Prevalence of endocrine dysfunction in HIV-infected men

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.     

Serum Morning Cortisol as A Screening Test for Adrenal Insufficiency

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI).Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC.Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value.Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted.Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol     

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay

IntroductionThe accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 μg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays.MethodsThe ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method.ResultsThe concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%).ConclusionWe recommend a threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 μg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.     

Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function.

The adrenocortical response to the simple 30-minute ACTH stimulation test was compared with the hypothalamic-pituitary-adrenocortical (HPA) response to insulin-induced hypoglycaemia in 25 patients with various degrees of hypothalamic-pituitary malfunction. The correlations between the increase in plasma cortisol during insulin hypoglycaemia and that during ACTH stimulation (r = 0-66) and between peak plasma cortisol levels during the two tests (r = 0-90) were highly significant. Peak plasma cortisol levels in individual patients were similar on both tests, no patient showing any major discrepancy between the two test results. Thus the simple 30-minute ACTH stimulation test seems to be reliable in detecting imparied HPA function.     

Significance of low-dose and standard-dose ACTH tests compared to overnight metyrapone test in the diagnosis of adrenal insufficiency in childhood

OBJECTIVE: To discover the value of low-dose (LDAT) and standard-dose ACTH tests (SDAT) as compared with the metyrapone test in the diagnosis of secondary adrenal insufficiency. PATIENTS AND METHODS: LDAT (0.5 microg/m2), SDAT (250 microg/m2) and overnight metyrapone (30 mg/kg) tests were carried out in 29 patients with suspected adrenal insufficiency. LDAT and SDAT were also performed in 36 control subjects. RESULTS: 18 of 29 patients were grouped in the adrenal-sufficient (AS) group and 11 of 29 patients in the adrenal-deficient (AD) group according to the metyrapone test results. The control group had significantly higher cortisol responses than the AS and AD groups during LDAT. The control group had similar cortisol responses to the AS group but higher cortisol responses than the AD group during SDAT. The AS group was divided into 2 subgroups: AS patients with multiple pituitary hormone deficiencies (AS-multiple) and AS patients with idiopathic growth hormone deficiencies (AS-isolated). The AS-multiple group had statistically lower cortisol responses than the control group during LDAT. Receiver-operating characteristics analysis revealed that the cortisol cutoff value in LDAT was 19.8 microg/dl (100% sensitivity, 89% specificity) and 30.4 microg/dl in SDAT (82% sensitivity, 78% specificity). CONCLUSION: LDAT is capable of identifying patients with adrenal insufficiency more effectively than SDAT. The cortisol cutoff value in LDAT was calculated as 19.8 microg/dl with 100% sensitivity. AS patients with multiple pituitary hormone deficiencies had lower cortisol responses to LDAT than the control group implying that these patients might have a lower cortisol secretory capacity than healthy subjects.     

Assessment of adrenal function by measurement of salivary steroids in response to corticotrophin in patients infected with human immunodeficiency virus

OBJECTIVE: Adrenal insufficiency has been reported among critically ill HIV-infected patients. This is the first study that attempts to detect subclinical hypoadrenal states in non-critical HIV patients through salivary steroids in response to intramuscular low-dose ACTH injection. PATIENTS AND METHODS: We studied 21 ambulatory adult HIV-infected patients without specific clinical signs or symptoms of adrenal insufficiency. Normal salivary flow-rate and salivary alpha-amylase activity confirmed adequate salivary gland function. Salivary cortisol (SAF) and salivary aldosterone (SAL) were obtained at baseline and 30 min after the injection of 25 microg of ACTH in the deltoid muscle (LDT(s)). Assessment of salivary steroids after stimulation with 250 microg of intramuscular ACTH (HDT(s)) was performed on those who hyporesponded to LDT(s). Basal blood samples were drawn for steroids, renin and ACTH measurements. RESULTS: At baseline SAF and SAL correlated significantly (p=0.0001) with basal serum cortisol and aldosterone (r=0.70 and 0.91, respectively). Plasma ACTH and renin concentrations were within the normal range in all patients. Eight of the twenty-one HIV(+) patients were LDT(s) hyporesponders in either SAF (n:1) or SAL (n:7). LDT(s) repeated in six cases after a year reconfirmed the impairment of aldosterone secretion. LDT(s) hyporesponders had normal steroid responses to HDT(s). CONCLUSIONS: LDT(s) is a simple, safe, well-accepted and non-invasive approach to assess adrenal function in HIV-infected ambulatory patients. It revealed subnormal cortisol (5%) and aldosterone responses (33%) when HDT(s) results were normal.     

