Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir-boosted darunavir

Abstract

Drug interactions involving human immunodeficiency virus protease inhibitors are common due to their inhibition of the cytochrome P450 3A4 isoenzyme. We describe the case of an HIV-infected patient treated with ritonavir-boosted darunavir who developed cushingoid features following an intra-articular injection of triamcinolone acetate. We review the probable mechanism for this interaction and describe similar cases of Cushing syndrome in patients receiving concomitant ritonavir and triamcinolone.

Keywords

HIV AIDS triamcinolone toxicity Cushing syndrome ritonavir cobicistat drug interactions HIV protease inhibitors antiretrovirals corticosteroids

Introduction

Triamcinolone acetonide, a synthetic steroid, is utilized as an anti-inflammatory agent for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, and other inflammatory arthritides.^1–3 Triamcinolone is extensively metabolized in the liver by hydroxylation; however, the specific cytochrome P450 (CYP P450) enzyme systems involved have not been defined. The isoenzyme CYP3A4 mediates the metabolism of many other synthetic corticosteroids.^3,4

Protease inhibitors (PIs) are commonly used agents in the management of human immunodeficiency virus (HIV) infection; these drugs are both substrates and inhibitors of CYP3A4.⁵ Ritonavir has the greatest inhibitory effect on CYP3A4, and is frequently used at low doses (100–200 mg/day) to ‘boost’ serum concentrations of other PIs enabling less frequent doses with improved potency.⁶

We describe a case in which an HIV-infected patient receiving combination antiretroviral therapy with ritonavir-boosted darunavir developed florid cushingoid features following an intra-articular injection of triamcinolone acetonide. In addition, we provide a review of the literature to highlight the similarities among previous case reports and the significance of this under-recognized drug interaction.

Description of case

A 53-year-old African woman diagnosed with HIV infection in 1999 was followed at a University-based outpatient HIV clinic. She was on an antiretroviral regimen consisting of darunavir 800 mg daily boosted by ritonavir 100 mg daily and raltegravir 400 mg twice daily, with an HIV viral load of 110 copies/mL and CD4 cell count of 290 cells/µL. Despite several previous intolerances to first-line regimens, the patient was tolerating this regimen well with a low or undetectable viral load for the previous year. Other relevant past medical history included hypertension and type 2 diabetes mellitus, managed with valsartan 160 mg daily and metformin 500 mg twice daily.

The patient received triamcinolone acetonide 40 mg as a single intra-articular injection for left shoulder pain. A magnetic resonance imaging scan performed six months earlier had shown a low-grade tendon tear, tendinosis, and degenerative joint changes. Two weeks following the injection, she re-presented to her family physician’s office complaining of insomnia, elevated mood, emotional lability, dry mouth with polydipsia and polyuria, elevated self-monitored blood glucose (ranging 25–30 mmol/L), increased blood pressure (systolic ranging 160–180 mmHg), nausea, and increased appetite. Her blood glucose and blood pressure had previously been well controlled (haemoglobin A1C of 6.6% one month prior to the injection and patient reported self-monitored systolic blood pressure consistently between 130 and 140 mmHg). Laboratory investigations revealed a serum sodium of 130 mmol/L, potassium of 5.4 mmol/L, and white blood cell count of 12.1 × 10⁹/L. Four days later, the patient presented to the emergency department complaining of weakness and blurred vision. A non-fasting blood glucose was 26 mmol/L and she was given two doses of insulin; her metformin dose was increased and glibenclamide was added. She was told to follow-up with her family physician within one week.

One month following the triamcinolone injection, the patient presented to the HIV clinic with complaints of anxiety, palpitations, uncontrolled blood glucose, dry mouth, polyuria, polydipsia, facial puffiness, and dizziness. Striking facial and submental swelling and fat redistribution to her upper thighs were noted on examination. Her blood pressure was 177/117 mmHg and a non-fasting blood glucose was 21 mmol/L. The patient denied use of inhaled or other corticosteroids and the provincial electronic health record, which includes pharmacy dispensed medications, did not reveal corticosteroid use.

