Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay

Author(s):  
Kyle P. McNerney ◽  
Ana Maria Arbeláez

Abstract Objectives The diagnosis of adrenal insufficiency relies on clear cut-offs and accurate measurement of cortisol levels. Newer monoclonal antibody assays may increase the rate of diagnosis of adrenal insufficiency if traditional cortisol cut-off levels <18 mcg/dL (500 nmol/L) are applied. Determine if the rate of diagnosis of adrenal insufficiency using a 1 mcg Cosyntropin stimulation test varied with the change in cortisol assay from a polyclonal to a monoclonal antibody assay. Methods Cortisol levels obtained during the 1 mcg Cosyntropin stimulation test performed in the last semester of 2016 using a polyclonal antibody cortisol assay were compared to tests performed using a monoclonal antibody cortisol assay during the first semester of 2017. Cosyntropin tests included cortisol values obtained at baseline, 20 min and 30 min after IV administration of 1 mcg Cosyntropin. Peak cortisol cut-off value <18 mcg/dL was used to diagnose adrenal insufficiency. Results Stimulated cortisol values after 1 mcg Cosyntropin using the monoclonal assay in 2017 (n=38) were significantly lower (33%) compared to those obtained with the polyclonal assay in 2016 (n=27) (p-value <0.001). The number of passing tests with a peak cortisol value >18 mcg/dL fell from 74% in 2016 (20 out of 27 tests) to 29% in 2017 (11 out of 38 tests). Conclusions The change in cortisol assay substantially increased the number of patients diagnosed with adrenal insufficiency after 1 mcg Cosyntropin stimulation testing. Standardization of cortisol assays and diagnostic criteria is critical for the accurate diagnosis of adrenal insufficiency.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rama Priyanka Nagireddi ◽  
Htet Htet Win ◽  
Sarah Wagstaff ◽  
Moira Neal ◽  
Kathryn Friedman ◽  
...  

Abstract Introduction: Mild Traumatic Brain Injury (mTBI) is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. We reviewed the utility of the fixed dose Glucagon Stimulation Test (GST) compared with the high dose Cosyntropin Stimulation test (CST) for hypothalamic-pituitary-adrenal (HPA) reserve over time in these patients with mTBI. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; age and BMI, 31.5±7.0 years and 30.4±6.2, mean±SD, respectively) for baseline pituitary hormone levels and cortisol response to the CST. In 22 subjects growth hormone and cortisol responses to GST were tested at baseline (Year 0). Follow-up testing was done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 10 subjects in Year 3 and 5 subjects in Year 4. The same baseline data were obtained for 14 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,12 male; age and BMI 34.4±6.8 years and 30.5±4.9, mean±SD, respectively). Cortisol cutoffs of &lt;18 mcg/dL with the CST and &lt;9.0 mcg/dL with the GST were used for the diagnosis of adrenal insufficiency. Results: Secondary adrenal insufficiency (AI), likely partial, was identified during this study on 6 occasions: 3/22 subjects at Year 0, 1/18 at Year 1, 0/13 at Year 2, 1/10 at Year 3 and 1/5 at Year 4. Two baseline subjects with AI reverted to normal in Years 1-3, one relapsed in Year 4 and a third had no further testing. Correlations of the cortisol levels from GST vs the 60-minute cortisol from CST were significant at Year 0 (n=22, r=0.553, p=0.008) and at Year 1 (n=18, r=0.802, p&lt;0.0001). Due to decreased numbers, there were no significant correlations at Years 2 through 4. Similar correlations were obtained using the 30-minute CST values. However, the CST cortisol value predicted the low GST value in only 2/6 subjects. The mean GST cortisol levels and 60-minute CST cortisol levels for subjects at each year were not significantly different over Years 0 through 4 based on ANOVA analyses (CST: F=1.519, p= 0.206; GST: F= 0.796, p=0.532). Conclusions: Secondary adrenal insufficiency, likely partial, related to mTBI was detected by GST on 6 occasions (twice in one patient) over 4 years of observation. GST can provide useful information about HPA axis reserve, and appears to be more reliable than CST. Identification of potential secondary adrenal insufficiency using the GST in Veterans with mTBI can provide a beneficial combined test for these patients when other testing is not feasible.


