0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review Article |

Adrenal Function in the Human Immunodeficiency Virus–Infected Patient FREE

Jose Mayo, MD; Julio Collazos, MD; Eduardo Martínez, MD; Sofía Ibarra, MD
[+] Author Affiliations

From the Section of Infectious Diseases, Hospital de Galdakao, Vizcaya, Spain.


Arch Intern Med. 2002;162(10):1095-1098. doi:10.1001/archinte.162.10.1095.
Text Size: A A A
Published online

Although clinical manifestations of adrenal dysfunction are uncommon in patients infected with human immunodeficiency virus (HIV), subclinical functional abnormalities of the hypothalamic-pituitary-adrenal axis are frequent. Patients infected with HIV usually have higher basal serum cortisol and lower serum dehydroepiandrosterone concentrations than HIV-seronegative individuals. This imbalance has been related to progression of the infection by inducing a shift from TH 1 to TH 2 immunologic responses. Although, adrenal reserve may be marginal in HIV-infected patients, clinically evident adrenal insufficiency is uncommon and, when present, it is observed in advanced stages of the infection. Hypocortisolemia should be treated regardless of the existence of associated symptoms. On the contrary, hypercortisolemia in the absence of features of Cushing syndrome is common and should not promote treatment nor specific studies. The possible influence that alterations of the adrenal function could have on the patients' immune status and the eventual effect of antiretrovirals on these alterations merit further investigation.

Adrenal gland involvement has been documented in as many as two thirds of patients with acquired immunodeficiency syndrome (AIDS) at postmortem examination.1 However, adrenal insufficiency is seldom diagnosed in clinical practice because symptoms do not appear until more than 80% of the gland has been destroyed, and the extent of necrosis in the most frequent autopsy finding, cytomegalovirus adrenalitis, rarely exceeds 60%.2,3 Nevertheless, 2 (3%) of 75 autopsies performed in unselected patients with AIDS at a single center revealed greater than 80% destruction of the adrenal cortex by cytomegalovirus4; this is in agreement with the 3% of patients who had an antemortem diagnosis of adrenal insufficiency in another necropsy series.1

Less common pathological processes include other opportunistic infections (Mycobacterium tuberculosis and Mycobacterium avium–intracellulare, Cryptococcus neoformans, Histoplasma capsulatum, Pneumocystis carinii, and Toxoplasma gondii), neoplasms (Kaposi sarcoma and lymphoma), hemorrhage, fibrosis, infarction, and more subtle abnormalities such as cortical lipid depletion, a likely surrogate of long-lasting severe stress.2,3,5,6 Adrenocortical antibodies are detected in a substantial proportion of patients with AIDS,3,5 probably as an epiphenomenon linked to nonspecific B-cell activation and devoid of clinical significance. Finally, several drugs have been found to be responsible for adrenal insufficiency by decreasing steroidogenesis (ketoconazole), enhancing cortisol metabolism (rifampin), or suppressing pituitary secretion of corticotropin due to their intrinsic glucocorticoid activity (megestrol acetate).3,7 In fact, Cushing syndrome induced by continuous administration of megestrol acetate has been reported.8

Subclinical functional abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis are much more prevalent than clinical manifestations of these disturbances. Basal serum cortisol levels seem to be higher in patients infected with human immunodeficiency virus (HIV) than in controls,9,10 with a negative linear correlation between CD4 cell counts and cortisol found in some,11 but not all,12 studies. This elevation is usually associated with normal levels of 17-deoxysteroids (ie, corticosterone, deoxycorticosterone, and 18-OH-deoxycorticosterone), subnormal increase of both 17-deoxysteroids9 and cortisol9,1315 in response to cosyntropin, and an altered circadian rhythm of pituitary and adrenocortical hormone secretion.10,16 These patients also have a normal suppression of cortisol synthesis by dexamethasone, and lower levels of corticotropin10 and dehydroepiandrosterone (DHEA),1012,17 an adrenal androgen that has a positive correlation with CD4 cell counts.11,12,17

Although basal aldosterone levels tend to be lower in HIV-infected individuals, and both hyporeninemic and hyperreninemic hypoaldosteronism have been reported,18 response of plasma aldosterone to angiotensin III infusion and postural stimulation was normal in a study9; these findings have been interpreted as a preferential involvement of the zona fasciculata over the zona glomerulosa.2,3,5 There are 2 case reports of primary aldosteronism in HIV-infected patients,19 perhaps mediated through a reninlike activity of the HIV aspartic protease, but the causal relationship is far from clear.