An urgent endocrinology consult was obtained at which point the patient recalled receiving a triamcinolone injection. The patient was diagnosed with cushingoid features likely secondary to triamcinolone and the endocrinologist recommended initiation of insulin. Evaluation of serum cortisol or an adrenocorticotropic hormone (ACTH)-stimulation test was not undertaken at that time, potentially because of the drug interaction with ritonavir, and hence the potential for prolonged adrenal suppression, was not recognized. No supplemental steroid was prescribed.

The patient returned to the HIV clinic 10 weeks post-injection. She reported normalization of sleep, appetite, and thirst eight weeks after the triamcinolone injection. Upon examination, her facial swelling had started to subside, however, she still complained of fat redistribution to her upper thighs and poorly controlled blood glucose. Her blood pressure was 137/93 mmHg. A 24-h urine free cortisol and serum morning cortisol were obtained 11 weeks post-injection, and were 6 nmol/24 h (reference range <230 nmol/24 h) and 313 nmol/L (reference range 120–620 nmol/L), respectively. An ACTH-stimulation test 12 weeks post-injection was also found to be normal (morning cortisol 263 nmol/L, cortisol 30 and 60 min post ACTH were 507 and 576 nmol/L, respectively, reference range >500 nmol/L or increase of >190 nmol/L). Although triamcinolone levels were requested, they could not be performed at our institution.

Discussion

Triamcinolone acetonide is formulated to release slowly from the injection site, enabling high synovial fluid concentrations without substantially elevated plasma levels, in order to avoid systemic effects and hypothalamic–pituitary–adrenal (HPA) axis suppression.⁷ However, synthetic steroids injected intra-articularly and intrathecally have been shown to suppress endogenous cortisol secretion for days to weeks (duration of HPA axis suppression unpredictable) and synthetic steroid levels can be correlated with plasma cortisol, ACTH, and 24-h urine free cortisol.⁷ The recommended dosing range of triamcinolone is 2.5–40 mg, although doses up to 80 mg are common.³

Cushing's syndrome is a predictable complication of high-dose systemic corticosteroids, however, it has also been rarely associated with intra-articular triamcinolone. Several case reports and case series in adult and paediatric patients have demonstrated the development of cushingoid features approximately two weeks after injection, most commonly after multiple or a series of injections. In these cases, the usual adult dose was 40 mg per joint and many of the patients developed HPA axis suppression. Complete resolution of symptoms ranged from 2 to 6 months after the injection(s), with only one patient requiring hydrocortisone replacement therapy.^8,9

Patients receiving ritonavir-boosted PIs are at an increased risk of drug interactions due to the effect on CYP3A4.⁵ While there are no published pharmacokinetic data evaluating the interaction between ritonavir and triamcinolone, ritonavir has been shown to increase prednisolone area-under-the-curve and half-life in HIV-infected patients.¹⁰ In addition, inhibition of CYP3A4 metabolism of inhaled and intranasal fluticasone by ritonavir has repeatedly been shown to lead to significant adrenal suppression, leading to the recommendation that concomitant use of these agents be avoided.¹¹ More recently, the use of oral and inhaled budesonide with concomitant ritonavir therapy has also been reported to cause cushingoid features.¹²

