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Antiretroviral therapies for HIV may cause systemic toxicities when coadministered with corticosteroids. Potential drug-drug interactions may occur, leading to iatrogenic Cushing syndrome or adrenal insufficiency. This article highlights the drug-drug interactions of antiretroviral therapies with corticosteroids. Practice implications are discussed.

This case study concerns a 53-year-old female presenting to an eye-hospital in London with uveitis, on a background of well-controlled HIV. After investigation, no cause for the uveitis was found other than the HIV itself, and the patient was treated with immunosuppressants. Because of the nature of her underlying HIV infection, help was sought from HIV specialists, who gave advice on the management, including alteration of corticosteroid dosing due to the risk of drug-interactions between her uveitis and HIV treatments. Of particular concern was the risk of cytochrome P450 3A inhibition by cobicistat and the potential for iatrogenic Cushing syndrome through elevated steroid doses. This case is used as an example to highlight the importance of the multi-disciplinary team in the management of complex conditions, as well as to add to the literature in support of the HIV virus itself as a cause of uveitis.

Corticosteroid-containing creams, pomades and ointments are frequently prescribed for the treatment of atopic dermatitis by allergologists and immunologists, dermatologists and many other physicians. This case is about a 1-month old infant who acquired iatrogenic Cushing syndrome after being applied diflucortolone valerate, a strong corticosteroid, ointment 3 to 4 times a day over the course of 4 months after being prescribed by a primary care physician.

Iatrogenic Cushing syndrome induced by oral and parenteral corticosteroid administration is a well-known complication, and necessary precautions have to be taken. Cushing syndrome, however, following treatment with glucocorticoid-containing eye drops is a very rare complication. To the best of our knowledge, there have been only four reported cases in the literature. Herein, we present an infant boy who developed Cushing syndrome after receiving dexamethasone-containing eye drops after bilateral cataract extraction to prevent postoperative inflammatory complications. At the age of 5months, after approx. 3months of dexamethasone therapy, the patient presented with cushingoid facies, nephrocalcinosis and failure to grow. Iatrogenic Cushing syndrome was diagnosed and dexamethasone-containing eye drops were reduced and eventually stopped. Follow-up examinations revealed catch-up growth. Conclusion: Ocularly administered corticosteroids may have substantial systemic side effects in infants.

Cushing syndrome is an endocrinological disorder characterized by increased free plasma glucocorticoids level. It is either due to an excessive endogenous release of steroids (e.g., pituitary adenoma or adrenal hyperplasia) or exogenous administration of steroids. In children, iatrogenic Cushing syndrome is the most common form of Cushing syndrome occurring in this age group. The vast majority of cases are due to oral or parenteral preparation of steroids, which are commonly prescribed for pulmonary, hematological, renal, or autoimmune pathologies. Topical preparations can rarely cause Cushing syndrome in young children, and only a few cases were reported in the literature, where the patients were older than 5 months of age. In this report, we present a three-month-old girl who developed iatrogenic Cushing syndrome due to prolonged and inappropriate use of topical clobetasol cream for napkin dermatitis.

Objective: Topical steroid use is common, but its association with Cushing syndrome is rare. We report the rapid development of iatrogenic Cushing syndrome in a patient on ritonavir who applied a moderate-potency topical steroid cream, triamcinolone, on his genital mucosa for treatment of phimosis. Methods: Clinical and diagnostic challenges associated with topical steroid use are presented and discussed. Results: A 41-year-old man with human immunodeficiency virus infection on stable antiretroviral therapy that included ritonavir, a cytochrome P450 3A4 inhibitor, presented with new onset diabetes and development of overt cushingoid features over a 4-week period. He reported no known history of steroid use. A midnight salivary cortisol using a quantitative enzyme immunoassay was obtained and reported at >15.0 μg/dL (normal

© BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur.

Children with down syndrome often have an increased predisposition to recurrent viral related wheezing episodes and other issues like increased oropharyngeal secretions due to hypotonia. Lower airway anomalies such as tracheobronchomalacia and tracheal stenosis are also common. Children with tracheal abnormalities may have a chronic cough or noisy breathing and these conditions are often misdiagnosed as asthma. Here, we present a case report of a six-month-old baby with down syndrome who was misdiagnosed as having bronchial asthma at two months of age because of recurrent episodes of noisy breathing and was prescribed oral steroids which the parents continued in an unsupervised manner. The child presented with increased buccal fat and buffalo hump and was diagnosed as iatrogenic cushing syndrome after investigations. Steroids were gradually tapered and stopped gradually. On follow-up the child had fully recovered and had no signs of hypercortisolism.

