Serum steroid metabolome on the day of oocyte retrieval in women with polycystic ovarian syndrome and its association with pregnancy outcome of in vitro fertilization.

Steroid hormone level is a crucial factor affecting the outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The purpose of this study was to evaluate serum steroid metabolome on the day of oocyte retrieval in women with polycystic ovarian syndrome (PCOS) and explore whether specific steroids can be potential indicators to improve the prediction of pregnancy outcomes in PCOS patients undergoing IVF/ICSI. In this study, the serum levels of 21 steroids in 89 women with PCOS and 73 control women without PCOS on the day of oocyte retrieval of the first IVF/ICSI treatment cycle were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). All patients subsequently received good-quality embryo transfer, and the correlation between their steroid profiles and pregnancy outcomes of the first embryo transfer (ET) was retrospectively analyzed. We found PCOS patients had aberrant levels of 11 out of 21 steroid hormones compared to control individuals, with androgen steroid hormones being considerably enhanced. Enzyme activity evaluation indicated that PCOS women might have abnormal activity of CYP17A1, CYP21A2, CYP11B2, CYP19A1, HSD3B, HSD11B, and HSD17B. Additionally, the level of 18-hydroxycorticosterone (p = 0.014), corticosterone (p = 0.035), and 17-hydroxypregnenolone (p = 0.005) were markedly higher in live birth group than in non- live birth group for PCOS women following frozen embryo transfer (FET). Multiple logistic regressions indicated that 18-hydrocorticosterone and 17-hydroxypregnenolone were independently associated with live birth outcomes of PCOS women following FET. Receiver operating characteristic (ROC) curve analysis revealed that 0.595 ng/mL for 18-hydrocorticosterone level (AUC: 0.6936, p = 0.014).and 2.829 ng/mL for 17-hydroxypregnenolone level (AUC: 0.7215, p = 0.005) were the best cutoff values to predict live birth outcomes of PCOS. In conclusion, the blood steroid metabolome was closely related to the IVF/ICSI outcomes of PCOS patients. 18-hydroxycorticosterone and 17-hydroxypregnenolone might be potential indicators to predict pregnancy outcomes of PCOS undergoing IVF/ICSI treatment.

Primary Neurolymphomatosis Presenting With Polyradiculoneuropathy Affecting One Lower Limb.

OBJECTIVES: We report a case of primary neurolymphomatosis (NL) with unusual presentation and excellent treatment response. METHODS: Chart review. RESULTS: A 64-year-old woman presented with 2 months of progressive pain, weakness, and numbness in her right leg. Nerve conduction study/electromyogram suggested a right lumbosacral radiculoplexus neuropathy with associated acute right peroneal neuropathy at the fibular head. L/S spine and right leg magnetic resonance imaging showed thickening and contrast enhancement of the right S1 nerve root and the right distal sciatic, tibial, and common peroneal nerves, as well as a lobular enhancing lesion of the right superficial peroneal nerve. Whole-body fludeoxyglucose-positron emission tomography scan showed no other lesions. A right superficial peroneal nerve lesion biopsy revealed infiltration of the nerve by diffuse large B-cell lymphoma. The lymphoma cells expressed BCL2 but not CD10, suggesting an origin in peripheral blood not lymph nodes. Despite the expression of BCL2, which is considered as a poor prognosis marker, our patient responded very well to the combined radiotherapy and chemotherapy with the R-MPV (rituximab, MTX, procarbazine, and vincristine) regimen. The patient showed marked clinical improvement and complete resolution of lymphoma lesions on the PET scan. CONCLUSIONS: Our case broadens the clinical spectrum and illustrates the importance of early diagnosis and aggressive treatment of primary NL.

18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes.