We believe, for several reasons, that the development of florid cushingoid features in our patient was due to an interaction between ritonavir and triamcinolone. First, our patient’s symptoms began approximately two weeks after the triamcinolone acetonide intra-articular injection while receiving ritonavir-boosted darunavir. She had no history of concomitant inhaled, intranasal, or topical steroids, and this was her first dose of intra-articular steroids. Second, several case reports have described iatrogenic Cushing's syndrome following intra-articular or epidural administration of triamcinolone acetonide to HIV-infected individuals on ritonavir-boosted PI-based regimens (Table 1, available online). Similar to our patient, the average time to onset of cushingoid symptoms was usually two weeks after triamcinolone administration, however, the severity of symptoms and sequelae differed, as did patient management.^13–20 Other similarities in previous case reports include a triamcinolone dose of 40–80 mg given on one or two occasions, objective evidence of steroid excess and adrenal suppression (clinical signs and symptoms and/or laboratory findings), and several weeks to months for symptoms to resolve. Finally, while formal pharmacokinetic studies between triamcinolone and ritonavir have not been done, the case reported by Ramanathan et al. provides support for the interaction between triamcinolone and ritonavir-boosted PIs.¹⁵ Six weeks after a triamcinolone epidural injection, the exogenous steroid level remained elevated and the cortisol level was undetectable. In that case, the patient was changed from co-formulated lopinavir–ritonavir, emtricitabine, and tenofovir to unboosted atazanavir, stavudine, and lamivudine, which resulted in a decrease in the triamcinolone serum concentration. Three weeks later, the patient’s initial regimen was re-introduced with a subsequent increase in the triamcinolone concentration once again. More than three months after the initial injection, nevirapine, a potent CYP3A4 inducer (along with stavudine and lamivudine), was substituted for co-formulated lopinavir–ritonavir leading to a rapid decline in the triamcinolone concentration and a normal cortisol level.

Table 1.

Reports of adrenal suppression and Cushing's syndrome in patients receiving ritonavir and intra-articular triamcinolone.^a

