Adrenal Crisis - Definition, Prevention and Treatment: Results from a Delphi Survey.

Based on recent data, a total number of about 29 000 patients with adrenal insufficiency can be calculated for Germany, and about 1500 fatalities due to adrenal crises have to be expected within the next decade. Management of adrenal crises is still unsatisfactory. The objectives of this study were to establish consensus for diagnostic criteria, prevention strategies, and treatment recommendations for adrenal crises. The study was conducted from January 2022 to April 2023, using Delphi technique. Four rounds of questionnaires were sent to 45 experts, selected by a coordinating group on behalf of the adrenal section of the German Society of Endocrinology. The survey was implemented online using the REDCap web application. Responses were captured anonymously. During the Delphi process the expert panel developed diagnostic criteria to identify patients likely to have an adrenal crisis. Education about adrenal insufficiency among patients as well as non-endocrine medical personnel were regarded as highly important. It was suggested that recommendations for the management of adrenal insufficiency have to be simplified and made widely available. This study provides pragmatic strategies to identify and treat patients prone to adrenal crisis, thereby highlighting the need for an improved management of patients with adrenal insufficiency.

[New aspects of glucocorticoid substitution in adrenal insufficiency]. / Neue Aspekte der Glukokortikoidsubstitution bei Nebennierenrindeninsuffizienz.

BACKGROUND: Appropriate glucocorticoid dose adjustment in specific situations significantly impacts quality of life and performance of patients with adrenal insufficiency. It is also pivotal for the prevention of adrenal crisis. OBJECTIVES: Improving medical care for patients with adrenal insufficiency. MATERIALS AND METHODS: Selective literature research focussing on the most recent studies. RESULTS: Optimal glucocorticoid substitution aims at closely mimicking physiological fluctuations of cortisol levels. In recent years glucocorticoid preparations with modified pharmacokinetics have expanded the therapeutic arsenal. Adrenal crises occur with an incidence of 4.8-9.3 crises per 100 patient years. With a mortality of 0.5 per 100 patient years adrenal crisis is a life-threatening event. Therefore, it is of the utmost importance to adjust glucocorticoid dose in situations with increased cortisol demand in order to prevent as well as appropriately treat adrenal crisis. CONCLUSIONS: To prevent life-threatening adrenal crisis, patients, their families and medical staff require training.

Increasing normality-persisting barriers: Current socio-demographic characteristics of 350 individuals diagnosed with gender dysphoria.

INTRODUCTION: The number of individuals requesting medical treatment for gender dysphoria has increased significantly within the past years. Our purpose was to examine current biographic and socio-demographic characteristics and aspects of legal gender reassignment. DESIGN: Medical files from n = 350 individuals of a German Endocrine outpatient clinic were collected from 2009 to 2017 and analysed retrospectively. RESULTS: Ratio of transwomen to transmen equates to 1:1.89 with a remarkable increase of transmen by the year 2013, showing a reversal of gender distribution compared with previous studies for the first time. Use of illegal substances or self-initiated hormone therapy was rare (4.6 and 2.1%). Satisfaction with gender-affirming hormone therapy was significantly higher in transmen than in transwomen (100% vs 96.2%, P = .005). Use of antidepressants declined significantly after onset of hormone treatment in transmen (13% vs 7%; P = .007). The number of individuals with a graduation diploma was only about half as high as in the general population (14.3% vs 27.3%), whereas unemployment rate was more than twice as high (14% vs 6.9%). Median latency between application for legal gender reassignment and definitive court decision was 9 months. CONCLUSIONS: Our data provide possible indications for a decline of psychosocial burden in individuals diagnosed with gender dysphoria over the last years. However, affected individuals are still limited in their occupational and financial opportunities as well as by a complex and expensive procedure of legal gender reassignment in Germany.

Daily adjustment of glucocorticoids by patients with adrenal insufficiency.

BACKGROUND: Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement. AI patients need to adjust GC dosage in response to stressful events and illness in order to prevent life-threatening adrenal crisis (AC). AIM: To evaluate self-management of patients with AI. METHODS: Four German centres, which are using patient's diary as part of their routine clinical practice, instructed AI patients to prospectively document any discomfort, intercurrent illness or stressful events as well as changes in GC therapy on a daily basis. Diaries of 80 patients (44 females, 52.9 ± 15.9 years, 34 primary AI) were collected and analysed. A symptom score sheet was used to evaluate severity of discomfort. RESULTS: In total, 34 074 patient days (93.4 years) were recorded. 4622 days with discomfort were documented. On 35% of those days (n = 1621), patients increased their GC dose (4.8% of all days). Patients who recorded discomfort had a median of four episodes of discomfort, which lasted a median of 2 days. Women documented significantly more episodes of discomfort than men (P = 0.014). Low-to-median symptom scores resulted in GC increase by 50%-60%, whereas high symptom scores and/or fever resulted in doubling GC daily dose. However, dose increase was only 55% in situations indicating gastrointestinal (GI) infection. CONCLUSION: Severe discomfort did not always result in dose increase, especially in GI infection. However, low symptom scores resulted in an inappropriate GC increase in some patients. This underscores an urgent need for improved training methods. Keeping daily records might be a useful tool for continued and individualized patient education.

Management of adrenal emergencies in educated patients with adrenal insufficiency-A prospective study.

OBJECTIVE: To evaluate the management of adrenal emergencies (AE) requiring parenteral glucocorticoid (GC) treatment in patients with chronic adrenal insufficiency (AI). DESIGN: Prospective, multicentre, questionnaire-based study. PATIENTS AND MEASUREMENTS: Participating patients (n = 150) with chronic AI were provided with a questionnaire on the management of emergency situations, which had to be completed and sent back in case of an AE. In addition, patients were contacted by phone on a regular basis. RESULTS: Fifty-nine AE in 39 patients were documented. The time interval from contact to arrival of a medical professional was 20 minutes (1-240). In total, in 43 AE, patients received parenteral GC by a medical professional. The time interval between showing the emergency card and GC injection by a medical professional was 60 minutes (5-360). A total of 26 patients administered GC by self-injection. The time from the beginning of symptoms to GC injection was significantly shorter in case of self-injection (self-injection vs injection by medical professional; 85 minutes [20-280] vs 232.5 minutes [1-3135]; P < .001). After self-injection, 62% of the patients were treated outpatient, compared to 27% of the patients after exclusive injection by a medical professional (P = .008). To improve the emergency management, most of the patients (84%) indicated a need for an easier way of self-injection. CONCLUSION: While management of AE by both patients and medical professionals still shows high variability, patients profit from the option of self-injection. Patient care, including education of patients and health-professionals, as well as the way of GC administration, needs further optimization.

Addison's disease with polyglandular autoimmunity carries a more than 2·5-fold risk for adrenal crises: German Health insurance data 2010-2013.

OBJECTIVE: Adrenal crises are potentially life-threatening complications in patients with adrenal insufficiency (AI). Our objective was to investigate the frequency of adrenal crises in different forms of AI. DESIGN/PATIENTS: The Statutory Health Insurance (SHI) database of the Techniker Krankenkasse - covering more than 12% of the German population - was analysed for diagnostic codes from 1 January 2010 to 31 December 2013. MEASUREMENTS: By analysis of routine data from a large healthcare provider. Diagnoses of AI were recorded and classified in primary AI, secondary AI and autoimmune polyglandular syndrome (APS). The ICD-code E27·2 (AC) was retrieved in all cohorts. RESULTS: We found a prevalence of 222/million for secondary and 126/million for primary AI. AC was documented with a frequency of 4·8/100 patient years. Crises were significantly more frequent in patients with primary (7·6/100 patient years) compared to those with secondary AI (3·2/100 patient years; P < 0·0001). Prevalence of crises was higher in individuals with APS (10·9/100 patient years) and highest in patients with primary AI and type 1 diabetes (12·5/100 patient years). CONCLUSIONS: Applying a SHI database comprising more than 9 million individuals, we identified robust data about the risk of AC in different groups of patients with AI. Our data confirm and extend the clinical observation that patients with APS are at highest risk for AC. Approximately 1 of 8 patients with primary AI and type 1 diabetes suffers from an AC each year. Specific targeting of efforts aiming at the prevention of AC is necessary.

