Monitoring adrenal insufficiency through salivary steroids: a pilot study.

BACKGROUND: Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. RESULTS: Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. CONCLUSIONS: None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting as cortisone sensible psychosis with reversible leukoencephalopathy.

INTRODUCTION: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a frequently discussed neuropsychiatric syndrome with elevated thyroid antibodies in the context of various clinical neuropsychiatric phenotypes. MRI abnormalities are usually nonspecific and treatment can be complex. CASE STUDY: We present a case of a woman in her sixties with SREAT whose psychosis kept worsening under cortisone tapering. After three years with cortisone side effects, therapy was changed to plasmapheresis and rituximab treatment with an excellent initial response, subacute unexplained deterioration with extensive leukoencephalopathy on MRI shortly after, and full recovery with regression of leukoencephalopathy afterwards. DISCUSSION: SREAT varies in clinical and diagnostic presentation. Its precise pathophysiology is unknown, as are the best treatment protocols. The case illustrates that some patients with SREAT syndrome might end up in constellations, in which it proves difficult to wean off steroid treatment and illustrates treatment alternatives such as plasmapheresis and/or rituximab. In addition, it highlights leukoencephalopathy as possible MRI finding in the context of SREAT. Further research is necessary to fully comprehend the (potentially different) pathomechanisms and courses of SREAT.

An 11-Beta Hydroxysteroid Dehydrogenase Type 1 Inhibitor, JTT-654 Ameliorates Insulin Resistance and Non-obese Type 2 Diabetes.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is the only enzyme that converts inactive glucocorticoids to active forms and plays an important role in the regulation of glucocorticoid action in target tissues. JTT-654 is a selective 11ß-HSD1 inhibitor and we investigated its pharmacological properties in cortisone-treated rats and non-obese type 2 diabetic Goto-Kakizaki (GK) rats because Asians, including Japanese, are more likely to have non-obese type 2 diabetics. Systemic cortisone treatment increased fasting plasma glucose and insulin levels and impaired insulin action on glucose disposal rate and hepatic glucose production assessed by hyperinsulinemic-euglycemic clamp, but all these effects were attenuated by JTT-654 administration. Cortisone treatment also reduced basal and insulin-stimulated glucose oxidation in adipose tissue, increased plasma glucose levels after administration of the pyruvate, the substrate of gluconeogenesis, and increased liver glycogen content. Administration of JTT-654 also inhibited all of these effects. Cortisone treatment decreased basal and insulin-stimulated 2-deoxy-D-[1-3H]-glucose uptake in 3T3-L1 adipocytes and increased the release of free fatty acids and glycerol, a gluconeogenic substrate, from 3T3-L1 adipocytes, and JTT-654 significantly attenuated these effects. In GK rats, JTT-654 treatment significantly reduced fasting plasma glucose and insulin levels, enhanced insulin-stimulated glucose oxidation in adipose tissue, and suppressed hepatic gluconeogenesis as assessed by pyruvate administration. These results demonstrated that glucocorticoid was involved in the pathology of diabetes in GK rats, as in cortisone-treated rats, and that JTT-654 ameliorated the diabetic conditions. Our results suggest that JTT-654 ameliorates insulin resistance and non-obese type 2 diabetes by inhibiting adipose tissue and liver 11ß-HSD1.

Evidence of Persistent Mild Hypercortisolism in Patients Medically Treated for Cushing Disease: the Haircush Study.

CONTEXT: Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing disease (CD). OBJECTIVE: This work aimed to assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and hair-cortisone (HE) measurement. METHODS: This multicenter prospective study included 3 groups of female patients: CushMed = 16 treated with a stable cortisol-lowering drug dosage and normal urinary free cortisol (UFC); CushSurg = 13 cured by pituitary surgery; CushBla = 15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy. Patients were evaluated for 3 months with their usual treatments. Two late-night saliva and 24-hour urine samples were collected monthly in CushMed, and at study end in CushSurg and CushBla patients. A 3-cm hair sample was collected at study end from all patients. Main outcome measures included clinical score and centralized measurement of UFC, late-night salivary cortisol (LNSF), late-night salivary cortisone (LNSE), HE, HF. RESULTS: Despite having almost all UFCs normalized, CushMed patients exhibited increased HE as compared to CushSurg controls (P = .003). CushMed patients also had increased clinical score (P = .001), UFC (P = .03), LNSF, LNSE (P = .0001), and variability in the latter parameters (P = .004). CushBla patients had increased HF and HE, contrasting with LNSEs similar to CushSurg patients. Six of 15 CushMed patients exhibited increased HE concentrations and had increased antihypertensive drug dosage compared to CushMed patients with normal HE (P = .05). CONCLUSION: Despite normalized UFCs, a subset of medically treated CD patients displays an altered circadian rhythm of serum cortisol. A single HE measurement identifies chronic mild persistent hypercortisolism and could replace multiple saliva analyzes to monitor medical treatments in CD patients once UFC is normalized.