Several pathogenic mechanisms have been proposed to explain the relative hypercortisolemia present in untreated HIV-positive individuals. First, the shift of steroid metabolism from aldosterone, DHEA, and 17-deoxysteroids to cortisol may represent an adaptive response to stress.2,3,5,6 Second, the cortisol-binding globulin of HIV-infected patients shows a higher number of binding sites compared with controls.20 Some authors have also found increased plasma concentrations of cortisol-binding globulin associated with progression of the disease,21 whereas others found normal levels of cortisol-binding globulin in all HIV disease stages.22 Third, the increased cortisol synthesis in the absence of an increase in corticotropin suggests that some nonpituitary factors derived from infected immune cells, such as interleukin (IL)-1β and IL-6,10,23,24 might directly stimulate the adrenal cortex. In patients with hypercortisolemia and increased corticotropin levels, these abnormalities may result from a stimulatory effect of cytokines (eg, interferon-α, IL-1β, IL-2, and IL-6)25 or the HIV envelope protein gp12026 on the hypothalamic corticotropin-releasing hormone release. However, patients with advanced HIV disease often have reduced or blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone infusion,27 and cases of secondary adrenal insufficiency with normal corticotropin stimulation tests have been described.28 Fourth, some patients with AIDS have a syndrome of peripheral cortisol resistance due to acquired abnormalities of the glucocorticoid receptor (GR), characterized by an increase in GR density and a decrease in GR affinity for the substrate.29 These individuals have a high-cortisol, low-corticotropin state with paradoxical Addisonian features, but it is conceivable that a clinical spectrum exists, ranging from subclinical alterations to overt adrenal failure. Finally, the HIV vpr gene product has been reported to act as a GR coactivator in human lymphoid and muscle-derived cell lines,30 which could result in an enhanced effect of glucocorticoids on the target cells.

It has been suggested that this pattern of high cortisol and low DHEA levels could induce a worsening in immune status by shifting the cytokine production from the so-called TH 1 or cellular-type response (interferon-γ, IL-2, and IL-12) to the TH 2 or humoral-type response (IL-4, IL-5, IL-6, and IL-10),31 a hallmark of HIV disease progression. In fact, cortisol suppresses interferon-γ and IL-2 production, favors IL-4 production, and stimulates programmed cell death (apoptosis).31 In this regard, cortisol-resistant AIDS patients have a type 1 cytokine profile.32 In contrast, DHEA appears to enhance immune function,12 probably by antagonizing some effects of cortisol on lymphocytes3; indeed, both decreased concentrations of DHEA33,34 and increased cortisol/DHEA ratio35 are independent predictors of progression to AIDS in some studies.

How and whether highly active antiretroviral therapy modifies this profile is largely unknown. Shortly after the release of protease inhibitors (PIs) for clinical use, disorders in the body adipose tissue distribution, including truncal obesity, visceral fat deposition, peripheral wasting, breast hypertrophy, and enlargement of the dorsocervical pad ("buffalo hump"), often associated with hyperlipidemia, hyperinsulinemia, and insulin resistance, were recognized.36,37 The similarities in their phenotypic characteristics led some authors to use the term pseudo-Cushing syndrome to denominate this clinical picture,38 but soon it became clear that, unlike the pseudo-Cushing syndrome seen in alcoholism or severe depression, the vast majority of PI-treated patients had normal or slightly elevated cortisol levels in the morning serum or in the 24-hour urinary determinations, and showed normal dexamethasone suppression tests.37,3942 Due to a number of clinical and laboratory features shared with classic generalized lipodystrophic syndromes, these changes in fat distribution and metabolic profile have been commonly referred to as antiretroviral-associated lipodystrophy. Lately, lipodystrophy has been linked to antiretrovirals other than PIs (eg, nucleoside-analogue reverse-transcriptase inhibitors) or even to the HIV infection itself,43 and ascribed to a large array of pathogenic mechanisms, such as inhibition by the PIs of several host-cell proteins involved in lipid and carbohydrate metabolism,44 PI-induced subcutaneous adipocyte apoptosis,45 mitochondrial damage attributable to nucleoside-analogue reverse-transcriptase inhibitors,46 and cytokine dysregulation in the setting of immune recovery,47 among others.

