Biomedical subjects

M Boscaro

Publications and source records attributed to M Boscaro.

At least 55 records · Page 3Linked to original sources

PubMed1998

Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man.

A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid feedback suppression seems to occur with aging. To investigate possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg as an i.v. bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr) men. Blood samples for ACTH and cortisol determinations were collected at -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both groups. In old men, in concomitance with the cortisol increase, ACTH levels showed only a slight and nonsignificant decrease within the first 15 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, followed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and young men, whereas the remaining part of the curve (from 60-180 min) showed no differences between the two groups. The slower response in glucocorticoid feedback inhibition of ACTH in old men supports the concept of some alteration in the central regulation by steroids in aging. Age-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnormalities could be involved in the fast component of hypothalamic-pituitary-adrenal axis feedback regulation.

Adolescent↗

PubMed1998

Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene.

Aldosterone suppression by dexamethasone, and high 18-hydroxycortisol and 18-oxocortisol levels are used to differentiate glucocorticoid-remediable aldosteronism (GRA) from other forms of primary aldosteronism. These methods are time consuming, expensive, and impractical for large studies. Moreover, diagnosis of GRA requires a confirmatory genetic test. We evaluated 117 patients with primary aldosteronism referred to our centers by the use of a long PCR technique to reveal the chimeric gene of GRA. In 60 of 117 patients, the response of aldosterone to dexamethasone (2 mg/day for 4 days) was also assessed. None of our patients, including 2 pairs of siblings, was positive for the chimeric gene. The results of long PCR were confirmed by Southern blotting. Despite a negative genetic test, 6 patients (1 with aldosterone-producing adenoma and 5 with idiopathic hyperaldosteronism) had plasma aldosterone suppressed by dexamethasone (i.e. < or = 2 ng/dL). Of 117 patients, 43 were identified as having aldosterone-producing adenoma and 74 as having idiopathic hyperaldosteronism. In our experience, the long PCR technique is a reliable and simple test to at least exclude GRA in patients with primary aldosteronism. A short term dexamethasone suppression test of aldosterone can be misleading in identifying GRA. The prevalence of GRA in primary aldosteronism remains to be established.

Adult↗

PubMed1998

Life events and neurocirculatory asthenia. A controlled study.

OBJECTIVES: The purpose of this study was to assess the occurrence of stressful life events in the year before the onset of neurocirculatory asthenia. DESIGN: Case-control retrospective study. SETTING: A university medical outpatient clinic. SUBJECTS: A consecutive series of 50 patients with neurocirculatory asthenia and a control group of 50 healthy subjects, matched for sociodemographic variables, were studied. MAIN OUTCOME MEASURES: Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients and controls. RESULTS: Patients with neurocirculatory asthenia reported significantly more stressful life events than the control group (P < 0.05) and had significantly more of the following: exits (P < 0.05), undesirable (P < 0.05) and uncontrolled (P < 0.01) events. More events that had an objective negative impact (P < 0.001) and more independent events (P = 0.07) were also reported. Ratings of impact and independence were carried out by a blind rater who was unaware whether the event had occurred in patients or controls. CONCLUSIONS: The results are suggestive of a strong relationship between stressful life events and neurocirculatory asthenia. This is in agreement with a multifactorial model of pathogenesis in neurocirculatory asthenia and with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes.

Adult↗

PubMed1997

Coexistence of aldosteronoma and contralateral nonfunctioning adrenal adenoma in primary aldosteronism.

A case of primary aldosteronism is presented in which computed tomography showed bilateral adrenal tumors. Adrenal scintigraphy during dexamethasone suppression revealed bilateral radiotracer uptake, with markedly predominant visualization of the left side. The left adrenal gland was removed, and an aldosterone-producing adenoma was confirmed by histologic examination. Fifteen months after surgery, serum potassium and plasma aldosterone were normal, and a marked decrease of blood pressure was observed, indicating that the right adrenal tumor was a benign nonfunctioning mass. Unilateral adrenalectomy on the side of the scintigraphically predominant lesion reversed the clinical syndrome of primary aldosteronism.

