Secondary Adrenal Suppression Research Articles

Secondary adrenal suppression related to high doses of inhaled corticosteroids in patients with severe asthma

Asthma management guidelines recommend inhaled corticosteroids (ICS) as first-line therapy. Although long-time ICS use in patients with asthma has a more favorable safety profile than oral corticosteroids (OCS), it is still associated with adrenal suppression (AS) even in the absence of OCS use.1,2 Subsequent secondary adrenal insufficiency (AI) has been reported. Still, there are limited data on the magnitude of the effect in patients with severe asthma treated with high ICS doses.1

Administering steroids with HIV treatment‐boosting agents

Co‐administration of a steroid with an HIV treatment‐boosting agent such as ritonavir or cobicistat increases the risk of iatrogenic Cushing syndrome and subsequent secondary adrenal suppression. This article discusses the strategies to help prevent this and describes how to identify and manage such interactions.

Abstract #113: Iatrogenic Cushing & Secondary Adrenal Suppression Because of Drug Interaction in a Patient on H.A.A.R.T. for H.I.V

Abstract #113: Iatrogenic Cushing & Secondary Adrenal Suppression Because of Drug Interaction in a Patient on H.A.A.R.T. for H.I.V

Iatrogenic Cushing’s Syndrome with Secondary Adrenal Suppression Misdiagnosed as Protease Inhibitor-Induced Lipodystrophy in an HIV Positive Patient: Case Report

Iatrogenic Cushing’s Syndrome with Secondary Adrenal Suppression Misdiagnosed as Protease Inhibitor-Induced Lipodystrophy in an HIV Positive Patient: Case Report

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

Injecting epidural and intra-articular triamcinolone in HIV-positive patients on ritonavir: beware of iatrogenic Cushing’s syndrome

We report two HIV-positive patients on highly active antiretroviral therapy (HAART) who developed clinical features in keeping with secondary adrenal suppression following epidural and subacromial triamcinolone. Both patients were on ritonavir-boosted protease inhibitor containing HAART and both required maintenance hydrocortisone therapy following diagnosis. This highlights the need for radiologists and clinicians practicing these injections to be aware of this complication, to elicit an accurate drug history, and to take adequate measures to minimize these adverse effects.

Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report

Two HIV-1 infected patients developed signs and symptoms consistent with adrenal suppression after being exposed to intra-articular triamcinolone acetate while also receiving ritonavir as part of their highly active antiretroviral therapy. Laboratory evaluation confirmed secondary adrenal suppression in both cases. Both patients recovered without the need for chronic replacement steroids. Adrenal suppression has been described as an adverse outcome in patients treated with fluticasone and concomitant ritonavir. In the reported cases, the adrenal suppression likely developed as a result of increased systemic concentrations of triamcinolone due to an inhibition of cytochrome p450 3A4 metabolism. Practitioners of HIV medicine should be aware of the potential negative interaction of injected triamcinolone and ritonavir.

A Case of Recurrent Erythema Multiforme and its Therapeutic Complications

Introduction: We report a patient with recurrent erythema multiforme (recurrent EM) who developed iatrogenic Cushing’s syndrome due to prolonged corticosteroid use. Clinical Picture: The patient had been treated with multiple courses of oral and intramuscular prednisolone over a 10-year period to suppress his recurrent and episodic symptoms. This resulted in the development of iatrogenic Cushing’s syndrome with secondary adrenal suppression and steroid-induced osteoporosis. Treatment: The patient was treated with continuous acyclovir therapy in addition to azathioprine. This combination controlled his disease and enabled us to stop his requirement for high-dose prednisolone. Outcome: The patient responded well to this treatment regimen and has been in remission to date. Conclusion: This represents a severe case of recurrent EM and the side effects associated with years of chronic high-dose steroid usage. We discuss the therapeutic options to aid physicians in treating this disabling condition.

Unexpected Effects of Inhaled Fluticasone in an HIV Patient with Asthma

International guidelines recommend prescription of inhaled corticosteroïds to improve asthma control. Chronic secondary adrenal suppression due to inhaled corticosteroids has been described. We report a case of acute adrenal suppression due to drug interaction between Fluticasone and antiretroviral therapy in a HIV patient. Seeing an increased prevalence of hyperresponsiveness among HIV‐infected men, we conclude that coprescription of Fluticasone and highly active antiretroviral therapy must be carefully controlled.