ARVs (daily dose)	Injectable triamcinolone acetonide dose; location	Onset of reaction	Signs and symptoms	Laboratory values	Management	Outcome	DIPS score
ATV 300 mg ddI 250 mg TDF 300 mg RTV 100 mg (Ref. 13)	80 mg × 1; Right hip	3 days	Polydipsia, polyuria, fatigue, malaise, and weight loss	- ↑ blood glucose 42.5 mmol/L - At 7 weeks: triamcinolone 89.7 mmol/L, ↑a.m. cortisol 44 mmol/L, ↓ACTH <1.1 pmol/L	- ARVs discontinued - High dose insulin initiated & maintained for 7 weeks	- Full recovery of HPA axis 8 weeks after ARVs discontinued - Same ARV regimen subsequently restarted, insulin discontinued	8/11 (probable)
ATV 300 mg FTC 200 mg TDF 300 mg RTV 100 mg (Ref. 14)	80 mg (×2, 1 month apart); epidural	∼2 weeks after 2nd injection	- Non-healing abdominal bruising, weight gain, pruritic rash, increased HR and BP, moon facies, purple striae on abdomen, acneiform lesions	At ∼8 weeks: - Random cortisol 13.8 nmol/L; ↓ACTH <0.22 pmol/L - Triamcinolone acetonide 98.9 mmol/L	- Counseled on symptoms of adrenal crisis - No change to ARVs	- 5 months after initial injection, developed avascular hip necrosis - Full recovery of HPA axis 6 months after presentation	7/11 (probable)
ATV 300 mg FTC 200 mg TDF 300 mg RTV 100 mg (Ref. 14)	40 mg ×1; right shoulder	2 weeks	- Weight redistribution around neck and upper thighs, weakness, heat intolerance, blurry vision, heart palpitations, fatigue, hyperexcitability, insomnia, increased appetite, increased BP	At ∼5 weeks: - Random cortisol 55.2 nmol/L; ↓ACTH <0.22 pmol/L - Cosyntropin-stimulation test (250 mcg) raised cortisol to 386 nmol/L at 60 min	- HC 30 mg × 3 days to prevent adrenal crisis, no change to ARVs	- 2 months after initial presentation had recovery of HPA axis	6/11 (probable)
LPV 800 mg FTC 200 mg TDF 300 mg RTV 200 mg (Ref. 15)	60 mg, 80 mg (×2, 1 week apart); epidural	1 week	- New hypertension, dorsocervical fat pad, moon facies with plethora, poor wound healing, weight gain, elevated fasting blood glucose; suicidal ideation at 6 weeks post-injection	At ∼4 weeks: - ↑fasting blood glucose 7.8 mmol/L - ↓a.m. cortisol <27.6 nmol/L; - Cosyntropin-stimulation test (250 mcg) raised cortisol to 287 nmol/L at 60 min - Triamcinolone acetonide 159 mmol/L - CD4 + declined from 470 to 69 cells/mm³; HIV RNA remained suppressed	- Change to ATV, d4T, 3TC - Change back to initial regimen 3 weeks later - Change to NVP, d4T, 3TC 2 weeks later	- Initial improvement in symptoms and decrease in triamcinolone level lost when RTV restarted at 2 weeks after initial regimen change - Complete resolution of symptoms at 5 months (off of RTV boosted regimen and on NVP, an enzyme inducer) - However, developed avascular necrosis of right hip at 11 months	10/11 (highly probable)
LPV 800 mg 3TC 300 mg ddI 400 mg RTV 200 mg (Ref. 15)	40 mg × 1; left knee	2 weeks	- Weight gain, swelling/erythrosis of face and upper trunk, hyperexcitability, insomnia, elevated blood pressure - At 5 weeks, hospitalized with adrenal suppression (severe fatigue, abdominal pain, nausea, vomiting, anorexia)	At 5 weeks: - ↓a.m. cortisol 4 nmol/L, ↓ACTH 0.44 pmol/L	- HC 20 mg/day × 8 months - No change to ARVs	- Full recovery of HPA axis at 8 months	6/11 (probable)
IDV 1200 mg d4T 80 mg 3TC 300 mg RTV 200 mg (Ref. 16)	40 mg × 1; cervical	2 weeks	- Swollen face, weight gain, nervousness, insomnia - At 6 weeks: nausea, profound fatigue, proximal muscle weakness	At 6 weeks: - ↓a.m. cortisol <27 nmol/L, ↓ACTH 0.88 pmol/L	- HC 10 mg/d × 4 months - No change to ARVs	- Full recovery of HPA axis at 4 months	5/11 (probable)
IDV 1200 mg 3TC 300 mg AZT 500 mg RTV 200 mg (Ref. 16)	40 mg × 1; right shoulder	2–3 weeks	- Abdominal/facial swelling, weight gain, insomnia - At 8 weeks: severe and persisting fatigue	At 8 weeks: - ↓a.m. cortisol 13 nmol/L, ↑ACTH 36 pmol/L	- No change to ARVs	- Spontaneous recovery of HPA axis at 5 months	6/11 (probable)
FTC 200 mg TDF 300 mg FPV 1200 mg RTV 100 mg (Ref. 17)	Unknown dose; epidural	4 weeks	- Generalized swelling, fatigue, weakness, dyspnoea, tremor, insomnia, weight gain, increased BP, dorsocervical hump, ecchymosis	At 4 weeks: - CD4 + declined from 400 to 150 cells/mm³ - ↓a.m. cortisol 24.8 nmol/L, cosyntropin-stimulation test (250 mcg) raised cortisol to 223 nmol/L at 60 min	- No change to ARVs	- Symptoms resolved at ≥10 weeks	6/11 (probable)
FTC TDF ATV RTV (Ref. 18)	40 mg × 2; IA	Unknown	- Fatigue, dizziness upon standing, chest infection	At 2 weeks: - ↓serum cortisol <50 nmol/L	- No change to ARV’s	- Recovery of HPA axis at 6 months	5/11 (probable)
LPV RTV (Ref. 18)	80 mg × 1; IA	Unknown	- Nausea, vomiting, diarrhea, urine infection, worsened diabetes control	At 3 weeks: - ↓serum cortisol <50 nmol/L	- No change to ARV’s	- Recovery of HPA axis at 5 months	5/11 (probable)
MVC RAL ATV RTV (Ref. 18)	40 mg × 2; IA	Unknown	- No symptoms as recognized early	At 2 weeks: - ↓serum cortisol <50 nmol/L	- No change to ARV’s - HC replacement therapy given	- Unknown	5/11 (probable)
TDF FTC DRV RTV (Ref. 15)	40 mg × 2; IA	Unknown	- Weight gain, acne, moon facies, oral candidiasis, worsening depression	At 4 weeks: - ↓serum cortisol <50 nmol/L	- Change DRV + RTV to RAL at month 4 - HC replacement therapy given	- Recovery of HPA axis at 5 months	5/11 (probable)
NVP TDF ATV RTV (Ref. 18)	80 mg × 1; IA	Unknown	- Severe proximal myopathy	At 2 weeks: - ↓serum cortisol <50 nmol/L	- No change to ARV’s	- Recovery of HPA axis at 3 months	5/11 (probable)
TDF FTC ATV RTV (Ref. 18)	40 mg × 2; IA	Unknown	- No symptoms as recognized early	At 2 weeks: - ↓serum cortisol <50 nmol/L	- Change ATV + RTV to RAL at week 3 to expedite triamcinolone clearance	- Recovery of HPA axis at 3 months	5/11 (probable)
TDF 3TC ATV RTV (Ref. 19)	60 mg × 1; IM	Unknown	- Weight gain, round facies, hirsutism - Low blood pressure	At 3 months: - ↓serum cortisol 60.7 nmol/L - ↓ACTH <1.1 pmol/L	- No change to ARV’s	- Recovery of HPA axis and resolution of symptoms at 6 months	6/11 (probable)
TDF FTC ATV RTV (Ref. 20)	80 mg × 3 (∼5 months apart each); epidural	∼3 weeks after 2nd injection	- Facial fullness, dorso-cervical hump, muscle atrophy, supraclavicular fat pads	At 3 weeks after 2nd injection: - ↑ haemoglobin A1C and lipids Several weeks after 3rd injection: - ↓ random cortisol <22 nmol/L - ↓ACTH <2.2 pmol/L - Triamcinolone 253 mmol/L	- RTV discontinued 1 year after initial injection - HC 20 mg/day with ‘extended taper’	- Recovery of HPA axis and resolution of symptoms over several months	9/11 (highly probable)

3TC: lamivudine; ACTH: adrenocorticotropic hormone; ARV: antiretroviral; ATV: atazanavir; AZT: zidovudine; BP: blood pressure; d4T: stavudine; ddI: didanosine; DRV: darunavir; FTC: emtricitabine; FPV: fosamprenavir; HC: hydrocortisone; HPA: hypothalamic–pituitary–adrenal axis; HR: heart rate; IA: intra-articular; IDV: indinavir; IM: intramuscular; LPV: lopinavir; MVC: maraviroc; NVP: nevirapine; RAL: raltegravir; RTV: ritonavir; TDF: tenofovir. ^aNormal values: • Early morning cortisol 120–620 nmol/L and ACTH 1.1–11 pmol/L. • Cosyntropin/ACTH-stimulation test – serum cortisol at 0, 30, 60 min after 250 mcg ACTH: peak cortisol >500 nmol/L. • Triamcinolone <6.9 mmol/L. • Fasting blood glucose 3.9–6.1 mmol/L; random blood glucose 3.3–11 mmol/L.

Definitive adrenal insufficiency: • Early morning cortisol <120 nmol/L and ACTH >22 pmol/L. • Standard cosyntropin/ACTH test: peak cortisol <500 nmol/L.

Although we were unable to objectively demonstrate altered cortisol concentrations (drawn 11 and 12 weeks post-injection) due to the delayed recognition of this drug interaction, the Drug Interaction Probability Scale (DIPS) suggests this interaction is probable (score of 6/11; Table 2).²¹ The DIPS is a tool that can be used to assess the likelihood that a drug interaction is the cause of an adverse event. As opposed to the Naranjo ADR Probability Scale,²² which has proven a useful tool for evaluating adverse events associated with one drug, the DIPS takes into consideration the drug that is affected (object drug) and the drug that causes a change (the precipitant drug), utilizing 10 questions rated from −1 to +2 (Table 2).²¹

Table 2.

