Addison's disease) were included, or if the absolute cortisol increment above baseline was used for interpretation, we would find figures closer to those previously reported (23 and 24%, respectively). These data reflect that non-systematic evaluation or selection of a substandard criterion to interpret the test overestimates the frequency of adrenocortical insufficiency in PM.

The human P450c17 alpha gene (CYP17) is a single copy gene located in chromosome 10, consisting of 8 exons and 7 introns. 17 alpha-Hydroxylase/17,20-lyase deficiency is one of two hypertensive forms of congenital adrenal hyperplasia and is inherited as an autosomal recessive trait; although rare, it probably exists with twice the frequency of the 11 beta-hydroxylase deficiency. Deficient 17 alpha-hydroxylation of pregnenolone and progesterone and subsequent deficiency of the cleavage of the C-17,20 carbon bond result in the absence of sex hormone formation in both the adrenal glands and the gonads, causing hypogonadism and male pseudohermaphroditism. Elevated and glucocorticoid-suppressible levels of the ZF 17-deoxysteroids--DOC and corticosterone--as well as their 18-hydroxylated products--18-OHDOC and 18-OHB (in addition to 19-nor-DOC)--are responsible for hypertension, hypokalemia, and renin and aldosterone suppression. A few cases, reported primarily among Japanese families, have basal hyperaldosteronism, an enigmatic condition that still demands adequate explanation. Like other forms of congenital adrenal hyperplasia, treatment of 17 alpha-hydroxylase deficiency consists of replacement doses of glucocorticoid hormones and supplemental estrogen therapy in the young adult patient. Heterozygotes may be detected by slightly exaggerated responses of some or all the ZF 17-deoxysteroids to ACTH stimulation, and by the elevated ratio of total urinary metabolites of corticosterone to the total metabolites of cortisol.

1. Different results concerning distal NaCl reabsorption have been reported for patients with Bartter's syndrome in tests of renal diluting ability. We describe clearance studies performed on 3 patients with Bartter's syndrome using different routes for body fluid content expansion: water was given orally and 0.45% NaCl solution intravenously. The impact of fluid composition was evaluated in one patient who additionally underwent a "reverse test": i.e., intravenous 5% glucose in water and an oral load of 0.45% NaCl solution. 2. Urine flow per ml glomerular filtration rate (GFR) reached higher levels when the iv route was used (20.6 +/- 1.8 vs 11.8 +/- 5.7%, P < 0.05). Fractional excretion of Na+, Cl- and osmoles increased during NaCl infusion but not during the oral load. Also, distal delivery of solute increased and was greater than that observed in the oral test (21.9 +/- 5.5 vs 11.4 +/- 2.1%, P < 0.05). 3. In contrast, fractional distal chloride reabsorption in the iv test reached subnormal values which were lower than in the oral load test (65.0 +/- 11.2 vs 86.8 +/- 11.0%, P < 0.05). A positive correlation was observed between distal delivery and Cl- fractional excretion (r = 0.87; P < 0.005). In one patient, the 5% glucose infusion resulted in greater urine flow and distal delivery when compared to distilled water or 0.45% NaCl taken orally (28.1 vs 13.3 ml/min and 27.3 vs 12.8%, respectively). These values were as high as those observed during iv administration of hypotonic saline. 4. The iv route was always associated with lower rates of fractional distal chloride reabsorption (70.7 vs 89.1%) regardless of the solute composition and should be recommended when testing the renal diluting ability of patients suspected of Bartter's syndrome.

1. Somatostatin may play a role in the inhibition of growth hormone (GH) response to GH-releasing hormone (GHRH) in hypercortisolism. To examine this hypothesis we studied the effect of pyridostigmine, a cholinergic agonist that decreases hypothalamic somatostatin, on the GH response to GHRH in 8 controls, in 6 patients with endogenous hypercortisolism (3 with Cushing's disease and 3 with adrenal adenomas) and in 8 patients with exogenous hypercortisolism (lupus erythematosus chronically treated with 20-60 mg/day of prednisone). Each subject received GHRH(1-29)NH2,100 micrograms iv twice, preceded by pyridostigmine (120 mg) or placebo, orally. 2. The GH response to GHRH was significantly blunted in all hypercortisolemic patients compared to controls both after placebo (GH peak, 5.8 +/- 1.6 vs 46.2 +/- 15.9 micrograms/l, mean +/- SEM) and after pyridostigmine (15.7 +/- 5.6 vs 77.2 +/- 19.8 micrograms/l). 3. The GH response was absent in endogenous hypercortisolemic patients compared to the exogenous group, both after placebo (2.2 +/- 0.3 vs 8.5 +/- 2.4 micrograms/l) and after pyridostigmine (4.9 +/- 2.5 vs 23.8 +/- 8.7 micrograms/l). The GH release after GHRH/pyridostigmine for the exogenous group was similar to the response of controls treated with GHRH/placebo. 4. These results confirm that the GH response to GHRH is blunted in hypercortisolism, although more pronounced in the endogenous group. Pyridostigmine partially reversed this inhibition in the exogenous group. Therefore, somatostatin may play a role in the inhibition of GHRH-induced GH release in exogenous hypercortisolemic states.

