cosyntropin and HIV-Infections

Adrenal insufficiency is known to be a complication of HIV infection, although estimates of its prevalence and severity vary. Adrenal insufficiency is the most serious endocrine complication that occurs in persons with HIV infection. Patients with acquired immune deficiency syndrome (AIDS) are considered to be at high risk for primary or secondary adrenal insufficiency. We describe 3 patients with AIDS who had clinical features suggestive of adrenal insufficiency, but their corticotropin (ACTH) stimulation tests were normal. Repeat testing confirmed the diagnosis in one patient, and further testing with the overnight metyrapone test revealed evidence of secondary adrenal insufficiency in the other patients. Persistent clinical improvement was evident on subsequent glucocorticoid therapy. A normal response to the ACTH stimulation test can be dangerously misleading. Patients with AIDS and suspected adrenal insufficiency who have normal screening by the ACTH stimulation test should undergo further testing for secondary adrenal disease.

Topics: Adrenal Glands; Adrenal Insufficiency; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Combined Modality Therapy; Cosyntropin; Cytomegalovirus Infections; Dexamethasone; False Negative Reactions; Fluid Therapy; HIV Infections; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Metyrapone; Mycobacterium avium-intracellulare Infection; Pituitary Gland; Pituitary-Adrenal System; Risk; Sarcoma, Kaposi; Stomach Neoplasms

Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg p.o. qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/- 0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/- 0.5 microg/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11beta-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adult; Androgens; Androstenedione; Cortodoxone; Cosyntropin; Dehydroepiandrosterone; Double-Blind Method; Enzyme Inhibitors; Female; HIV Infections; Humans; Hydrocortisone; Metyrapone; Middle Aged; Steroid 11-beta-Hydroxylase; Testosterone; Time Factors

The occurrence of endocrine diseases in people who are infected with HIV is traditionally thought to occur in the setting of AIDS with opportunistic infections and malignancies. However, recent studies find the correlation between hypocortisolism and stage of HIV (CD4 count and WHO clinical stage) inconsistent.. This descriptive cross-sectional study included three hundred and fifty (350) consecutive patients with HIV infection. They were interviewed, and subsequently underwent laboratory evaluation for the detection of hypocortisolism. Blood samples for serum cortisol estimation were taken at baseline and at 30 minutes following the administration of 1µg of tetracosactrin (Synacthen). In addition, the patients had blood samples taken at 0 minutes (baseline) for CD4+ lymphocyte cell counts.. At baseline, 108 (30.9%) participants had serum cortisol levels below 100 µg/L with a median value of 55.48 µg/L (11.36-99.96 µg/L), but only 57 (16.3%) study participants had stimulated serum cortisol levels below 180 µg/L with median of 118 µg/L (19.43-179.62). There was no significant difference in the occurrence of clinical features between participants with low and normal serum cortisol, nor WHO clinical stage, CD4 count and ART regimen. The occurrence of hypocortisolism was higher among participants who had been on ART for a longer period of time.. There is a high prevalence of hypocortisolism among HIV patients by biochemical testing, especially those who have been on ARVs for a longer duration. Hypocortisolism cannot be predicted based on the participants' WHO clinical stage of disease, CD4 cell count, or the treatment regimen.. Personal Funds.

Topics: Adrenal Insufficiency; Adult; Antiviral Agents; CD4 Lymphocyte Count; Cosyntropin; Cross-Sectional Studies; Female; HIV Infections; Humans; Hydrocortisone; Logistic Models; Male; Middle Aged; Nigeria; Prevalence; Time Factors

Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 +/- 9 vs. 36 +/- 5 microg/24 h (99 +/- 26 vs. 100 +/- 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contra

Topics: Adrenal Glands; Adult; Androgens; Area Under Curve; Body Weight; CD4 Lymphocyte Count; Chorionic Gonadotropin; Cosyntropin; Dehydroepiandrosterone Sulfate; Energy Intake; Female; HIV Infections; HIV Wasting Syndrome; Humans; Ovary

Recent evidence suggests that 10 microg cosyntropin test has higher sensitivity for detecting hypothalamus-hypophysis-adrenal axis (HHA-A) dysfunction. Our objective was to determine prevalence of glucocorticoid insufficiency with the 10 microg cosyntropin test and the level of the HHA-A defect. One hundred and four HIV-infected patients underwent the 10 microg cosyntropin test. In abnormal and borderline respondents, insulin-induced hypoglycaemia test and human corticotropin releasing hormone test were used to confirm and localize the level of the HHA-A defect. Thirty-two patients with HIV infection and 72 with AIDS were identified. Prevalence of glucocorticoid insufficiency by the 10 microg cosyntropin test was 21.2%. By clinical categories, the frequency in AIDS and HIV infection patients was 26.4% and 9.4%, respectively. Confirmed glucocorticoid insufficiency by insulin-induced hypoglycaemia test was found in 16 out of 19 cases. Twelve cases had primary glucocorticoid insufficiency, 7 had secondary glucocorticoid insufficiency and 3 were false positive. In conclusion, adrenocortical dysfunction occurs in approximately 20% of the cases with HIV disease. Clinical findings commonly occurring in HIV disease as well as adrenocortical insufficiency are not reliable indicators for performing adrenocortical laboratory assessment. Our results suggest screening all AIDS patients with the 10 microg cosyntropin test.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Cosyntropin; Female; Glucocorticoids; HIV Infections; Humans; Hypoglycemia; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Insulin; Male; Middle Aged; Pituitary-Adrenal System

Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone [ACTH (1-39)], alpha-melanocyte-stimulating hormone [alpha-MSH (1-13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication.