Adenoma↗

PubMed1997

I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison's disease.

Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylases (21-OH), steroid 17 alpha-hydroxylase (17 alpha-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17 alpha-OH and/or P450scc. During the prospective study, overt Addison's disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison's disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17 alpha-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison's disease.

Addison Disease↗

PubMed1997

II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison's disease.

Adrenal cortex autoantibodies (ACA) were measured by immunofluorescence in 808 children with organ-specific autoimmune diseases without adrenal insufficiency. ACA were found in 14 children (1.7%), mostly in hypoparathyroidism (48%). Ten ACA-positive and 12 ACA-negative children were followed up for a maximum of 10 yr by evaluation of adrenocortical function (ACTH test) and autoantibody status. In all patients steroid-producing cell autoantibodies were assessed by immunofluorescence and autoantibodies to steroid 21-hydroxylase, 17 alpha-hydroxylase, and cytochrome P450 side-chain cleavage enzyme by immunoprecipitation assay. All 10 ACA-positive patients were positive for 21-hydroxylase autoantibodies. Six were positive for steroid-producing cell autoantibodies and 5 also for autoantibodies to 17 alpha-hydroxylase and/or P450 side-chain cleavage enzyme. Overt Addison's disease developed in 9 (90%) ACA/21-OH-antibody-positive children after 3-121 months, and 1 remaining child had subclinical hypoadrenalism. By contrast, all ACA/21-OH antibody-negative children maintained normal adrenal function. Adrenal failure was not related to ACA titres, sex, adrenal function, type of preexisting autoimmune disorder, or human leucocyte antigens D-related status. In conclusion, in children with autoimmune endocrine diseases, ACA/21-hydroxylase autoantibodies are important predictive markers for the development of Addison's disease.

Addison Disease↗

PubMed1996

Effect of surgical treatment on hypertension in Cushing's syndrome.

The effect of a surgical cure of hypercortisolism on hypertension in 54 patients with Cushing's syndrome was assessed. The correlation between preoperative duration of hypertension and posttreatment blood pressure was significant (P < .01). Restoration of normal cortisol was associated with blood pressure normalization in 39 out of 54 cases. Duration of hypertension of patients with normalized blood pressure was significantly shorter than that of patients with persistent hypertension postoperatively (P < .0001). Duration of hypertension, ie, long-lasting exposure to increased cortisol, appears to be the determinant of persistent hypertension following successful surgery in Cushing's syndrome.

Adolescent↗

PubMed1996

Effects of taxol on the human NCI-H295 adrenocortical carcinoma cell line.

We investigated the effects of taxol, an antimicrotubule agent active in different cancers, on the human NCI-H295 steroid-secreting adrenocortical carcinoma cell line. Cells were incubated for 48, 72 or 96 h with taxol 10(-10)-10(-4) M. Cell viability was evaluated by MTT assay with IC50 calculation. Apoptosis was investigated by measuring DNA fragmentation with ELISA assay after cell exposure to taxol at IC50 for 24 h. For secretion studies, aldosterone, cortisol, testosterone and dehydroepiandrosterone-sulphate (DHEA-S) were measured by RIA in the conditioned medium after 96 h exposure to taxol 10(-10)-10(-6) M, and expressed as percentage of steroid production by control cells. By MTT, taxol induced a dose-dependent inhibition of cell proliferation, with ICs50 at 72-96 h corresponding to blood levels achieved in vivo in patients with other types of cancer. Nuclear fragmentation, morphologically confirmed at electron microscopy, showed a 4-fold increase after exposure to taxol. With 10(-6) M taxol, aldosterone decreased to 48%, cortisol to 61%, testosterone to 76% and DHEA-S to 89% of steroid production by control cells. Taxol is an effective cytotoxic and antiproliferative agent in a human adrenocortical steroid-secreting carcinoma cell line. Apoptosis induced by the drug is involved in neoplastic cell death.

Adrenal Cortex Neoplasms↗

PubMed1996

Risk factors and long-term outcome in pituitary-dependent Cushing's disease.