CONTEXT: Diagnosis of primary aldosteronism (PA) is made by screening, confirmation testing, and subtype diagnosis (computed tomography scan and adrenal vein sampling). However, some tests are costly and unavailable in most hospitals. OBJECTIVE: The aim of the study was to evaluate the role of serum 18-hydroxycorticosterone (s18OHB), urinary and serum 18-hydroxycortisol (u- and s18OHF), and urinary and serum 18-oxocortisol (u- and s18oxoF) in the diagnosis of PA and its subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). PATIENTS: The study included 62 patients with low-renin essential hypertension (EH), 81 patients with PA (20 APA, 61 BAH), 24 patients with glucocorticoid-remediable aldosteronism, 16 patients with adrenal incidentaloma, and 30 normotensives. INTERVENTION AND MAIN OUTCOME MEASURES: We measured s18OHB, s18OHF, and s18oxoF before and after saline load test (SLT) and 24-h u18OHF and u18oxoF. RESULTS: PA patients displayed significantly higher levels of s18OHB, u18OHF, and u18oxoF compared to EH and normal subjects; APA patients displayed s18OHB, u18OHF, and u18oxoF levels significantly higher than BAH patients. Similar results were obtained for s18OHF and s18oxoF. SLT significantly reduced s18OHB, s18OHF, and s18oxoF in all groups, but steroid reduction was much less for APA patients compared to BAH and EH. The s18OHB/aldosterone ratio after SLT more than doubled in EH but remained unchanged in APA patients. CONCLUSIONS: u18OHF, u18oxoF, and s18OHB measurements in patients with a positive aldosterone/plasma renin activity ratio correlate with confirmatory tests and adrenal vein sampling in PA patients. If verified, these steroid assays would refine the diagnostic workup for PA.

Liver lesion detection and characterization in patients with colorectal cancer: a comparison of low radiation dose non-enhanced PET/CT, contrast-enhanced PET/CT, and liver MRI.

OBJECTIVES: To compare low-radiation dose non-enhanced fluorine 18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) (NE-PET/CT), contrast-enhanced fluorine 18 fluorodeoxyglucose PET/CT (CE-PET/CT), and gadolinium-enhanced liver magnetic resonance imaging (MRI) for the detection and characterization of liver lesions in patients with colorectal cancer (CRC). METHODS: In this retrospective review of imaging database of CRC patients with suspected liver metastases, 33 patients (22 men, 11 women; mean age, 63 years) evaluated with low-radiation dose NE-PET/CT, CE-PET/CT, and liver MRI were studied. The final diagnosis was established either by pathological examination or follow-up imaging over a period of at least 6 months for lesion stability or growth. The liver lesions were characterized on an ordinal scale of 0 to 6 (0 = absent, 1 = definitely benign, and 6 = definitely malignant). Receiver operating characteristic analysis was performed to compare performance of the 3 imaging methods. RESULTS: A total of 110 lesions were present on follow-up. The detection rate on low-radiation dose NE-PET/CT, CE-PET/CT, and MRI was 73.6%, 90.9%, and 95.4%, respectively. Magnetic resonance imaging (P < 0.001) and CE-PET/CT (P < 0.001) had a higher detection rate than low-radiation dose NE-PET/CT. There was no significant statistical difference in lesion detection between MRI and CE-PET/CT (P = 0.11). The sensitivity, specificity, and accuracy for characterization of detected liver lesions on low-radiation dose NE-PET/CT were 67%, 60%, and 66%, respectively; those on CE-PET/CT were 85%, 100%, and 86%, respectively; and those on MRI were 98%, 100%, and 98%, respectively. Comparative receiver operating characteristic analysis showed an area under curve of 0.74 for low-radiation dose NE-PET/CT, 0.86 for CE-PET/CT, and 0.97 for MRI. There were statistically significant differences in the accuracy of MRI, low-radiation dose NE-PET/CT, and CE-PET/CT for lesion characterization. CONCLUSIONS: When performing PET/CT, optimal detection and characterization of liver lesions require the use of a fused contrast-enhanced CT. Magnetic resonance imaging and CE-PET/CT have similar lesion detection rates. Magnetic resonance imaging is the best test for liver lesion characterization in patients with CRC.