Case assessment based on the Drug Interaction Probability Scale.²¹

Abbreviated questions	Points assigned
Abbreviated questions	Yes	No	Unknown or NA	Our case
Previous credible reports in humans?	+1	−1	0	+1
Consistent with known properties of the precipitant drug?	+1	−1	0	+1
Consistent with known properties of the object drug?	+1	−1	0	+1
Consistent with known time course (onset/offset)?	+1	−1	0	+1
Remit with de‐challenge of precipitant drug?	+1	−2	0	0
Reappear with re-administration?	+2	−1	0	0
Reasonable alternative cause?	−1	+1	0	+1
Object drug detected in blood?	+1	0	0	0
Confirmed by objective evidence consistent with effects of the object drug?	+1	0	0	+1
Affected by dose changes?	+1	−1	0	0
Total^a	6

Total score reflects likelihood of the drug interaction: highly probable (>8), probable (5–8), possible (2–4), and doubtful (<2).

Health care professionals caring for the aging HIV population need to be aware of this potential drug interaction and have a high index of suspicion when patients present with new onset cushingoid features. A thorough medication history should be undertaken to discover any form of exogenous steroid that the patient has been exposed to, in particular intra-articular injections or inhaled steroids. One must also be careful to differentiate cushingoid features from antiretroviral lipodystrophy, though less common now, through the use of serum cortisol and ACTH-stimulation testing and presence of electrolyte disturbances and other features not commonly seen with lipodystrophy (such as the lack of peripheral atrophy and presence of abdominal striae, easy bruising, and/or facial plethora).¹¹

The frequency and magnitude of interactions between glucocorticoids as a class and ritonavir-boosted PIs are unknown, regardless of the route of administration (e.g. oral, intra-articular, inhaled, topical, ophthalmic). It is also unknown whether a decrease in the steroid dose or the use of a less soluble steroid (such as triamcinolone hexacetonide) would compensate for the interaction with ritonavir-boosted PIs due to the complex interplay of pharmacokinetic and pharmacodynamic properties of these drugs. For patients receiving ritonavir-boosted PI therapy, triamcinolone should be avoided where possible.

Although there are no known case reports of Cushing's syndrome with cobicistat, a novel CYP3A inhibitor currently utilized to boost elvitegravir concentrations, caution should be exercised when utilizing intra-articular steroids as a similar interaction may occur.

For patients with a high risk of drug–drug interactions who require corticosteroids including triamcinolone, consideration should be given to switching to a PI- or cobicistat-sparing regimen for the duration of glucocorticoid treatment. If this is not feasible, then careful monitoring for signs and symptoms of Cushing's syndrome and secondary adrenal insufficiency (by both the healthcare team and the patient) is recommended. If the patient becomes symptomatic, a morning cortisol and ACTH level, with or without an ACTH-stimulation test, may be performed to assess for adrenal suppression, recognizing that adrenal suppression may last two or more weeks even in patients not receiving 3A4 inhibitors and that the usual onset of cushingoid features occurs at two weeks.⁷ Physiological doses of glucocorticoid replacement therapy with hydrocortisone may be necessary if adrenal suppression occurs as exogenous steroid concentrations decrease, to prevent complications of adrenal insufficiency. Changing the antiretroviral regimen to one that does not contain ritonavir or cobicistat may also be necessary to enable clearance of the exogenous steroid. Monitoring for long-term sequelae such as avascular hip necrosis is also recommended after the resolution of other clinical and laboratory findings.

Conclusion

Ongoing vigilance regarding drug interactions in the HIV-infected population is warranted, particularly when initiating new medications. Particular attention should be given to the concomitant use of inhaled or locally injected corticosteroids in patients on ritonavir-boosted PI regimens or potentially cobicistat. With increasing involvement by primary care physicians in the care of HIV-infected patients, detailed communication between primary care physicians, HIV specialists, and pharmacists is essential.

