scholarly journals An Overlooked Sequela of Long-Term Opioid Analgesic Use: A Case Report on Central Adrenal Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A115-A116
Author(s):  
Wei Zhao ◽  
Issa Mohamed ◽  
Derrek Humphries ◽  
Elizabeth Bankstahl
Keyword(s):  
Chronic Pain ◽  
Adrenal Insufficiency ◽  
Case Reports ◽  
Opioid Analgesic ◽  
Total Duration ◽  
Gastrointestinal Symptoms ◽  
Adrenal Crisis ◽  
Opioid Epidemic ◽  
Opioid Use ◽  
Central Adrenal Insufficiency

Abstract Background: Opioid use began to surge since late 1990s and has evolved into a full-fledge opioid epidemic. 2 million Americans aged 12 or older are estimated to have opioid use disorder. We hereby present a case of opioid-induced adrenal insufficiency (OIAI), an overlooked endocrinopathy in which chronic opioid use suppresses the hypothalamic-pituitary-adrenal axis. Clinical Case: A 53-year-old African American female with past medical history of chronic pain syndrome presented with worsening fatigue and generalized weakness for a week, to the extent that she required full assistance to ambulate at home. Upon further inquiry, she also suffered from postprandial eipgastric pain and non-bloody diarrhea for several months. She has a 2-year use of Norco 10 mg/325 mg three times daily to manage her chronic pain. Her blood pressure was running low at 85/57 mmHg with no other abnormal vitals. Our first visual impression of her was a debilitated lady with low voice and slow body movements. Adrenal insufficiency was suspected and subsequently confirmed with low morning cortisol level (1.1 mcg/dL), low DHEAS level (25.3 mcg/dL) and subnormal response of cortisol (16.8 mcg/dL) to the cosyntropin stimulation test. Her ACTH level was less than 3 pg/mL. These laboratory findings were consistent with central adrenal insufficiency. Chronic steroid use, the most common culprit for adrenal insufficiency, was not found in her home medication list or prescription records. To further evaluate the underlying etiologies, we checked the pituitary hormones and found normal levels of LH, FSH, TSH, prolactin and IGF-1. Head CT 2 years prior was negative for any discernible mass. The suspicion for pituitary mass that markedly suppresses ACTH secretion only was reasonably low. The diagnosis of OIAI was made by excluding other causes. Endocrinology was consulted for the dosing of hydrocortisone. She improved physically after receiving hydrocortisone replacement therapy. Collaborative efforts were made to cut down her opioid dose. Conclusions: OIAI is a longstanding overlooked condition in chronic opioid users of which clinicians should raise their awareness. The estimated prevalence of OIAI ranges from 9% to 29% depending on the daily dosage and total duration of opioid use. The case reports of OIAI, however, are only a few. Patients with OIAI could present with fatigue, weight loss, gastrointestinal symptoms, headache or muscular aches. Not only does OIAI impair patients’ quality of life and potentially escalate their opioid dosage by inexperienced prescribers, it also leads to catastrophic adrenal crisis following acute insults. The challenge clinicians face is to uncover the clinical clues suggesting OIAI, which are often hidden in a myriad of symptoms caused by chronic pain and other co-morbidities. Timely diagnosing OIAI is thus never more important in the midst of the unprecedented opioid epidemic.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Fertility, pregnancy and lactation in women with adrenal insufficiency

2018 ◽  
Vol 178 (2) ◽  
pp. R45-R53 ◽  
Author(s):  
Gurpreet Anand ◽  
Felix Beuschlein
Keyword(s):  
Pregnant Women ◽  
Adrenal Insufficiency ◽  
Case Reports ◽  
Obstetric Care ◽  
Normal Pregnancy ◽  
Clinical Situation ◽  
Adrenal Crisis ◽  
Substitution Therapy ◽  
Fetal Outcomes ◽  
Pregnancy And Lactation

