Unrecognized Adrenal Insufficiency Research Articles

Secondary adrenal insufficiency in patient with COVID-19 and head and neck cancer

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion is an endocrinological disorder which occurs when there is an evidence of continued antidiuretic hormone (ADH) secretion in the absence of an appropriate osmotic volume stimulus. Most commonly it is caused by different types of cancer or medications (eg. diuretics, antidepressants, antipsychotics...). Secondary adrenal insufficiency is caused by the insufficient adrenocorticotropic hormone (ACTH) secretion and cortisol production. In the hypocortisolism, the inhibitory mechanism on ADH secretion vanishes causing increased ADH secretion and leading to SIADH-like state. Both conditions, SIADH and hypocortisolism, manifest in euvolemic hyponatremia, however, its cause can be misdiagnosed and result in an inadequate treatment and potentially fatal outcome. Our case is about fifty-seven-year-old male patient who was treated with chemoradiotherapy for hematological malignancy of the oropharynx and who presented with severe hyponatremia se-veral times that almost ended fatally. Considering his malignant disease, patient was diagnosed with SIADH as a cause of hypona-tremia and was treated with hypertonic saline fluids and fluid intake restriction. However, after having suffered Covid-19 infection the patient was given glucocorticoids according to the protocol at the time. The sodium levels finally corrected, and the secondary adrenal insufficiency has been declared as the real cause of hyponatremia. SIADH is often thought to be the cause of hyponatremia in patients with malignant disease. However, SIADH represents a diagnosis of exclusion. Before making a final diagnosis, thyroid and secondary adrenal insufficiency must be ruled out. Moreover, secondary adrenal insufficiency imitates SIADH and results in euvolemic hyponatremia but the management and potential outcomes of these two conditions differ significantly. In patients who have been previously treated for malignancies with the treatment options that increase the risk of adrenal insufficiency (chemotherapy, neck or skull base radiotherapy, immunotherapy), adrenal reserve must be evaluated. If introduced, the glucocorticoid therapy should be carefully deescalated in these patients because of the risk of previously unrecognized adrenal insufficiency. This especially applies to conditions that include glucocorticoid therapy in the treatment protocol, such as Covid-19 infection.

Current Knowledge and Practices of Heath Care Professionals on Opioid-Induced Adrenal Insufficiency

Objective: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. The aim of the present study was to assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness. Methods: We carried out a cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids. Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n = 33, 36%), followed by endocrinologists (n = 13, 14%) and various other specialties (n = 45, 49%). While 61 (67%) of respondents prescribed opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among nonendocrine providers, 53 (68%) identified adrenal insufficiency as a known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% versus 24%, P = .01) and to identify the correct symptoms for OIAI (38% versus 9%, P <.001). One in four nonendocrine providers reported discomfort in managing glucocorticoid replacement therapy. The majority (60%) of providers indicated that online resources and continuing medical education lectures would improve knowledge of OIAI. Conclusion: Our study identified several deficiencies in HCP knowledge of opioid-induced endocrine effects, especially in nonendocrine providers. As many symptoms of OIAI overlap with those of underlying conditions, OIAI could be potentially missed, highlighting the need to further educate providers about opioid-induced endocrinopathies. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CME = continuing medical education; HCP = healthcare professional; OIAI = opioid-induced adrenal insufficiency.

Beneficial effect of intra-operative methylprednisolone on immediate post liver transplant intensive care course.

Concern about the effect of corticosteroids on outcomes following liver transplantation (LT), especially in recipients with hepatitis C infection (HCV) has lead many centres to abandon the use of perioperative steroids. Avoidance of corticosteroids in immunosuppressive regimens may have beneficial effects in terms of reducing the incidence of infection, new onset diabetes mellitus and HCV recurrence however perioperative use may have beneficial effects such as attenuation of ischaemia-reperfusion injury (IR) and treatment of underlying adrenal insufficiency (AI). Due to a high prevalence of adrenal insufficiency in patients on our waiting list for LT, we reintroduced the use of intraoperative methyl-prednisolone and hypothesised that this would improve early post operative outcome. 90 consecutive patients were studied, 45 before (group 1) and 45 (group 2) after the protocolised reintroduction of methylprednisolone (1g IV) intraoperatively prior to reperfusion. Peri- and post-transplant requirements for colloid, crystalloid, blood products, vasopressors, renal replacement therapy and ventilation were compared between groups. No other changes to the transplant protocol occurred during the study period. Patients who received intraoperative methlyprednisolone had significantly shorter post operative ITU stay, vasopressor and colloid requirement post LT, and were dependent on mechanical ventilation for less time. These data suggest that the use of intraoperative methylprednisolone can modify the immediate post transplant course of LT, either by attenuating reperfusion induced inflammation, or by addressing hitherto unrecognized adrenal insufficiency.

