Hypothalamic-pituitary-adrenal Suppression Research Articles

FRI233 Adrenal Insufficiency Due To An Unusual Culprit

Abstract Disclosure: S. Decamps: None. K.T. Yeung: None. K. McCowen: None. Background: Chronic exogenous use of glucocorticoids is the most common cause of reversible secondary adrenal insufficiency (AI). There is a significant risk of cortisol deficiency if the medication is abruptly discontinued. Chronic glucocorticoid therapy may cause hypothalamic-pituitary-adrenal (HPA) axis suppression, resulting in low ACTH, atrophy of the adrenal zona fasciculata and decreased cortisol production. Immunotherapy rarely causes reversible central AI, usually permanent. We present a case of an immunotherapy-receiving patient who presented with biochemical evidence of adrenal insufficiency after using an oral solution (swish and spit) of dexamethasone as prophylaxis for mucositis. Patient Summary: A 52-year-old woman with stage IIb triple negative breast cancer receiving neoadjuvant Datopotamab, Dertuxtecan and Durvalumab was evaluated for adrenal insufficiency. Prior to starting therapy, serum cortisol level measured 7.9 mcg/dL at 11 AM (normal 6.0-18.4 mcg/dL at 6-10 A.M). She had received a single dose of dexamethasone 10 mg IV with her first cycle, but not thereafter. As part of the immunotherapy protocol, serial cortisol levels were obtained, and 2 weeks after the baseline, noon serum cortisol was 1.0 ug/dL. Patient was asymptomatic. At no point were glucocorticoids replaced, but 1-week later serum cortisol level was 0.6ug/dL at 11:00 AM along with an ACTH of 5 pg/mL. Immunotherapy-induced AI was strongly suspected. Her only glucocorticoid exposure had been a dexamethasone oral mouth rinse (swish 10mL for 1 minute and spit out, four times daily). Cortisol level at 7AM a week later measured 3.5 mcg/dL with ACTH 18.7 pg/mL and a dexamethasone level 108.2 ng/dL (normal < 50 ng/dL for patients not on dexamethasone). Technique of swish and spit was reviewed with the patient, and she was not ingesting the medication. An observational approach was pursued at this time given hemodynamic stability, treatment was continued and several weeks later repeat labs showed cortisol levels of 3.3 (7AM), with a dexamethasone level of 84.3 ng/dL. Her course of therapy has been completed, so she has been off the dexamethasone solution, continues to be asymptomatic and repeat labs now show a 9AM Cortisol level of 9.5 mcg/dL and, given lack of other sources, it is most likely that these low cortisol levels along with elevated dexamethasone levels are related to the use of dexamethasone swish and spit rather than immunotherapy induced permanent HPA axis suppression. Conclusion: There is no literature on dexamethasone swish and spit being absorbed systemically possibly leading to potentially reversible HPA suppression. Our case will raise awareness of help guide clinicians expand their differential when working up these patients. Presentation: Friday, June 16, 2023

25709 Halobetasol propionate lotion 0.05% in patients 12 to 16 years 11 months of age with plaque psoriasis: Results from an open label study evaluating adrenal suppression potential

Introduction: Halobetasol propionate (HBP) lotion 0.05% is a high-potency corticosteroid approved for topical treatment of plaque psoriasis in adults. Adverse events (AEs) associated with corticosteroids include reversible hypothalamic-pituitary-adrenal (HPA) axis suppression. Effects of HBP on the HPA axis in children have not been previously evaluated. We present results of a study examining the effects of HBP on HPA suppression in patients <18 years of age with plaque psoriasis.