With the introduction of hormonal substitution therapy in the 1950s, adrenal insufficiency (AI) has been turned into a manageable disease in pregnant women. In fact, in the light of glucocorticoid replacement therapy and improved obstetric care, it is realistic to expect good maternal and fetal outcomes in patients with AI. However, there are still a number of challenges such as establishing the diagnosis of AI in pregnant women and optimizing the treatment of AI and related comorbidities prior to as well as during pregnancy. Clinical and biochemical diagnoses of a new-onset AI may be challenging because of overlapping symptoms of normal pregnancy as well as pregnancy-induced changes in cortisol values. Physiological changes occurring during pregnancy should be taken into account while adjusting the substitution therapy. The high proportion of reported adrenal crisis in pregnant women with AI highlights persistent problems in this particular clinical situation. Due to the rarity of the disease, there is no prospective data-guiding management of pregnancy in patients with known AI. The aim of this review is to summarize the maternal and fetal outcomes based on recently published case reports in patients with AI and to suggest a practical approach to diagnose and manage AI in pregnancy.

Adverse childhood experiences predict autonomic indices of emotion dysregulation and negative emotional cue-elicited craving among female opioid-treated chronic pain patients

2019 ◽  
Vol 31 (3) ◽  
pp. 1101-1110 ◽  
Author(s):  
Eric L. Garland ◽  
Sarah E. Reese ◽  
Carter E. Bedford ◽  
Anne K. Baker
Keyword(s):  
Chronic Pain ◽  
Adverse Childhood Experiences ◽  
Emotion Dysregulation ◽  
Opioid Analgesic ◽  
Opioid Use ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Chronic Pain Patients ◽  
Pain Patients

AbstractThrough autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N= 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.

An observational study assessing high dose opioid prescribing and associated adrenal insufficiency

2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X696641 ◽  
Author(s):  
Sophie Hayhoe ◽  
Simon Rudland ◽  
Damian Morris
Keyword(s):  
Adrenal Insufficiency ◽  
Case Reports ◽  
Serum Cortisol ◽  
Adrenal Suppression ◽  
Endocrine Function ◽  
High Dose ◽  
Opioid Use ◽  
Practice List ◽  
Opioid Dose

BackgroundLong-term opioid use is known to affect endocrine function, with case reports indicating an association with adrenal insufficiency.AimThis study aims to investigate long-term, high-dose opioid use (≥80mg morphine or equivalent per day) at a Suffolk (UK) General Practice and its effect on adrenal function.MethodFrom a practice list of 18,300, retrospective data was collected for patients prescribed high-dose opioids for non-cancer pain for at least three months on current repeat prescription. Patient demographics and prescribing information were collected using SystmOne. Cortisol levels in the high-dose opioid patients, and short synacthen testing if indicated, were performed.ResultsThe 35 identified patients (0.2% of practice list) were predominantly female (77%) ≥70 years old (37%), and taking opioids prescribed for osteoarthritis or back pain (77%). 6% were prescribed >280mg morphine or equivalent per day, with one patient prescribed 705 mg. Routine evaluation for development of adrenal suppression and subsequent management was poor. 31% (11 of 35) had developed symptoms potentially indicative of adrenal insufficiency. One of these patients was among the 21% (7 of 35) with suppressed serum cortisol. Adrenal insufficiency secondary to opioids was confirmed in one patient using short synacthen testing. There was no statistical difference in either opioid dose or months of use for those with or without early morning cortisol suppression.ConclusionThe investigation highlights both the considerable use of high-dose opioids for non-malignant pain and their apparent association with adrenal suppression, demonstrating the need for formal guidelines to aid recognition and diagnosis.

scholarly journals Current status of opioid epidemic in the United Kingdom and strategies for treatment optimisation in chronic pain

2020 ◽  
Author(s):  
Aziza Alenezi ◽  
Asma Yahyouche ◽  
Vibhu Paudyal
Keyword(s):  
Chronic Pain ◽  
United Kingdom ◽  
The United States ◽  
Opioid Use Disorder ◽  
Morbidity And Mortality ◽  
Current Status ◽  
Opioid Epidemic ◽  
Opioid Use ◽  
The United Kingdom ◽  
Treatment Optimisation