Although transphenoidal pituitary microsurgery has become the treatment of choice in Cushing's disease, other procedures, such as bilateral adrenalectomy and pituitary irradiation, are currently in use in its management. Indeed, no treatment has proven to be fully satisfactory for this condition. The rates of cure and recurrence after pituitary surgery or irradiation and the incidence of Nelson's syndrome after bilateral adrenalectomy are still open issues. A population of 162 patients with pituitary-dependent Cushing's disease was studied at 1 institution and had a follow-up of at least 2 yr after treatment (median, 7 yr). Patients were divided in subgroups according to the type of treatment: transsphenoidal pituitary microsurgery, bilateral adrenalectomy, or pituitary irradiation. Survival analysis was employed to characterize the outcome of treatment in each subgroup. Predictive factors for success of pituitary surgery were also evaluated. The estimated cumulative percentage of patients remaining in remission after successful pituitary surgery (n = 79) was 93.7% after 2 yr, 80.6% after 5 yr, 78.5% after 7 yr, and 74.1% after 10 yr. Of 8 risk factors examined, the following attained statistical significance: age, clinical severity, presence of major depression, pre- and posttreatment urinary cortisol levels, and posttreatment ACTH level. Pituitary surgery was successful in 79 of 103 patients (76.7%). Surgical failure was significantly associated with lack of pituitary adenoma and the clinical severity and presence of major depression. Of patients treated by bilateral adrenalectomy (n = 63), the estimated cumulative percentage remaining free of Nelson's syndrome was 87.1% after 2 yr, 79.3% after 7 yr, and 71.2% after 10 yr. The occurrence of Nelson's syndrome was significantly related to the pretreatment urinary cortisol level and the presence of pituitary adenoma at previous pituitary surgery. After cure by pituitary irradiation (n = 23), the estimated cumulative percentage of patients remaining in remission was 100% after 2 yr, 81.8% after 5 yr, 71.6% after 7 yr, and 65.1% after 10 yr. Previous pituitary surgery, although unsuccessful, appeared to be a protective factor for relapse. The results indicate that relapse after cure by either pituitary surgery or irradiation is a considerable clinical problem that increases over time. Our findings ascribe new importance to the clinical presentation of patients and indicate subgroups that are at high risk for relapse after pituitary surgery or irradiation and for developing Nelson's syndrome after bilateral adrenalectomy.

Adenoma↗

PubMed1996

Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity inhibition in vivo.

Adrenal autoantibodies (ACA) are markers of adrenal cortex involvement in idiopathic Addison's disease. Recently the 21-hydroxylase (21-OH) enzyme has been discovered to be the major autoantigen of the ACA. A potential role of these antibodies in determining adrenal failure by inhibition of the 21-OH has been recently postulated. To test this hypothesis, cortisol and aldosterone (final products of adrenal steroid synthesis) and 17-hydroxyprogesterone (17-OH-progesterone) (as a marker of 21-OH impairment) have been investigated in baseline conditions and after ACTH (1-24) stimulation test in a group of 42 patients positive for both ACA and 21-OH autoantibodies. Patients were divided into five groups according to the stages (0-4) of adrenal failure. With progression toward overt Addison's disease, baseline 17-OH-progesterone, cortisol, and aldosterone remained almost unchanged but with impairment of their responses to ACTH (1-24) stimulation. The 17-OH-progesterone/cortisol ration remained normal both in basal conditions and after stimulation at stages 0-3. At stage 4 (overt Addison's disease), this ratio increased in baseline condition with no changes after ACTH (1-24), probably because of persistent 17-OH-progesterone gonadal production. In conclusion, there was a progressive and concomitant impairment of the synthesis of all steroids tested over various phases of adrenal failure. The pattern of response of the 17-OH-progesterone/cortisol ratio to ACTH stimulation in patients with 21-OH autoantibodies was not consistent with the autoantibodies inhibiting the 21-OH activity. This suggests that the inhibiting effect of 21-OH autoantibodies on 21-OH activity is not usually evident in vivo.