Invasive electrical stimulation in the treatment of avascular osteonecrosis of the femoral head - mid-term results.

The study aimed to evaluate the outcomes of osteonecrosis of the femoral head (ONFH) in adults after surgical treatment including invasive electromagnetic osteostimulation (E-Stim). Further, the influence of disease stage and several comorbidities on the joint preservation rate should be examined. Sixty patients (66 hip joints) with ONFH were included in this retrospective cross-sectional analysis (mean follow-up: 58 months, 19-110 months). Potential ONFH risk factors and comorbidities (ONFH stage, age, sex, alcohol, smoking, cortisone medication, chemotherapy) were recorded. The influence of specific parameters on the joint preservation rates was evaluated by a multivariate logistic regression analysis. Finally, patients with preserved hip joints underwent an assessment of their last available X-rays. The joint preservation rate depended on the initial ONFH Steinberg stage (I+II: 82.8%, III: 70.8%, ≥ IVa: 38.5%). Initially collapsed ONFH (p ≤ 0.001) and cortisone therapy (p = 0.004) significantly decreased the joint preservation rates. In case of progressed ONFH, the presence of ≥ 2 risk factors resulted in higher THA conversion rates (stage III: OR 18.8; stage ≥IVa: OR 12). In 94% of the available X-rays, the ONFH stage improved or did not progress. No complications could be attributed to the E-Stim device or procedure. The present surgical protocol including minimally invasive E-Stim revealed high joint preservation rates for non-collapsed ONFH after mid-term postoperative follow-up. Especially in progressed ONFH, the-risk profile seems to be crucial and hence, for joint preserving surgery, careful patient selection is recommended.

Reversibility of Acute Adrenal Insufficiency After Hip Replacement: A Case Series.

BACKGROUND: Acute adrenal insufficiency is a rare but potentially lethal condition, that is important to identify promptly and treat with replacement therapy. It can be consequent to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure should be definitive. The extension of adrenal damage can be different, so justifying a partial, or potentially complete, recovery of adrenal function. The aim of our article is to highlight the opportunity of a periodical revaluation of adrenal reserve in order to identify those patients which are able to interrupt replacement therapy. CASE PRESENTATION: We had recently described one case of acute adrenal insufficiency, which developed short time after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We collected other two cases of acute adrenal insufficiency, developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 µg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands' volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively spent from the acute event. CONCLUSION: The present finding suggests the opportunity that patients developing acute adrenal insufficiency after major orthopedic surgery undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or it can be safely withdrawn.

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia.

BACKGROUND: Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. CASE REPORT: This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. CONCLUSION: The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

Curcuma longa aqueous extract: A potential solution for the prevention of corneal scarring as a result of pterygium surgical excision (Review).

Curcumin has been used since ancient times as a treatment for a wide range of pathologies. For centuries, it has been considered to be an effective aid for common human diseases. Curcuma longa has been reported to possess various beneficial properties and actions, including anti­inflammatory, proapoptotic, antiangiogenic and cortisone­like actions. Pterygium is a degenerative disorder of the conjunctiva indicative of a strong inflammatory condition that requires surgical treatment, which often results in disfiguring sclerocorneal scars. The delay in the healing of superficial corneal wounds caused by topical administration of light­cortisone results in improved restoration of corneal functions and anatomy compared with physiological healing processes. The present review is focused on the medicinal properties of curcumin, the main component of Curcuma longa extract, in particular its strong cortisone­like effect, and its potential use for the prevention and treatment of sclerocorneal scars resulting from pterygium surgical excision.

[Lichen sclerosus in children]. / Lichen sclerosus im Kindesalter.