The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis

ObjectiveTo study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection.MethodsMorning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease.ResultsThe median morning cortisol level was 196 (31-587) nmol/L. It was <100 nmol/L in 8 patients (28.6%), <200 nmol/L in 14 patients (50%), and <300 nmol/L in 18 patients (64.3%). The corresponding ACTH values had a median of 18.5 ng/L (range 4-38 ng/L), and the ACTH level was <10 ng/L in 7 patients (26.9%), <20 ng/L in 17 patients (60.7%), and <30 ng/L in 23 patients (82.1%). The repeated testing on different days showed a similar pattern. Overall, if a cutoff level of <300 nmol/L is considered abnormal in the setting of acute disease, 9 patients (32%) had cortisol levels below this limit, regardless of whether the test was done only once (3 patients) or 3 times (6 patients). When the disease was more severe, the patients had lower cortisol and ACTH levels, suggesting a direct link between the COVID-19 infection and impaired glucocorticoid response.ConclusionUnexpectedly, the adrenocortical response in patients with COVID-19 infection was impaired, and a significant percentage of the patients had plasma cortisol and ACTH levels consistent with central adrenal insufficiency.     

The Low-Dose Acth Stimulation Test: is 30 Minutes Long Enough?

Objective: Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration.Methods: Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency.Results: We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes.Conclusion: Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.Abbreviations: ACTH = adrenocorticotropic hormone AI = adrenal insufficiency BMI = body mass index LDST = low-dose ACTH stimulation test MRI = magnetic resonance imaging     

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.     

Corticotropin-releasing factor in humans. II. CRF stimulation in patients with diseases of the hypothalamo-pituitary-adrenal axis

A stimulation test with 100 micrograms ovine or human corticotropin-releasing factor (CRF) is a useful diagnostic tool in diseases of the hypothalamo-pituitary-adrenal axis. No serious side effects were observed during the test procedure. The results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome (n = 42). The CRF test was also repeated after transsphenoidal surgery in 25 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal adrenocorticotropic hormone (ACTH) responses to CRF (n = 15), whereas patients who did not show remission remained hyperresponsive (n = 10). In patients with autonomous adrenal cortisol secretion, the ACTH response to CRF was suppressed (n = 10). After surgery the ACTH response to CRF can already be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy and another patient under corticoid therapy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRF deficiency. The decrease of the ACTH responses to CRF in glucocorticoid-treated patients correlated directly to the daily corticoid dosage. Since the ACTH hyperresponse to CRF in 6 patients with Cushing's disease was also suppressed by short-term dexamethasone treatment, the pituitary level as target site for the acute feedback inhibition is also demonstrated. The evaluation of the CRF-induced ACTH response in patients with secondary adrenal failure without detectable pathology in the sella and suprasellar region (n = 6) enables the differentiation between hypothalamic and pituitary adrenal insufficiency. In patients with hypothalamic lesions the ACTH response to CRF was normal whereas insulin hypoglycemia failed to induce an ACTH rise.     

Plasma acth and cortisol levels in depressed patients: Relation to dexamethasone suppression test

Blood samples collected from normal subjects and newly hospitalized depressed patients at 8 AM on the day before and at 8 AM and 4 PM the day after receiving dexamethasone, 1 mg orally at 11 PM, were analyzed for ACTH and cortisol. The mean plasma ACTH values of these two groups were not significantly different at any of the times, while the cortisol levels of the depressed patients were significantly higher than those of the normal subjects at 8 AM pre-dexamethasone (P<0.001). There was no correlation between plasma ACTH and cortisol values in either group. The cortisol responses to dexamethasone in depressed patients revealed two subgroups. In one subgroup, the cortisol was suppressed as much as in normal subjects, but in the other, cortisol levels were not suppressed. The post-dexamethasone ACTH rebounded at 4 PM in the latter subgroup to higher values than in the subgroup with suppressed cortisol levels and in the normal subjects. After dexamethasone, the ACTH values were negatively correlated with plasma cortisol only in the normal subjects (P<0.01), not in the depressed patients. These results indicate that ACTH levels do not account for the elevated cortisol and the failure of dexamethasone to suppress cortisol levels in some depressed patients.     

Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women.

