We present the case of a 58-year-old HIV-infected patient with adrenal insufficiency after local injection of triamcinolone, most likely due to drug–drug interaction with his ritonavir-boosted antiretroviral therapy (ART). This is the first case of adrenal insufficiency occurring without prior symptoms of Cushing’s syndrome in a patient on a booster-containing ART. We want to draw attention to this seemingly rare, but potentially life-threatening medical condition that can occur even in short-term use of glucocorticoids in low doses in patients on booster-containing ART and summarize some considerations for management.
WassnerCMaitiSKodroffKet al.
Iatrogenic adrenal insufficiency secondary to combination therapy with elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine and interlaminar triamcinolone injection in an AIDS patient. J Int Assoc Provid AIDS Care2017;
16: 535–539.
2.
EpperlaNMcKiernanF.Iatrogenic Cushing syndrome and adrenal insufficiency during concomitant therapy with ritonavir and fluticasone. Springerplus2015;
4: 455.
3.
BlondinMCBeauregardHSerriO.Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review. Endocr Pract2013;
19: e138–e141.
4.
BerneckerCWestTBMansmannGet al.
Hypercortisolism caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 Case reports and a review of the literature. Exp Clin Endocrinol Diabetes2012;
120: 125–127.
5.
BoydSDHadiganCMcManusMet al.
Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone. J Acquir Immune Defic Syndr2013;
63: 355–361.
6.
FrankelJKPackerCD.Cushing's syndrome due to antiretroviral-budesonide interaction. Ann Pharmacother2011;
45: 823–824.
7.
SaberiPPhengrasamyTNguyenDP.Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management. HIV Med2013;
14: 519–529.
8.
YoganathanKDavidLWilliamsCet al.
Cushing's syndrome with adrenal suppression induced by inhaled budesonide due to a ritonavir drug interaction in a woman with HIV infection. Int J STD AIDS2012;
23: 520–521.
9.
ChenFKearneyTRobinsonSet al.
Cushing's syndrome and severe adrenal suppression in patients treated with ritonavir and inhaled nasal fluticasone. Sex Transm Infect1999;
75: 274.
10.
FoisyMMYakiwchukEMChiuIet al.
Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med2008;
9: 389–396.
11.
GrayDRouxPCarrihillMet al.
Adrenal suppression and Cushing's syndrome secondary to ritonavir and budesonide. S Afr Med J2010;
100: 296–297.
12.
Hillebrand-HaverkortMEPrummelMFten VeenJH.Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone. AIDS1999;
13: 1803.
13.
KedemEShaharEHassounGet al.
Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient. J Asthma2010;
47: 830–831.
14.
RouanetIPeyriereHMauboussinJMet al.
Cushing's syndrome in a patient treated by ritonavir/lopinavir and inhaled fluticasone. HIV Med2003;
4: 149–150.
15.
SoldatosGSztal-MazerSWoolleyIet al.
Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction. Intern Med J2005;
35: 67–68.
16.
MathiasAAGermanPMurrayBPet al.
Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther2010;
87: 322–329.
17.
MoyleGJBackD.Principles and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med2001;
2: 105–113.
18.
GuengerichFP.CYTOCHROME P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol1999;
39:1–17.
19.
BeckerDE.Basic and clinical pharmacology of glucocorticosteroids. Anesth Prog2013;
60: 25–32.
20.
YombiJCMaiterDBelkhirLet al.
Iatrogenic Cushing's syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir. Clin Rheumatol2008;
27: S79–S82.
21.
RamanathanRPauAKBusseKHet al.
Iatrogenic Cushing syndrome after epidural triamcinolone injections in an HIV type 1-infected patient receiving therapy with ritonavir-lopinavir. Clin Infect Dis2008;
47: e97–e99.
22.
DortKPadiaSWispelweyBet al.
Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report. AIDS Res Ther2009;
6: 10.
23.
HeroldMAGunthardHF.Cushing syndrome after steroid-infiltration in two HIV-patients with antiretroviral therapy. Praxis (Bern 1994)2010;
99: 863–865.
24.
LevineDAnanthakrishnanSGargA.Iatrogenic Cushing syndrome after a single intramuscular corticosteroid injection and concomitant protease inhibitor therapy. J Am Acad Dermatol2011;
65: 877–878.
25.
GriersonMJHarrastMA.Iatrogenic Cushing syndrome after epidural steroid injections for lumbar radiculopathy in an HIV-infected patient treated with ritonavir: a case report highlighting drug interactions for spine interventionalists. PM R2012;
4: 234–237.
26.
AlbertNEKaziSSantoroJet al.
Ritonavir and epidural triamcinolone as a cause of iatrogenic Cushing's syndrome. Am J Med Sci2012;
344: 72–74.
27.
MavikiMCowleyPMarmeryH.Injecting epidural and intra-articular triamcinolone in HIV-positive patients on ritonavir: beware of iatrogenic Cushing's syndrome. Skeletal Radiol2013;
42: 313–315.
28.
FesslerDBeachJKeelJet al.
Iatrogenic hypercortisolism complicating triamcinolone acetonide injections in patients with HIV on ritonavir-boosted protease inhibitors. Pain Physician2012;
15: 489–493.
29.
JohnGOlloDMeyerPet al.
Pulmonary embolism and iatrogenic Cushing's syndrome after co-administration of injected-triamcinolone and ritonavir. AIDS2013;
27: 2827–2828.
30.
McConkeyHZWilliamsHKulasegaramRet al.
Orbital floor triamcinolone causing Cushing's syndrome in a patient treated with Kaletra for HIV 1. BMJ Case Rep2013;
2013. DOI: 10.1136/bcr.02.2012.5849.
31.
Schwarze-ZanderCKlingmullerDKlumperJet al.
Triamcinolone and ritonavir leading to drug-induced Cushing syndrome and adrenal suppression: description of a new case and review of the literature. Infection2013;
41: 1183–1187.
32.
HallJJHughesCAFoisyMMet al.
Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir-boosted darunavir. Int J STD Aids2013;
24: 748–752.
33.
SongYSchroederJRBushLM.Iatrogenic Cushing syndrome and secondary adrenal insufficiency related to concomitant triamcinolone and ritonavir administration: a case report and review. J Int Assoc Provid AIDS Care2014;
13: 511–514.
34.
SadaranganiSBergMLMauckWet al.
Iatrogenic Cushing syndrome secondary to ritonavir-epidural triamcinolone interaction: an illustrative case and review. Interdiscip Perspect Infect Dis2014;
2014: 849432.
35.
JakemanBConklinJBouchonvilleMet al.
Iatrogenic Cushing's syndrome after triamcinolone plus ritonavir-boosted atazanavir. J Am Pharm Assoc2015;
55: 193–197.
36.
DubrocqGEstradaAKellySet al.
Acute development of Cushing syndrome in an HIV-infected child on atazanavir/ritonavir based antiretroviral therapy. Endocrinol Diabetes Metab Case Rep2017;
2017. DOI: 10.1530/EDM-17-0076.
37.
BroersenLHPereiraAMJorgensenJOet al.
Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab2015;
100: 2171–2180.
38.
BornsteinSRAllolioBArltWet al.
Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab2016;
101: 364–389.
39.
VeilleuxOLeeTCMcDonaldEG.Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide. CMAJ2017;
189: E1188.