A low-dose adrenocorticotropin test reveals impaired adrenal function in cancer patients receiving megestrol acetate therapy

Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 μg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 μg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 μg) ACTH (1-24) were <18 μg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 μg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 μg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7±10.3 μg/24 h) than normal responders (35±12.7 μg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.

Megestrol acetate therapy and secondary adrenal suppression

BACKGROUND Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer. METHODS Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), lutenizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients. RESULTS Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article. CONCLUSIONS MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness. Cancer 1999;86:1044–9. © 1999 American Cancer Society.

Megestrol acetate therapy and secondary adrenal suppression

Adrenal suppression has been noted in patients who are receiving medroxyprogesterone acetate (MPA). Megestrol acetate (MA) is used to treat patients with advanced breast carcinoma, cachaexia related to acquired immune deficiency syndrome, and disseminated carcinomatosis, and it is believed to have fewer side effects than MPA. The aim of this study was to test for secondary adrenal suppression in patients receiving MA therapy for advanced metastatic cancer. Ten postmenopausal female patients receiving long term MA therapy, nine with advanced metastatic breast carcinoma and one with metastatic ovarian carcinoma, were recruited consecutively from the oncology outpatient clinic at Ninewells Hospital in Dundee, Scotland. A short synacthen test and a corticotrophin-releasing hormone (CRH) stimulation test were performed on two separate occasions. Urine collection for 24-hour urinary free cortisol was performed on 6 patients. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (T4) were measured in eight patients. An insulin stress test (IST) was performed on two patients. Nine of 10 patients had a poor cortisol response to the short synacthen test. The CRH test had abnormal results in eight of nine patients. In all patients tested, 24-hour urinary free cortisol excretion was low, indicating adrenal suppression. Basal serum FSH, LH, TSH, and free T4 values indicated normal pituitary function. Adrenocorticotrophic hormone response in the CRH test varied and is discussed in this article. MA causes secondary adrenal suppression that is thought to be due to its effect at the hypothalamic level. The authors recommend a short course of steroid replacement for patients receiving MA at times of acute illness.

Effects of adrenalectomy on 8-OH-DPAT induced hypothermia in mice

Complex interactions exist between the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system, and it has been suggested that these interactions may be fundamental to the pathophysiology and treatment of depressive illnesses. It has previously been found that chronic administration of corticosterone leads to adrenal suppression and an attenuation of somatodendritic 5-HT1A receptor function. Adrenalectomy (ADX) has been shown to cause an increase in postsynaptic 5-HT1A receptor numbers and possibly function. However, other reports have suggested that ADX does not alter somatodendritic 5-HT1A receptor mRNA or binding, though little is known of the effect of ADX on the function of somatodendritic 5-HT1A receptors. This study investigated the effect of markedly reducing corticosterone levels by ADX on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)-induced hypothermia in mice, an in vivo model of somatodendritic 5-HT1A receptor function. The degree of 8-OH-DPAT-induced hypothermia did not differ between control, sham, and ADX animals 14 days post operatively. Although repeated administration of corticosterone attenuates somatodendritic 5-HT1A receptor function, these data demonstrate that lowering of corticosteroid levels by ADX have no effect. This suggests that the effects of repeated corticosterone administration is not mediated by a secondary adrenal suppression. The difference in the effects of ADX on somatodendritic as opposed to postsynaptic 5-HT1A receptors may reflect the differential expression of corticosteroid receptor subtypes at postsynaptic and somatodendritic sites.

HYPOTHALAMIC/PITUITARY/ADRENAL FUNCTION IN PATIENTS TREATED WITH INTERMITTENT HIGH-DOSE PREDNISOLONE AND CYTOTOXIC CHEMOTHERAPY

Hypothalamic/pituitary/adrenal (H.P.A.) function was assessed in ten patients receiving intermittent high-dose prednisolone and cytotoxic chemotherapy for myeloma or lymphoma in order to predict their possible requirement for additional steroid therapy between and at the end of treatment courses. Standard insulin hypoglycæmia tests performed 36 hours after the last dose of prednisolone often demonstrated impairment of corticotrophin (adrenocorticotrophic hormone, A.C.T.H.) and growth-hormone responses, indicating hypothalamic/pituitary suppression; plasma-corticosteroid responses to endogenous A.C.T.H. and tetracosactrin were abnormal in two patients, indicating secondary adrenal suppression. Such hypothalamic/pituitary and adrenal suppression may make these patients susceptible to acute adrenal insufficiency in times of stress. H.P.A. function should be fully assessed on completion of chemotherapy.