Footnotes

Authors’ note

This case was presented at the 21st Annual Conference on HIV/AIDS Research, Montreal, QC, Canada, 19–22 April 2012 (Poster).

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee (updated February 2005). http://www.rheumatology.org/practice/clinical/guidelines/oa-mgmt.asp (2000, accessed 12 September 2012).

Bykerk

Akhavan

Hazlewood

Schieir

Dooley

Haroui

. Canadian rheumatology association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol 2012; 39: 1559–1582.

Triamcinolone acetonide. DRUGDEX System. Greenwood Village, CO: Thomson Micromedex. www.thomsonhc.com (accessed 12 September 2012).

Zhou

Zue

Wang

. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007; 29: 687–710.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 27 March 2012. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (accessed 12 September 2012).

Zeldin

Petruschke

. Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients. J Antimicrob Chemother 2004; 53: 4–9.

Derendorf

Möllmann

Grüner

Haack

Geselby

. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther 1986; 39(3): 313–317.

Jansen

TLTA

van Roon

. Four cases of a secondary Cushingoid state following local triamcinolone acetonide (Kenacort®) injection. Neth J Med 2002; 60(3): 151–153.

O’Sullivan

Rumfeld

Jones

Williams

. Cushing’s syndrome with suppression of the hypothalamic-pituitary–adrenal axis after intra-articular steroid injections. Ann Rheum Dis 1985; 44: 561–563.

10.

Busse

Formentini

Alfaro

Kovacs

Penzak

. Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals. J Acquir Immune Defic Syndr 2008; 48: 561–566.

11.

Foisy

Yakiwchuk

EMK

Chiu

Singh

. Adrenal suppression and Cushing’s syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med 2008; 8: 389–396.

12.

Frankel

Packer

. Cushing’s syndrome due to antiretroviral-budesonide interaction. Ann Pharmacother 2011; 45: 823–824.

13.

Danaher

Salsbury

Delmar

. Metabolic derangement after injection of triamcinolone into the hip of an HIV-infected patient receiving ritonavir. Orthopedics 2009; 32: 450–452.

14.

Dort

Padia

Wispelwey

Moore

. Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report. AIDS Res Ther 2009; 6: 10–13.

15.

Ramanathan

Pau

Busse

Zemskova

Neiman

Kwan

. Iatrogenic Cushing’s syndrome following epidural triamcinolone in an HIV-1 infected patient undergoing therapy with ritonavir-lopinavir. Clin Infect Dis 2008; 47: e97–e99.

16.

Yombi

Maiter

Belkhir

Nzeusseu

Vandercam

. 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 Rheumatol 2008; 27(Suppl. 2): S79–S82.

17.

Albert

Kazi

Santoro

Dougherty

. Ritonavir and epidural triamcinolone as a cause of iatrogenic Cushing's syndrome. Am J Med Sci 2012; 344(1): 72–74.

18.

Marshall NJ, Gurazada K, Bouloux P, Khoo B and Johnson MA. Secondary adrenal suppression and Cushing’s syndrome caused by ritonavir-boosted effects of inhaled fluticasone, injected triamcinolone, and topical clobetasol: a case series. In: Presented at Society for Endocrinology BES 2012, Harrogate, UK, 18–22 March 2012 (Poster).

19.

Levine

Ananthakrishnan

Garg

. Iatrogenic Cushing syndrome after a single intramuscular corticosteroid injection and concomitant protease inhibitor therapy. J Am Acad Dermatol 2011; 65(4): 877–878.

20.

Grierson

Harrast

. 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. Phys Med Rehabil 2012; 4(3): 234–237.

21.

Horn

Hansten

Chan

. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother 2007; 41: 674–680.

22.

Naranjo

Busto

Sellers

Sandor

Ruiz

Roberts

. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239–245.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB