Oral Cortisone Research Articles

Immune checkpoint inhibitor-associated adrenal insufficiency in Chinese cancer patients: a retrospective analysis.

Immune checkpoint inhibitors (ICIs) are of great success in cancer therapy. This study aimed to identify adrenal insufficiency (AI) associated with immune checkpoint inhibitor (ICI) treatment in cancer patients receiving steroid replacement therapy and report the clinical characteristics of ICI-associated AI and concurrent immune-associated adverse events (irAEs). Patients prescribed cortisone acetate between January 2020 and March 2022 were reviewed to identify AI associated with ICI treatment. Data collected included indication of ICI (cancer type), drug characteristics, and outcomes. A total of 101 patients were diagnosed with AI following treatment with ICIs. The median age was 64years (range 22-83years); 73.3% of the patients were male. Median time to develop primary AI and secondary AI after starting ICI therapy was 200.5 (35-280) days and 178 (16-562) days, respectively. Concurrent irAEs occurred in 67 (66.3%) patients and included 63 (62.4%) endocrine irAEs. Log-rank test showed that there was a trend toward higher likelihood of death at 120-day follow-up in patients initially receiving intravenous hydrocortisone compared with those receiving oral cortisone acetate after diagnosis of AI (p = 0.029). This retrospective study comprehensively documented the clinical characterization of ICI-associated AI. Those initially receiving intravenous hydrocortisone after diagnosis of AI were associated with higher likelihood of death. Physicians should be aware of the variability of ICI-associated irAEs early in the treatment, early diagnoses, and timely management should be made.

Endobronchial Valve Replacements in Patients with Advanced Emphysema After Endoscopic Lung Volume Reduction.

Up to 41% of patients with endobronchial valve implantation need revision bronchoscopies and valve replacements most likely due to valve dysfunction or lack of benefit. So far, no data is available whether valve replacements lead to the desired lobar volume reduction and therapy benefit. We conducted a single-center retrospective analysis of patients with endobronchial valve implantation and at least one valve replacement. Indications and number of revision bronchoscopies and valve replacements were evaluated. Therapy benefit regarding lung function and exercise capacity as well as development of complete lobar atelectasis was investigated and possible predictors identified. We identified 73 patients with 1-12 revision bronchoscopies and 1-5 valve replacements. The main indication for revision bronchoscopy in this group was lack of therapy benefit (44.2%). Lung function and exercise capacity showed improvements in about one-third of patients even years after the initial implantation. A total of 26% of all patients showed a complete lobar atelectasis at the end of the observation period, 56.2% had developed lung volume reduction. The logistic regression revealed the development of a previous complete lobar atelectasis as predictor for a complete lobar atelectasis at final follow-up. Oral cortisone long-term therapy was also shown as predictive factor. The probability for a final complete lobar atelectasis was 69.2% if a lobar atelectasis had developed before. Valve replacements are more likely to be beneficial in patients who develop a re-aeration of a previous lobar atelectasis following valve implantation. Every decision for revision bronchoscopy must be taken carefully.

HERPES ZOSTER OPHTALMICUS IN AN IMMUNOCOMPETENT PATIENT

HZO (Herpes Zoster Ophthalmicus) is defined as the reactivation of VZV (Varicella Zoster Virus) in the ophthalmic branch of the trigeminal nerve, leading to the appearance of well-demarcated erythematousvesicular lesions along the dermatome. Antiviral therapy is mandatory and preferably initiated within the first 72 hours of the rash onset, as it is most effective in preventing ocular involvement. Raising awareness of the importance of early diagnosis and management of herpes zoster ophthalmicus, with the involvement of an ophthalmologist is critical in limiting visual morbidity. We present a 40-year-old patient without significant medical history or background treatment, immunocompetent, whose symptoms began suddenly with a few erythematous- vesicular lesions on the left fronto-parietal scalp preceded by burning pain and hyperesthesia. At her first medical exam, she was recommended antiviral treatment with oral acyclovir and cortisone. She was admitted in our clinic 48 hours from the onset, with the extension of the lesions to the left forehead and peri-orbital, periorbital itching, left occipital hypoesthesia, and painful pre-, retro-auricular, and left latero-cervical lymphadenopathy. Intravenous antiviral treatment with acyclovir was started (7 days), and corticosteroid therapy was discontinued, with a favorable outcome. The particularity of this case lies in the reactivation of VZV in an immunocompetent patient, with a sudden onset and rapid progression. Additionally, the initial suspicion of diagnosis was not supported by the subsequent course of the disease, and corticosteroid treatment was discontinued. It is important to perform a differential diagnosis correlated with each stage of the disease to avoid inappropriate therapeutic management, which can have long-term adverse effects on the patient.