Cancer-related fatigue: can it be due to adrenal suppression secondary to high-dose steroids used as antiemetic?

To the editor: The use of dexamethasone for cancer-related fatigue (CRF) in patients with advanced cancer is a controversial issue. Beneficial effects of dexamethasone may be counterbalanced by its serious side effects. The exact mechanism of the action of steroids on cancer-related fatigue is unknown. Recently, Yennurajalingam et al. hypothesized that dexamethasone exerts its effects on CRF mainly by interfering with the peripheral effects of proinflammatory cytokines [1]. We believe that this may not be the case for some of patients with CRF. The exact pathogenesis of CRF is unknown. A role of systemic inflammation or imbalance between hypothalamicpituitary-adrenal (HPA) axis and systemic cytokines has been proposed [2, 3]. Advanced stage cancer represents a state of chronic stress. Low levels of endogenous cortisol, which may be associated with symptoms in advanced cancer, had been demonstrated by Lundstrom et al. [4]. Major symptoms of adrenal insufficiency (i.e., fatigue, nausea, loss of appetite) may be misinterpreted as CRF. Indeed, some patients treated for CRF may have unrecognized adrenal insufficiency. High dose of dexamethasone (8–16 mg/day) is commonly used as antiemetic therapy in highly and moderately emetic regimens. Updated ASCO guidelines on antiemetics recommend a 4-day course of dexamethasone (12 mg on day 1 and 8 mg on days 2–4) for highly emetogenic chemotherapy and 1–3-day 8 mg course for moderately emetogenic chemotherapy [5]. Highdose steroids may suppress the hypothalamic pituitary and adrenal axis, even with short-term use [6]. Han et al. published their article on adrenal suppression related to the use of dexamethasone as an antiemetic therapy in patients with cancer in July 2012 [7]. Patients receiving dexamethasone as an antiemetic for at least 3 days per cycle and for more than 3 months were included in this study. Adrenal suppression was demonstrated biochemically in 45 of the 103 patients (43.7 %). Adrenal suppression was more common in patients receiving megestrol acetate concomitantly. Daily replacement therapy with 7.5–10 mg of prednisolone for 1–2 weeks in patients with suppressed HPA axis resulted in the improvement of symptoms associated with adrenal insufficiency. This dose of prednisolone is approximately equivalent to 1 mg of dexamethasone [8]. This is about one eighth of the dose recommended in the study of Yennurajalingam et al. We believe that this lower dose may allow the use of steroid for longer periods and spare some of the patients with CRF from serious side effects of higher doses of steroids. Metabolic (i.e., hyperglycemia, hypokalemia) and muscular side effects (i.e., proximal muscle weakness) of long-term use of steroids may be confused with CRF or even increase the severity of CRF. Lower dexamethasone dose will probably cause less metabolic and muscular side effects. For those patients with continuing symptoms of CRF, steroid dose may be gradually increased. In the current study, no follow up for the quality of life was made after cessation of dexamethasone [1]. As CRF is a chronic problem, symptoms may become worse after cessation of high-dose dexamethasone. Lesser dose of dexamethasone may be used more safely for longer periods of time for some patients with this chronic problem. There are still unanswered questions about CRF: What should be done for patients without biochemical evidence of HPA axis suppression? Should we search for biochemical evidence of inflammation (i.e., C-reactive protein) in this group of patients? Should we start with higher doses of dexamethasone when we have laboratory evidence of both systemic inflammation and HPA axis suppression? Should adrenal insufficiency be in the routine checklist of evaluation O. O. Eren (*) :B. Oyan Medical Oncology Section, Department of Internal Medicine, Yeditepe University Hospital, Devlet yolu, Ankara Caddesi, 102-104 Istanbul, Turkey e-mail: droneren@hotmail.com