In a cross-sectional study,48 the serum steroid hormone concentrations of patients taking highly active antiretroviral therapy who presented symptoms of lipodystrophy, according to a subjective clinical score, were compared with those of nonlipodystrophic individuals. Serum cortisol levels were elevated in patients compared with HIV-negative controls, but no differences were found between individuals with or without lipodystrophy. However, serum DHEA levels were significantly lower and cortisol/DHEA ratio higher in patients with lipodystrophy, and cortisol/DHEA ratio correlated positively with both dyslipidemia and the subjective clinical score. Christeff et al48 speculated that the increased cortisol and decreased DHEA concentrations were due to the effect of PIs on cytochrome P450 isoforms involved in steroid metabolism, producing an imbalance between lipolysis and lipogenesis that could account for the peripheral fat loss and central fat accumulation.48

In another study,49 patients with antiretroviral-related lipodystrophy, defined by changes in body shape and abdominal computed tomographic scan findings, were compared with HIV-negative controls for multiple parameters of the HPA axis; unfortunately, there was no group of untreated HIV-positive individuals. Lipodystrophic patients showed normal values of serum cortisol levels, cortisol response after corticotropin-releasing hormone stimulation, cortisol-binding globulin concentration, and GR number and affinity, ruling out hyperactivity of the HPA axis as a cause of lipodystrophy. However, basal and corticotropin-releasing hormone–stimulated plasma corticotropin concentration, as well as 24-hour urinary 17-OH-corticosteroid concentrations, were significantly greater, whereas urinary free cortisol excretion was significantly lower in patients than in controls. The authors hypothesized that 1 or more of the antiretroviral drugs taken by these patients alter the metabolism of cortisol by enhancing the renal 11-ketosteroid reductase activity or by partially inhibiting the adrenal 11-hydroxylase. According to this study, lipodystrophy cannot be attributed to hypercortisolism, and other possible mechanisms, such as selective changes in the glucocorticoid sensitivity of different adipose tissue depots, are worth exploring.49 We are aware of a single study that compared serum cortisol levels in nucleoside-analogue reverse-transcriptase inhibitor–treated and naive HIV-infected patients, excluding therefore the effect of PI, and no difference was found between the 2 groups.50

Clinically evident adrenal insufficiency constitutes an uncommon event in HIV infection. When present, it usually involves patients in advanced stages of the infection, with cytomegalovirus disease or under treatment with drugs that interfere with cortisol metabolism. Even in this setting, the rate of adrenal insufficiency is probably lower than 5%. However, adrenal reserve may be marginal, as suggested by a subnormal response to corticotropin stimulation tests in many cases, and this diagnosis should be kept in mind whenever a patient who undergoes stressing conditions, such as infection or trauma, develops hypotension, profound weakness, untreatable fever, or electrolyte abnormalities. Basal hypocortisolemia, even asymptomatic, should be treated with lifelong substitutive glucocorticoids, but cortisol supplementation for only very stressing situations (eg, surgery) is probably sufficient in patients with normal serum cortisol levels and corticotropin hyporesponsiveness.

Hypercortisolemia without clinical features suggestive of Cushing syndrome is frequent enough to not warrant a complete workup of adrenal disease. Antiretroviral-associated lipodystrophy is usually distinguishable from Cushing syndrome on a clinical basis. However, if lipodystrophy coexists with marked hypercortisolemia, measurement of 24-hour free urinary cortisol level and a dexamethasone suppression test would clarify this issue. The extent to which alterations in the HPA axis are related to these patients' immune dysfunction, as well as the possible changes induced by antiretroviral treatment, should be further investigated. At present, no intervention for these subclinical abnormalities is likely to be useful.

Accepted for publication September 6, 2001.

Corresponding author and reprints: Julio Collazos, MD, Section of Infectious Diseases, Hospital de Galdakao, 48960 Vizcaya, Spain.

Bricaire  FMarche  CZoubi  DRegnier  BSaimot  AG Adrenocortical lesions and AIDS. Lancet. 1988;1881
Link to Article
Grinspoon  SKBilezikian  JP HIV disease and the endocrine system. N Engl J Med. 1992;3271360- 1365
Link to Article
Hofbauer  LCHeufelder  AE Endocrine implications of human immunodeficiency virus infection. Medicine (Baltimore). 1996;75262- 278
Link to Article
McKenzie  RTravis  WDDolan  SA  et al.  The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases. Medicine (Baltimore). 1991;70326- 343
Link to Article
Brown  LS  JrSinger  FKillian  P Endocrine complications of AIDS and drug addiction. Endocrinol Metab Clin North Am. 1991;20655- 673
Lo  JCSchambelan  M Endocrine disease. Dolin  RMasur  HSaag  MSeds.AIDS Therapy Philadelphia, Pa Churchill Livingstone1999;740- 751
Leinung  MCLiporace  RMiller  CH Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med. 1995;122843- 845
Link to Article
Padmanabhan  SRosenberg  AS Cushing's syndrome induced by megestrol acetate in a patient with AIDS. Clin Infect Dis. 1998;27217- 218
Link to Article
Membreno  LIrony  IDere  WKlein  RBiglieri  EGCobb  E Adrenocortical function in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1987;65482- 487
Link to Article
Villette  JMBourin  PDoinel  C  et al.  Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus. J Clin Endocrinol Metab. 1990;70572- 577
Link to Article
Christeff  NGherbi  NMammes  O  et al.  Serum cortisol and DHEA concentrations. Psychoneuroendocrinology. 1997;22 (Suppl 1) S11- S18
Link to Article
Wisniewski  TLHilton  CWMorse  EWSvec  F The relationship of serum DHEA-S and cortisol levels to measures of immune function in human immunodeficiency virus-related illness. Am J Med Sci. 1993;30579- 83
Link to Article
Raffi  FBrisseau  JMPlanchon  BRémi  JPBarrier  JHGrolleau  JY Endocrine function in 98 HIV-infected patients: a prospective study. AIDS. 1991;5729- 733
Link to Article
Abbott  MKhoo  SHHammer  MRWilkins  EG Prevalence of cortisol deficiency in late HIV disease. J Infect. 1995;311- 4
Link to Article
Kumar  MKumar  AMMorgan  RSzapocznik  JEisdorfer  C Abnormal pituitary-adrenocortical response in early HIV-1 infection. J Acquir Immune Defic Syndr. 1993;661- 65
Malone  JLOldfield  ECWagner  KF  et al.  Abnormalities of morning serum cortisol levels and circadian rhythms of CD4 + lymphocyte counts in human immunodeficiency virus type 1-infected adult patients. J Infect Dis. 1992;165185- 187
Link to Article
de la Torre  Bvon Krogh  GSvensson  MHolmberg  V Blood cortisol and dehydroepiandrosterone sulphate (DHEAS) levels and CD4 T cell counts in HIV infection. Clin Exp Rheumatol. 1997;1587- 90
Seney  FD  JrBurns  DKSilva  FG Acquired immunodeficiency syndrome and the kidney. Am J Kidney Dis. 1990;161- 13
Link to Article
Stricker  RBGoldberg  DAHu  CHsu  JWGoldberg  B A syndrome resembling primary aldosteronism (Conn syndrome) in untreated HIV disease. AIDS. 1999;131791- 1792
Link to Article
Martin  MEBenassayag  CAmiel  CCanton  PNunez  EA Alterations in the concentrations and binding properties of sex steroid-binding protein and corticosteroid-binding globulin in HIV + patients. J Endocrinol Invest. 1992;15597- 603
Link to Article
Schurmeyer  THMuller  Vvon zur Muhlen  ASchmidt  RE Thyroid and adrenal function in HIV-infected outpatients. Eur J Med Res. 1997;2220- 226
Lambert  MZech  FDe Nayer  PJamez  JVandercam  B Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection. Am J Med. 1990;89748- 751
Link to Article
Tauveron  IThieblot  PLaurichesse  H The Cushing syndrome associated with AIDS. Ann Intern Med. 1994;120620- 621
Link to Article
Biglino  ALimone  PForno  B  et al.  Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection. Eur J Endocrinol. 1995;133173- 179
Link to Article
Raber  JSorg  OHorn  TF  et al.  Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function. Brain Res Brain Res Rev. 1998;26320- 326
Link to Article
Costa  ANappi  REPolatti  FPoma  AGrossman  ABNappi  G Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide. Exp Neurol. 2000;166376- 384
Link to Article
Lortholary  OChristeff  NCasassus  P  et al.  Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. J Clin Endocrinol Metab. 1996;81791- 796
Eledrisi  MSVerghese  AC Adrenal insufficiency in HIV infection: a review and recommendations. Am J Med Sci. 2001;321137- 144
Link to Article
Norbiato  GBevilacqua  MVago  T  et al.  Cortisol resistance in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74608- 613
Kino  TGragerov  AKopp  JBStauber  RHPavlakis  GNChrousos  GP The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med. 1999;18951- 62
Link to Article
Clerici  MTrabattoni  DPiconi  S  et al.  A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus. Psychoneuroendocrinology. 1997;22 (Suppl 1) S27- S31
Link to Article
Norbiato  GBevilacqua  MVago  TTaddei  AClerici  M Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients. J Clin Endocrinol Metab. 1997;823260- 3263
Jacobson  MAFusaro  REGalmarini  MLang  W Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499. J Infect Dis. 1991;164864- 868
Link to Article
Mulder  JWFrissen  PHKrijnen  P  et al.  Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men. J Infect Dis. 1992;165413- 418
Link to Article
Clerici  MBevilacqua  MVago  TVilla  MLShearer  GMNorbiato  G An immunoendocrinological hypothesis of HIV infection. Lancet. 1994;3431552- 1553
Link to Article
Carr  ASamaras  KBurton  S  et al.  A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12F51- F58
Link to Article
Roth  VRKravcik  SAngel  JB Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis. 1998;2765- 67
Link to Article
Miller  KKDaly  PASentochnik  D  et al.  Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients. Clin Infect Dis. 1998;2768- 72
Link to Article
Lo  JCMulligan  KTai  VWAlgren  HSchambelan  M "Buffalo hump" in men with HIV-1 infection. Lancet. 1998;351867- 870
Link to Article
Hirsch  MSKlibanski  A What price progress? pseudo-Cushing's syndrome associated with antiretroviral therapy in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998;2773- 75
Link to Article
Gervasoni  CRidolfo  ALTrifirò  G  et al.  Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy. AIDS. 1999;13465- 471
Link to Article
Wanke  CA Epidemiological and clinical aspects of the metabolic complications of HIV infection: the fat redistribution syndrome. AIDS. 1999;131287- 1293
Link to Article
Kotler  DPRosenbaum  KWang  JPierson  RN Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20228- 237
Link to Article
Carr  ASamaras  KChisholm  DJCooper  DA Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998;3511881- 1883
Link to Article
Domingo  PMatias-Guiu  XPujol  RM  et al.  Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy. AIDS. 1999;132261- 2267
Link to Article
Brinkman  KSmeiting  JARomijn  JAReiss  P Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral therapy-related lipodystrophy. Lancet. 1999;3541112- 1115
Link to Article
Ledru  EChristeff  NPatey  Ode Truchis  PMelchior  JCGougeon  ML Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood. 2000;953191- 3198
Christeff  NMelchior  JCde Truchis  PPerronne  CNunez  EAGougeon  ML Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS. 1999;132251- 2260
Link to Article
Yanovski  JAMiller  KDKino  T  et al.  Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab. 1999;841925- 1931
Link to Article
Saint-Marc  TPartisani  MPoizot-Martin  I  et al.  A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS. 1999;131659- 1667
Link to Article

Figures

Tables

References

Bricaire  FMarche  CZoubi  DRegnier  BSaimot  AG Adrenocortical lesions and AIDS. Lancet. 1988;1881
Link to Article
Grinspoon  SKBilezikian  JP HIV disease and the endocrine system. N Engl J Med. 1992;3271360- 1365
Link to Article
Hofbauer  LCHeufelder  AE Endocrine implications of human immunodeficiency virus infection. Medicine (Baltimore). 1996;75262- 278
Link to Article
McKenzie  RTravis  WDDolan  SA  et al.  The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases. Medicine (Baltimore). 1991;70326- 343
Link to Article
Brown  LS  JrSinger  FKillian  P Endocrine complications of AIDS and drug addiction. Endocrinol Metab Clin North Am. 1991;20655- 673
Lo  JCSchambelan  M Endocrine disease. Dolin  RMasur  HSaag  MSeds.AIDS Therapy Philadelphia, Pa Churchill Livingstone1999;740- 751
Leinung  MCLiporace  RMiller  CH Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med. 1995;122843- 845
Link to Article
Padmanabhan  SRosenberg  AS Cushing's syndrome induced by megestrol acetate in a patient with AIDS. Clin Infect Dis. 1998;27217- 218
Link to Article
Membreno  LIrony  IDere  WKlein  RBiglieri  EGCobb  E Adrenocortical function in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1987;65482- 487
Link to Article
Villette  JMBourin  PDoinel  C  et al.  Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus. J Clin Endocrinol Metab. 1990;70572- 577
Link to Article
Christeff  NGherbi  NMammes  O  et al.  Serum cortisol and DHEA concentrations. Psychoneuroendocrinology. 1997;22 (Suppl 1) S11- S18
Link to Article
Wisniewski  TLHilton  CWMorse  EWSvec  F The relationship of serum DHEA-S and cortisol levels to measures of immune function in human immunodeficiency virus-related illness. Am J Med Sci. 1993;30579- 83
Link to Article
Raffi  FBrisseau  JMPlanchon  BRémi  JPBarrier  JHGrolleau  JY Endocrine function in 98 HIV-infected patients: a prospective study. AIDS. 1991;5729- 733
Link to Article
Abbott  MKhoo  SHHammer  MRWilkins  EG Prevalence of cortisol deficiency in late HIV disease. J Infect. 1995;311- 4
Link to Article
Kumar  MKumar  AMMorgan  RSzapocznik  JEisdorfer  C Abnormal pituitary-adrenocortical response in early HIV-1 infection. J Acquir Immune Defic Syndr. 1993;661- 65
Malone  JLOldfield  ECWagner  KF  et al.  Abnormalities of morning serum cortisol levels and circadian rhythms of CD4 + lymphocyte counts in human immunodeficiency virus type 1-infected adult patients. J Infect Dis. 1992;165185- 187
Link to Article
de la Torre  Bvon Krogh  GSvensson  MHolmberg  V Blood cortisol and dehydroepiandrosterone sulphate (DHEAS) levels and CD4 T cell counts in HIV infection. Clin Exp Rheumatol. 1997;1587- 90
Seney  FD  JrBurns  DKSilva  FG Acquired immunodeficiency syndrome and the kidney. Am J Kidney Dis. 1990;161- 13
Link to Article
Stricker  RBGoldberg  DAHu  CHsu  JWGoldberg  B A syndrome resembling primary aldosteronism (Conn syndrome) in untreated HIV disease. AIDS. 1999;131791- 1792
Link to Article
Martin  MEBenassayag  CAmiel  CCanton  PNunez  EA Alterations in the concentrations and binding properties of sex steroid-binding protein and corticosteroid-binding globulin in HIV + patients. J Endocrinol Invest. 1992;15597- 603
Link to Article
Schurmeyer  THMuller  Vvon zur Muhlen  ASchmidt  RE Thyroid and adrenal function in HIV-infected outpatients. Eur J Med Res. 1997;2220- 226
Lambert  MZech  FDe Nayer  PJamez  JVandercam  B Elevation of serum thyroxine-binding globulin (but not of cortisol-binding globulin and sex hormone-binding globulin) associated with the progression of human immunodeficiency virus infection. Am J Med. 1990;89748- 751
Link to Article
Tauveron  IThieblot  PLaurichesse  H The Cushing syndrome associated with AIDS. Ann Intern Med. 1994;120620- 621
Link to Article
Biglino  ALimone  PForno  B  et al.  Altered adrenocorticotropin and cortisol response to corticotropin-releasing hormone in HIV-1 infection. Eur J Endocrinol. 1995;133173- 179