Oxytocin (OT) administration has been shown to inhibit adrenocorticotropic hormone (ACTH)/cortisol secretion in several experimental conditions. In the present study, the plasma OT responses to suckling in 7 lactating women or to mechanical breast stimulation in 6 normally menstruating women (experimental tests) or to sham stimuli in the same subjects (control tests) were measured and correlated with the simultaneous changes in plasma ACTH/cortisol levels. All women showed similar basal levels of OT, ACTH and cortisol, which remained unmodified after sham stimulation. In contrast, both suckling and breast stimulation produced a significant increase in plasma OT levels and a significant decrease in plasma ACTH concentrations. When OT and ACTH data were considered together, a significant negative correlation was found between the OT increase and the simultaneous ACTH decline. Plasma cortisol levels were lower during suckling or breast stimulation than in control conditions. These data show an inverse relationship between plasma OT and ACTH levels during suckling and breast stimulation in humans, suggesting an inhibitory influence of OT on ACTH/cortisol secretion in a physiological condition.     

Recovery of Adrenal Function after Long-Term Glucocorticoid Therapy for Giant Cell Arteritis: A Cohort Study

Objectives

Giant cell arteritis (GCA) is a chronic systemic vasculitis of large and medium-sized arteries, for which long-term glucocorticoid (GC) treatment is needed. During GC withdrawal patients can suffer adrenal insufficiency. We sought to determine the time until recovery of adrenal function after long-term GC therapy, and to assess the prevalence and predictors for secondary adrenal insufficiency.

Subjects and Design

150 patients meeting the ACR criteria for GCA between 1984 and 2012 were analyzed. All received the same GC treatment protocol. The low-dose ACTH stimulation test was repeated annually until adrenal recovery. Biographical, clinical and laboratory data were collected prospectively and compared.

Results

At the first ACTH test, 74 (49%) patients were non-responders: of these, the mean time until recovery of adrenal function was 14 months (max: 51 months). A normal test response occurred within 36 months in 85% of patients. However, adrenal function never recovered in 5% of patients. GC of >15 mg/day at 6 months, GC of >9.5 mg/day at 12 months, treatment duration of >19 months, a cumulative GC dose of >8.5 g, and a basal cortisol concentration of <386 nmol/L were all statistically associated with a negative response in the first ACTH test (p <0.05).

Conclusion

Adrenal insufficiency in patients with GCA, treated long-term with GC, was frequent but transitory. Thus, physicians’ vigilance should be increased and an ACTH test should be performed when GC causes the above associated statistical factors.     

Diagnostic value of salivary cortisol in children with abnormal adrenal cortex functions

AIMS: It has been shown that the free cortisol level in saliva may reflect plasma free cortisol. The measurement of cortisol in saliva is a simple method, and as such it is important in the pediatric age group. In this research, the diagnostic value of measurement of salivary cortisol (SC) measurement was examined in adrenal insufficiency (AI). METHODS: Fifty-one patients, mean age 10.8 +/- 4.29, who were investigated for possible AI, were included. Basal cortisol levels were below 18 microg/dl. Adrenal function was determined by low-dose ACTH test. During the test, samples for SC were obtained simultaneously with serum samples (at 0-10-20-30-40 min). RESULTS: Mean basal serum cortisol level was 8.21 +/- 4.10 microg/dl (mean +/- SD). Basal SC was correlated to basal serum cortisol (r = 0.64, p < 0.001). A cut-off of 0.94 microg/dl for SC differentiated adrenal insufficient subjects from normals with a sensitivity and specificity of 80 and 77%, respectively. A peak SC less than 0.62 microg/dl defined AI with a specificity of 100%; however, sensitivity was 44%. CONCLUSION: Measurement of SC may be used in the evaluation of AI. It is well-correlated to serum cortisol. Peak SC in low-dose ACTH test can be used to differentiate patients with AI in the initial evaluation of individuals with suspected AI.     