Risk of adrenal crisis in dental patients: Results of a systematic search of the literature

The authors performed a systematic search of the literature to identify the frequency of, risk of experiencing and factors associated with adrenal crises in dental patients.The authors searched PubMed and Ovid MEDLINE (1947-June 20, 2012) and Embase (1974-2012) for English-language articles related to cases of adrenal crisis in dentistry and extracted and analyzed data from the articles. The six authors determined whether the cases identified met a consensus definition of adrenal crisis.Of 148 articles identified in the initial screening, 34 articles were included in the final review, from which six cases met the criteria of adrenal crisis. The authors categorized four cases as "suggestive of adrenal crisis" and two cases as "consistent with adrenal crisis." Risk factors were significant adrenal insufficiency, pain, infection, having undergone an invasive procedure, having received a barbiturate general anesthetic, and poor health status and stability at the time of presentation. The authors estimated risk to be less than one in 650,000 in patients with adrenal insufficiency.Adrenal crisis is rare in dental patients, with only six reports of it having been published in the past 66 years. Risk is associated with unrecognized adrenal insufficiency, poor health status and stability at the time of treatment, pain, infection, having undergone an invasive procedure and having received a barbiturate general anesthetic.Risk of adrenal crisis is reduced through proper evaluation of the patient, identification of risk factors and following appropriate preventive measures.

Unrecognized adrenal insufficiency in patients undergoing laparoscopic adrenalectomy

Unrecognized adrenal insufficiency in patients undergoing laparoscopic adrenalectomy

Unrecognized adrenal insufficiency in patients undergoing laparoscopic adrenalectomy

Subclinical Cushing's syndrome (SCS) is a well-described phenomenon where abnormalities of the hypothalamic-pituitary-adrenal axis exist in the absence of overt signs and symptoms of classic Cushing's syndrome. While this has been shown to exist in 5-20% of patients with adrenal lesions, no standardized biochemical regimen exists to screen for SCS. Consequently, many of these patients may not be diagnosed prior to adrenalectomy with the risk of postoperative adrenal insufficiency. We began checking morning (a.m.) serum cortisol levels on postoperative day 1 (POD1) following unilateral adrenalectomy for nonfunctioning adrenal lesions to determine the incidence of unrecognized adrenal insufficiency (AI) in these patients. One hundred and five patients undergoing adrenalectomy at a tertiary care center from 1999 to 2007 were retrospectively evaluated. Patients with Cushing's syndrome, conditions associate with bilateral disease, and those receiving perioperative steroids were excluded, leaving 41 patients for analysis. A.m. serum cortisol levels were obtained in all patients POD1. Multiple factors were analyzed as possible predictors of AI. Analysis of variance (ANOVA), t-test, and chi-square test were used to determine statistical significance. The 41 patients' diagnoses included 13 pheochromocytomas, 15 nonsecreting adenomas, 5 aldosteronomas, 5 metastatic lesions, 1 adrenocortical carcinoma, and 2 other benign lesions. Three groups were identified based on POD1, a.m. cortisol levels: sufficient (>10 microg/dl; n = 25, 61%), low-normal (3.4-10 microg/dl; n = 7, 17%), and insufficient (<3.4 microg/dl; n = 9, 22%). Tumor size and presence of diabetes, hypertension, and obesity were predictive of postoperative AI (p < 0.05). AI after unilateral adrenalectomy without evidence of cortisol hypersecretion on preoperative screening was present in a significant number of patients in our series. Patients with diabetes, hypertension, obesity, and larger tumors may be at higher risk for postoperative AI. More thorough screening for cortisol hypersecretion may be warranted in patients with these characteristics, and obtaining routine postoperative cortisol levels may avoid potentially dangerous unrecognized adrenal insufficiency following adrenalectomy.

The Hypothalamic-Pituitary-Adrenal Axis in Pregnancy: Challenges in Disease Detection and Treatment

Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed. CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing's disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used. Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed.

Adrenal insufficiency in critically ill emergency department patients: a Taiwan preliminary study.