Patterns of poverty across adolescence predict salivary cortisol stress responses in Mexican-origin youths

Poverty is a chronic stressor associated with disruptions in psychophysiological development during adolescence. This study examined associations of chronic poverty and income changes experienced from pre- to mid-adolescence with hypothalamic-pituitary-adrenal (HPA) axis stress responses in late adolescence. Participants (N = 229) were adolescents of Mexican-origin (48.7% female). Household income (converted to income-to-needs ratios) was assessed annually when children were 10–16 years old. At 17 years, adolescents completed Cyberball, a social exclusion simulation task while undergoing a functional magnetic resonance imaging scan. Saliva samples were collected prior to and five times over a 50-minute period following the scan, from which salivary cortisol was assayed. Results showed that differential trajectories of poverty from ages 10–16 predicted HPA axis activity at age 17. Relative to others, distinct HPA suppression (hyporeactivity) was demonstrated by youth who started adolescence in deep poverty and were still living in poverty at age 16 despite experiencing some income gains. Youth from more economically secure families evinced typical cortisol increases following the lab stressor. These results suggest that subsequent HPA functioning varies as a function of economic status throughout adolescence, and that efforts to increase family income may promote healthy HPA functioning for youths in the most impoverished circumstances.

Repeat Epidural Injections of SP-102 (Dexamethasone Sodium Phosphate Injectable Gel) in Subjects with Lumbosacral Radiculopathy.

PurposeSP-102 is a novel epidural steroid injection (ESI) formulation of 10 mg dexamethasone sodium phosphate in a viscous gel solution. Repeat dosing of ESIs is possible if required for pain relief, but with consideration of hypothalamic–pituitary–adrenal (HPA) axis suppression from prolonged systemic exposure. This phase I/II study investigated the effect of initial and repeat SP-102 injections on HPA suppression and analgesia.MethodsSubjects with lumbosacral radiculopathy received an initial epidural SP-102 injection (T1) on day 1, followed by a repeat injection (T2) on ≥28 days later. To determine HPA suppression, area under the effect curve over 28 days and maximum change from baseline were calculated for cortisol, glucose levels, and white blood cell (WBC) count. Equivalent effect on HPA suppression of T1 relative to T2 was determined if the 90% CIs for ratios of these measures were within 80%–125%. The effect of repeat injections on leg and back pain was also assessed.ResultsBased on the responder analysis, all subjects had achieved a cortisol response by day 3 after initial injection and by day 2 after repeat injection. The repeat injection had similar effects on glucose levels and WBC count to the initial injection. Pain scores decreased after each injection and remained low for the 28-day follow-up, with some evidence of improved analgesic effect of the second dose compared with the first. There were no serious adverse events or discontinuations due to adverse events.ConclusionThe lack of cumulative effect and rapid resolution of HPA suppression following repeated SP-102 dosing suggests that consideration of HPA pharmacodynamics is not clinically relevant when making decisions regarding repeat dosing. SP-102 ESIs provided prolonged pain relief, with preliminary evidence of greater efficacy after repeat injection. A phase III trial is ongoing.Clinical Trial IdentifierClinicalTrials.gov: NCT03613662.

Relationship Between Epidural Steroid Dose and Suppression of Hypothalamus-Pituitary-Adrenal Axis

Background: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown. Objectives: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI. Study Design: A double-blind, parallel-group, randomized controlled trial. Setting: Pain clinics in a university hospital. Methods: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used. Results: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P &lt; 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction. Limitations: There were selection bias and no placebo control. Conclusions: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids. Key words: Adrenal insufficiency, adverse effects, cushing’s syndrome, epidural injections, glucocorticoids, optimal dosage, pituitary-adrenal system, salivary cortisol

Spectrum of diagnosis of hereditary angioedema: Seven case reports

Hereditary angioedema (HAE) is a potentially life-threatening disorder, due to a mutation in complement one-inhibitor (C1-INH) gene, which blocks the activity of various components of complement – fibrinolytic and bradykinin control system. Our seven cases of HAE give different clinical presentations of TYPE I/II/III HAE as facial, abdominal, laryngeal, and genital involvement along with comorbidities (5 cases) such as hypothyroidism, rhinosinusitis, and hypothalamic–pituitary–adrenal suppression, and four cases have had history of recurrent abdominal attacks. Treatment with Pdc-INH concentrate and self-administrated Icatibant provides consistent and reliable efficacy in those who have had multiple successive HAE attacks, with the involvement of all body parts. However, if pdc-INH concentrate is not available, then fresh frozen plasma and androgens (Danazol) can be used in emergency. Our cases demonstrate the importance of diligent clinical and family history with special tests: C4, C1-INH quantitative, and C1-INH functional.