Measurement of 18-hydroxycorticosterone during adrenal vein sampling for primary aldosteronism.

CONTEXT: In primary aldosteronism, elevated serum 18-hydroxycorticosterone (18OHB) suggests aldosterone-producing adenoma (APA) rather than bilateral, idiopathic hyperaldosteronism (IHA), but little is known about the relative production of 18OHB and aldosterone (A) in APAs compared with IHA. OBJECTIVES: We measured 18OHB, A, and cortisol (F) in blood from adrenal vein sampling (AVS) studies. We compared the discriminatory power of gradients in 18OHB/A and 18OHB/F ratios with A/F ratio gradients for distinguishing APA from IHA. DESIGN, SETTING, AND SUBJECTS: We measured 18OHB and A in excess serum from 23 AVS studies performed at our university hospitals. MAIN OUTCOME MEASURES: We calculated the ratios 18OHB/A, 18OHB/F, and A/F for all specimens, and determined the adrenal vein gradients for these ratios. RESULTS: The 18OHB/A ratios were much lower in blood draining APAs (2.17 +/- 0.62) than in blood draining the contralateral adrenals (12.96 +/- 12.76; P < 0.001) but similar to blood draining IHA adrenals (4.69 +/- 4.32; P = 0.02). In contrast, the 18OHB/F ratios were elevated in specimens from APAs (26.03 +/- 11.51) compared with IHA adrenals (9.22 +/- 5.18; P < 0.001) or the contralateral adrenals (6.23 +/- 2.97; P < 0.001). Using 18OHB/F gradient greater than two or 18OHB/A gradient less than 0.5 as criteria for lateralization, interpretations agreed with lateralizations based on A/F gradients in 21 of 23 cases. CONCLUSIONS: High serum 18OHB in APA reflects augmented production of both 18OHB and A, not disproportionate 18OHB secretion relative to A. The 18OHB/A and 18OHB/F gradients are useful adjuncts but not as reliable as A/F gradients for A lateralization during AVS.

Ghrelin, an endogenous ligand for the growth hormone-secretagogue receptor, is expressed in the human adrenal cortex.

Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which was originally isolated from rat stomach. Ghrelin and GHS-R are also expressed in several peripheral tissues, including adrenal glands, and this prompted us to study ghrelin expression and ghrelin-binding site localization in the human adrenal cortex, and the possible effect of this peptide on corticosteroid-hormone secretion. Reverse transcription-polymerase chain reaction (RT-PCR) and radioimmune assay (RIA) showed sizeable expression of ghrelin mRNA and protein in six human adrenal cortexes. Autoradiography evidenced abundant [125I]ghrelin binding sites in the adrenal zona glomerulosa and outer zona fasciculata. However, ghrelin (10(-6) M) did not significantly affect either basal or agonist (ACTH and angiotensin-II)-stimulated early and late steps of steroid-hormone synthesis from adrenocortical slices (as measured by quantitative high pressure liquid chromatography). Since zona glomerulosa is the cambium layer involved in the growth maintenance of adrenal cortex, the present coupled RT-PCR, RIA and autoradiographic findings could suggest the involvement of ghrelin in the autocrine-paracrine regulation of human adrenal growth.

Analysis of biological samples by gas chromatography-mass spectrometry without a reference standard: measurement of urinary 18-hydroxytetrahydro-11-dehydrocorticosterone excretion rate in human subjects.