Topics: Adrenocorticotropic Hormone; Adult; alpha-MSH; Cosyntropin; Female; HIV Envelope Protein gp120; HIV Infections; Humans; In Vitro Techniques; Interleukin-1; Male; Monocytes; Tumor Necrosis Factor-alpha

In order to determine the prevalence of cortisol deficiency in advanced HIV disease and to examine whether it may be predicted by clinical features or biochemical abnormalities, we conducted a prospective study which assessed responses to a rapid ACTH stimulation test (short-duration synthetic corticotrophin test, synacthen test) in HIV-positive patients with a CD4 count of < or = 50 x 10(6)/l. Subjective fatigue, postural drop in blood pressure, electrolyte changes, presence of concurrent opportunist infection and drug treatment were recorded. Cortisol responses were defined as 'normal' (a post stimulation cortisol level > or = 450 nmol/l), 'abnormal' (post stimulation cortisol level < 350 nmol/l) or 'impaired' (an intermediate response). Of 49 patients tested (42 male, seven female), a suboptimal response (abnormal or impaired) was found in 14 (29%) and frank insufficiency in eight (16%). Cortisol deficiency was not predicted by postural drop in blood pressure, biochemistry or symptoms of fatigue. Patients with an impaired/abnormal test were not more likely to have cytomegalovirus or mycobacterial disease but were more likely to be taking megestrol acetate (P = 0.05, Fisher's exact test). Two of three patients with initially normal tests developed impaired/abnormal cortisol responses on re-testing 6-9 months later. Cortisol deficiency is common in late stage HIV disease, but symptoms of fatigue and postural hypotension, as well as biochemical findings, are poor predictors of cortisol deficiency. We found good subjective response to therapy. Routine screening by a rapid ACTH stimulation test is recommended in HIV-positive patients with CD4 count < or = 50 x 10(6)/l. Re-testing at regular intervals may be necessary. The interaction between megestrol acetate, cortisol metabolism and synacthen testing requires further investigation.

Topics: Adrenal Cortex; Adult; CD4 Lymphocyte Count; Cosyntropin; Female; HIV Infections; HIV Seropositivity; Humans; Hydrocortisone; Male; Middle Aged; Predictive Value of Tests; Prevalence; Prospective Studies; Time Factors

Adrenal dysfunction has been reported in patients infected with the human immunodeficiency virus (HIV). To evaluate the prevalence and degree of adrenal dysfunction in HIV-infected patients, we performed a longitudinal study in 53 ambulatory HIV patients. The plasma cortisol, aldosterone, and dehydroepiandrosterone (DHEA) responses to cosyntropin (250 micrograms, i.v.) were evaluated at 6-month intervals for 24 months and compared to those of normal subjects. The basal and peak cortisol responses to cosyntropin were normal in all HIV patients during the study. There was no difference in the mean basal or stimulated cortisol measurements between Center for Disease Control (CDC) class II-III and CDC class IV patients. Although the mean peak aldosterone response to cosyntropin in HIV patients did not differ from that in normal subjects during the study, the aldosterone secretory capacity was significantly less in CDC class IV than CDC class II-III patients at 6- and 18-month intervals. In addition, there was an impaired aldosterone response to cosyntropin in 31-53% of CDC class IV patients and in only 0-26% of CDC class II-III patients. The mean peak DHEA response to cosyntropin in HIV patients was significantly less than that in normal subjects during the entire study. Basal plasma aldosterone, PRA, cortisol, and DHEA levels did not change in 25 HIV patients who were followed for the entire 24-month period. However, plasma ACTH in these 25 patients was significantly increased at 24 months (9.7 +/- 0.9 pmol/L) compared to that at study entry (7.0 +/- 0.7 pmol/L). Of these 25 patients, 8 had plasma ACTH concentrations that exceeded the normal range at 24 months. The subnormal aldosterone and DHEA secretion with normal cortisol production in these HIV patients is similar to the alterations in adrenal function reported in seriously ill patients without HIV infection. Although we found that clinically significant adrenal insufficiency is uncommon, the elevations in plasma ACTH in several patients at the end of our 2-yr study suggest that adrenocortical capacity may become compromised.

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adult; Cosyntropin; Electrolytes; Female; HIV Infections; Hormones; Humans; Longitudinal Studies; Male; Reference Values