Continued administration of ACTH to patients with hypopituitarism produced normal increases in steroids dependent on microsomal cytochrome P450(21) and P450(17 alpha) but reduced responses of steroids dependent on mitochondrial cytochrome P450(11 beta-18). To explore possible mechanisms and to determine whether this dissociation occurs with short-term ACTH suppression, we have examined the steroid responses to ACTH after 1 h in 12 normal subjects after equilibration on sodium intakes of 124 mmol/d [normal sodium diet (NSD)], 22 mmol/d [low sodium diet (LSD)], and 240 mmol/d [high sodium diet (HSD)] before and during continued ACTH suppression with dexamethasone (DEX). Two distinct patterns of steroid responses were observed. Deoxycorticosterone (DOC) responses were initially reduced during LSD-DEX but eventually returned to the NSD-control (NSD-CONT) values; in contrast 18-hydroxydeoxycorticosterone and corticosterone remained suppressed. 11-Deoxycortisol and 21-deoxycortisol showed patterns similar to DOC, with a return to normal ACTH responses on LSD-DEX. Basal cortisol levels were reduced and the ACTH response was unchanged by LSD. HSD-DEX reduced basal levels of all steroids as well as their ACTH responses. LSD and/or increased activity of the renin-angiotensin system have a significant impact on 17 alpha- and 21-hydroxylation functions in the zona fasciculata to maintain a normal ACTH response of microsomally dependent steroids under these conditions. In contrast, on HSD-DEX with the renin-angiotensin system suppressed, there is generalized impairment of steroid responses to ACTH.

Postural stimulation tests (PST) from 146 patients with primary aldosteronism were reviewed: 83 had an aldosterone-producing adenoma (APA), 48 idiopathic hyperaldosteronism (IHA), nine primary adrenal hyperplasia (PAH), and six aldosterone-producing renin-responsive adenoma (AP-RA). Plasma aldosterone and cortisol levels were measured after overnight recumbency and in response to upright posture for 2 to 4 h. The test was considered invalid in 32% of the patients because cortisol levels increased during the maneuver. As both cortisol and aldosterone are responsive to ACTH in subjects with primary aldosteronism, as well as in normal subjects, we examined their percent variation instead of the absolute values. In order to validate those tests in which cortisol increased, we subtracted the percent cortisol change from the percent aldosterone response. An aldosterone increase of less than 30% (considered a positive response for the presence of an adenoma) identified 76 of the 89 patients with an adenoma (APA and AP-RA) (sensitivity of 85%). Among the 13 false-negative tests, six were proven cases of AP-RA. In each and every case an adenoma was detected by CT/MRI scanning (or bilateral adrenal vein catheterization). Hypertension was ameliorated or cured by surgery. A postural response of less than 30% was also present in 11 of the 57 patients who did not have a discrete adenoma confirmed by imaging techniques (specificity of 81%). Among these false-positive results there were the nine cases of PAH where the hypertension could be ameliorated or cured by partial removal of hyperplastic adrenal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Some methodological aspects of the rapid ACTH stimulation test (RST) and the prolonged ACTH stimulation test (PST) remain heterogeneous, e.g. administration routes, time of the day, duration, interpretation criteria and clinical indications. To standardize both tests we studied the serum cortisol responses to ACTH in 16 normal subjects, 16 patients with Addison's disease (AD), 14 with hypopituitarism (HP) of different etiologies and 13 patients on chronic glucocorticoid (CG) treatment (doses equivalent to 5-20 mg/d of prednisone for at least 6 months). For the RST, 250mcg of Cortrosina Organon were injected as an IV bolus and blood collected before and 60 minutes later, whereas for the PST, 250mcg of Cortrosina-Depot Organon were injected IM, every 8 hours for 3 days, and blood drawn daily between 8 and 9 o'clock AM. The post-ACTH cortisol value was the single parameter chosen to interpret both tests (the absolute or percent increase was of no further value). The 95% lower confidence limits (mean minus 1.64 SD) for the RST and the 3rd day of PST were 19.1 and 49.0mcg/dL, respectively. AD patients did not increase cortisol in response to both the RST (1.1 +/- 1.2 to 1.2 +/- 1.1mcg/dL) or the PST (1.2 +/- 1.3 to 2.0 +/- 1.7mcg/dL). However, whereas 22 out of 27 patients with HP and CG showed a modest cortisol increase to the RST (1.6 +/- 2.3 to 5.6 +/- 4.7 mcg/dL), all had a gradual and nearly normal response on the 3rd day of the PST (1.6 +/- 2.1 to 29.6 +/- 16.6mcg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD. None of these disturbances result in hypertension. In the only other form of juvenile hypertension due to congenital adrenal hyperplasia, 11 beta-OHD, androgen excess leads to female pseudohermaphroditism and precocious puberty in the male patient. Patients with dexamethasone-suppressible hyperaldosteronism present with no sexual abnormalities. A diagnosis of 17 alpha-OHD can be readily assumed in the female patient with primary amenorrhea, hypertension, and hypokalemia. The absence of aldosterone, a measurement that is readily available, establishes this diagnosis even without the measurement of DOC.