Reference standards for some minor urinary steroid metabolites are sometimes unavailable. We describe a novel procedure to quantitate a urinary steroid metabolite of known structure and mass spectrum, using as a standard a compound which produces ions in common with it and has a similar retention time in gas chromatography-mass spectrometry. The steroid of interest was 18-hydroxy-11-dehydrotetrahydrocorticosterone (18-OH-THA), the major urinary metabolite of 18-hydroxycorticosterone (18-OH-B), a putative intermediate in the conversion of 11-deoxycorticosterone to aldosterone. The steroid used as an alternative to the authentic 18-OH-THA standard was beta-cortol which, like 18-OH-THA, produces a fragmentation ion at m/z 457. Allo-tetrahydrodeoxycorticosterone (5alpha-THDOC) was used as the internal standard. beta-Cortolone also has the fragmentation ion at m/z 449 (in common with beta-cortol) and an authentic standard is available commercially. To validate the procedure, we quantitated beta-cortolone urinary excretion rate against this alternative standard and also against authentic beta-cortolone standards. Both methods produced similar results (adjusted R(2): 0.998, P<0.001). The method was then used to measure urinary excretion of 18-OH-THA rate in healthy volunteers. The reference range obtained was 20-204 microgram/24 h (n=32). This is similar to the few results available by conventional assay. Method performance was also similar to other assays of urinary steroids. This procedure could be generally applicable for assays when authentic standards are not available but mass spectra are known or can be predicted.

["High pouch output" syndrome. Role of mineralocorticoid diagnosis after restorative proctocolectomy]. / "High-Pouch-Output"-Syndrom. Stellenwert der Mineralocorticoiddiagnostik nach restaurativer Proktocolektomie.

UNLABELLED: The two-phase restorative proctocolectomy is the treatment of choice for surgical therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative colitis (UC). Besides the well-known complications the entire removal of the colorectum leads to an impairment of fluid and electrolyte resorption. PATIENTS AND METHODS: Over a time period of two years we observed 320 proctocolectomized patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch output but without organic malfunction were identified. The organic reasons were excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated routine parameters, the kidney function, the electrolyte changes, the acid-base balance and the urine pH, as well as the hormonal changes of the suprarenal glands. We identified seven patients with 'high pouch output' out of 320 patients observed. The control group consisted of 14 proctocolectomized patients without hints of complications in the endoscopic, radiographic and routine laboratory diagnostics. RESULTS: Neither group showed any significant differences in the analysis of the routine parameters. A significant drop of the urine sodium concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was observed in the group with 'high pouch output'. In this group the plasma aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl). Neither group of patients showed increased activity of free corticosterone and free cortisol. Only free 11-desoxycorticosterone was elevated in the group with 'high pouch output'. CONCLUSION: Our results prove that the mineralocorticoid adrenal activity plays a central role in order to preserve the volume and electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications in realms of the restorative proctocolectomy proves the excellent compensation of the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic marker encapsulating the reabsorption problems of intestinal salt and volume losses after proctocolectomy.

Adrenocortical adenoma producing 18-hydroxycorticosterone.

A 30-year-old man presented at our hospital with microscopic hematuria. Ultrasonography and computed tomography scanning revealed a right adrenal mass measuring 20 x 20 mm. The tumor was asymptomatic, but there was obvious accumulation on the right side when scintigraphy was performed with radioactive iodine (131I)-labeled adosterol. Endocrinology studies showed elevation of the plasma cortisol and renin concentrations, while the plasma aldosterone level was low. Right laparoscopic adrenalectomy was done on July 4, 1994. Histologic examination showed an adrenocortical adenoma. Serum levels of adrenocortical hormones were measured before and after surgery, and the tissue content for the same hormones was determined in the resected tumor. The hormonal studies showed that the tumor produced 18-hydroxycorticosterone.

[Adrenal adenoma or hyperplasia? Problems of differential diagnosis in an unusual case of primary hyperaldosteronism]. / Adenoma surrenalico o iperplasia? Problemi di diagnostica differenziale in un caso inusuale di iperaldosteronismo primitivo.

