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JAMA Surgery Oct 2022Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal...
IMPORTANCE
Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered operative techniques and indications.
OBJECTIVE
To develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy.
EVIDENCE REVIEW
A multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included.
FINDINGS
Patients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics.
CONCLUSIONS AND RELEVANCE
Twenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Cosyntropin; Glucocorticoids; Humans; Hydrocortisone; Pheochromocytoma; Surgeons
PubMed: 35976622
DOI: 10.1001/jamasurg.2022.3544 -
The Cochrane Database of Systematic... Jul 2015This is an updated version of the original Cochrane review published in Issue 8, 2011, on 'Drug therapy for treating post-dural puncture headache'.Post-dural puncture... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 8, 2011, on 'Drug therapy for treating post-dural puncture headache'.Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture, an invasive procedure frequently performed in the emergency room. Numerous pharmaceutical drugs have been proposed to treat PDPH but there are still some uncertainties about their clinical effectiveness.
OBJECTIVES
To assess the effectiveness and safety of drugs for treating PDPH in adults and children.
SEARCH METHODS
The searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 6), MEDLINE and MEDLINE in Process (from 1950 to 29 July 2014), EMBASE (from 1980 to 29 July 2014) and CINAHL (from 1982 to July 2014). There were no language restrictions.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) assessing the effectiveness of any pharmacological drug used for treating PDPH. Outcome measures considered for this review were: PDPH persistence of any severity at follow-up (primary outcome), daily activity limited by headache, conservative supplementary therapeutic option offered, epidural blood patch performed, change in pain severity scores, improvements in pain severity scores, number of days participants stay in hospital, any possible adverse events and missing data.
DATA COLLECTION AND ANALYSIS
Review authors independently selected studies, assessed risk of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because the included studies assessed different sorts of drugs or different outcomes. We performed an intention-to-treat (ITT) analysis.
MAIN RESULTS
We included 13 small RCTs (479 participants) in this review (at least 274 participants were women, with 118 parturients after a lumbar puncture for regional anaesthesia). In the original version of this Cochrane review, only seven small RCTs (200 participants) were included. Pharmacological drugs assessed were oral and intravenous caffeine, subcutaneous sumatriptan, oral gabapentin, oral pregabalin, oral theophylline, intravenous hydrocortisone, intravenous cosyntropin and intramuscular adrenocorticotropic hormone (ACTH).Two RCTs reported data for PDPH persistence of any severity at follow-up (primary outcome). Caffeine reduced the number of participants with PDPH at one to two hours when compared to placebo. Treatment with caffeine also decreased the need for a conservative supplementary therapeutic option.Treatment with gabapentin resulted in better visual analogue scale (VAS) scores after one, two, three and four days when compared with placebo and also when compared with ergotamine plus caffeine at two, three and four days. Treatment with hydrocortisone plus conventional treatment showed better VAS scores at six, 24 and 48 hours when compared with conventional treatment alone and also when compared with placebo. Treatment with theophylline showed better VAS scores compared with acetaminophen at two, six and 12 hours and also compared with conservative treatment at eight, 16 and 24 hours. Theophylline also showed a lower mean "sum of pain" when compared with placebo. Sumatriptan and ACTH did not show any relevant effect for this outcome.Theophylline resulted in a higher proportion of participants reporting an improvement in pain scores when compared with conservative treatment.There were no clinically significant drug adverse events.The rest of the outcomes were not reported by the included RCTs or did not show any relevant effect.
AUTHORS' CONCLUSIONS
None of the new included studies have provided additional information to change the conclusions of the last published version of the original Cochrane review. Caffeine has shown effectiveness for treating PDPH, decreasing the proportion of participants with PDPH persistence and those requiring supplementary interventions, when compared with placebo. Gabapentin, hydrocortisone and theophylline have been shown to decrease pain severity scores. Theophylline has also been shown to increase the proportion of participants that report an improvement in pain scores when compared with conventional treatment.There is a lack of conclusive evidence for the other drugs assessed (sumatriptan, adrenocorticotropic hormone, pregabalin and cosyntropin).These conclusions should be interpreted with caution, due to the lack of information to allow correct appraisal of risk of bias, the small sample sizes of the studies and also their limited generalisability, as nearly half of the participants were postpartum women in their 30s.
Topics: Adrenocorticotropic Hormone; Adult; Amines; Analgesics; Blood Patch, Epidural; Caffeine; Cyclohexanecarboxylic Acids; Female; Gabapentin; Humans; Hydrocortisone; Male; Middle Aged; Pain Measurement; Post-Dural Puncture Headache; Randomized Controlled Trials as Topic; Spinal Puncture; Sumatriptan; Theophylline; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 26176166
DOI: 10.1002/14651858.CD007887.pub3 -
American Family Physician Apr 2014Primary adrenal insufficiency, or Addison disease, has many causes, the most common of which is autoimmune adrenalitis. Autoimmune adrenalitis results from destruction...
Primary adrenal insufficiency, or Addison disease, has many causes, the most common of which is autoimmune adrenalitis. Autoimmune adrenalitis results from destruction of the adrenal cortex, which leads to deficiencies in glucocorticoids, mineralocorticoids, and adrenal androgens. In the United States and Western Europe, the estimated prevalence of Addison disease is one in 20,000 persons; therefore, a high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis (i.e., shock, hypotension, and volume depletion). The clinical manifestations before an adrenal crisis are subtle and can include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving. Cortisol levels decrease and adrenocorticotropic hormone levels increase. When clinically suspected, patients should undergo a cosyntropin stimulation test to confirm the diagnosis. Treatment of primary adrenal insufficiency requires replacement of mineralocorticoids and glucocorticoids. During times of stress (e.g., illness, invasive surgical procedures), stress-dose glucocorticoids are required because destruction of the adrenal glands prevents an adequate physiologic response. Management of primary adrenal insufficiency or autoimmune adrenalitis requires vigilance for concomitant autoimmune diseases; up to 50% of patients develop another autoimmune disorder during their lifetime.
Topics: Addison Disease; Adrenal Glands; Diagnosis, Differential; Hormone Replacement Therapy; Humans
PubMed: 24695602
DOI: No ID Found -
Journal of the Endocrine Society Apr 2021The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH) is considered to be ≥18 μg/dL (500 nmol/L). This threshold is based on older serum cortisol...
CONTEXT
The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH) is considered to be ≥18 μg/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response.
OBJECTIVE
To calculate serum cortisol cutoff values for adrenocorticotropic hormone (ACTH) stimulation testing with newer specific cortisol assays.
METHODS
Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS.
RESULTS
A total of 110 patients were evaluated. Using 18 μg/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 μg/dL. For 30-minute values, new cutoffs were 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS. Baseline cortisol <2 μg/dL was predictive of subnormal stimulated cortisol values.
CONCLUSION
To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14 to 15 μg/dL depending on the assay used (instead of the historical value of 18 μg/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.
PubMed: 33768189
DOI: 10.1210/jendso/bvab022 -
The Journal of Clinical Endocrinology... Mar 2016Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF).
CONTEXT
Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF).
OBJECTIVE
The objective of the study was to evaluate the diagnostic utility of SFF responses during a 250-μg CST.
DESIGN
We recruited healthy volunteers (HV; n = 27), patients with primary and secondary adrenal insufficiency (n = 19 and n = 24, respectively), and subjects with Child-Pugh class A cirrhosis (CH; n = 15). Each received 250 μg cosyntropin with measurement of ACTH and corticosteroid binding globulin (CBG) at time 0 and TF and SFF at 0, 30, and 60 minutes. Salivary cortisol was measured at all time points in CH subjects.
RESULTS
Peak SFF and TF were significantly higher in HVs vs both AI groups (P < .05). Peak SFF and TF (6.8 μg/dL vs 2.2 μg/dL; [188 nmol/L vs 62 nmol/L]; P < .01) were significantly higher in the secondary adrenal insufficiency vs primary adrenal insufficiency patients. The optimal peak SFF criterion to identify adrenal insufficiency patients vs HV was 0.9 μg/dL (25 nmol/L) (sensitivity of 95%, specificity of 100%). Mean CBG and albumin levels were similar among all four groups. CH patients had a higher peak SFF than HV (2.4 vs 2.0 μg/dL; P = .02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (rs = 0.84, P = .005). CBG levels were similar among the groups.
CONCLUSION
We provide normative data for SFF values in HV and AI during the CST. Normal CBG levels in mild cirrhosis did not affect the interpretation of the CST.
Topics: Addison Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Cosyntropin; Female; Hepatitis, Viral, Human; Humans; Hydrocortisone; Liver Cirrhosis; Male; Middle Aged; Saliva; Transcortin
PubMed: 26647150
DOI: 10.1210/jc.2015-2285 -
The Lancet. Neurology Jan 2017Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone.
METHODS
In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27.
FINDINGS
Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1-24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment.
INTERPRETATION
Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up.
FUNDING
The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich.
Topics: Anticonvulsants; Cosyntropin; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Female; Follow-Up Studies; Hormones; Humans; Infant; Male; Prednisolone; Spasms, Infantile; Treatment Outcome; Vigabatrin
PubMed: 27838190
DOI: 10.1016/S1474-4422(16)30294-0 -
Contact in Context 2021Intra-lot and inter-lot variability in cosyntropin was detected in the DQS using Fourier transform near-infrared spectrometry. One vial of 12 sampled from Sandoz...
Intra-lot and inter-lot variability in cosyntropin was detected in the DQS using Fourier transform near-infrared spectrometry. One vial of 12 sampled from Sandoz Lot0200062 appeared 6.9 SDs from the center of the rest of the vials, and another was 4.3 SDs away. Spectra of 102 vials from 7 lots in the library clustered in two groups (p=0.02).
PubMed: 35035309
DOI: 10.6084/m9.figshare.17363048 -
Diagnostics (Basel, Switzerland) May 2023The diagnosis of adrenal insufficiency (AI) requires a high index of suspicion, detailed clinical assessment including detailed drug history, and appropriate laboratory... (Review)
Review
The diagnosis of adrenal insufficiency (AI) requires a high index of suspicion, detailed clinical assessment including detailed drug history, and appropriate laboratory evaluation. The clinical characteristics of adrenal insufficiency vary according to the cause, and the presentation may be myriad, e.g. insidious onset to a catastrophic adrenal crisis presenting with circulatory shock and coma. Secondary adrenal insufficiency (SAI) often presents with only glucocorticoid deficiency because aldosterone production, which is controlled by the renin angiotensin system, is usually intact, and rarely presents with an adrenal crisis. Measurements of the basal serum cortisol at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) remain the initial tests of choice. The cosyntropin stimulation (short synacthen) test is used for the confirmation of the diagnosis. Newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of AI. The salivary cortisol test is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels such as pregnancy. Children and infants require lower doses of cosyntropin for testing. 21-hydoxylase antibodies are routinely evaluated to rule out autoimmunity, the absence of which would require secondary causes of adrenal insufficiency to be ruled out. Testing the hypothalamic-pituitary-adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of AI. Cancer treatment with immune checkpoint inhibitors (ICI) is an emerging cause of both primary AI and SAI and requires close follow up. Several antibodies are being implicated, but more clarity is required. We update the diagnostic evaluation of AI in this evidence-based review.
PubMed: 37238296
DOI: 10.3390/diagnostics13101812 -
Frontiers in Endocrinology 2021Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of... (Review)
Review
Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.
Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Adrenal Insufficiency; Aldosterone; Diagnostic Techniques, Endocrine; Humans; Hydrocortisone
PubMed: 34512551
DOI: 10.3389/fendo.2021.720769 -
Medicina 2021After a stressful event, adaptative mechanisms are carried out to support vital functions. Hypothalamic-pituitary-adrenal axis plays a key role in stress response... (Review)
Review
After a stressful event, adaptative mechanisms are carried out to support vital functions. Hypothalamic-pituitary-adrenal axis plays a key role in stress response regulating metabolism, cardiovascular function and immune system. This review addresses pathophysiological changes of the adrenal axis during critical illness, recognizing limitations of methods applied for its evaluation in this special context and defining indications for corticosteroid replacement in critically ill patients. The concept of relative adrenal insufficiency should be abandoned; cosyntropin stimulation test should not be performed for diagnosis of adrenal insufficiency in critical illness nor for establishing the need of treatment.
Topics: Adrenal Insufficiency; Critical Illness; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 33611247
DOI: No ID Found