Lichen sclerosus (LS) is a chronic inflammatory disease of the skin. It mainly affects the anogenital area. More knowledge of the disease is needed to avoid delay in diagnosis as early treatment may cure the disease in some and reduce or prevent scarring. Initial treatment for girls and boys comprises the daily application of a potent cortisone ointment for 3 months. After remission the treatment should be continued long-term intermittently. If there is no complete remission in boys complete circumcision is recommended. LS usually cannot be healed but only well suppressed, and also after circumcision recurrences may occur years later. Therefore, patients have to be well informed and should be followed up long-term.

Impact of Candida auris Infection in a Neutropenic Murine Model.

Candida auris has become a global public health threat due to its multidrug resistance and persistence. Currently, there are limited murine models to study C. auris infection. Those models use a combination of cyclophosphamide and cortisone acetate, suppressing both innate and adaptive immunity. Here, we compare C. auris infection in two neutrophil-depleted murine models in which innate immunity is targeted using the monoclonal antibodies 1A8 and RB6-8C5.

[The Schmidt's Syndrome]. / Das Schmidt-Syndrom.

HISTORY AND CLINICAL FINDINGS: We report the case within a 22-year-old patient, initially seen because of fatigue, weight loss and discoloration of the skin. A Hashimoto-Thyroditis had been diagnosed a few months prior to the clinical presentation. DIAGNOSTICS: Blood samples showed a hyponatremia and hyperkalemia. Addison's disease was diagnosed by management of cortisol, ACTH and adrenal antibodies. In combination with the previously diagnosed Autoimmune thyreoiditis the criteria for a Schmidt's Syndrome were fulfilled. TREATMENT AND CLINICAL COURSE: We initiated the substitution of Hydrocortisone (20 mg/d) and Fludrocortisone (0.1 mg/d) in combination with an increased levothyroxin-dosage (100 µg/d). The patient's condition improved over the course of a few days. CONCLUSION: The presented case underlines the importance of focused examinations and diagnostics when dealing with a patient with unspecific symptoms and a pre-existing autoimmune disease. This also applies to patients with a positive family history for autoimmune disorders.

Lost in Translation? Cortisone and the Treatment of Rheumatoid Arthritis in Britain, 1950-1960. [corrected].

Cortisone, initially known as 'compound E' was the medical sensation of the late 1940s and early 1950s. As early as April 1949, only a week after Philip Hench and colleagues first described the potential of 'compound E' at a Mayo Clinic seminar, the New York Times reported the drug's promise as a 'modern miracle' in the treatment of rheumatoid arthritis (RA). Given its high profile, it is unsurprising that historians of medicine have been attracted to study the innovation of cortisone. It arrived at the end of a decade of 'therapeutic revolutions', kicked off by penicillin transforming the treatment of bacterial infections and ending with hopes of a revolution in the treatment of non-infectious, chronic inflammatory diseases. Despite these studies of cortisone's introduction, few historians have taken the story forward and considered how cortisone was adopted and adapted into clinical practice. This article tells the longer of how the drug and its derivatives were taken from research laboratories and integrated into clinical practice; what has in recent decades become known as translational medicine (TM). In exploring cortisone's first decade in Britain, we focus specifically on its role in the treatment of RA. Our approach is always to consider cortisone's use in the context of other treatments available to clinicians, and at local and national institutional settings. We do not discuss the many other therapeutic uses of cortisone, which ranged for topical applications for skin diseases to the management of cancers, especially childhood leukaemia, nor do we discuss its close analogue ACTH-AdenoCorticoTropic Hormone. We think there are lessons in our study for TM policies today.

Giant isolated transcranial Rosai-Dorfman disease with diffuse involvement of nasal and paranasal tissues: case report and literature review.

Rosai-Dorfman disease (RDD) is an uncommon systemic histioproliferative disease process characterized by sinus histiocytosis with massive lymphadenopathy, and isolated transcranial RDD (ITRDD) is extremely rare. We report a patient with giant ITRDD with diffuse involvement of nasal and paranasal tissues, showing favorable response to postoperative steroid therapy.

The 70th anniversary of glucocorticoids in rheumatic diseases: the second youth of an old friend.

Seventy years ago, the first administration of cortisone in a patient with RA marked a milestone in the treatment of inflammatory diseases. However, the initial enthusiasm rapidly vanished as the administration of high doses for lengthy periods revealed worrisome adverse effects. It has taken several decades to overcome the (sometimes excessive) mistrust and to achieve a more differentiated evaluation of the benefit-risk profile and the adequate usage of glucocorticoids (GCs). Today, GCs remain indispensable for the treatment of many inflammatory conditions and their usefulness in RA as a disease-modifying low-dose co-medication is widely acknowledged. Recent studies show promising results concerning both traditional GCs and new formulations. Still, decades of relatively little scientific attention have resulted in a continuing lack of detailed evidence. Hence there is an ongoing need for further research regarding mechanisms of GC actions, the further optimization of treatment parameters for traditional GCs and new formulations.

Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy.

Context: Two tyrosine kinase inhibitors (TKIs), lenvatinib and vandetanib, are often used to treat advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) and medullary thyroid cancer (MTC), respectively. Fatigue is a common adverse event during treatment with these and other TKIs and a common cause of drug discontinuation or dosage reduction. Cases Description: We evaluated the basal and stimulated adrenal function in 12 patients with advanced RAI-R DTC and MTC treated with lenvatinib or vandetanib, respectively. Ten patients complaining of fatigue showed a progressive ACTH increase with normal cortisol levels. Moreover, six of 10 patients had a blunted cortisol response after ACTH stimulation, thus confirming the diagnosis of primary adrenal insufficiency (PAI). The causal relationship between TKIs and PAI onset was also demonstrated by the repeated testing of adrenal function before and during treatment. Patients with PAI received cortisone acetate replacement therapy, with a substantial and prompt improvement in the degree of fatigue, as assessed by the Common Terminology Criteria for Adverse Events version 4.03, thus supporting the major impact of impaired adrenal function in the genesis of this adverse event. Conclusions: We show that the occurrence of PAI may be a common cause of fatigue during lenvatinib and vandetanib treatment, and we therefore recommend testing adrenal function for a prompt start of replacement therapy to avoid treatment discontinuation, dosage reduction, and potentially severe PAI complications.

"I would like to tatoo the illness on my arm". The Integrated Personalized Nursing Diagnosis (IPND).

BACKGROUND AND AIM: The nursing diagnosis can based on two different approaches: the standard diagnosis, searching for regularities that can fall within pre-existing categories identified by the nurse, as the expert of the disease; the narrative diagnosis, based on personal meaning attributed to the illness, of which only the patient is the expert. The aim of this work is to underline the usefulness of integration between standard diagnosis and narrative diagnosis, through the Integrated Personalized Nursing Diagnosis (IPND). METHODS: A 31 years old man, suffering from leukaemia, is welcomed at an Italian Oncological Day Hospital, by a nurse trained in the IPND approach. She used the Gordon functional models on objective data, and collected a narration about patient's experience, which has been analyzed with a Grounded Theory methodology. RESULTS: The narrative revealed critical issues and the priorities that patient assigns, which would not have been obtained from a standard diagnosis. From the standard diagnosis, however, emerge several aspects that the patient has neglected to narrate and that does not directly address in his story. The diagnostic integration allowed the nurse to define a conceptual map of problems and resources in a personalized manner. CONCLUSION: The IPND not only gives importance to the priorities of the patient, but also underlines the dynamic path, in which not only the static analysis of needs becomes significant, but also the changes that occur in attributing new meanings to the life experience, as well as the evolution of the person him/herself in this process.

The Positive Effect of Sialendoscopy with Irrigation Lavage for Sialadenitis without Sialolithiasis or Stenosis.

AIMS: The aim of the study was to evaluate different irrigation solutions during sialendoscopy to reduce complaints caused by sialodochitis. METHODS: The investigators designed and implemented a retrospective study composed of 94 patients with sialodochitis but no sialolithiasis or relevant stenosis of the salivary duct system. Three different irrigations (normal saline, cortisone single-shot, and cortisone) were used. After the sialendoscopy, the patients were asked about the current status of the affected salivary gland, and the quantity and quality of the gland swelling/inflammation over a follow-up period of 11.6 months (6-24 months). RESULTS: At the time of follow-up, 41 patients (43.6%) no longer had any complaints with the salivary gland in question. In 75.5% of the patients, a satisfying result was achieved. In total, only 3 patients needed submandibulectomy in the course of the study due to persistent complaints. The outcome showed no statistical differences between the mean of the 3 groups (p = 0.149). CONCLUSION: Sialendoscopy with flushing/lavage seems to be a good treatment option for patients with sialodochitis lacking sialolithiasis. The results of this study suggest that the type of irrigation used during sialendoscopy seems to be secondary.