We present a case of iatrogenic Cushing syndrome and adrenal insufficiency in a newborn secondary to an overuse of triamcinolone cream 0.1% prescrived for the treatment of diaper dermatitis.This case highlignts the risks of systemic absorption when prescribing topical medications in the diaper area of an infant, and the importance of caution and proper follow up when prescribing even mid potency steroids to pediatric patients. .

Background Lichen sclerosus is a chronic inflammatory dermatological condition with a predilection for the anogenital area. Case We describe a case of iatrogenic Cushing syndrome from the administration of high-potency topical steroids for vulvar lichen sclerosus in a 6-year-old girl. Her symptoms resolved after the cessation of topical steroid treatment. Summary and Conclusion This case brings attention to iatrogenic Cushing syndrome as a potential complication when using high-potency topical corticosteroids in the anogenital region.

Introduction Cushing syndrome (CS) is an endocrinological abnormality that results from a high level of glucocorticoids in the blood. Iatrogenic CS due to the overuse of topical corticosteroids is rarely reported. The current study aims to present a rare case of topical corticosteroid induced iatrogenic CS in an infant. Case presentation A 4-month-old female infant presented with an insidious onset of face puffiness that progressed over a 2-month period. The mother reported to have used a cream containing Betamethasone corticosteroid 5–8 times a day for a duration of 3 months to treat diaper dermatitis. Laboratory findings revealed low levels of adrenocorticotrophic hormone (ACTH) and serum. Abdominal ultrasound showed normal adrenal glands. The topical corticosteroid was halted and physiologic topical hydrocortisone doses were administered. Clinical discussion Infants are more likely to acquire topical corticosteroid induced iatrogenic CS due to their thin and absorptive skin, higher body surface area, and the high prevalence of conditions that necessitates the use of these medications. Most iatrogenic CS cases following topical steroid application have been reported in infants with diaper dermatitis that are most commonly treated with Clobetasol and Bethamethasone. Conclusion Infants are susceptible to develop CS due to topical corticosteroid overuse. Hence, physicians need to consider this in infantile CS cases, and take appropriate measures to avoid their occurrence., Highlights • Cushing syndrome is an abnormality resulting from high level of blood glucocorticoids. • Iatrogenic Cushing syndrome due to the overuse of topical corticosteroids is rarely reported. • This report presents a case of topical corticosteroid induced iatrogenic Cushing syndrome in an infant.

Key Clinical Message Our case report discusses the usefulness of administering romiplostim as a second-line treatment before splenectomy in a cirrhotic patient with immune thrombocytopenia who developed corticosteroid-induced Cushing's syndrome. Corticosteroids were tapered and consequently withdrawn. The patient made a full recovery postsplenectomy.

Objective: Chronic exogenous steroid therapy can lead to iatrogenic Cushing syndrome (CS). However, concomitant presence of endogenous CS in a patient on exogenous steroids has not been previously reported. We report a case of a 23-year-old who had manifestations of both exogenous as well as endogenous CS.Methods: We present a case report and literature review.Results: A 23-year-old woman presented to us with severely deforming polyarthritis of both small and large joints since childhood, associated with recurrent bouts of uveitis. She was on triamcinolone therapy for the last 16 years, with cushingoid features and severely reduced bone mineral density, presumably due to exogenous CS. Anthropometry revealed severely retarded height for age and weight for age. She underwent hormonal profile assessment for evaluation of her hypothalamic-pituitary-adrenal axis status, which revealed the concurrent presence of adrenocorticotropic hormone-independent endogenous hypercortisolemia. Abdominal imaging showed bulky and nodular adrenal glands. A diagnosis of primary pigmented nodular adrenal disease in the background of juvenile idiopathic arthritis was considered, as was therapy with chronic glucocorticoid treatment. She was started on methotrexate and analgesics. Surgery was also recommended, however she refused bilateral adrenalectomy.Conclusion: This case highlights that both exogenous and endogenous CS can coexist in an individual. Furthermore, diagnosis of endogenous CS in a patient on chronic steroid therapy requires a high degree of clinical suspicion.Abbreviations: ACTH = adrenocorticotropic hormone; CECT = contrast-enhanced computed tomography; CS = Cushing syndrome; JIA = juvenile idiopathic arthritis; PPNAD = primary pigmented nodular adrenal disease

Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction. Several case series have been described.-Fluticasone is the one with the greatest potential risk of producing iatrogenic adrenal insufficiency given its pharmacokinetic characteristics. Clinical Case: 44-year-old woman diagnosed with HIV (human immunodeficiency virus) category B3 diagnosed in 1989; multiple antiretroviral treatments. Severe lipodystrophy Also HCV genotype IA. Bronchial asthma since 2000. A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day. He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it. Likewise, she presented progressive proximal weakness in the lower limbs, with increased hair, capillary fragility and alopecia, which is why she was referred to Endocrinology. Moderate hirsutism, muscle atrophy were observed and in the analytical study: normal FSH and LH. Testosterone 0.05 ng / ml (0.1–0.9), ACTH 1.0 pg / ml (7.2–63.3), Cortisol am 0.65 µg / dl (4.30–22.40). Urinary free cortisol 3.74 µg / 24h (36–137). A Synacten Test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and a diagnosis of iatrogenic independent ACTH Cushing Syndrome associated with secondary adrenal insufficiency. With this diagnosis, he was referred to the pulmonology clinic for a change from inhaled corticosteroid to beclomethasone and replacement treatment with hydroaltenesone was started. Three months later, he was admitted for a fever after stopping hydroaltesone. It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir). Clinical Lesson: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 enzyme CYP3A4, which is inhibited or enhanced by a multitude of drugs, including ritonavir. As it is not metabolized, there is an increase in circulating levels, causing a decrease in ACTH secretion and therefore a suppression of the adrenal gland with its insufficiency and cushing syndrome. In our case and usually, the initial signs are difficult to detect due to their overlap with lipodystrophy associated with protease inhibitors. Although there is no agreement in the literature: the options are the replacement of fluticasone with another corticosteroid that is not a CYP3A4 substrate such as beclomethasone and the replacement of ritonavir with another antiretroviral (as in our case) or the reduction of the dose of fluticasone. It is recommended to avoid the initiation of fluticasone in patients receiving ritonavir. Substitution treatment with a progressive reduction in dose is performed with hydroaltesona. Most cases resolve in 9–12 months.

In recent decades there has been an undeniable advance in the development of new drugs, which have increased the patient's quality of life, as well as extended the life expectancy of the world population to which they have reach. However, it should be considered that exogenous substances, at supraphysiological levels, or even within normal levels, can mostly cause with deleterious effects, as is the case of corticosteroids, the focus of the study of this study. Articles from MEDLINE, PubMed, Elsevier, Nature Review were analyzed in order to explore the evolution of iatrogenic Cushing Syndrome (CS), which is related to the chronic use of Glucocorticoides (CG). For this purpose, biochemistry, mechanism of action, pharmacokinetics and metabolic effects of CG were described. The parallel with iatrogenic CS was traced in the description of the clinical diagnosis of the disease, based on the previous history of corticosteroid therapy of the patients, as well as the main techniques recommended for weaning the CG, which are with a lower degree of recurrence of the underlying disease and lower risk of adrenal insufficiency (dysfunctions of the Hypothalamus-Pituitary-Adrenal axis).

Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking. Methods: A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas. Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival. Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities. Funding Statement: Supported in part by the grant AZV 16-32665A to Sarka Dvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng. Declaration of Interests: None of the authors have relevant conflicts of interest. Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.

Objectives : The purpose of this study is to report the improvement of a patient diagnosed as iatrogenic Cushing syndrome treated with herbal medicine. Methods : We treated a patient diagnosed as iatrogenic Cushing syndrome with s Wiryeong-tang gagam and Sinbeopbanha-tang for 10days. While being treated with herbal medicine, the patient got acupuncture treatment two times a day. Results : After treatment, weakness of lower limb and tremor got improved. Vomiting and disgusting also got better. Conclusion : Using herbal medicine may improve various symptoms of iatrogenic Cushing syndrome effectively.