Unrecognized adrenal insufficiency can have serious consequences in critically ill emergency department (ED) patients. This prospective pilot study of adrenal function in patients with severe illness was undertaken to determine the prevalence of adrenal dysfunction and any relation to prior herbal drug use. In a high-volume urban tertiary care ED, adult patients with sepsis or acute myocardial infarction (AMI) were eligible for the study. Over a two-month period, a convenience sample was enrolled by the authors on arrival to the ED. Inclusion criteria were systemic inflammatory response syndrome (SIRS) criteria plus evidence of at least one organ dysfunction or cardiac marker plus electrocardiogram-proven AMI. Exclusion criteria included known corticosteroid use. Serum cortisol was measured on arrival and for those patients with a level of <15 microg/dL (<414 nmol/L), an adrenocorticotropic hormone (ACTH) stimulation test was performed. Of the 30 enrolled patients, 23 (77%) were suffering from severe sepsis and the other seven (23%) had an AMI. Thirteen of the 30 patients (43%; 95% CI = 25% to 65%) had serum cortisol levels of <15 microg/dL, consistent with adrenal insufficiency, nine with severe sepsis and four with an AMI. Eight (62%; 95% CI = 32% to 86%) of the 13 patients with low cortisol levels reported using herbal medications, while only two (12%; 95% CI = 1% to 36%) of the 17 with normal cortisol levels reported taking herb drugs (p = 0.01). Only two (15%; 95% CI = 2% to 45%) of the patients with low cortisol levels failed their corticotropin stimulation test, suggestive of true adrenocortical insufficiency. Both reported using herbal preparations. These results indicate that adrenal dysfunction is common among a group of critically ill patients seen in this Taiwanese ED. Moreover, the use of herbal drugs was high in the patients with low serum cortisols. Further studies are required to both confirm these findings and clarify whether a number of herbal medications contain corticosteroids.

HIV infection and endocrine disease

The endocrine system recently has become appreciated as a potential target site for HIV infection. Abnormal endocrine gland function can occur as a result of direct HIV Infection, secondary infectious or malignant processes, or as a complication of therapies for AIDS. In this context, the adrenals are most important because unrecognized adrenal insufficiency in AIDS inevitably will lead to rapid demise of the patient. Fortunately, frank adrenal insufficiency is most uncommon. Also. uncommon are clinical manifestations of other endocrine organ dysfunction, but the thyroid gland, pancreas, and gonads are all potential targets. Electrolyte abnormalities and disordered energy metabolism are additional potential complications of HIV infection

Screening for congenital adrenal hyperplasia: Distribution of 17 α-hydroxyprogesterone concentrations in neonatal blood spot specimens

In a retrospective analysis of 24 cases of congenital adrenal hyperplasia (CAH) in neonates born in the province of Manitoba during the last 20 years, we set out to determine whether patients, in particular male infants with salt-losing CAH, were being missed by the usual forms of clinical ascertainment. Although the overall incidence of 1/14,500 live births was similar to that found in several screening surveys, a skewed female/male sex ratio of 2.2:1 suggested probable death among male infants with unrecognized adrenal insufficiency. These results led to a prospective analysis of 17 alpha-hydroxyprogesterone (17-OHP) levels in 1194 neonatal blood specimens by a solid-phase direct radioimmunoassay procedure to determine whether this method would be suitable for CAH screening. In 1103 neonates weighing greater than 2500 gm at birth, all 17-OHP values were less than 30 nmol/L (approximately 1000 ng/dl), with a mean of 8.2 nmol/L; values in male infants were slightly higher than in female infants. In 89 neonates with a birth weight less than 2500 gm, 17-OHP values were skewed, with nine having levels greater than 30 nmol/L and two greater than 50 nmol/L. Postnatal age (1 to 24 days) at the time of specimen collection had no effect on 17-OHP levels, although higher values occur during the first 24 hours. One unsuspected case of CAH in a male infant was discovered during the trial period. We conclude that neonatal CAH screening can permit diagnosis and therapy of affected male infants who are being missed by normal clinical evaluation. This radioimmunoassay method is relatively simple and inexpensive, and it has the specificity and sensitivity necessary to provide such mass screening.