Although primary hyperaldosteronism is an uncommon cause of hypertension, it is the most common form of renin-independent hypermineralocorticoidism. The plasma aldosterone concentration and PRA with orthostatic test and saline infusion test are very useful aids to make a diagnosis. In this case the inconsistency between hormonal data and morphologic images (TC and NMR) led us to a dilemma: it was a question of adrenal adenoma or hyperplasia? Because it was impossible to dose the 18-OH-corticosterone, we had to perform a iodocholesterol scintigraphy NP 59. To distinguish an hyperplasia as cause of this kind of hyperaldosteronism made us able to define a therapeutic program useful to hypertension control.

Stable expression of rat cytochrome P450 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in MA-10 cells.

Glucocorticoids and mineralocorticoids are synthesized in the adrenal cortex through the action of two different cytochrome 11 beta-hydroxylases, CYP11B1 (11 beta-hydroxylase) and CYP11B2 (aldosterone synthase) which are distributed in the zona fasciculata and glomerulosa, respectively. We have created stably transfected cell lines using the Leydig tumor cell line MA-10 with CYP11B1 and CYP11B2 cDNA-containing plasmids which have a selectable gene to confer resistance to geneticin. The expression of the transfected cDNA in the cells was characterized by Northern-blot and measurement of enzymatic activity. The cell lines express the enzymes stably for many generations. CYP11B1 transfected cells converted DOC into corticosterone, 18-OH-DOC and small amounts of 18-OH-corticosterone, in a time and concentration dependent manner. Incubation of the cells with corticosterone generated 18-OH-corticosterone especially at concentrations of 30 and 100 microM. The production of 18-OH-corticosterone from corticosterone at these doses was significantly higher than incubations with similar concentrations of DOC. CYP11B2 transfected cells converted DOC into corticosterone, 18-OH-corticosterone, aldosterone and small amounts of 18-OH-DOC in a time and concentration dependent manner. They converted corticosterone into 18-OH-corticosterone and aldosterone in a time and concentration dependent manner. The absolute and relative production of aldosterone from DOC was significantly higher than when cells were incubated with corticosterone, and the ratio of aldosterone to 18-OH-corticosterone was higher at all concentrations of DOC compared to corticosterone. CYP11B2 transfected cells (but not the CYP11B1 transfected cells) transform 18-OH-DOC into 18-OH-corticosterone, but can not convert 18-OH-DOC into aldosterone. In conclusion, stably transfected MA-10 cells with the cDNAs for the CYP11B1 and CYP11B2 enzymes were prepared and their enzymatic activity studied. These cells are useful in the study of inhibitors of the specific enzymes, as well as determining the roles that each enzyme plays in zone-specific steroidogenesis in the adrenal cortex.

Suramin: an inhibitor of the final steps of the mineralocorticoid pathway?

The authors used incubated adrenal mitochondria to study the in vitro effect of suramin, an antiparasitic drug, on the transformation of corticosterone and 18-hydroxycorticosterone into aldosterone. The results show that, under conditions preserving membrane integrity, the "impermeance" of suramin meant that concentrations similar to the plasma-levels reached in treated patients induced only slight inhibition of the final intramitochondrial steps in aldosterone synthesis. However, suramin strongly inhibited mitochondrial respiration. The inhibition of two intramitochondrial mechanisms (respiration and steroid synthesis) suggests that the effect of suramin involves partial inhibition of metabolic intermediate carriers. The inhibition of the activity of various extramitochondrial enzymes involved in intermediate metabolism, suggests that the inhibition of steroid biosynthesis can be explained only on the basis of an extramitochondrial action of suramin. The action of suramin must, therefore, primarily and directly affect extramitochondrial steroid synthesis and only indirectly affect intramitochondrial steroid synthesis as a result of an impact on the reducing equivalent supply. However, even if suramin does not bind to cytochrome P450 11 beta which catalyzes the final steps of aldosterone biosynthesis pathway, this does not imply that suramin has no direct effect on steroid synthesis within the mitochondria, in addition to its toxic effects, particularly if the cell structure is disrupted (as is often the case in tumor tissues).

Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells.

Etomidate has been shown to inhibit corticosteroid secretion in the normal adrenal gland, but its direct effect in human pathologic adrenals has not been clearly established. In the present study the effect of varying doses of etomidate (10(-11)-10(-5) M) was investigated on basal and adrenocorticotrophic hormone (ACTH)-stimulated corticosteroid secretions in isolated adrenocortical cells obtained from two patients with primary aldosteronism (adenoma and micronodular hyperplasia) and in those from a patient with Cushing's syndrome (adenoma). In cells from primary aldosteronism, increasing concentrations of etomidate (10(-11)-10(-5) M) produced a dose-dependent decrease of basal and ACTH-stimulated cortisol, aldosterone, 18-hydroxycorticosterone, and corticosterone secretions (ED50: 10(-9)-10(-8) M for each of these corticosteroids). In the same cells, the secretions of 11-deoxycortisol and deoxycorticosterone were increased in the presence of low (10(-9)-10(-7) M) but not high doses of etomidate (10(-6)-10(-5) M). In cells from Cushing's syndrome the changes in corticosteroid secretion were similar to those found in primary aldosteronism except that aldosterone and 18-hydroxycorticosterone could not be determined due to their low levels. Thus the potent inhibition of corticosteroids in human pathologic adrenocortical cells in the presence of low concentrations of etomidate may be predominantly due to inhibition of the 11 beta-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway.

In vitro glucocorticosteroid and mineralocorticosteroid biosynthesis in Conn's adenoma tissues.

The in vitro metabolism of [1,2-3H] deoxycorticosterone (DOC), [1,2-3H] 18-hydroxy-11-deoxycorticosterone (18-OHDOC) and [1,2-3H] 11-deoxycortisol (S) was studied in adrenal adenoma homogenates from patients with primary hyperaldosteronism. Tumor tissues actively converted deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone to 18-hydroxycorticosterone and aldosterone. Yields of cortisol and cortisone were also large showing that the tissues did not lack the zona fasciculata-like 11 beta-hydroxylation ability.

Hypoaldosteronism accompanied by normal or elevated mineralocorticosteroid pathway steroid: a marker of adrenal carcinoma.

In order to find a biochemical marker to assist the physician in the difficult differential diagnosis between malignant and nonmalignant adrenal tumors, plasma levels of the mineralocorticosteroids (deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, and aldosterone) were determined. The same method (RIA which is preceded by a crucial separation step) was used to measure all these steroids including aldosterone. The subjects included 15 adults presenting various clinical signs of adrenocortical tumors (histopathologically: 6 with adrenal carcinoma, 1 with a history of adrenal carcinoma, 1 with adrenal metastasis from other forms of cancer, 6 with adenoma, and 1 with hyperplasia). The results show that both presurgery and during a recurrence of adrenal carcinoma, hypoaldosteronism occurs which contrasts with the normal or even elevated levels of some aldosterone precursors. In the 7 cases of adrenal cortical carcinoma, this dysfunction of the aldosterone pathway was detected regardless of the impairment of the other steroidogenesis pathways, whereas it was never found with a nonmalignant tumor. Despite the limited number of cases so far available, these findings suggest that detection of abnormalities of the aldosterone pathway, and particularly the detection of hypoaldosteronism by an assay method involving a crucial steroid separating step, could contribute to a differential diagnosis between benign and malignant adrenocortical tumor and between adrenal metastasis and other forms of cancer.

Urinary excretion of 19-noraldosterone, 18, 19-dihydroxycorticosterone and 18-hydroxy-19-norcorticosterone in patients with aldosterone-producing adenoma or idiopathic hyperaldosteronism.