The unresolved riddle of glucocorticoid withdrawal.

Glucocorticoid (GC) therapy is the most common cause of adrenal insufficiency (AI). The real prevalence of AI after GC is unknown but it could involve more than 30% of patients. Some gene variation has been associated with the variability of hypothalamic-pituitary-adrenal (HPA) axis and this issue could contribute to the individual variation of adrenal function after GC treatment. Symptoms and signs of AI are nonspecific and frequently the diagnosis is delayed. Dosage, duration of treatment, administration route and serum cortisol value are not completely useful to predict AI. Clinical estimation of HPA suppression is difficult and biochemical testing is needed to confirm the diagnosis of AI. The different tapering regimens are based on a very low quality of evidence and considering the sizable individual variation, it is improbable that future research will find a secure GC tapering schedule for all patients. The aim of this review is to address the most important aspects in management of GC withdrawal in light of current knowledge.

S15 * ALCOHOL DEPENDENCE AND NEUROENDOCRINOLOGY - NEW FINDINGS AND PERSPECTIVES

S15 * ALCOHOL DEPENDENCE AND NEUROENDOCRINOLOGY - NEW FINDINGS AND PERSPECTIVES

Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects

Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

Stress Responsiveness Decreases With Age in Precocial, Juvenile Chukar

Abstract Development of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent corticosterone (CORT) release in newly hatched birds is a balance between limiting exposure to the detrimental effects of CORT on growth and development, and the necessity of mounting an acute stress response. We measured the stress responsiveness of juvenile Chukar (Alectoris chukar) 20 to 60 days post-hatch prior to molting into full adult plumage. The integrated CORT response during 60 min of restraint in these individuals decreased with age. Comparisons to mean adult integrated CORT values imply the youngest juveniles have greater responses than adults while the oldest juveniles have reduced CORT responses. This pattern is currently an anomaly within the altricial-precocial range and suggests specific tradeoffs, such as molting into adult plumage, may affect timing of HPA suppression during development.

Adrenal function in HIV infection

Adrenal dysfunction can increase morbidity and mortality among patients with HIV infection. Disorders and medications affecting cortisol, aldosterone or adrenal androgens in patients with HIV infection are reviewed. Iatrogenic Cushing's syndrome and hypothalamic-pituitary-adrenal suppression from concomitant use of ritonavir with nonsystemic corticosteroids such as intra-articular triamcinolone in addition to the previously reported interactions with inhaled fluticasone are increasingly recognized in HIV patients. Integrated measure of aldosterone throughout the day is higher in patients with HIV-associated visceral adipose tissue accumulation. Abnormalities in adrenal function are more common in HIV patients than in the general population. HIV care providers should pursue workup for adrenal dysfunction in HIV patients when symptoms or signs are present, especially in patients with advanced AIDS or receiving medications that can affect adrenal function. The clinical implications of aldosterone elevation in HIV patients with visceral adiposity will need to be examined in future research studies.

Long-term Corticosteroid Use

Long-term Corticosteroid Use

Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS.

We have studied the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term, intravenous high-dose, corticosteroid therapy (IVHDCT) without subsequent oral replacement therapy in 10 patients with relapsing-remitting or progressive multiple sclerosis (MS) using the human corticotrophin-releasing hormone (hCRH) test. There was significant HPA suppression with profoundly decreased basal and peak plasma ACTH and cortisol levels 24 h after cessation of therapy. However, at 48 h the pituitary response was greatly enhanced with peak ACTH concentrations rising by more than 100% over baseline values in 7 of 10 patients. Basal and stimulated ACTH concentrations returned to pre-treatment levels at 120 h. Basal and stimulated plasma cortisol levels remained subnormal in 6 patients 120 h after IVHDCT. We conclude that IVHDCT without oral replacement therapy in MS patients is endocrinologically safe.

Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals

Objective. The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low-dose dexamethasone test in a group of healthy individuals (n=157). Material and methods. Pre- and post-dexamethasone morning serum cortisol was analysed. All participants completed questionnaires regarding symptoms of IBS (GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) and symptoms of anxiety and depression (HADS (Hospital Anxiety and Depression Scale)). After exclusions, 124 subjects were available for analysis (F/M: 60/64, mean age 55.8 years, SD 15.4, range 21–80 years). Results. A positive correlation was found between the GSRS-IBS score and HADS score (rs=0.36; p<0.001). There was no linear correlation between either pre- (rs=0.145; p=0.11) or post-dexamethasone cortisol levels (rs=0.087; p=0.337) and GSRS-IBS scores. By subgrouping the subjects at the lower and higher 25th percentiles of their post-dexamethasone morning cortisol levels, we found a trend towards a higher GSRS-IBS score (median 7.0 versus 5.0; p=0.069) (multivariate adjusted OR 2.6; CI 0.80–8.3) and a significantly higher diarrhoea score (median 2 versus 0; p=0.021) (multivariate adjusted OR 5.7; CI 1.5–22), and a higher early satiety score (p=0.008) (multivariate adjusted OR 6.7; CI: 1.9–23) in the subjects with high post-dexamethasone cortisol levels (low HPA suppression) compared with the subjects with intermediate post-dexamethasone cortisol levels. Furthermore, individuals with low post-dexamethasone cortisol levels (high HPA suppression) showed a significant, higher score for diarrhoea (median 2.0 versus 0; p=0.010) (multivariate adjusted OR 6.1; CI 1.8–20) and early satiety (p=0.076) (multivariate adjusted OR 3.2; CI 1.0–10) compared with those with intermediate cortisol levels. Conclusions. A trend toward a non-linear relationship between IBS-like symptoms and post-dexamethasone cortisol levels was observed in healthy individuals, with significantly more symptoms of diarrhoea and early satiety in individuals with high or low post-dexamethasone cortisol levels in comparison with those with intermediate post-dexamethasone cortisol levels.

Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

Background High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity due to an enhanced corticotropin-releasing hormone (CRH) drive and glucocorticoid feedback resistance. In humans, PTSD and MDD are associated with decreased and increased resistance to glucocorticoid feedback, respectively, which might reflect persistent changes in neuroendocrine sequelae following childhood abuse. Methods We investigated the relationship between childhood abuse and HPA axis function using a combined dexamethasone/CRH (DEX/CRH) test in 39 BPD patients with ( n = 24) and without ( n = 15) sustained childhood abuse and comorbid PTSD ( n = 12) or MDD ( n = 11) and 11 healthy control subjects. Results Chronically abused BPD patients had a significantly enhanced corticotropin (ACTH) and cortisol response to the DEX/CRH challenge compared with nonabused subjects. Comorbid PTSD significantly attenuated the ACTH response. Conclusions Hyperresponsiveness of the HPA axis in chronically abused BPD subjects might be due to the enhanced central drive to pituitary ACTH release. Sustained childhood abuse rather than BPD, MDD, or PTSD pathology accounts for this effect. Possibly due to an enhanced efficacy of HPA suppression by dexamethasone, PTSD attenuates the ACTH response to DEX/CRH.

