Search

Objective and Design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection., Patients and Measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone., Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395-479, 138-142, and 3.7-4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138-690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135-145 nmol/L) was detected in five patients, without being related to cortisol levels., Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency., (© 2024. The Author(s).)

Objective: COVID-19 is a potentially serious new infection first reported in North East Italy in Spring, 2020. Patients with adrenal insufficiency (AI) have a known increased risk of infections that could precipitate to adrenal crisis. Even COVID-19-related psycho-social impact could affect their health, requiring a dynamic adaptation of daily glucocorticoid (GC) therapy. The aim of this study was to evaluate the incidence of COVID-19 infection and self-reported outcomes in AI patients after the first pandemic waves., Methods: It was an open-label, cross-sectional monocentric study on 84 (65 primary, 19 secondary) AI patients resident in Veneto and followed-up in our clinical Endocrine Unit. All patients underwent serological investigation of anti-SARS-CoV2 IgG, answered the purpose-built "ADDICOVID" questionnaire in August, 2020, and were re-contacted to reevaluate COVID-19 infection occurrence in March-April, 2021., Results: All patients resulted negative to the serological test for anti-SARS-CoV2 IgG at the end of the first pandemic wave. After the third wave, COVID-19 infection occurred in 8 patients without the need for hospitalization. Half patients felt an increased risk of COVID-19 infection, significantly associated with increased stress and GC stress dose. Only one patient reported stress-correlated adrenal crisis. The majority of AI workers changed working habits, significantly reducing COVID- 19-related stress., Conclusion: AI patients did not show an increased incidence of COVID-19, but the perception of increased COVID-19 infection risk significantly impacted their psychological well-being, working habits, and GC daily doses. Therapeutic patient education is crucial, especially for AI workers, to prevent and treat situations that could lead to an adrenal crisis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Context: Fludrocortisone (FC) is the mineralocorticoid (MC) replacement treatment for patients with primary adrenal insufficiency (PAI)., Objective: To explore the dose of FC treatment and its relationship with glucocorticoid therapy, sodium, potassium, renin and clinical parameters., Setting: Monocentric cohort., Patients: Data of 193 patients with PAI (130 autoimmune) were collected during baseline (T0), intermediate (T1) and last follow-up visit (T2, respectively, after a mean of 38 and 72 months)., Main Outcome Measure: Utility of endocrine and clinical parameters to titrate FC dose., Results: FC dose (50-75 μg/daily) was stable in the follow-up in half patients. The MC activity of FC was dose-dependent: we observed a reduced but significant positive linear correlation between FC dose and sodium (r = 0.132) and negative linear correlation between FC and potassium (r = - 0.162) or renin (r = - 0.131, all p < 0.01). An overall reduction in the FC dose was observed at T2 in the group with longer follow-up (> 60 months, p < 0.05). Higher doses of FC were observed in patients with low-normal renin, especially in autoimmune PAI (86 vs 65 μg/daily, p < 0.05). On the contrary, reduced sodium and increased potassium levels were observed in patients with high renin at T2. The number of cardiovascular events (15 in the whole cohort) was similar in patients sorted by renin levels or FC dose., Conclusions: Renin and electrolytes can indicate the MC activity of FC treatment: they should be routinely evaluated and used to titrate its dose that can be reduced in the long-term follow-up., (© 2022. The Author(s).)

Adrenal insufficiency (AI) is a life-threatening disorder, with increased morbidity and mortality, especially in case of an acute illness that can increase the requirement of cortisol. A novel infectious disease, termed Coronavirus Disease 2019 (COVID-19), appeared in 2020. Therefore, AI patients are experiencing a novel challenge: the risk of infection. In our experience, a prompt contact to the Endocrine center (with a telemedicine consultation) and a full awareness of diseases (cortisol deficiency, COVID-19 and the self-management of an adrenal crisis) are important to motivate patients. Vaccine is an effective treatment to prevent hospitalization and aggressive course of COVID-19. Some patients manifest challenges due to inequitable access and vaccine hesitancy, resulting in a delay in the acceptance of vaccines despite the availability of vaccination services. Therefore, an effort of all physicians must be conducted in order to advise patients with AI. In this short review, we try to answer some frequently asked questions regarding the management of patients with AI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sabbadin, Betterle, Scaroni and Ceccato.)