Urinary excretion of 19-noraldosterone, 18. 19-dihydroxycorticosterone (18, 19(OH)2-B), 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), 18-hydroxycorticosterone (18-OH-B), 18-hydroxycortisol (18-OH-F) and aldosterone were measured in 25 patients with primary aldosteronism, 16 with an aldosterone-producing adenoma and 9 with idiopathic hyperaldosteronism. In patients with idiopathic hyperaldosteronism, urinary 19-noraldosterone (207 +/- 51 pmol/day), 18, 19(OH)2-B (21 +/- 4.2 nmol/day) and 18-OH-19-nor-B (879 +/- 213 pmol/day) levels were lower but not significantly different from 19-noraldosterone (263 +/- 56 pmol/day), 18, 19(OH)2-B (40 +/- 8.7 nmol/day) and 18-OH-19-nor-B (1322 +/- 267 pmol/day) seen in patients with aldosterone-producing adenoma. Urinary aldosterone did not differ significantly between patients with idiopathic hyperaldosteronism and those with aldosterone-producing adenoma. Both urinary 18-OH-B and 18-OH-F excretion were significantly higher in aldosterone-producing adenoma (39 +/- 5.2 nmol/day, 1660 +/- 318 nmol/day, respectively) compared with patients with idiopathic hyperaldosteronism (19 +/- 3.3 nmol/day, 541 +/- 93 nmol/day, respectively) (p less than 0.05). Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, the mineralocorticoid steroids which we can only now measure, 19-noraldosterone, 18, 19(OH)2-B and 18-OH-19-nor-B, could not be used to distinguish the two subsets of primary aldosteronism.

Diagnosis of primary hyperaldosteronism: importance of correlating CT findings with endocrinologic studies.

Twenty patients with primary hyperaldosteronism had endocrinologic and radiologic studies to distinguish aldosterone-producing adenoma from idiopathic hyperaldosteronism due to bilateral micro- or macronodular hyperplasia of the adrenal cortex. In addition to examination for changes in the plasma level of aldosterone associated with postural changes and measurement of the plasma level of 18-hydroxycorticosterone, all 20 patients had CT examination of the adrenal glands. In three patients with normal adrenal glands on CT and three patients with CT evidence of two solitary nodules, one in each adrenal gland, a diagnosis of idiopathic hyperaldosteronism was confirmed by endocrinologic findings (five patients) or 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy (one patient). In nine patients with a solitary adrenal nodule on CT, a diagnosis of aldosterone-producing adenoma was confirmed by surgery (seven patients) or hormone sampling via the adrenal veins (two patients). However, in three patients with a solitary adrenal nodule on CT, a diagnosis of idiopathic hyperaldosteronism was suggested by endocrinologic findings (three patients) and confirmed by the results of NP-59 scintigraphy (two patients) or adrenal venous sampling (one patient). In addition, in two patients with CT evidence of three adrenal nodules (two in one gland, one in contralateral gland), a diagnosis of aldosterone-producing adenoma was suggested by endocrinologic findings in both patients and confirmed by surgery in one. Although high-resolution CT is highly accurate for the detection of aldosterone-producing adenoma, significant diagnostic errors can occur in patients with primary hyperaldosteronism if CT findings are not correlated with results of endocrinologic studies.

In vitro uptake of 18-hydroxycorticosterone by regions of the central nervous system

Estudiamos la unión específica de la 18-hidroxicorticosterona (18-OH-B) a fracciones nucleares y citoplasmáticas de células provenientes de bulbo, protuberancia, amígdala, pituitaria anterior, hipotálamo, hipocampo, área preóptica y pulmón de animales adrenalectomizados, después de incubar los tejidos con el ligando radiactivo. Encontramos que 18-OH-B tiene una mayor unión específica a núcleos obtenidos de bulbo y protuberancia; este perfil difiere de observaciones previas en las que otros corticosteroide íntimamente relacionados, como la corticosterona y la aldosterona, se encuentran principalmente concentrados en el sistema límbico