AbstractThe increase in opioid prescriptions in the United States has been accompanied by an increase in misuse as well as overdose and toxicity related morbidity and mortality. However, the extent of the increased opioid use, including misuse in the United Kingdom, currently remains less debated. Recent studies in the United Kingdom have shown a rise in opioid use and attributed deaths, particularly in areas with higher deprivation. There are also large variations amongst the devolved nations; Scotland has the highest drug-related deaths and year-on-year increase within Europe. Better clinical guidelines that can enable person-centred management of chronic pain, medicines optimisation, and early diagnosis and treatment of opioid use disorder are crucial to addressing opioid-related morbidity and mortality in the United Kingdom.

scholarly journals Medical Marijuana and Opioids (MEMO) Study: protocol of a longitudinal cohort study to examine if medical cannabis reduces opioid use among adults with chronic pain

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e043400
Author(s):  
Chinazo O Cunningham ◽  
Joanna L Starrels ◽  
Chenshu Zhang ◽  
Marcus A Bachhuber ◽  
Nancy L Sohler ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cohort Study ◽  
Adverse Events ◽  
Opioid Analgesic ◽  
Monitoring Program ◽  
Cannabis Use ◽  
People Living With Hiv ◽  
Medical Cannabis ◽  
Opioid Use ◽  
Analgesic Use

IntroductionIn the USA, opioid analgesic use and overdoses have increased dramatically. One rapidly expanding strategy to manage chronic pain in the context of this epidemic is medical cannabis. Cannabis has analgesic effects, but it also has potential adverse effects. Further, its impact on opioid analgesic use is not well studied. Managing pain in people living with HIV is particularly challenging, given the high prevalence of opioid analgesic and cannabis use. This study’s overarching goal is to understand how medical cannabis use affects opioid analgesic use, with attention to Δ9-tetrahydrocannabinol and cannabidiol content, HIV outcomes and adverse events.Methods and analysesWe are conducting a cohort study of 250 adults with and without HIV infection with (a) severe or chronic pain, (b) current opioid use and (c) who are newly certified for medical cannabis in New York. Over 18 months, we collect data via in-person visits every 3 months and web-based questionnaires every 2 weeks. Data sources include: questionnaires; medical, pharmacy and Prescription Monitoring Program records; urine and blood samples; and physical function tests. Using marginal structural models and comparisons within participants’ 2-week time periods (unit of analysis), we will examine how medical cannabis use (primary exposure) affects (1) opioid analgesic use (primary outcome), (2) HIV outcomes (HIV viral load, CD4 count, antiretroviral adherence, HIV risk behaviours) and (3) adverse events (cannabis use disorder, illicit drug use, diversion, overdose/deaths, accidents/injuries, acute care utilisation).Ethics and disseminationThis study is approved by the Montefiore Medical Center/Albert Einstein College of Medicine institutional review board. Findings will be disseminated through conferences, peer-reviewed publications and meetings with medical cannabis stakeholders.Trial registration numberClinicalTrials.gov Registry (NCT03268551); Pre-results.

scholarly journals SUN-308 Central Adrenal Insufficiency Is Rare in Adults with Prader-Willi Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anna G W Rosenberg ◽  
Karlijn Pellikaan ◽  
Christine Poitou ◽  
Anthony P Goldstone ◽  
Charlotte Hoybye ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Cortisol Level ◽  
Multiple Dose ◽  
Tolerance Test ◽  
Adrenal Crisis ◽  
Pituitary Hormone ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Baseline Cortisol ◽  
Central Adrenal Insufficiency