Iatrogenic Cushing syndrome (CS) is a well-known complication of treating patients with systemic steroids. More rarely, it has been described in HIV-positive patients on ritonavir (RTV) while using the inhaled corticosteroid fluticasone, which is metabolized through the cytochrome P450 3A4 (CYP3A4) enzyme system. In the presence of RTV, a known CYP3A4 enzyme inhibitor, the interaction can result in impaired metabolism and systemic accumulation of inhaled fluticasone resulting in iatrogenic CS. Iatrogenic CS has been less often described with inhaled budesonide compared to inhaled fluticasone. Therefore, inhaled budesonide is often used as an alternative therapy for patients on RTV to avoid iatrogenic CS. We report the fifth case report of budesonide-induced iatrogenic CS in an HIV-positive patient on RTV. We highlight the importance of early recognition of the syndrome and distinguishing it from HIV lipodystrophy. Finally, we review the literature for cases of iatrogenic CS involving RTV and commonly used steroids.

With increasing use of intranasal steroids for a wide range of pediatric upper airway disorders, the potential for iatrogenic CS with these agents should be considered. We describe a case of a 7-month-old infant who developed CS secondary to intranasal use of dexa-methasone. Written informed consent was obtained from the parents for publication of this case report.

The uncontrolled sale of topical corticosteroids has become an important risk factor for the development of iatrogenic Cushing syndrome in children, especially in countries where medications are sold over the counter. This is exacerbated by the lack of information for both the patients and pharmacists. This report documents a series of eight cases of iatrogenic Cushing syndrome secondary to an inappropriate use of topical steroids, due to a misdiagnosis of scabies.

We report a rare case of spontaneous eyeball luxation associated with exophthalmos due to iatrogenic Cushing syndrome (CS). The normalization of serum hormones led to the regression of the picture.A 64-year-old man presented with spontaneous globe luxation of the left eye after a 6-month history of bilateral, painless, and slowly progressive exophthalmos. The patient had been receiving weekly infusions of methylprednisone over the previous 6 months. His best-corrected visual acuity (BCVA) at presentation was 20/40 in the right eye and 20/20 in the left eye. The patient demonstrated full extraocular motility. The intraocular pressure (IOP) was elevated in the right eye (24 mHg) and normal in the left eye (18 mmHg). Exophthalmometry demonstrated bilateral proptosis with measurements of 27 mm in the right eye and 28 mm in the left eye. Computed tomography scan of the brain and orbits revealed increased orbital and cervical fat. Clinical, radiographic and serologic findings ruled out potential diagnoses including orbital metastasis, thyroid orbitopathy, carotid-cavernous fistula, and idiopathic orbital pseudotumor. Clinical suspicion of iatrogenic CS was high, and additional serologic testing confirmed the diagnosis.Exophthalmos is an uncommon sign of CS, but to our knowledge, this is the first reported case of spontaneous globe luxation secondary to CS. In our case, normalization of cortisol was sufficient to resolve the clinical symptoms and eliminated the need for surgical intervention such as orbital decompression surgery.

Isolated Facial nerve palsy is a less common neurological manifestation of intracranial tuberculoma. Again, tuberculoma can arise following development of Cushing syndrome after prolonged intake of steroids due to origin of immunosuppressed state. Thus exogenous steroid administration leading to iatrogenic Cushing Syndrome which again causing tuberculoma, with facial nerve palsy developing as a manifestation of tuberculoma is not unnatural but definitely a unique scenario. The author reports an interesting case where a patient developed left sided facial palsy following development of intracranial tuberculoma from iatrogenic Cushing syndrome after longterm intake of Dexamethasone as a treatment for low back pain. This situation is rarely reported before.

We report the first case of a human immunodeficiency virus type 1 (HIV-1)-infected individual receiving combination antiretroviral therapy, which included ritonavir, who developed Cushing syndrome with profound complications after epidural triamcinolone injections. This case highlights the potential of ritonavir interactions even with local injections of a corticosteroid.

Copyright © 2015 by the University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina. 1Clinic for Dermatology and venereology DermaPlus Zagreb, Coratia, 2University Hospital Centre “Sestre milosrdnice”, Department of Dermatology and venereology, Zagreb, Coratia, 3Clinical Hospital “Sveti Duh”, Department of Neonatology, Zagreb Croatia, 4University Hospital Centre “Sestre milosrdnice”, Department of Paediatric Edocrinology Zagreb, Croatia Images in clinical paediatrics Paediatrics Today 2015;11(2):186-187 DOI 10.5457/p2005-114.127