Selective percutaneous venous catheterization (SPVC) was performed to ascertain the source of androgen excess (AE) in 3 virilized women (12, 50 and 58y) in whom hormonal and radiologic investigation (ultrasonography and computerized tomography) was inconclusive. In all cases, elevated testosterone levels remained unsuppressed with dexamethasone, but were adequately suppressed by normal basal DHEA-S and cortisol. SPVC for T and F determinations (and the T/F ratio) were performed before surgery in all cases and during surgery in case 3. A T/F ratio of 152.4 and 71.8 (with an ovary-peripheral vein gradient [OPG] of 637 and 1173 ng/dl) identified the right and left ovary as the source of androgen excess respectively in cases 1 and 2, whereas the T/F ratio (87.4 and 97.2) and OPG (749 and 1162 ng/dl) were increased in both ovaries in patient 3. Thus, lateralization was evident in cases 1 (R ovary Leydig cell tumor) and 2 (L ovary hemangioma and stromal luteinization) whereas bilateral production in case 3 was confirmed by biopsy (PCO). Pre-operative identification of the origin of AE by SPVC is essential in defining proper treatment for patients suspected of harboring a neoplasia. Because it is not widely available nor devoid of complications, SPVC should only be indicated in hirsute/virilized women whose basal plasma testosterone and DHEA-S levels are in the tumoral range, i.e. higher than 150 ng/dl and 700 micrograms/dl, respectively.

While hypertension is observed in only two of the three major subtypes of congenital adrenal hyperplasia (CAH), 11 beta- and 17 alpha-hydroxylase deficiencies, deoxycorticosterone (DOC) production is increased in all. The elevated zona fasciculata (ZF) DOC produces mineralocorticoid hypertension with suppressed renin and reduced potassium concentrations. The DOC levels in 21-hydroxylase deficiency are in part produced by renin stimulation of the Zona glomerulosa (ZG) along with aldosterone. Assessment of the mineralocorticoid hormones of the ZF and ZF (17-deoxy steroids) provides additional unique characteristics of each subtype. Dissociation of DOC from cortisol is not unique to CAH. This dissociation is seen in other disorders and contrived conditions. There is a strong suggestion of a non-ACTH regulator of 17-deoxy steroids (DOC) that may contribute significantly to DOC production in general and effect DOC levels in CAH.

Short term suppression of ACTH by dexamethasone effects limited reduction in plasma deoxycorticosterone (DOC) while cortisol levels are almost completely suppressed in normal control subjects. The zona fasciculata (ZF) microsomal cytochrome P-450(21) appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450(11 beta-18). Eleven patients with hypopituitarism were studied to quantitate basal ZF microsomal and mitochondrial derived steroids and their acute and extended responses to ACTH. Basal levels of 11-deoxycortisol (S) and DOC were modestly reduced (70% and 53%, respectively), while other ZF steroids were almost completely absent. Acute and prolonged ACTH treatment amplified the discrepancy in both plasma levels and production rates. DOC and S demonstrated prompt and sustained increases similar to those in normal controls, while cortisol, 18-hydroxydeoxycorticosterone, and corticosterone showed a slow subnormal recovery of steroid production. The preservation of microsomal cytochrome P-450(21) and P-450(17 alpha) to maintain DOC and S levels contrasts the reduced and delayed responses of steroids dependent on mitochondrial cytochrome P-450(11 beta-18), cortisol, corticosterone, and 18-hydroxydeoxycorticosterone. A greater effect of ACTH deficiency on mitochondrial over microsomal cytochrome P-450 activity is demonstrated, and in addition, the possibility is raised that other non-ACTH regulators sustain microsomal cytochrome P-450(21) and P-450(17 alpha) in a setting of reduced ACTH-stimulated factors.