Abstract Introduction: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. This is partly due to the variable results of the synacthen test, compared with the more robust metyrapone test (MTP) and insulin tolerance test (ITT). In some countries, patients with PWS receive stress-dose corticosteroids during physical or psychological stress. Side effects of frequent corticosteroids use are weight gain, osteoporosis, diabetes mellitus and hypertension, already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity or even mortality. To prevent over- and undertreatment with corticosteroids, we assessed the prevalence of CAI in a large international cohort of adults with this rare disorder. Methods: The hypothalamic-pituitary-adrenal axis was tested in 81 adult subjects (55 Dutch, 10 British, 10 French, 6 Swedish) with genetically confirmed PWS. For multiple-dose MTP, 11-deoxycortisol >230 nmol/L (7.6 g/dL) was considered sufficient. For Dutch, French and Swedish patients who underwent ITT, cortisol >500 nmol/L (18.1 μg/dL) was considered sufficient. For British patients cortisol >450 nmol/L (16.3 μg/dL) was considered sufficient, as this center used a different assay. Additionally, we reviewed medical files of 645 adults with PWS from Italy (240), France (110), the Netherlands (110), Australia (60), Spain (45), Sweden (38) and the United Kingdom (42) for symptoms of hypocortisolism/adrenal crisis during surgery. Results: Data on 81 adult subjects (46 males and 35 females), median age (range) 25.2 yr (18.0 – 55.5), median BMI (range) 29.1 kg/m2 (20.0 – 62.0), with genetically confirmed PWS were collected. 33 subjects (41%) were using GH treatment since childhood. Multiple-dose MTP was performed in 45 subjects and ITT in 36 subjects. Both tests were well tolerated by all individuals. CAI was excluded in 80 of 81 patients. One patient with a peak cortisol level of 494 nmol/L (just below cut-off level of 500 nmol/L) was prescribed hydrocortisone for use during physical stress. There was no relation between baseline cortisol and ITT/multiple-dose MTP results. Even patients with a low baseline cortisol level (lowest: 102.0 nmol/L) had normal responses. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative corticosteroids treatment. None of them displayed any features of hypocortisolism/adrenal crisis. Conclusions: CAI is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing corticosteroids stress-doses in adults with PWS. Funding: CZ foundation.

Silent, isolated ACTH deficiency in malignant melanoma patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 14 (5) ◽  
pp. e241981
Author(s):  
Ansgar Heck ◽  
Anna K Winge-Main
Keyword(s):  
Malignant Melanoma ◽  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Adrenal Crisis ◽  
Suspected Case ◽  
Acth Deficiency ◽  
Melanoma Patients ◽  
Central Adrenal Insufficiency

Treatment with immune checkpoint inhibitors (ICI) has drastically improved the prognosis for melanoma patients, but immune-mediated adverse events can occur in any organ, including the pituitary. In ICI-induced hypophysitis, lymphocytic infiltration and hypersensitivity reactions cause headache and pituitary deficiency. Most cases with ICI-induced hypophysitis develop central adrenal insufficiency. Here, we describe three patients treated with anticytotoxic T-lymphocyte-associated protein 4 (ipilimumab) for metastatic malignant melanoma: case 1 was asymptomatic when hypocortisolism was suspected; case 2 had symptoms of hypocortisolism and suspected severe systemic infection; case 3 had unspecific fatigue. In all cases, routine cortisol measurements and clinical suspicion (cases 2 and 3) led to the diagnosis of adrenocortical hormone (ACTH) deficiency and thereby central adrenal insufficiency. Undiagnosed and untreated, central adrenal insufficiency results in adrenal crisis. In patients treated with ICI, particularly, ipilimumab, hypophysitis and ACTH deficiency must be considered if morning cortisol is low or unspecific clinical symptoms of hypocortisolism are present.

scholarly journals Reexamining opioid addiction as a co-occurring disorder: A clinical perspective on the “Chronic Pain Paradox”

2021 ◽  
pp. 26
Author(s):  
Keyword(s):  
Mental Health ◽  
Chronic Pain ◽  
Medical Condition ◽  
Opioid Analgesics ◽  
Psychological Trauma ◽  
Opioid Epidemic ◽  
Care Providers ◽  
Medical Providers ◽  
Opioid Use ◽  
Integrated Healthcare