Estimation of selection criteria through multi-year assessment of variability parameters, association studies and genetic diversity of Solanum khasianum CB Clarke

Solanum khasianum Clarke belonging to the Solanaceae family contains a steroidal alkaloid, solasodine which has commercial and medicinal importance. Solasodine acts as a starting material for the synthesis of steroid hormones, such as oral contraceptives and cortisone. In the present study, a total of 273 accessions were collected out of which 186 accessions rich in solasodine content (>0.8 %) were selected for the study. These selected lines were planted in bed size of 3.6 × 3.6 m in a randomized complete block design (RCBD) with plant to plant spacing of 60 cm with three replications during kharif 2018, kharif 2019, and kharif 2020 for which pooled data were analyzed. Analysis of variance revealed significant differences among the genotypes for all the studied characters revealing high variability among them. Highest GCV (Genotypic coefficient of variation), PCV (Phenotypic coefficient of variation) along with high heritability with high genetic advance was depicted in 100 fresh fruit weight and the number of fruits/plant indicating high variability due to additive genes action which makes it useful in the selection program. Low magnitude between GCV and PCV was observed in the trait plant spread indicating minimum environmental influence and high effect of environment was observed in 100 fresh fruit weight. Based on the genotypic and phenotypic correlation, the number of fruits/plant, plant height, plant spread, and fruit diameter was found to be significantly and positively correlated with100 fresh fruit weight. However, the solasodine content was negatively correlated with 100 fresh fruit weight and the number of fruits/plant. The path coefficient analysis suggested that the number of fruit per plant and plant spread were the direct contributing traits for the fruit yield. In contrast, days to maturity were the direct contributing factor via 100 fresh fruit weight for solasodine content. Diversity using Mahalanobis D2 analysis revealed 80.54% variability which was contributed by the number of fruit per plant, 100 fresh fruit weight, leaf width, leaf length, plant spread, fruit diameter, and days to maturity. The present variability and multivariate analysis among the high solasodine content lines of S. khasianum will help in the breeding, conservation, and varietal development program of this industrially important crop. This is the first report on the variability parameters, association, and diversity study among 186 germplasm of S. khasianum.

Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report

BackgroundTherapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia.Case presentationWe report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk–benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission.ConclusionsThis case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed.

Controverse de diagnostic și tratament în sindromul Marshall

Defined by recurrent febrile episodes af angina, adenitis and stomatitis, Marshall syndrome is frequently encountered in clinical practice in children. The diagnosis is clinical, aided by the dramatic resolution of the symptoms after administration of oral cortisone. The authors report 2 cases of Marshall syndrome and discuss their treatment, based on clinical datas from literature and their own experience in a children emergency department.

Migliorare la comunicazione in ambulatorio riduce la prescrizione degli antibiotici per le infezioni respiratorie: i risultati di un RCT

How does oral cortisone work in acute bronchospasm in preschool age? ARCT with not reassuring results The 2021 guide of the Global Initiatve for Asthma (GINA) states that the use of oral steroids in preschool children with acute bronchospasm is only recommended in cases of severe exacerbation, however the literature continues to present conflicting results. The Wheeze and Steroids in Preschoolers (WASP) Study, conducted in 3 New Zealand emergency rooms, randomized 477 children aged 24–59 months with acute bronchospasm to receive oral prednisolone for 3 days versus placebo. The respiratory outcomes measured were conflicting: the change in severity score (PRAM) at 24 hours was not different between the 2 groups, while the absolute value of the score at both 4 and 24 hours (secondary outcomes) was significantly lower in the prednisolone group. Hospitalization rate, need for further oral prednisolone treatment, and intravenous drug use were also lower in the prednisolone group. It is debated whether the equivalence design of the study and the margins chosen by the authors for the primary outcome have attenuated the difference between the treatments.

Hypereosinophilia with Gastrointestinal Involvement: A Case Report

Hypereosinophilic syndrome is currently defined by an absolute blood eosinophil count of more of 1500 cell per μL for more than 1 month and by multiorgan system infiltration. Eosinophilic colitis is an exceptionally rare inflammatory condition in which eosinophils infiltrate the colonic gut. It represents the least frequent manifestation of the wide spectrum of eosinophilic gastrointestinal disorders. We describe a case of an adult male patient with persistent eosinophilia for at least twenty-five years. During this long period he had repeated abdominal colics caused by acute appendicitis with peritonitis, enterocolitis, and pancreatitis: all episodes were associated with a marked increase in blood eosinophils, but without Ig E modification. Malignant transformation of hypereosinophilia has not been detected. Oral cortisone treatment was administered only for short periods of time.

Reduced longitudinal cardiac strain in asthma patients

ABSTRACTObjective: There is limited knowledge about the potential relationship between asthma and heart function. Aim of our present study was to examine if asthma may be associated with manifest or subclinical heart dysfunction. Methods: Seventy-two allergic mild-to-moderate and severe asthma patients and 20 matched controls were enrolled in the study. Depending on the anti-asthmatic therapy, four subgroups of asthma patients were created: patients under long-acting beta2-agonists (LABA) and inhaled cortisone without oral cortisone treatment with (1a) versus without (1b) additional omalizumab therapy; patients with LABA, inhaled cortisone and omalizumab treatment with (2a) versus without (2b) oral cortisone. Standard echocardiographic parameters as well as global longitudinal left and right ventricular strains as determined by ultrasound-based speckle-tracking method were evaluated. Furthermore, NT-pro-brain natriuretic peptide (NT-pro-BNP), immunoglobulin E (IgE), C-reactive protein (CRP), and blood count were assessed in asthma and control groups. Results: There were no relevant differences in standard echocardiographic measures between both asthma groups and the control collective. Longitudinal left ventricular strain values were reduced significantly in severe and mild-to-moderate asthma groups (−12.91 ± 0.84% and −13.92 ± 1.55%, respectively), whereas longitudinal right ventricular strain values were additionally relevantly decreased in severe asthma (−10.35 ± 1.04%) compared to the control (−16.55 ± 0.49% and −18.48 ± 1.90%, respectively). Cardiac strains were similar in subgroups 1a and 1b. In contrast, patients from subgroup 2a presented reduced heart strains and decreased lung function compared to those from 2b. CRP, IgE, and eosinophils were significantly increased in asthma versus control individuals. Conclusions: Allergic asthma, especially severe asthma is associated with subclinical impaired left and right ventricular function as determined by speckle-tracking analysis.

Metformin Increases Cortisol Regeneration by 11βHSD1 in Obese Men With and Without Type 2 Diabetes Mellitus.

Context:The mechanism of action of metformin remains unclear. Given the regulation of the cortisol-regenerating enzyme 11βhydroxysteroid dehydrogenase 1 (11βHSD1) by insulin and the limited efficacy of selective 11βHSD1 inhibitors to lower blood glucose when co-prescribed with metformin, we hypothesized that metformin reduces 11βHSD1 activity.Objective:To determine whether metformin regulates 11βHSD1 activity in vivo in obese men with and without type 2 diabetes mellitus.Design:Double-blind, randomized, placebo-controlled, crossover study.Setting:A hospital clinical research facility.Participants:Eight obese nondiabetic (OND) men and eight obese men with type 2 diabetes (ODM).Intervention:Participants received 28 days of metformin (1 g twice daily), placebo, or (in the ODM group) gliclazide (80 mg twice daily) in random order. A deuterated cortisol infusion at the end of each phase measured cortisol regeneration by 11βHSD1. Oral cortisone was given to measure hepatic 11βHSD1 activity in the ODM group. The effect of metformin on 11βHSD1 was also assessed in human hepatocytes and Simpson-Golabi-Behmel syndrome adipocytes.Main Outcome Measures:The effect of metformin on whole-body and hepatic 11βHSD1 activity.Results:Whole-body 11βHSD1 activity was approximately 25% higher in the ODM group than the OND group. Metformin increased whole-body cortisol regeneration by 11βHSD1 in both groups compared with placebo and gliclazide and tended to increase hepatic 11βHSD1 activity. In vitro, metformin did not increase 11βHSD1 activity in hepatocytes or adipocytes.Conclusions:Metformin increases whole-body cortisol generation by 11βHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin. Co-prescription with metformin should provide a greater target for selective 11βHSD1 inhibitors.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied. Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity. To assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS. Case-control study. Medical center. A total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634). Cortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies. Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls. Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.

Dual-release Hydrocortisone in Addison’s Disease—A Review of the Literature

In patients with adrenal insufficiency, glucocorticoids (GCs) are insufficiently secreted and GC replacement is essential for health and, indeed, life. Despite GC-replacement therapy, patients with adrenal insufficiency have a greater cardiovascular risk than the general population, and suffer from impaired health-related quality of life. Although the aim of the replacement GC therapy is to reproduce as much as possible the physiologic pattern of cortisol secretion by the normal adrenal gland, the pharmacokinetics of available oral immediate-release hydrocortisone or cortisone make it impossible to fully mimic the cortisol rhythm. Therefore, there is an unmet clinical need for the development of novel pharmaceutical preparations of hydrocortisone, in order to guarantee a more physiologic serum cortisol concentration time-profile, and to improve the long-term outcome in patients under GC substitution therapy.

Orbital Apex Syndrome in Herpes Zoster Ophthalmicus

Orbital apex syndrome is a rare manifestation of Herpes Zoster Ophthalmicus. Herein we report on a case of orbital apex syndrome secondary to Herpes Zoster Ophthalmicus. A 75 year-old male complained of vision loss, conjunctival hyperemia and proptosis on the left eye, was referred to our clinic. Visual acuity was 5/10 Snellen lines and he had conjunctival hyperemia, chemosis, minimal nuclear cataract and proptosis on the left eye. A diagnosis of orbital pseudotumor was demonstrated firstly. The patient received oral and topical corticosteroids, antiinflammatory and antibiotic agents. On day 2, vesiculopustular lesions were observed, Herpes Zoster Ophthalmicus was diagnosed and corticosteroid treatment stopped, oral acyclovir treatment initiated. Two days later, total ophthalmoplegia, ptosis and significant visual loss were observed on the left. The diagnosis of orbital apex syndrome was considered and the patient commenced on an intravenous acyclovir treatment. After the improvement of acute symptoms, a tapering dose of oral cortisone treatment initiated to accelarate the recovery of ophthalmoplegia. At 5-month follow-up, ptosis and ocular motility showed improvement. VA did not significantly improve because of cataract and choroidal detachment on the left. We conclude that ophthalmoplegia secondary to Herpes Zoster Ophthalmicus responds favourably to intravenous acyclovir and steroids.

11β–Hydroxysteroid Dehydrogenase Type 1 Activity in Short Small-For-GA Children and in Response to GH Therapy

Small for GA (SGA) children are at risk for developing the metabolic syndrome. Those who do not catch up, and remain short (SSGA), may benefit from GH therapy. 11β Hydroxysteroid dehydrogenase type 1 (11β-HSD-1) is expressed in visceral fat and is implicated in metabolic morbidity. We hypothesized that SSGA children will have increased basal and glucocorticoid (GC)-stimulated 11β-HSD-1 activity. Twenty SSGA children, aged 7.1 ± 1 y (mean ± SD), were studied before and while on GH therapy and compared with 12 normal age-matched controls. 11β-HSD-1 activity was evaluated by gas chromatography mass spectrometry (GCMS) of urinary steroid product/substrate ratios. GC-stimulated 11β-HSD-1 activity was assessed after overnight dexamethazone (DEX), by oral cortisone conversion to cortisol. In SSGA children, 11β-HSD-1 activity was lower (p < 0.05) and GC-stimulated activity enhanced. SSGA children had maximal cortisol generation of 883 ± 108 compared with 690 ± 63 nmol/L in controls (p < 0.04). GH treatment suppressed 11β-HSD-1 activity. GC-stimulated enzyme activity correlated negatively with GA (r = -0.53, p < 0.01) and birth weight (r = -0.55, p < 0.01). SSGA is associated with enhanced GC-stimulated 11β-HSD-1 activity. This may be programmed in utero, as it is not a function of body composition or secondary metabolic derangement. GH therapy normalizes GC-stimulated 11β-HSD-1 activity.

Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition

OBJECTIVEThe cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. 11β-HSD1 inhibitors are being developed to treat type 2 diabetes. In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects.RESEARCH DESIGN AND METHODSTen obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[2H]4cortisol (40%) and cortisol (60%) at 1.74 mg/h. Adrenal cortisol secretion was suppressed with dexamethasone. Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution.RESULTSIn obese type 2 diabetic subjects, the appearance rate of 9,12,12-[2H]3cortisol in arterialized blood was increased (35 ± 2 vs. 29 ± 1 nmol/min, P < 0.05), splanchnic 9,12,12-[2H]3cortisol production was not reduced (29 ± 6 vs. 29 ± 6 nmol/min), and cortisol appearance in the hepatic vein after oral cortisone was unchanged.CONCLUSIONSWhole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects.

Dual-release Hydrocortisone in Addison's Disease - A Review of the Literature.

In patients with adrenal insufficiency, glucocorticoids (GCs) are insufficiently secreted and GC replacement is essential for health and, indeed, life. Despite GC-replacement therapy, patients with adrenal insufficiency have a greater cardiovascular risk than the general population, and suffer from impaired health-related quality of life. Although the aim of the replacement GC therapy is to reproduce as much as possible the physiological pattern of cortisol secretion by the normal adrenal gland, the pharmacokinetics of available oral immediate-release hydrocortisone or cortisone make it impossible to fully mimic the cortisol rhythm. Therefore, there is an unmet clinical need for the development of novel pharmaceutical preparations of hydrocortisone, in order to guarantee a more physiological serum cortisol concentration time-profile, and to improve the long-term outcome in patients under GC substitution therapy.

Tissue-Specific Increases in 11β-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Nonoperative management of adhesive capsulitis of the shoulder: Oral cortisone application versus intra-articular cortisone injections

Oral and intra-articular injections of cortisone will lead to significant improvement and comparable results in the treatment of adhesive capsulitis of the shoulder. In a prospective randomized evaluation, 40 patients with idiopathic adhesive capsulitis of the shoulder were treated with an oral corticoid treatment regimen or 3 intra-articular injections of corticosteroids. Follow-up was after 4, 8, and 12 weeks, and 6 and 12 months. For the clinical evaluation, the Constant-Murley (CM) score, the Simple Shoulder Test (SST) and visual analog scales (VAS) for pain, function, and satisfaction were used. In the patients treated with oral glucocorticoids, significant improvements were found for the CM score (P < .0001), SST (P=.035), VAS (P < .0001), and range of motion (P < .05) at the 4-week follow-up. The patients treated with an intra-articular glucocorticoid injection series also significantly improved in the CM score (P < .0001), SST (P < .0001), the VAS (P < .0001), and range of motion (P < .05) after 4 weeks. These results were confirmed at all other follow-up visits. Superior results were found for intra-articular injections in range of motion, CM score, SST, and patient satisfaction (P < .05). Differences in the VAS for pain and function were not significant (P > .05). The use of cortisone in the treatment of idiopathic shoulder adhesive capsulitis leads to fast pain relief and improves range of motion. Intra-articular injections of glucocorticoids showed superior results in objective shoulder scores, range of motion, and patient satisfaction compared with a short course of oral corticosteroids.

Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism

ObjectiveEvidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer.DesignObservational studies of GH withdrawal and reintroduction in patients with hypopituitarism.MethodsTwelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-2H4-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies.ResultsGH withdrawal and reintroduction had no effect on 9,12,12-[2H]3-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30–180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5α-reduced cortisol metabolites.ConclusionsIn this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term.