Acute and Chronic Social Defeat Suppresses Humoral Immunity of Male Syrian Hamsters (Mesocricetus auratus)

Stressors, both physical and psychological, can activate the hypothalamic–pituitary–adrenal (HPA) axis, leading to a wide range of physiological responses including increased glucocorticoid release and suppression of immune function. The majority of studies published to date have focused on the effects of physical stressors (e.g., cold exposure, electric shock) on immunity. The present study examined the role of a stressor, social defeat, on humoral immune function of Syrian hamsters (Mesocricetus auratus). Specifically, adult male Syrian hamsters experienced social defeat (i.e., exposure to a dominant animal in that animal's home cage) that was either acute (i.e., a single exposure) or chronic (i.e., daily exposures across 5 days). A control group of animals was placed in a resident's home cage without the resident animal present and did not experience defeat. After the last encounter, blood samples were drawn and animals were subsequently injected with keyhole limpet hemocyanin (KLH). Blood samples were again taken 5 and 10 days postimmunization and serum was analyzed to determine serum cortisol and anti-KLH immunoglobulin G (IgG) concentrations. Cortisol concentrations were elevated in both acutely and chronically defeated hamsters compared with control animals. In contrast, serum IgG concentrations were significantly reduced in both groups of defeated hamsters compared with control animals. Collectively, these results demonstrate that both acute social defeat and chronic social defeat lead to activation of the HPA axis and suppression of humoral immune function. These data suggest that social defeat is an important, ecologically relevant model with which to examine stress-induced immune suppression in rodents.

Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis.

Topical glucocorticoids (GCs) fail to produce a clinical response in some children with atopic dermatitis (AD), suggesting that GC resistance may be present. To determine whether such resistance is generalized or specific to diseased skin, hypothalamic-pituitary-adrenal (HPA) axis function has been assessed in children with moderate to severe AD, who showed a variable response to treatment with topical GC. Thirty-five patients (.7-18.7 years old; median: 9.3 years) with AD requiring topical GCs from infancy underwent a low-dose adrenocorticotrophin hormone (ACTH; Synacthen) test (LDST) (500 ng/1.73 m(2) ACTH). Groups 1 (7 patients), 2 (17 patients), and 3 (4 patients) used mild, moderate, or potent/very potent topical preparations, respectively. Group 4 (7 boys with severe, treatment-resistant disease) had received GC in at least 1 form (inhaled +/- intranasal +/- oral) in addition to varying potencies of topical GC. Fourteen healthy subjects (3.8-17.3 years old) served as control subjects. Group 4 patients had a daytime plasma cortisol profile and 08.00 hours measurement of plasma ACTH and its precursors. The response to ACTH for groups 1 and 2 did not differ from that of control subjects. Group 3 had lower peak, increment, and area under curve cortisol responses than those in controls, whereas group 4 had lower baseline, peak, and area under curve cortisol responses. Eight patients failed the LDST (peak cortisol <500 nmol/L and increment <200 nmol/L): controls = 0/14, group 1 = 0/7, group 2 = 1/17, group 3 = 4/4, and group 4 = 3/7. Treatment score (based on GC potency, area treated, and duration) was the only factor to influence peak cortisol response on LDST (r(2) = 24%). In group 4, only 1 of 7 patients had a cortisol profile within the normal range but he failed the LDST. In the 5 subjects with an 08.00 hours cortisol <300 nmol/L, the matched ACTH level was inappropriately low. HPA suppression was rarely found in children or adolescents with moderate to severe AD who used mild or moderately potent topical GCs over many years. However, HPA suppression was common in those receiving potent topical GC preparations or a combination of GC routes of administration. In those with severe AD, evidence of HPA suppression but lack of clinical response to GC treatment excluded significant generalized GC resistance. This would suggest that localized resistance to GCs within the diseased skin may be part of the aetiopathogenesis of severe AD.