Context: The human corticotropin-releasing hormone (CRH) test (hCRHtest) is used to differentiate Cushing disease (CD) from ectopic adrenocorticotropin (ACTH) secretion (EAS), to assess autonomous cortisol secretion by the adrenal glands, and to characterize pseudo-Cushing syndrome (CS) or adrenal insufficiency (AI)., Main Outcome Measure: The main outcome measure of this study was to assess the diagnostic accuracy of the hCRHtest., Methods: We measured ACTH and cortisol levels; collected the peak values (peakACTH and peakcortisol), and calculated the percentage increases (∆%ACTH and ∆%cortisol) after an intravenous bolus of 100 μg hCRH., Design and Setting: This cross-sectional study of hCRH tests from 2010 to 2019 took place in a referral university hospital center., Patients: We enrolled 200 patients: 86 CD, 15 EAS, 18 adrenal CS, 25 mild adrenal autonomous cortisol secretion, 31 pseudo-CS, and 25 suspected AI., Results: The hCRHtest was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions (P = .048). PeakACTH and peakcortisol were higher in CD, and ∆%ACTH and ∆%cortisol were able to differentiate CD from EAS with a sensitivity and specificity greater than 80%. In patients with low (< 10 pg/mL) or indeterminate (10-20 pg/mL) basalACTH levels, an absent or reduced peakACTH response was able to differentiate adrenal from ACTH-dependent forms. PeakACTH and peakcortisol after hCRHtest were lower in pseudo-CS than in CD, but ∆%ACTH and ∆%cortisol were similar. The role of hCRHtest in patients with AI was limited., Conclusions: The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Central adrenal insufficiency (CAI) is characterized by impaired adrenocorticotropin (ACTH) secretion because of a disease or injury to the hypothalamus or the pituitary, leading to a reduced cortisol production. CAI suspicion arises more frequently in patients with pituitary tumors, cranial irradiation/surgery/injury/infections, as well as after exogenous glucocorticoid withdrawal. Nevertheless, a late diagnosis is not uncommon because CAI may present with nonspecific signs or symptoms, as fatigue or hyponatremia. Content The PubMed database was searched (years 1980-2018), using "central adrenal insufficiency" and "ACTH deficiency" as keywords. Subsequently, reference sections of the retrieved articles were searched. Summary Dynamic tests are needed when morning basal cortisol levels are not sufficient to exclude or to confirm CAI. Short Synacthen Test (SST) is the most used, and Endocrine Society's guidelines recommend a cortisol peak >500 nmol/L to exclude CAI. Despite thresholds, understanding the pretest probability of ACTH deficiency (the clinical background of the patient) is essential because the diagnostic accuracy of SST in case of a negative result is suboptimal. Glucocorticoid replacement therapy, able to replicate cortisol circadian rhythm, is required in patients with CAI; fludrocortisone treatment is not necessary. Short-acting glucocorticoid drugs (hydrocortisone or cortisone acetate) are the most used; lower doses than previously used are nowadays recommended to reduce cortisol-related comorbidities. Promising results have been obtained with modified-release hydrocortisone, especially regarding glucose metabolism in patients with primary adrenal insufficiency. Outlook An accurate clinical diagnosis and a careful individualized therapy are mandatory in patients with CAI.

Background and Aim: Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement therapy. Cortisol measurement in saliva is increasingly being used: we assessed salivary cortisol rhythm in outpatients with AI, to provide new insights regarding the management of GC treatment., Materials and Methods: Nineteen AI outpatients collected six saliva samples from awakening (F a , before taking the morning GC therapy), during the day (F 1.5 h , F 6 h before the afternoon GC dose, F 8.5 h , F 12 h ) until bedtime (F b ). We measured daily cortisol exposure by calculating the area under the curve (AUC Fa→Fb ). Saliva samples were collected at baseline and one year after GG dose reduction (by at least 5 mg of hydrocortisone)., Results: Hydrocortisone equivalents decreased from median 25 mg/d (baseline, interquartile range IQR 20-27.5) to 15 mg/d (IQR 15-20, P < .01). As expected, we observed a reduction in both daily cortisol exposure (AUC Fa→Fb 23 982 nmol·h/L, IQR 12 635-45 369, to 14 689 nmol·h/L, IQR 7168-25 378, P < .001) and salivary cortisol levels at F 6 h (24.8 nmol/L, IQR 20.1-35.7, to 21 nmol/L, IQR 8.7-29.2, P < .05) and F b (8.7 nmol/L, IQR 3.4-20.2, to 3.7 nmol/L, IQR 3.0-5.8, P < .05). None of the patients developed signs or symptoms consistent with AI after GC reduction. Median diastolic blood pressure (DPB) values fell from baseline to the end of follow-up (87.5 mm Hg, IQR 80-90, to 80 mm Hg, IQR 80-85, P < .05). The AUC Fa→Fb of patients at baseline was above the reference value (90th percentile of controls) in 12 patients (60%); after the dosage reduction, 30% of patients normalized their daily cortisol exposure (AUC Fa→Fb )., Conclusions: The reduction in GC treatment in patients with AI resulted in better control of daily cortisol rhythm, measured with salivary cortisol, and in an improvement of DPB. Further studies are needed to ascertain if salivary cortisol could be used as a biomarker to manage GC replacement therapy., (© 2017 John Wiley & Sons Ltd.)