High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.

The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer.

Glucocorticoid Replacement for Adrenal Insufficiency and the Development of Non-Alcoholic Fatty Liver Disease.

Glucocorticoid excess is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Our objective was to analyse the impact of glucocorticoid replacement therapy on the development of NAFLD and NAFLD-related fibrosis and, therefore, on cardiovascular as well as hepatic morbidity in patients with adrenal insufficiency. Two hundred and fifteen individuals with primary (n = 111) or secondary (n = 104) adrenal insufficiency were investigated for hepatic steatosis and fibrosis using the fatty liver index (FLI), NAFLD fibrosis score (NAFLD-FS), Fibrosis-4 Index (FiB-4) plus sonographic transient elastography. Results were correlated with glucocorticoid doses and cardiometabolic risk parameters. The median dose of hydrocortisone equivalent was 20 mg daily, with a median therapy duration of 15 years. The presence and grade of hepatic steatosis and fibrosis were significantly correlated with cardiometabolic risk factors. We could not find any significant correlations between single, daily or cumulative doses of glucocorticoids and the grade of liver steatosis, nor with fibrosis measured via validated sonographic techniques. In patients with adrenal insufficiency, glucocorticoid replacement within a physiological range of 15-25 mg hydrocortisone equivalent per day does not appear to pose an additional risk for the development of NAFLD, subsequent liver fibrosis, or the cardiovascular morbidity associated with these conditions.

NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer.

PURPOSE: Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in ~ 2% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC). METHODS: A total of 184 TC patients with testing for NTRK gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method in six patients with NTRK fusion-positive TC who underwent TRK inhibitor therapy. RESULTS: 8/184 (4%) patients harbored NTRK gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring NTRK1 (n = 4) and NTRK3 (n = 2) gene fusions were treated with larotrectinib. Five patients (83%) had received ≥ 1 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23 months (95% confidence interval [CI], 0-57.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1-3. CONCLUSION: The prevalence of NTRK gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of NTRK gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile.

Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST" (Taper Or Abrupt Steroid STop) multicenter trial.

BACKGROUND: Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. METHODS: We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. CONCLUSION: This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1.

Shear Wave Elastography Reveals a High Prevalence of NAFLD-related Fibrosis even in Type 1 Diabetes.

BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and advanced stages of non-alcoholic fatty liver disease is well known. Some studies indicate a relevant prevalence also in type 1 diabetes mellitus (T1DM), but so far there is only limited data. OBJECTIVE: To determine the prevalence of non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis in individuals with T1DM and compare to those with type 2 diabetes. METHODS: Diabetic patients from a single diabetes care centre were screened for liver fibrosis by sonographic shear wave elastography (SWE). In addition, all patients received laboratory evaluation including non-alcoholic fatty liver fibrosis score and Fibrosis-4 Index. RESULTS: Three hundred and forty patients were included in the study, of these, 310 received SWE. Overall 254 patients (93 with type 1 and 161 with type 2 diabetes) had reliable measurements and were included in the final analysis. In patients with type 1 diabetes, the prevalence of NAFLD-related liver fibrosis was 16-21%, depending on the method of detection. Significant liver fibrosis was observed in 30-46% of patients with type 2 diabetes. CONCLUSIONS: Our data revealed an unexpectedly high prevalence of NAFLD-related liver fibrosis in patients with type 1 diabetes. To our knowledge, this is one of the first studies using SWE to diagnose advanced NAFLD in type 1 diabetes in a non-preselected cohort. Considering the findings of our study, regular screening for hepatic complications must be recommended for all diabetic patients, even for those with type 1 diabetes.

Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe.

Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results: Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4-5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions: This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH.

Vitamin D status and pathway genes in five European autoimmune Addison's disease cohorts.

OBJECTIVE: While vitamin D regulates immune cells, little is known about it in autoimmune Addison's disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes. DESIGN: Cross-sectional study. METHODS: A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP). RESULTS: Vitamin D deficiency (25(OH)D3 10-20 ng/mL) was highly prevalent in AAD patients (34-57%), 5-22% were severely deficient (<10 ng/mL), 28-38% insufficient (20-30 ng/mL) and only 7-14% sufficient (>30 ng/mL). Lower 25(OH)D3 and 1,25(OH)2D3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 × 10-5/< 1 × 10-7, respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)2D3. CONCLUSION: Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

Hormonal Gender Reassignment Treatment for Gender Dysphoria.

BACKGROUND: No data are available at present on the prevalence of gender dysphoria (trans-identity) in Germany. On the basis of estimates from the Netherlands, it can be calculated that approximately 15 000 to 25 000 persons in Germany are affected. Persons suffering from gender dysphoria often experience significant distress and have a strong desire for gender reassignment treatment. METHODS: This review is based on pertinent publications retrieved by a selective search in the PubMed database employing the searching terms "transsexualism," "transgender," "gender incongruence," "gender identity disorder," "gender-affirming hormone therapy," and "gender dysphoria." RESULTS: In view of its far-reaching consequences, some of which are irreversible, hormonal gender reassignment treatment should only be initiated after meticulous individual consideration, with the approval of the treating psychiatrist/psychotherapist and after extensive information of the patient by an experienced endo - crinologist. Before the treatment is begun, the patient must be extensively screened for risk factors. The contraindications include severe preexisting thromboembolic diseases (mainly if untreated), hormone-sensitive tumors, and uncontrolled pre - existing chronic diseases such as arterial hypertension and epilepsy. Finding an appropriate individual solution is the main objective even if contraindications are present. Male-to-female treatment is carried out with 17ß-estradiol or 17ß-estradiol valerate in combination with cyproterone acetate or spironolactone as an antiandrogen, female-to-male treatment with transdermal or intramuscular testosterone preparations. The treatment must be monitored permanently with clinical and laboratory follow-up as well as with gynecological and urological early-detection screening studies. Prospective studies and a meta-analysis (based on low-level evidence) have documented an improvement in the quality of life after gender reassignment treatment. Female-to-male gender-incongruent persons often have difficulty being accepted in a gynecological practice as a male patient. CONCLUZION: Further prospective studies for the quantification of the risks and benefits of hormonal treatment would be desirable. Potential interactions of the hormone preparations with other medications must always be considered.

Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ.

Context: Autoimmune polyglandular syndrome (APS-2: autoimmune Addison's disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk. Methods: APS-2 patients (n = 30) and healthy controls (n = 30) were genotyped for HLA DQA1/DQB1 and their CD14+ monocytes stimulated with IL1ß and/or 1,25(OH)2D3 for 24 h. Immune regulatory molecules (IL-6, IL-10, IL-23A, IL-15, CCL-2, PD-L1), vitamin D pathway gene transcripts (CYP24A1, CYP27B1, VDR), and CD14 were analyzed by enzyme-linked immunosorbent assay and RTqPCR. Results: Pro-inflammatory CCL-2 was higher in APS-2 patients than in controls (p = 0.001), whereas IL-6 showed a trend - (p = 0.1). In vitro treatment with 1,25(OH)2D3 reduced proinflammatory cytokines (IL-6, CCL-2, IL-23A, IL-15) whereas anti-inflammatory cytokines (IL-10 and PD-L1) rose both in APS-type 1 diabetes and APS-Addison´s disease. Patients with adrenal autoimmunity showed a stronger response to vitamin D. Expression of IL-23A and vitamin D pathway genes VDR and CYP27B1 varied by HLA genotype and was lower in healthy individuals with high-risk HLA (p = 0.0025; p = 0.04), while healthy controls with low-risk HLA showed a stronger IL-10 and CD14 expression (p = 0.01; p = 0.03). Conclusion: 1,25(OH)2D3 regulates the monocytic response in APS-2 disorders type 1 diabetes or Addison´s disease. The monocytic cytokine profile of individuals carrying HLA high-risk alleles is proinflammatory, enhances polyglandular autoimmunity and can be targeted by vitamin D.

Safety and rapid efficacy of guideline-based gender-affirming hormone therapy: an analysis of 388 individuals diagnosed with gender dysphoria.

OBJECTIVE: Hormone treatment is an important part of gender reassignment therapy in gender dysphoria. Previous data about efficacy and safety are commonly based on small cohorts or they comprise former cohorts under meanwhile obsolete therapy regimes. Our objective was to investigate these topics in a large cohort of individuals under guideline-based treatment. DESIGN/METHODS: Cohort study of medical files of n = 155 male-to-female (transwomen) and n = 233 female-to-male transgender persons (transmen) of an Endocrine outpatient clinic between 2009 and 2017. RESULTS: Median time to reach amenorrhoea in transmen under testosterone monotherapy was 3 months, regardless of whether testosterone undecanoat or gel was used. Transmen with higher levels of hemoglobin 3-4 months after onset of GAHT had a greater chance to reach amenorrhea early, whereas testosterone levels showed no significant correlation (hemoglobin: HR: 1.639; 95% CI: 1.036-2.591, P = 0.035; testosterone: HR: 0.999; 95% CI: 0.998-1.001, P = 0.490). Estradiol levels (ρ -0.117; P = 0.316) had no significant influence on breast development in transwomen. Testosterone levels (ρ -0.398; P < 0.001) and FAI (ρ 0.346; P = 0.004) were significantly negatively correlated with reached Tanner stage. Liver values and blood lipids showed an alignment to reference range of the required sex in both groups. Relevant elevations of liver values were rare (2.44% in transmen, 4.23% in transwomen) and transient in most cases. Most relevant side effects were acne (44.8%), respectively erythrocytosis (up to 5.6%) in transmen and venous thrombembolism (1.9%) in transwomen. CONCLUSIONS: Gender-affirming hormone therapy in accordance with current clinical practice guidelines is efficient and safe.

Standardised patient education in adrenal insufficiency: a prospective multi-centre evaluation.

OBJECTIVE: Patients with adrenal insufficiency (AI) suffer from impaired quality of life and are at risk of adrenal crisis (AC) despite established replacement therapy. Patient education is regarded an important measure for prevention of AC and improvement of AI management. A standardized education programme was elaborated for patients with chronic AI in Germany. DESIGN: Longitudinal, prospective, questionnaire-based, multi-centre study. METHODS: During 2-h sessions, patients (n = 526) were provided with basic knowledge on AI, equipped with emergency cards and sets and trained in self-injection of hydrocortisone. To evaluate the education programme, patients from eight certified centres completed questionnaires before, immediately after and 6-9 months after training. RESULTS: 399 completed data sets were available for analysis. Questionnaire score-values were significantly higher after patient education, indicating successful knowledge transfer (baseline: 17 ± 7.1 of a maximum score of 29; after training: 23 ± 4.2; P < 0.001), and remained stable over 6-9 months. Female sex, younger age and primary cause of AI were associated with higher baseline scores; after education, age, cause of AI and previous adrenal crisis had a significant main effect on scores. 91% of patients would dare performing self-injection after training, compared to 68% at baseline. An improvement of subjective well-being through participation in the education programme was indicated by 95% of the patients 6-9 months after participation. CONCLUSION: Patient group education in chronic AI represents a helpful tool for the guidance of patients, their self-assurance and their knowledge on prevention of adrenal crises. Repeated training and adaptation to specific needs, for example, of older patients is needed.

Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey.

CONTEXT: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. OBJECTIVE: Multicenter survey on current clinical approaches in managing AI during pregnancy. DESIGN: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. SETTING AND PATIENTS: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). RESULTS: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. CONCLUSIONS: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.