The use of opioids as an anodyne for chronic pain was not prevalent before the 1980s1. Students in medical schools had learnt to avoid prescribing opioids, considered highly addictive for treatment of non-malignant chronic pain1. Yet, from the early 1990s, prescription opioids emerged as a widely accepted method of treating chronic pain and palliative care2. Previously, chronic pain was treated in multidisciplinary clinics with coordinated care which included physical exams, medication management, biopsychosocial evaluation, cognitive behavioral treatment, physical therapy, and occupational therapy2. Starting in the early 1990’s, under dubious antecedence, opioid analgesics were promoted as the proprietary remedy for chronic pain and received endorsement and support from care providers across the United States3. Non-cancerous chronic pain, as a phenomenon, was thus elevated to an ailment or a medical condition by its own right from its erstwhile status as a corollary to another medical condition. This led to an increase in opioid analgesic prescriptions, followed by a wide-ranging abuse by patients, converting opioid use disorder (OUD) to a problem of epidemic proportions4. Apart from the legal course of action initiated against Perdue Pharma, in 2020, the maker and distributor of Oxycontin that resulted in a $3.8 billion lawsuit settlement, in which Perdue Pharma pleaded guilty; since the recognition of this problem, new measures have been adopted to counter the opioid epidemic by clinicians. There has been a significant shift towards circumvention by physicians prescribing opioids for non-cancerous chronic pain. In a few instances, providers have resorted to putting a temporary moratorium on prescribing opioids to all non-cancerous chronic pain cases5. The Center for Disease Control (CDC) and various state agencies have passed protocols, installed prescription monitoring programs (PMPs), and created taskforces to rein in flagrant prescription practices by medical providers. Mental health counseling and alternative, non-prescriptive pain management procedures have been reintroduced in treatment as a new way of approaching the problem6,7. The Substance Abuse and Mental Health Administration (SAMHSA) have suggested hybrid programs such as medically assisted treatment (MAT) which utilizes the medical approach of prescribing slow releasing drugs with concomitant counseling for patients, as one of the best practices to intervene with opioid use disorders8. An integrated healthcare approach brought primary care physicians, nurses, and physician’s assistants together with addiction counselors and social workers to coordinate and implement treatment for opioid misuse9,10. These new approaches are laudable and effective, yet we argue, in this paper, for ascertaining the treatment of chronic pain as a co-occurring disorder to addiction. While acknowledging the two original transgressions of the opioid epidemic: a) the delineation and decontextualization of chronic pain as an independent medical phenomenon, and b) the over-prescription of opioid analgesics to treat chronic pain; we argue that recognizing chronic pain as a co-occurring disorder with addiction and psychological trauma could help providers contextualize it better, leading to an improved treatment protocol. Over last two decades, persistent over-prescribing has set forth a culture of righteous demand among patients to obtain opioids and receive instant pharmacological sedation as an antidote to chronic pain. This culture, which may have taken roots, could cause resistance among chronic pain patients towards any change to alternative treatment plans. This could frustrate medical providers and reformers as they usher in the new treatment procedures promulgated by SAMHSA and the CDC. Thus, a co-occurring diagnostic framework could provide a pathway to better understand this treatment dilemma. The co-occurring disorder lens of diagnosis could provide a pathway to understand this treatment dilemma. In this paper, we do a critical, non-systematic review of existing literature that explores the intersection of chronic pain and OUD to make a case that these issues should be treated as co-occurring disorders and not as disconnected, independent phenomenon. We review the scope of the problem and provide an analysis of the complex relationship between chronic pain and usage of opioids from both pharmacological and psychological viewpoints and explore the challenges to treatment. We take an ecological and exchange theory perspective to understand the co-occurrence of pain and opioids addiction from a trauma-informed lens to unpack the complexity that OUD poses in juxtaposition to chronic pain. Furthermore, we explore the strategies to develop an integrated healthcare workforce from a co-occurring disorder perspective. Furthermore, we explain the context of co-occurring pain, addiction, and psychological trauma and identify the pertinent questions that such co-occurrences pose for treatment protocols. We draw our argument from a critical review of the literature as well as the incidence and prevalence of OUD.

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