Central adrenal insufficiency (CAI) in acromegaly may be related to pituitary adenoma or induced by various medical treatments, transsphenoidal neurosurgery (TNS) or radiotherapy (RT), alone or combined. We assessed the role of all available treatments for acromegaly in inducing CAI. We retrospectively studied 97 patients. CAI was diagnosed if morning serum cortisol was <138 nmol/l, or if its response was inadequate in the low-dose short synacthen test. Seventy-four subjects underwent TNS (and 17 of whom also underwent RT), and 23 were on primary medical therapy: overall we diagnosed 21 cases of CAI. Duration of acromegaly, invasion of cavernous sinus, disease control, and type of medical treatment were much the same for patients with and without CAI, which was identified in 18% of patients (10/57) after one TNS, and in 53% (9/17) after RT (p=0.01); repeat surgery increased the risk of CAI (p=0.02). The risk of CAI onset during the follow-up was lower among patients treated with TNS or medical therapy than after RT (p=0.035). Medical treatment did not raise the risk of CAI, whereas a 5- and 4-fold higher risk of CAI was associated with repeat TNS and RT, respectively. Basal or stimulated cortisol levels were similar among acromegalic patients without CAI and matched controls with nonsecreting pituitary lesions. A significant proportion of patients with acromegaly developed CAI over time. While primary or secondary medical treatment did not contribute to the risk of CAI, repeat TNS and RT correlated with pituitary-adrenal axis impairment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Salivary cortisol has recently been suggested for studies on the hypothalamic-pituitary-adrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing's syndrome (CS), and some authors have reported that low salivary cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of salivary cortisol in specific diagnostic settings of HPA axis disease., Subjects and Methods: We analyzed morning salivary cortisol (MSC) and late-night salivary CORTISOL (LNSC) levels in 406 SUBJECTS: 52 patients with Cushing's disease (CD), 13 with ectopic CS, 17 with adrenal CS, 27 with CD in remission (a mean follow-up of 66±39 months), 45 with adrenal incidentaloma, 73 assessed as having CS and then ruled out for endogenous hypercortisolism, 75 with adrenal insufficiency, and 104 healthy subjects., Results: A LNSC value above 5.24  ng/ml differentiated CS patients from controls with high sensitivity (96.3%) and specificity (97.1%); we found higher LNSC levels in ectopic CS patients than in CD patients. We found no difference in MSC and LNSC levels between patients with CD in remission and healthy subjects. Both MSC and LNSC levels were higher in patients with adrenal incidentaloma than in healthy controls. A MSC value below 2.65 ng/ml distinguished patients with adrenal insufficiency from controls with high sensitivity (97.1%) and specificity (93.3%)., Conclusions: Salivary cortisol is a useful tool to assess endogenous cortisol excess or adrenal insufficiency and to evaluate stable CD in remission.

Context: Appropriate glucocorticoid replacement therapy in adrenal insufficiency (AI) is crucial, given the risks of chronic under- or overtreatment, particularly in patients on multiple medications. Salivary sampling allows for non-invasive, stress-free cortisol measurement., Objective: To determine whether salivary cortisol measurement is helpful in assessing the adequacy of glucocorticoid therapy with cortisone acetate (CA) in patients with secondary AI., Design: A prospective cohort study at the Endocrinology Unit of Padua University Hospital., Methods: Six samples of salivary cortisol were collected from 28 patients with secondary AI on CA treatment and from 36 healthy volunteers at fixed times of the day, and used to calculate salivary cortisol levels at each time point and the area under the curve (AUC) across the different sampling times., Results: Salivary cortisol levels were lower in patients than in controls in the morning but no differences were found in the afternoon or at night before resting. Salivary cortisol levels were higher in patients immediately following CA administration. Ten patients showed an AUC above the 97.5th percentile of controls, without clinical signs of hypercortisolism, and salivary cortisol levels 90 min after each dose of CA predict the AUC. All patients had severe GH deficiency and there were no differences in salivary cortisol levels or AUC between patients treated or not with GH., Conclusions: Two salivary cortisol determinations, able to predict the daily AUC, may allow for assessing the adequacy of glucocorticoid replacement therapy in secondary AI and for identifying cases of over- or undertreatment.