A case of celiac plexus block causing iatrogenic Cushing's syndrome.

Treatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement.

Excessive pickle consumption: beware of adrenal crisis.

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock. We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made. Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

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.

Ventricular Tachycardia Crisis: Assessing Norepinephrine vs. Stress Steroids in the Battle Against Waterhouse-Friderichsen Syndrome With Distributive Shock.

Waterhouse-Friderichsen syndrome (WFS) is a rare but life-threatening complication associated with acute hemorrhagic necrosis of the adrenal glands, primarily linked to meningococcal infection. This report details the case of a 62-year-old female with HIV/AIDS and substance misuse who presented with ventricular tachycardia and hemodynamic instability. Subsequent evaluation revealed WFS in the context of disseminated meningococcal infection. The case highlights the diversity of WFS manifestations and the diagnostic challenges, particularly in patients with comorbidities. Managing WFS involves a delicate balance of steroids and vasopressors, necessitating a multidisciplinary approach. Timely diagnosis and intervention are critical in mitigating the high mortality associated with this syndrome.

Prevalence, Clinical Features, and Predictors of Adrenal Insufficiency in Adults With Tuberculosis or HIV: A Systematic Review and Meta-analysis.

Background: Despite the high frequency of adrenal insufficiency (AI) in patients with tuberculosis or HIV, its diagnosis is often missed or delayed resulting in increased mortality. This systematic review and meta-analysis aimed to document the prevalence, significant clinical features, and predictors of AI in adult patients with tuberculosis or HIV. Methods: We systematically searched databases (Medline, Embase, CINAHL, Cochrane Library, and Africa Journal Online) for published studies on AI in adult patients with tuberculosis or HIV. The pooled prevalence of AI was determined by a random-effect model meta-analysis. A narrative review was used to describe the significant clinical features and predictors of AI in adult patients with tuberculosis or HIV. Results: A total of 46 studies involving 4044 adults were included: 1599 with tuberculosis and 2445 with HIV. The pooled prevalence of AI was 33% (95% CI, 22%-45%; I2 = 97.7%, P < .001) in participants with tuberculosis and 28% (95% CI, 18%-38%; I2 = 98.9%, P < .001) in those with HIV. Presentation with multidrug-resistant tuberculosis, abdominal pain, salt craving, myalgia, increased severity and duration of tuberculosis disease, and the absence of nausea predicted AI in participants with tuberculosis in 4 studies. Cytomegalovirus antigenemia positivity, rifampicin therapy, and eosinophilia >3% predicted AI in participants with HIV in 2 studies. Conclusions: AI is relatively common in adults with tuberculosis or HIV. Its timely screening, diagnosis, and management in patients with these 2 conditions should be encouraged to avert mortality.

A retrospective review of the short Synacthen test in Queensland hospitals.

BACKGROUND: The short Synacthen test (SST) is widely used to investigate adrenal insufficiency, but it can be time-consuming, costly and labour-intensive to perform and is not without risk of adverse events. AIM: To review SST requesting patterns and practices across public hospitals in Queensland. METHODS: The electronic medical records of patients who underwent a SST with Pathology Queensland between January 2020 and December 2020 were reviewed to collect data regarding the indication for the test, the requesting speciality, SST results and any adverse events. RESULTS: Six hundred and fifty-two SSTs were identified, of which 363 individual patients were included in the analysis. The majority of the tests (n = 198, 54.5%) were performed in the inpatient setting. Endocrinology most commonly ordered SSTs (n = 188, 51.8%). The suspected aetiology of adrenal insufficiency was unclear in a large proportion of requests (n = 167, 46.0%). Static testing of morning cortisol prior to SST was performed in only 249 (68.6%) patients. Of 140 inpatients data, 17.9% (n = 25) showed a robust static cortisol of ≥400 nmol/L and were treated as having normal adrenal function, suggesting SST was unnecessary in these patients. Twenty-two (6.1%) patients had a documented adverse event occurring during or after the SST. CONCLUSIONS: There was wide variability in requesting patterns and practices for SSTs across Queensland. More than one in six SSTs could have been avoided if a static morning cortisol had been performed prior. Clinician education and the adoption of a structured referral form may improve testing practices.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

Frequency of stress dosing and adrenal crisis in paediatric and adult patients with congenital adrenal hyperplasia: a prospective study.

OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents. DESIGN: Prospective, observational study. METHODS: Data on AC and SD were collected via a patient diary. In case of AC, medical records were reviewed and patient interviews conducted. Adherence to sick day rules of the German Society of Endocrinology (DGE) and disease knowledge using the German version of the CAH knowledge assessment questionnaire (CAHKAQ) were assessed. RESULTS: In 187 adult patients, the AC incidence was 8.4 per 100 patient years (py) and 5.1 in 100 py in 38 children. In adults, 195.4 SD episodes per 100 py were recorded, in children 169.7 per 100 py. In children 72.3% and in adults 34.8%, SD was performed according to the recommendations. Children scored higher on the CAHKAQ than adults (18.0 [1.0] vs 16.0 [4.0]; P = .001). In adults, there was a positive correlation of the frequency of SD and the incidence of AC (r = .235, P = .011) and CAHKAQ score (r = .233, P = .014), and between the incidence of AC and CAHKAQ (r = .193, P = .026). CONCLUSION: The AC incidence and frequency of SD in children and adults with CAH are high. In contrast to the paediatric cohort, the majority of SD in adults was not in accordance with the DGE recommendations, underlining the need for structured and repeated education of patients with particular focus on transition.

A Case Report of Sheehan Syndrome: A Rare Cause of Hypopituitarism.

Sheehan syndrome is a rare cause of hypopituitarism characterized by pituitary gland necrosis after postpartum hemorrhage. It is a pertinent cause of maternal morbidity and mortality in developing countries with deficient obstetrical care but is frequently overlooked in developed countries where its occurrence is uncommon. We present the case of a 66-year-old female diagnosed with Sheehan syndrome more than 30 years after her last delivery complicated by postpartum hemorrhage. Although the patient presented several symptoms and signs of pituitary hormonal deficiencies, a diagnosis had never been established before. The complete laboratory analysis revealed a deficiency in the pituitary axis, and the cranial imaging showed an empty sella turcica. Hormonal replacement therapy resolved several impairments in terms of general energy, physical capacity, temperature regulation, skin characteristics, and sexual function. It also improved her cardiovascular and osteoporosis risk, and, most importantly, prevented a potential life-threatening adrenal crisis. This report highlights the subtle manifestations of Sheehan syndrome to help clinicians establish a prompt diagnosis. Even in developed countries such as Portugal, this condition should be regarded as a potential cause of hypopituitarism.

A 16-year-old boy presented with triple-A syndrome associated with neuromuscular disorders: a case report.

Introduction and importance: Allgrove syndrome (AS) (AAA syndrome) is a rare autosomal recessive disease caused by mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes for the ALADIN protein (alacrima, achalasia, adrenal insufficiency, neurologic disorder). AS can manifest with a plethora of symptoms. Early recognition of the syndrome remains challenging due to its rarity and progressive nature. This report presents an unusual case of triple-A syndrome (TAS) with concurrent neuromuscular manifestations. Understanding the atypical presentation of this syndrome is vital for early diagnosis and appropriate management. Case presentation: We report a 16-year-old boy with severe malnutrition presented with painful swallowing, fatigue, and bilateral congenital ptosis. Barium swallow, upper gastrointestinal endoscopy, and Shimmer test were performed, which led to the diagnosis of TAS. Treatment included laparoscopic Heller's procedure, artificial tears, hydrocortisone. Clinical discussion: TAS, also known as AS, is a rare multisystem disorder characterized by achalasia, Addison's disease, and alacrima. This syndrome is occasionally referred to as 4A syndrome due to the inclusion of autonomic dysfunction. There is no treatment for AS. Management includes artificial tears for alacrima, glucocorticoid replacement therapy to treat adrenal insufficiency, and treatment of achalasia. Conclusion: This case emphasizes the importance of considering atypical presentations of TAS. Early diagnosis and treatment are paramount in addressing the varied components of this rare disorder. Understanding the clinical complexities of this syndrome aids in improved patient care and underscores the necessity for comprehensive evaluation and management in similar cases.

Endocrinopathies in a Pediatric Patient Post-anatomical Hemispherectomy for Rasmussen's Encephalitis Treatment: A Case Report.

Hemispherectomy is a neurosurgical procedure that is frequently performed in pediatric patients diagnosed with Rasmussen's encephalitis. Postoperative complications include immediate complications such as hydrocephalus and hemorrhage and behavioral complications such as language impairments and contralateral weakness. However, there are limited studies or case reports that address the potential endocrinopathies associated with this and other pediatric epileptic surgeries. This case report describes the endocrinopathies following an anatomical hemispherectomy procedure. A four-year-old African-American female had a right anatomical hemispherectomy for the treatment of Rasmussen's encephalitis in 2020. The postoperative course was immediately complicated by central diabetes insipidus which was stabilized with desmopressin. The patient's labs in 2021 were consistent with central precocious puberty with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Additionally, the patient was found to have secondary adrenal insufficiency in which she failed a low-dose adrenocorticotropic hormone (ACTH) stimulation test. Oral hydrocortisone therapy was initiated for secondary adrenal insufficiency in addition to initiating leuprolide injections for central precocious puberty. Furthermore, at the age of seven years, the patient had her first menarche. This case report emphasizes the need for closer and long-term surveillance for endocrine issues in postepileptic surgical pediatric patients as well as a surveillance plan for the development of other potential endocrine abnormalities throughout the patient's life.

Cytokine Release Syndrome with Relative Adrenal Insufficiency Induced by Ipilimumab and Nivolumab Combination Therapy for Clear Cell Renal Cell Carcinoma.

Combination therapy with ipilimumab and nivolumab is indicated for many types of cancers; however, several patients experience immune-related adverse events (irAEs). We herein report a case of cytokine release syndrome (CRS) in a 63-year-old woman with stage IV left clear cell renal cell carcinoma. Our patient developed CRS while taking prednisolone, 43 days after the start of ipilimumab and nivolumab administration. The patient was treated with steroid pulse therapy, which improved the symptoms of shock and respiratory failure. Increased vascular permeability and relative adrenal insufficiency are considered to be the main pathogeneses. The early administration of high-dose steroids is crucial as a replacement for corticosteroids.

Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge.

Critical illness-related corticosteroid insufficiency or CIRCI is characterized by acute and life-threatening disfunction of hypothalamic-pituitary-adrenal (HPA) axis observed among intensive care unit- staying patients.It is associated with increased circulating levels of biological markers of inflammation and coagulation, morbidity, length of ICU stay, and mortality.Several mechanisms are involved in CIRCI pathogenesis: reduced CRH-stimulated ACTH release, peripheral resistance to glucocorticoids, altered cortisol synthesis, impaired cortisol-free fraction and bioavailability.Diagnostic and therapeutic management of this condition in children is still debated, probably because of the lack of agreement among intensive care specialists and endocrinologists regarding diagnostic criteria and prevalence of CIRCI in paediatric age.In the present narrative review, we focused on definition of CIRCI in paediatric age and we advise on how to diagnose and treat this poorly understood condition, based on current literature data.

Endocrinopathies Associated With Immune Checkpoint Inhibitor Use.

OBJECTIVE: To provide a clinical approach towards immune checkpoint inhibitor (ICI)-associated endocrinopathies, their link with cancer outcomes, factors which differentiate them from other immune related adverse events, and health systems innovation to improve care for these patients. METHODS: A literature search for articles pertaining to ICIs and endocrinopathies was performed and supplemented by expert opinions of the authors. RESULTS: While immune related adverse events can affect almost any organ, they frequently target the endocrine glands, most commonly thyroid. Different classes of ICIs have varying frequencies of endocrinopathies related to hypophysitis, thyroiditis, diabetes mellitus, and rarely hypoadrenalism and hypoparathyroidism. ICI-associated endocrinopathies share some features with classic endocrine autoimmunity but appear to be a distinct entity. They can be challenging to diagnose and manage due to nonspecific clinical features, use of exogenous glucocorticoids, and at times rapid and severe hormone deficiency. The role of anti-inflammatory high-dose glucocorticoids is minimal, and the ICI does not usually require permanent discontinuation. ICI-associated endocrinopathies usually cause permanent hormone deficiency necessitating long-term management and patient engagement. ICI-thyroiditis has been associated with improved survival, while other endocrinopathies have not shown a significant association with outcomes in cancer patients receiving ICIs. Oncoendocrinology teams can improve the care of patients with ICI-associated endocrinopathies. CONCLUSION: This narrative review provides guidance to clinicians prescribing ICIs and those managing ICI-associated endocrinopathies, and complements the frameworks provided by major scientific societies in this field.

Pituitary-Adrenal Axis and Peripheral Immune Cell Profile in Long COVID.

In Long COVID, dysfunction in the pituitary-adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary-adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.

Determination of cortisol cut-off limits and steroid dynamics in the ACTH stimulation test: a comparative analysis using Roche Elecsys Cortisol II immunoassay and LC-MS/MS.

PURPOSE: Measurement of cortisol concentrations is method dependent. The study aimed to establish assay-specific cut-off limits for cortisol after adrenocorticotropic hormone (ACTH) stimulation, comparing Roche Elecsys Cortisol II immunoassay to liquid chromatography-mass spectrometry (LC-MS/MS), and to assess the impact of patient characteristics, estrogen containing oral contraceptives as well as relation to other adrenocortical steroid hormone dynamics. METHODS: One hundred healthy participants underwent a 250 µg ACTH-test, with plasma samples analyzed using ElecsysCortI, ElecsysCortII, and LC-MS/MS. Cortisone, corticosterone, 17-OH-progesterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were additionally analyzed with LC-MS/MS. Cut-off limit for a normal cortisol response to the ACTH-test was defined as: 2.5th percentile-1.96 × SE. RESULTS: ElecsysCort II measured cortisol concentrations 21% (95% CI: 19-22%) lower than ElecsysCort I. Cut-off limits for cortisol 30 and 60 min after ACTH were 426 and 485 nmol/L (ElecsysCort II) and 411 and 470 nmol/L (LC-MS/MS). Cut-offs were unaffected by gender, or body-composition. The ACTH-test resulted in significantly increased adrenocortical steroid hormones, except for decreased cortisone concentrations (both sexes), and decreased testosterone in men (1.9 nmol/L, 95% CI: 1.3-2.5). Testosterone was increased in women (0.07 nmol/L, 95% CI: 0.02-0.13). CONCLUSION: ElecsysCort II has high analytical performance and yields significantly lower cortisol concentrations than prior polyclonal immunoassays. This clinically relevant difference underscores the necessity for revised cut-off limits for improved diagnostic precision. Suggested 30-minute cortisol cutoff limits are 411 nmol/L (LC-MS/MS) and 426 nmol/L (ElecsysCort II). Adrenocortical steroids increased upon ACTH stimulation, except for cortisone in both sexes and testosterone in men, both of which decreased.

Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.

Objective: It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users. Methods: Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency. Results: Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients. Conclusion: GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.

Adrenal insufficiency following cerebellar intracranial hemorrhage: a case report.

This report presents a case of a previously healthy 58 years-old man who had suffered from persistent weakness and dizziness after a cerebellar intracranial hemorrhage (ICH). Endocrine function tests revealed low levels of plasma cortisol (3.05 µg/dL; normal range: 5-25 µg/dL) and adrenocorticotropic hormone (ACTH) (6.0 pg/mL; normal range: 10-60 pg/mL). The subsequent ACTH stimulation test suggested partial or recent hypopituitarism, resulting in adrenal gland atrophy and a subnormal cortisol response. Ultimately, the dizziness was found to be caused by undiagnosed adrenal insufficiency, which was detected when a hypotensive fainting incident occurred during rehabilitation. The symptoms improved significantly with oral prednisone supplementation. Notably, the duration of impaired hypothalamic-pituitary-adrenal axis may last as long as a year. This case highlights that adrenal insufficiency can easily be overlooked since its symptoms are similar to those commonly seen with cerebellar stroke alone. Physicians must be aware of the symptoms of adrenal insufficiency in patients with brain insults and conduct the appropriate endocrine tests to clarify the underlying comorbidity.

Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial.

BACKGROUND: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. OBJECTIVES: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. MATERIALS AND METHODS: Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24 weeks after randomization. RESULTS: At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24 weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ = 0.478, p = 0.045). DISCUSSION: Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review.

Background: Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease. Methods: We comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded. Results: We identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD. Conclusion: IAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.