Adrenal Function Following High-Dose Steroids in Ovarian Cancer Patients

Purpose: Steroid doses similar to those used to prevent paclitaxel-associated hypersensitivity reactions and cisplatin-induced nausea have been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer. Patients and Methods: From January to July 1994, a cross-sectional study of HPA function was performed on patients receiving dexamethasone (DEX) as part of their paclitaxel and cisplatin chemotherapy regimen ( n = 9). Patients received 20 mg of DEX orally, 6 and 12 hr prior to paclitaxel (135 mg/m 2) and 10-20 mg intravenously before cisplatin (50-100 mg/m 2). In addition, patients received approximately 12 mg/day of DEX orally for 4 days after their chemotherapy as an antiemetic. HPA integrity was evaluated by the administration of synthetic adrenocorticotropic hormone (ACTH). The ACTH stimulation test was performed 11-19 days after the completion of the course of DEX. Patients had fasting baseline cortisol levels drawn at approximately 0800 followed by a 25-unit intravenous injection of ACTH. Post-ACTH cortisol levels were repeated at 30 and 60 min. Results: The mean (±SEM) fasting baseline level of cortisol was 12.4 ± 2.3 μg/dl (normal, 7-23 μg/dl). At 30 min following ACTH administration, the mean cortisol level rose 17.1 μg to 29.5 ± 1.8 μg/dl; at 60 min it rose 21.4 μg to 33.8 ± 2.5 μg/dl [ P < 0.001] (normal increase 9-39 μg). All patients demonstrated a sufficient increase in their plasma cortisol after ACTH stimulation, indicating normal HPA function on the days tested. However, there was a significant trend toward lower increases in plasma cortisol at 30 and 60 min as the interval from ACTH stimulation testing to the DEX regimen decreased ( r = 0.986; P < 0.0001). The chemotherapy cycle number had no impact on cortisol response in the multivariate analysis. Based on multiple linear regression, HPA function may be suppressed for approximately 8 days, but up to 14 days from the start of this DEX regimen. Conclusion: Current steroid regimens prescribed with chemotherapy transiently decrease HPA function, but do not appear to inhibit the HPA axis long term. HPA function may be suppressed for approximately 8 days from the commencement of chemotherapy cycles involving DEX. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may benefit from HPA axis testing.

BECLOMETHASONE DIPROPIONATE ENEMAS FOR TREATING INFLAMMATORY BOWEL DISEASE WITHOUT PRODUCING CUSHING'S SYNDROME OR HYPOTHALAMIC PITUITARY ADRENAL SUPRESSION

Since beclomethasone dipropionate (BDP) is a very potent glucocorticoid and since small oral doses (1 mg) seem to be metabolised (possibly in the gut wall or liver) before they reach the systemic circulation, a study was conducted to find out whether patients with inflammatory bowel disease could be treated with enemas containing small doses of BDP without their acquiring Cushing's syndrome or hypothalamic pituitary adrenal (HPA) suppression. The BDP in the 100 ml enemas used was stable and present in a concentration likely to be therapeutic (0·5 mg/dl). Single overnight BDP enemas, unlike conventional betamethasone (5 mg) enemas, did not interfere with the HPA axis in 6 healthy volunteers. In the double-blind randomised part of the study 2-week courses of BDP or betamethasone enemas were assessed in 9 patients having exacerbations of distal inflammatory bowel disease. The clinical and sigmoidoscopic responses as well as adrenocortical function (judged by the 'Cosyntropin' test) were evaluated on the morning after the last day of a course of enemas. Both types of enemas had similar beneficial effects, but only BDP enemas did not interfere with HPA function. Over a prolonged period, a patient with distal ulcerative colitis had been completely dependent on regular treatment with betamethasone enemas to control his symptoms. Substitution with BDP enemas successfully controlled his bowel symptoms, whilst his cushingoid features and HPA suppression regressed.

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 8:00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration. Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone. The basal cortisol level was not suppressed and the responsiveness to ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 5 mg betamethasone therapy. The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone in equivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression.