Adrenocortical hemorrhage following intravenous tetracosactide in a dog with hypercortisolism.

OBJECTIVE: To summarize findings from a case of adrenocortical hemorrhage following tetracosactide injection during ACTH stimulation testing for monitoring of trilostane therapy in a dog. ANIMAL: A 12-year old neutered male dog with adrenal-dependent hypercortisolism. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: 4 hours after ACTH stimulation testing, the patient developed vomiting, lethargy, and abdominal pain. Abdominal ultrasound was performed before and after an ACTH stimulation test. Following ACTH stimulation testing, there was progressive bilateral adrenal enlargement and free abdominal fluid had developed. This was considered to be caused by adrenocortical inflammation and hemorrhage secondary to the synthetic ACTH analog, tetracosactide, used during stimulation testing. A resting cortisol performed 5 hours after tetracosactide injection was not consistent with iatrogenic hypoadrenocorticism. TREATMENT AND OUTCOME: The patient was managed with analgesia, IV fluids, and corticosteroids and made a full recovery. CLINICAL RELEVANCE: To the authors' knowledge, this was the first reported case of adrenocortical hemorrhage following administration of a synthetic ACTH analog in a dog. This should be considered as a rare potential complication of ACTH stimulation testing.

Evaluation of psoriasis patients with long-term topical corticosteroids for their risk of developing adrenal insufficiency, Cushing's syndrome and osteoporosis.

PURPOSE: In this study, we will investigate the possible side effects of psoriasis patients using long-term topical corticosteroids (TCS) such as adrenal insufficiency, Cushing's Syndrome (CS) and osteoporosis and determine how these side effects develop. MATERIAL AND METHODS: Forty-nine patients were included in the study. The patients were divided into two groups based on the potency of the topical steroid they took and the patients' ACTH, cortisol and bone densitometer values were evaluated. RESULTS: There was no significant difference between the two groups regarding the development of surrenal insufficiency, CS and osteoporosis. One patient in group 1 and 4 patients in group 2 were evaluated as iatrogenic CS. ACTH stimulation tests of these patients in group 2 showed consistent results with adrenal insufficiency, while no adrenal insufficiency was detected in the patient in Group 1. Patients who used more than 50g of superpotent topical steroids per week compared to patients who used 50g of superpotent topical steroids per week. It was identified that patients who used more than 50g of superpotent topical steroids had significantly lower cortisol levels, with a negatively significant correlation between cortisol level and the amount of topical steroid use (p < .01).Osteoporosis was detected in 3 patients in group 1 and 8 patients in Group 2. Because of the low number of patients between two groups, statistical analysis could not be performed to determine the risk factors. CONCLUSIONS: Our study is the first study that we know of that investigated these three side effects. We have shown that the development of CS, adrenal insufficiency and osteoporosis in patients who use topical steroids for a long time depends on the weekly TCS dosage and the risk increases when it exceeds the threshold of 50 grams per week. therefore, our recommendation would be to avoid long-term use of superpotent steroids and to choose from the medium-potent group if it is to be used.

Iatrogenic cushing's syndrome post intralesional triamcinolone acetonide in oral submucous fibrosis: 2 case reports.

BACKGROUND: Oral Submucous Fibrosis (OFMF) is an oral potentially malignant disorder (OPMDs), strongly linked to betel quid chewing. It exhibits a significantly higher rate of malignant transformation compared to other OPMDs. The use of Intralesional Triamcinolone Acetonide Injection has emerged as a highly effective treatment option and has become the cornerstone of managing this condition. CASE PRESENTATION: A 44-year-old female and a 40-year-old male presented with burning sensation and limited mouth opening, leading to diagnosis of OSMF. Both patients were treated with Triamcinolone Acetonide (TAC) Intralesional injections. Following a few months of treatment, a significant improvement in mouth opening was observed. However, both patients began experiencing symptoms such as facial rounding (mooning of the face), a buffalo hump, uneven hair growth, and swelling in the lower extremities. Upon recognizing these symptoms as indicative of Cushing's Syndrome, the administration of TAC injection was discontinued. Both patients were referred to a higher-level medical facility for confirmatory tests, which revealed elevated cortisol levels in both morning (Cortisol A.M) and evening (Cortisol P.M). CONCLUSION: TAC injection has been established as an effective treatment for OSMF. However, it is crucial to closely monitor patients for any adverse effects resulting from the treatment, which may arise from high dosage or increased frequency.

Iatrogenic Cushing's syndrome in a case of allergic bronchopulmonary aspergillosis treated with oral itraconazole and inhaled budesonide.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing's syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.

[Cushing's syndrome with inhaled corticosteroid: Drug interactions to avoid]. / Syndrome de Cushing sous fluticasone inhalée : interactions médicamenteuses à éviter.

Cushing's syndrome is an iatrogenic event occurring during co-administration of inhaled corticosteroids and potent inhibitors of P450 cytochromes. We report the clinical case of a 29-year-old woman with a past history of asthma treated with inhaled fluticasone propionate (FP), chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) treated with itraconazole (ITZ), and Mycobacterium xenopi infection treated with moxifloxacin (MXF), ethambutol (EMB) and clarithromycin (CLR). Four months after initiation of antibiotic and antifungal medication, the patient contracted Cushing's syndrome. Its etiology consisted in interaction between FP, ITZ and CLR, which led to pronouncedly increased corticosteroid concentrations in circulating plasma cells. Following on the one hand cessation of FP and ITZ and on the other hand hydrocortisone supplementation, evolution was favorable. Several cases of iatrogenic Cushing's syndrome induced by co-administration of FP and potent CYP3A4 inhibitors have been reported in the literature. If possible, FP should be avoided in patients being treated with CYP3A4 inhibitors. Due to its differing physicochemical properties, beclometasone may be considered as the safest therapeutic alternative.

Iatrogenic Cushing syndrome in a child due to erroneous compounding of omeprazole containing glucocorticoid: A case report and literature review.

A 3-month-old infant was examined for inconsolable crying with polydipsia, polyuria, and rapid weight gain. Unexpectedly, the symptoms resolved spontaneously during hospitalization but were aggravated 2 weeks after discharge, with the patient presenting a Cushingoid appearance. Investigations ruled out diabetes mellitus and nephrogenic diabetes insipidus but indicated adrenocortical suppression by exogenous glucocorticoids, which were discovered via toxicologic analysis of her previously compounded omeprazole suspension. After discontinuing the omeprazole suspension, the infant recovered fully and the laboratory results normalized. This case shows us that the assumption of appropriate medication intake may conceal unexpected medication errors. Following this case, the current literature on the benefits and risks of compounding and its impact on patient health is discussed.

Factitious, or iatrogenic but unexpected Cushing's syndrome.

Prolonged exposition to supraphysiological doses of exogenous glucocorticoid eventually results in iatrogenic Cushing's syndrome, whose intensity depends on the dose and duration of the treatment and on individual susceptibility. In patients with chronic inflammatory diseases treated with oral glucocorticoids iatrogenic Cushing's is expected and recognized and it only imposes that the dose of glucocorticoid be maintained as low as possible and that there is no better alternative therapy available.In some cases, however, iatrogenic Cushing's syndrome may be unexpected by the prescribing physician as the true exposure to corticoids may depend largely on the patient: this is the case for topical steroids used in inflammatory skin diseases such as psoriasis. Factitious Cushing's syndrome (FCS) is another cause of exogenous Cushing's syndrome in whom the exposure to glucocorticoid is unexpected, as it is hidden to the physician by a patient suffering from Münchausen syndrome. FCS might be very difficult to diagnose depending on the type of glucocorticoid used, the specificity of the dosage used for cortisol, and the timing of the measurement of cortisol and ACTH. The best evidence for FCS is the demonstration by LC-MS/MS of exogenous glucocorticoid in his urine or plasma but this requires that the patient has not stopped to take glucocorticoid at the time of exploration. FCS related to hydrocortisone can be difficult to prove and to distinguish from cyclical Cushing's syndrome. Analysis of the literature shows that FCS has led to prolonged or invasive explorations and even to adrenal surgery, while unrecognized FCS has led to fatal infectious complications.

Glucocorticoid withdrawal syndrome: what to expect and how to manage.

PURPOSE OF REVIEW: Glucocorticoid withdrawal syndrome (GWS) can develop after withdrawing exposure to supraphysiological levels of endogenous or exogenous glucocorticoids due to an established physical dependence. It is characterised by symptoms similar to adrenal insufficiency but needs to be regarded as a separate entity. GWS is often under-recognised in clinical practice and affected patients can experience significant impairment in their quality of life. RECENT FINDINGS: A cornerstone in GWS management is adequate patient education and reassurance that symptoms are expected and typically temporary. Patients with endogenous Cushing's syndrome need to be aware that psychopathology may persist into the postoperative period. GWS is more likely to develop in severe Cushing's syndrome and in patients with very low levels of cortisol after surgery. Postoperatively, glucocorticoid replacement should be initiated and tapered in an individualised approach but there is currently no consensus on the best tapering strategy. If symptoms of GWS develop, glucocorticoid replacement ought to be temporarily increased to the previous, well tolerated dose. No randomised studies have thus far compared regimens for withdrawing glucocorticoids after treatment for anti-inflammatory or immunosuppressive causes to determine the best and safest tapering strategy. One open-label, single-arm trial in patients with asthma has recently proposed a personalised glucocorticoid tapering regimen which included the systematic assessment of adrenal function. SUMMARY: Awareness of GWS by treating physicians and patient education are essential. Evidence on optimal GWS management after Cushing's syndrome treatment is scarce, but new data are emerging for tapering after long-term glucocorticoid treatment.

Mifepristone induced liver injury in a patient with Cushing syndrome: a case report and review of the literature.

BACKGROUND: Mifepristone, also known as RU-486, is an anti-progestational steroid with similar chemical structure to anabolic steroids. Given as a single dose in conjunction with misoprostol, mifepristone is used to induce medical abortion. Mifepristone administered chronically at a higher dose is also approved for the management of hypercortisolism. There have been only 2 reported cases of mifepristone associated liver injury, in both cases, in the setting of Cushing syndrome. We report a third patient with Cushing syndrome with mifepristone induced liver injury with unique histological findings that provide insight to the pathophysiology of liver injury in mifepristone and anabolic steroids. CASE PRESENTATION: Patient is a 63-year-old Caucasian female Cushing disease with no prior history of liver disease. She was started on mifepristone and semaglutide. Ninety days after initiating mifepristone, she developed deep jaundice, severe pruritus, fatigue, and nausea. Liver tests revealed a mixed hepatocellular/cholestatic pattern. Viral and autoimmune serologies were negative and there was no biliary dilatation on imaging. Liver biopsy showed severe cholestasis but no bile duct injury. Focal endothelialitis was present within a central venule. Cholestatic symptoms persisted for one month after presentation before slowly subsiding. Four months after stopping mifepristone, the patient's symptoms completely resolved, and liver tests became normal. Compilation of Roussell Uclaf Causality Assessment Method score indicated probable causality. CONCLUSIONS: Mifepristone shares a similar chemical structure as synthetic anabolic/androgenic steroids and there are many similarities in the clinical presentation of liver injury. This case and the 2 other reported cases share similar clinical characteristics. The observation of endothelialitis in our patient may provide a mechanistic link between mifepristone, or anabolic steroids in general, and the development of vascular complications such as peliosis.

Betamethasone cream to treat diapers rash causing Cushing syndrome.

OBJECTIVES: Betamethasone causing iatrogenic Cushing's syndrome (CS) in infants are rarely reported. CASE PRESENTATION: In this case report, there were severe signs of CS, such as considerable weight acceleration and concurrent height deceleration, hirsutism and ecchymosis of the face, and buffalo pad, which are often found in adults. Clobetasol propionate, diflucortolone valerate, and dexamethasone nasal sprays were used in the majority of previously reported cases of corticosteroid abuse, whereas this is the first case of CS in an infant as a result of the use of betamethasone cream, also known as betnesol, which is frequently used by mothers in developing countries as a treatment for rashes. In this instance, a severe medication interaction caused by systemic betamethasone cream buildup led to the creation of CS. For the professionals, these patients are a challenge because of drug use without prescription. CONCLUSIONS: Topical corticosteroid usage puts infants at risk for CS. Because of excessive betamethasone treatment in this child with diaper dermatitis, he acquired CS. It is said to draw attention to the risks of self-medication in developing nations.

Topical Steroid-Induced Cushing's Syndrome in a Newborn Following Goniotomy for Glaucoma.

Iatrogenic Cushing's syndrome is a life-threatening condition which requires an early diagnosis multidisciplinary approach. Despite reports of iatrogenic Cushing's syndrome following nasal or inhaled steroids, its development after topical betamethasone eye drops for a short duration is a less frequently reported or anticipated condition. We describe a 6-week-old infant who developed exogenous Cushing's syndrome following topical steroids after bilateral goniotomy for newborn glaucoma. The child was kept under observation and managed with a physiological dose of hydrocortisone. Parental counselling regarding the proper method of eye drop instillation and signs of steroid toxicity is of vital importance in all cases of pediatric ocular surgeries, especially where bilateral surgeries are undertaken.

Topical glucocorticoid application causing iatrogenic Cushing's syndrome followed by secondary adrenal insufficiency in infants: two case reports.

BACKGROUND: Iatrogenic Cushing's syndrome induced by oral and parenteral glucocorticoid administration is a well-known complication. Immediate withdrawal from exogenous steroids can lead to life-threatening adrenal insufficiency. However, Cushing's syndrome caused by topical treatment with glucocorticoids, such as dexamethasone eye drops or dermal application, is rarely recognized. Young infants in particular are at high risk of suffering from iatrogenic Cushing's syndrome when treated with highly potent topical glucocorticoids. CASE PRESENTATION: We present a 6-month-old Syrian boy with cushingoid face after dermal clobetasol cream treatment and a 2-year-old Iranian girl with severe growth retardation after application of dexamethasone eye drops. Both families have a migration background and language barriers. In both cases no endogenous cortisol secretion was initially detected in serum and in 24-hour collected urine. After dose reduction of glucocorticoids, severity of symptoms was reversible and serum cortisol was detectable. DISCUSSION AND CONCLUSION: Young infants are at high risk of developing Cushing's syndrome from topically applied highly potent glucocorticoids. Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter. Monitoring of height and weight as well as regular pediatric follow-ups should be scheduled. Physicians should be aware of potential adrenal insufficiency following withdrawal from long-term topical glucocorticoid treatment, and hydrocortisone treatment should be considered.

Cushing's syndrome: a combined treatment with etomidate and osilodrostat in severe life-threatening hypercortisolemia.

Endogenous Cushing's syndrome (CS) is associated with increased morbidity and mortality. Early diagnosis and initiation of therapy are essential, but effective treatment remains a challenge. In a long-term follow-up, biochemical control of hypercortisolemia, especially when severe, is difficult to achieve. Life-threatening hypercortisolemia is difficult to control due to the limitations of pharmacotherapy, including its side effects, and may require etomidate infusion in the intensive care unit (ICU) to rapidly lower cortisol levels. The effectiveness of hypercortisolemia management can be increased by a dual blockade of cortisol production. We report the efficacy, safety, and tolerability of combined therapy with two steroidogenesis inhibitors, etomidate, and osilodrostat, in a 32-year-old woman diagnosed with severe ACTH-dependent hypercortisolemia, subsequently maintaining a stable level of cortisol with osilodrostat monotherapy. This approach enabled achievement of relatively rapid control of the hypercortisolemia while using an etomidate infusion and concomitant increasing doses of oral osilodrostat applying a "titrations strategy." Our experience shows that it is worth taking advantage of the synergistic anticortisolic action of etomidate with osilodrostat.

Long-term effects of glucocorticoid excess on the brain.

The metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of hypercortisolism, showing that both endogenous and exogenous glucocorticoid excess alter brain functioning on several time scales. Consequently, cognitive deficits and neuropsychological symptoms are highly prevalent during both active CS and CS in remission, as well as during glucocorticoid treatment. In this review, we discuss the effects of endogenous hypercortisolism and exogenously induced glucocorticoid excess on the brain, as well as the prevalence of cognitive and neuropsychological deficits and their course after biochemical remission. Furthermore, we propose possible mechanisms that may underly neuronal changes, based on experimental models and in vitro studies. Finally, we offer recommendations for future studies.

Iatrogenic Cushing syndrome in 24-hour urine free cortisol measurement.

Cushing syndrome (CS) is caused by an excess of glucocorticoids that results in a variety of symptoms such as central obesity, moon facies, hirsutism, and reddish-purple stretch marks. Cortisol is the most potent endogenous glucocorticoid, and measuring the total amount excreted in the urine over a 24-hour period is useful to screen for CS caused by a tumor. However, most cases of CS are believed to be caused by exogenous glucocorticoids, such as prednisone and prednisolone, which are administered for anti-inflammatory and immunosuppressive treatments. This is often referred to as iatrogenic (drug-related or exogenous) CS. We modified an LC-MS/MS method for urine free cortisol to detect the presence of prednisone and prednisolone in patient samples. We wanted to understand the potential prevalence of exogenous CS in our patient population.