Diagnostic value of salivary cortisol in end stage renal disease

OBJECTIVES: Salivary cortisol has been proposed a surrogate marker for free serum cortisol measurements. The aim of this study was to ascertain the diagnostic value of basal and stimulated salivary cortisol for the detection of adrenal insufficiency (AI) in hypotensive end stage renal disease (ESRD) patients. Basal salivary cortisol and basal total serum cortisol were studied in order to determine the accuracy of both biomarkers in predicting AI. PATIENTS AND METHODS: Twenty-nine ESRD patients with sustained hypotension were investigated for possible AI. Salivary cortisol was assessed at baseline and 30min after 25microg ACTH i.m. (LDTs). The dosage of salivary aldosterone was performed in salivary cortisol hypo-responders. Basal blood samples were drawn for steroids, renin and ACTH measurements. RESULTS: A clear separation between patients with normal and impaired adrenal function was obtained through salivary cortisol levels at 30min after ACTH. AI was detected in six cases (21%) through impaired salivary cortisol responses; stimulated salivary aldosterone helped to differentiate primary (n=3) from secondary AI (n=3). ROC curves showed that cutoff values for basal SAF < or =4.4nM and serum cortisol < or =232.0nM suggest AI (sensitivities: 93% and 69%; specificities: 86.4% and 91%, respectively). CONCLUSIONS: We conclude that ACTH stimulated SAF is an accurate biomarker for the diagnosis of AI in hypotensive ESRD patients. Neither basal salivary cortisol nor serum cortisol showed 100% sensitivities for the detection of AI.     

The use of the corticotropin-releasing hormone test to monitor the recovery of patients with Cushing's disease or Cushing's syndrome due to an adrenal adenoma after adenomectomy

Six patients with Cushing's disease and three with Cushing's syndrome due to an adrenal adenoma were monitored after their adenomectomy with the corticotropin-releasing hormone test to evaluate the progress of recovery of their pituitary adrenal function. Before surgery the patients with Cushing's disease showed either high, normal or low responses of plasma ACTH and cortisol to 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) administered intravenously, whereas all three patients with Cushing's syndrome due to an adrenal adenoma showed no response of plasma ACTH or cortisol to CRH. One or two months after surgery, the patients who had Cushing's disease had low levels of basal plasma ACTH and cortisol and their responses to CRH were extremely low. However, the same patients were tested later, it was found that their responses to CRH gradually increased and reached normal ranges approximately within one year after tumor removal, which coincided with the overall improvement in their clinical signs and symptoms due to adrenal insufficiency. In contrast, the recovery of the pituitary adrenal function in patients who had Cushing's syndrome due to an adrenal adenoma was not complete even one year after surgery. Thus the corticotropin-releasing factor test is a useful criteria to evaluate the recovery of the pituitary adrenal function in these patients after surgery, since the responses of plasma ACTH and cortisol to the administered CRH are parallel with the improvements in clinical signs and symptoms due to adrenal insufficiency in patients with Cushing's disease.     

Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.     

Coexistence of 21-hydroxylase and 11 beta-hydroxylase deficiency in adrenal incidentalomas and in subclinical Cushing's syndrome

OBJECTIVE: The prevalence of steroid secretion abnormalities was studied by evaluating the 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) responses to adrenocorticotropic hormone (ACTH) stimulation in 48 patients with 'nonfunctioning' incidentalomas and in 10 patients with 'subclinical' Cushing's syndrome. METHODS: In all patients the cortisol, 17-OHP, and S levels were measured after ACTH test. Eight patients were reinvestigated after surgery. RESULTS: In patients with nonfunctioning lesions, the ACTH test induced 17-OHP and S peaks higher than in normals (p < 0.005). In 10 cases an augmented rise of 17-OHP and S was observed. In patients with subclinical Cushing's syndrome, the 17-OHP peak after ACTH was greater than in patients with nonfunctioning lesions and in normals (p < 0.005); the S peak was also higher than in controls (p < 0.005). In 7 of 8 operated patients, the exaggerated 17-OHP peak was normalized. CONCLUSIONS: A combined impairment of different enzyme activities is frequently present in adrenal incidentalomas; the alteration of enzymatic pathways can also coexist with the presence of partial cortisol autonomy.     

Value of an ACTH Test in Assessing Hypothalamic-Pituitary-Adrenocortical Function in Glucocorticoid-treated Patients

Forty-eight patients receiving glucocorticoid treatment were tested with ACTH stimulation using α^{1, 24} ACTH (tetracosactrin). All patients subsequently underwent non-acute major surgery without any glucocorticoid administration, and their clinical course and plasma corticosteroids were followed closely. No case of adrenocortical insufficiency was observed. A highly significant correlation was found between the pre-operative adrenocortical response to ACTH and the hypothalmic-pituitary-adrenocortical (H.P.A.) response to surgery. A normal response to ACTH stimulation was never followed by a greatly impaired H.P.A. response to surgery. It seems that a simple ACTH stimulation test is reliable in predicting the integrated H.P.A. response to major stress in glucocorticoid-treated patients.     

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At approximately 138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 +/- 1.2 vs. 47.3 +/- 11.1 ng.ml(-1).2 h(-1)) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.