Adrenal Gland Diseases↗

PubMed1995

Fibrinolysis and coagulation abnormalities in systemic lupus erythematosus. Relationship with Raynaud's phenomenon, disease activity, inflammatory indices, anticardiolipin antibodies and corticosteroid therapy.

Endothelial cell damage in systemic lupus erythematosus (SLE) was evaluated by measuring fibrinolytic activity and von Willebrand factor levels. Tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, and von Willebrand factor antigen (vWF:Ag) and activity (vWF:RCof) were measured in 21 SLE patients (12 of whom were therapy free) and 22 controls. In addition, the relationship between such parameters and Raynaud's phenomenon, disease activity [according to personal criteria, Systemic Lupus Activity Measure (SLAM) and European Consensus Lupus Activity Measurement (ECLAM) scores] inflammatory indices [ESR, C-reactive protein (CRP), alpha 2-globulin], anticardiolipin antibodies and corticosteroid therapy was investigated. Lower levels of t-PA antigen (P = 0.003) and higher levels of vWF:Ag (P = 0.001) were found in SLE patients in comparison with controls. Moreover, t-PA antigen was lower (P = 0.02) in steroid-free patients in comparison with those taking steroids. No relationship was found between fibrinolysis and coagulation abnormalities and Raynaud's phenomenon, disease activity, inflammatory indices and anticardiolipin antibodies. Endothelial cell damage is probably a common feature in SLE patients; nevertheless, we were unable to clarify the nature of such abnormality. It is worth noting that low doses of steroids seem to be effective in improving endothelial cell function in SLE patients.

Adolescent↗

PubMed1995

GSTM1 and CYP2D6 genotype frequencies in patients with pituitary tumours: effects on P53, ras and gsp.

We describe studies to determine if susceptibility to pituitary tumours is associated with the putatively high risk GSTM1 null and CYP2D6 EM genotypes. Frequency distributions of these genotypes were similar in cases and controls though the frequency of CYP2D6 PM and GSTM1 B tended to be lower (P = 0.072 and P = 0.095 respectively) in the tumour group. Immunopositivity for p53 was found in 18/97 tumours. In these samples GSTM1 null (39%) and CYP2D6 EM (56%) frequencies were not different to those in controls. The frequencies of CYP2D6 PM and GSTM1 B in the p53 immunonegative tumours tended to be lower (P = 0.055 and P = 0.1185 respectively) than in controls. Mutations in gsp and ras were studied using the polymerase chain reaction and allele specific oligonucleotide analysis. Eight of 19 somatotrophinomas demonstrated mutations in gsp; frequencies of GSTM1 null and CYP02D6 EM were similar to controls. No ras mutations were identified in 55-tumour studies. The data indicate the GSTM1 null and CYP2D6 EM genotypes are not associated with altered expression of p53 or, mutation of gsp and ras in these adenomas and, suggest the CYP2D6 PM genotype is associated with a reduced risk of pituitary adenomas and, that GSTM1*B confers greater protection than GSTM1*A.

Adult↗

PubMed1995

Adrenocortical carcinoma: epidemiology and natural history.

Information about epidemiology, natural history and prognostic factors of adrenocortical carcinoma in Italy is extremely scarce. We report here 35 patients of adult age who were referred to our institution in the last two decades. Nine patients had non functioning, and 26 had functioning tumors. In non-functional tumors initial symptoms were abdominal pain in 90% of cases, fever, weakness, malaise, weight loss in 30%. Only one patient was asymptomatic. Of patients with functioning tumors, 18 presented with Cushing's syndrome, 6 with Cushing's syndrome and virilization, 1 with Cushing's syndrome and feminilization and 1 with hyperaldosteronism. Twenty-two of all cases (63%) had metastases at diagnosis; most frequent sites were lung, liver and distant lymph nodes. The results of tumor staging, according to MacFarlane system, were: stage I, 1 patient (3%); stage II, 10 patients (28%); stage III-IV, 24 patients (69%). Twenty-six out of 35 patients underwent removal of the mass with complete adrenalectomy. Twelve patients received mitotane alone; 8 mitotane and chemotherapy; 5 chemotherapy alone; 2 radiotherapy associated with mitotane or chemotherapy; 1 anthalgic radiotherapy. Survival time ranged from 1 to 108 months. One-year survival rate was 60%, and 5-year survival rate was 10%. Lower survival rate compared with that reported from other countries is probably related to the referring of patients at very advanced stages of disease. Early recognition and referral, in addition to optimization of therapeutic protocols by multicenter studies, may improve prognostic aspects.