Link to Article
Raber  JSorg  OHorn  TF  et al.  Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function. Brain Res Brain Res Rev. 1998;26320- 326
Link to Article
Costa  ANappi  REPolatti  FPoma  AGrossman  ABNappi  G Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide. Exp Neurol. 2000;166376- 384
Link to Article
Lortholary  OChristeff  NCasassus  P  et al.  Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. J Clin Endocrinol Metab. 1996;81791- 796
Eledrisi  MSVerghese  AC Adrenal insufficiency in HIV infection: a review and recommendations. Am J Med Sci. 2001;321137- 144
Link to Article
Norbiato  GBevilacqua  MVago  T  et al.  Cortisol resistance in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74608- 613
Kino  TGragerov  AKopp  JBStauber  RHPavlakis  GNChrousos  GP The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med. 1999;18951- 62
Link to Article
Clerici  MTrabattoni  DPiconi  S  et al.  A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus. Psychoneuroendocrinology. 1997;22 (Suppl 1) S27- S31
Link to Article
Norbiato  GBevilacqua  MVago  TTaddei  AClerici  M Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients. J Clin Endocrinol Metab. 1997;823260- 3263
Jacobson  MAFusaro  REGalmarini  MLang  W Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499. J Infect Dis. 1991;164864- 868
Link to Article
Mulder  JWFrissen  PHKrijnen  P  et al.  Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men. J Infect Dis. 1992;165413- 418
Link to Article
Clerici  MBevilacqua  MVago  TVilla  MLShearer  GMNorbiato  G An immunoendocrinological hypothesis of HIV infection. Lancet. 1994;3431552- 1553
Link to Article
Carr  ASamaras  KBurton  S  et al.  A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12F51- F58
Link to Article
Roth  VRKravcik  SAngel  JB Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis. 1998;2765- 67
Link to Article
Miller  KKDaly  PASentochnik  D  et al.  Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients. Clin Infect Dis. 1998;2768- 72
Link to Article
Lo  JCMulligan  KTai  VWAlgren  HSchambelan  M "Buffalo hump" in men with HIV-1 infection. Lancet. 1998;351867- 870
Link to Article
Hirsch  MSKlibanski  A What price progress? pseudo-Cushing's syndrome associated with antiretroviral therapy in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998;2773- 75
Link to Article
Gervasoni  CRidolfo  ALTrifirò  G  et al.  Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy. AIDS. 1999;13465- 471
Link to Article
Wanke  CA Epidemiological and clinical aspects of the metabolic complications of HIV infection: the fat redistribution syndrome. AIDS. 1999;131287- 1293
Link to Article
Kotler  DPRosenbaum  KWang  JPierson  RN Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20228- 237
Link to Article
Carr  ASamaras  KChisholm  DJCooper  DA Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998;3511881- 1883
Link to Article
Domingo  PMatias-Guiu  XPujol  RM  et al.  Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy. AIDS. 1999;132261- 2267
Link to Article
Brinkman  KSmeiting  JARomijn  JAReiss  P Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral therapy-related lipodystrophy. Lancet. 1999;3541112- 1115
Link to Article
Ledru  EChristeff  NPatey  Ode Truchis  PMelchior  JCGougeon  ML Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood. 2000;953191- 3198
Christeff  NMelchior  JCde Truchis  PPerronne  CNunez  EAGougeon  ML Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations. AIDS. 1999;132251- 2260
Link to Article
Yanovski  JAMiller  KDKino  T  et al.  Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. J Clin Endocrinol Metab. 1999;841925- 1931
Link to Article
Saint-Marc  TPartisani  MPoizot-Martin  I  et al.  A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS. 1999;131659- 1667
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 24

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com