Actuarial Analysis↗

PubMed1994

Disseminated nocardiosis in a patient with Cushing's syndrome.

Nocardia Asteroides infection may occur in corticosteroid treated patients. However, nocardiosis in the presence of endogenous Cushing's syndrome has been previously reported in rare cases. We report a patient with Cushing's syndrome from bilateral nodular adrenal hyperplasia, in whom a disseminated form of nocardiosis complicated his hypercortisolism.

Adult↗

PubMed1994

24-hour blood pressure profile in Addison's disease.

The purpose of this study was to evaluate the circadian blood pressure rhythmicity in patients with primary adrenal insufficiency. Ten newly diagnosed and untreated patients with Addison's disease, 17 addisonian patients (including the previous 10) following an adequate regimen of corticosteroid replacement therapy, and 15 healthy subjects as a control group were studied. Twenty-four-hour ambulatory blood pressure and heart rate were measured automatically every 30 min using a Takeda TM-2420 recorder. The runs test, used for detecting blood pressure diurnal rhythm, was compatible with a rhythm in 2 of 10 patients with untreated Addison's disease, in 13 of 17 patients with treated Addison's disease, and in 13 of 15 normals. Six of eight addisonian patients showing no evidence of blood pressure rhythm in the untreated state acquired circadian periodicity during therapy. An analysis of blood pressure readings by Fourier series with four harmonics showed that blood pressure mesor was lower in untreated than in treated addisonian and normal subjects (P < .05). The nocturnal fall was smaller for systolic and diastolic blood pressure in untreated than in treated addisonian and normal subjects (P < .05). Adrenocortical insufficiency is often characterized by loss of circadian blood pressure rhythm, and normal rhythm can be reestablished by replacement therapy. Lack of cortisol rhythm or persistent activation of the renin-angiotensin system and sympathetic tone may play a role in this phenomenon.

Addison Disease↗

PubMed1994

Patterns of ACTH response to oCRH in Cushing's disease: correlation with histological/immunocytochemical findings.

The most common lesion in Cushing's disease is an anterior pituitary adenoma. However, normal or hyperplastic corticotropic pituitary tissue has also been found in some cases. In an attempt to distinguish the patterns of ACTH response to oCRH in different forms of anterior pituitary hypersecretion, 17 patients with pituitary adenoma and 17 without pathological evidence of adenoma were studied. These patients underwent transsphenoidal pituitary surgery by the same surgeon and were retrospectively evaluated. The diagnosis of pituitary lesions was confirmed by microscopical and immunohistochemical studies. Patients without pituitary adenoma showed a higher and more prolonged mean plasma ACTH response than that observed in patients with pituitary tumors. In patients with pituitary adenoma, the peak ACTH response was observed within 30 min after oCRH administration, and was followed by a gradual decrease to basal levels in the following 30 min. In those cases in whom no pituitary adenoma was found, oCRH injection produced a marked increase in plasma ACTH levels during the first 60 min with a slower decline at the subsequent time points. The mean response curves of the two groups, analyzed by Beherens-Fischer nonparametric ANOVA, showed significant differences, either when they were compared globally (p < 0.01), or at single time points. Differences in ACTH response to oCRH stimulation support the hypothesis of different pathogenetic mechanisms leading to ACTH hypersecretion in Cushing's disease with and without pituitary adenoma.

Adenoma↗

PubMed1994

Molecular genetic studies of sporadic pituitary tumors.

Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of Gs alpha were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of Gs alpha were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of Gs alpha are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype.

Adenoma↗

PubMed1994

Early adrenal hypofunction in patients with organ-specific autoantibodies and no clinical adrenal insufficiency.

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

17-alpha-Hydroxyprogesterone↗