2020 ◽  
Vol 26 (11) ◽  
pp. 1291-1297 ◽  
Author(s):  
Taoran Li ◽  
Diane Donegan ◽  
W. Michael Hooten ◽  
Irina Bancos

Objective: Opioid-induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due to suppression of the hypothalamic-pituitary-adrenal axis. Our objective was to describe the clinical manifestations, biochemical presentation, and clinical course of OIAI. Methods: A retrospective study of adults diagnosed with OIAI between 2006 and 2018 at an academic center. Opioid daily dose was converted into morphine milligram equivalents (MMEs). Results: Forty patients (women, n = 29 [73%]) taking chronic opioids at a daily median MME dose of 105 (60 to 200) mg and median duration of 60 (3 to 360) months were diagnosed with OIAI. Patients reported fatigue (n = 29, 73%), musculoskeletal pain (n = 21, 53%), and weight loss (n = 17, 53%) for a median of 12 (range, 1 to 132) months prior to diagnosis, and only 7.5% (n = 3) of patients were identified with OIAI through case detection. Biochemical diagnosis of OIAI was based on ( 1) low morning cortisol, baseline adrenocorticotropic hormone and/or dehydroepiandrosterone sulfate in 59% (n = 26) of patients or ( 2) abnormal cosyntropin stimulation test in 41% (n = 14) of patients. With glucocorticoid replacement, 16/23 (70%) patients with available follow-up experienced improvement in symptoms. Opioids were tapered or discontinued in 15 patients, of whom 10 were followed for adrenal function and of which 7 (70%) recovered from OIAI. Conclusion: Minimum daily MME in patients diagnosed with OIAI was 60 mg. OIAI causes significant morbidity, and recognition requires a high level of clinical suspicion. Appropriate glucocorticoid treatment led to improvement of symptoms in 70%. Resolution of OIAI occurred following opioid cessation or reduction. Abbreviations: ACTH = adrenocorticotropic hormone; CST = cosyntropin stimulation test; DHEAS = dehydroepiandrosterone sulfate; HPA = hypothalamic-pituitary-adrenal; MME = morphine milligram equivalent; OIAI = opioid-induced adrenal insufficiency


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fiorella Sotomayor Villanueva ◽  
Huong Nguyen

Abstract Introduction: Cushing’s syndrome (CS) is a collection of signs and symptoms caused by hypercortisolism that results from endogenous or exogenous glucocorticoid excess. It is associated with increased morbidity and mortality from musculoskeletal, metabolic, thrombotic, infectious and cardiovascular complications. The most common cause of CS today is the use of corticosteroid medications. It′s reported that more than 10 million American receive pharmacological doses of glucocorticoids each year. Case reports have shown that CS can be caused by non-systemic use of corticosteroids. Clinical case: A 53-year-old patient with past medical history of osteoarthritis who presented to outpatient endocrinology office for new onset facial swelling of 2 months. His PCP had attributed it to adverse effect of recent neck glucocorticoid injections and treated him with prednisone for 7 days without any relief. Subsequently, he was referred to Endocrinology due to concern about Cushing′s syndrome. The patient reported associated easy bruising and decreased libido. On further questioning, patient mentioned he had been receiving several epidural steroid injections in the neck, shoulders and back in the past. Per record review, from June to November 2018, he had received multiple triamcinolone and dexamethasone injections as follows: 10mg dexamethasone in each C4-5, C5-6 and C6-7 facet joints; 5mg triamcinolone injections in the right C4-5, C6-C7, left C4-5, C6 and C7, and 40mg of triamcinolone in C7-T1. The patient also reported he had multiple injections in 2019, but these records were not available. Physical exam showed hypertension, facial plethora, and scattered bilateral arm ecchymosis. Laboratory study showed hyperglycemia. Given suspicion for CS, further workup, including morning serum cortisol, ACTH, and 24-hour urine cortisol were ordered, which were 0.5 ug/dl (6.2-19.4 ug/dl), 4.3 pg/ml (7.2-63.3 pg/ml) and &lt;2 ug/24 hours (5-64 ug/24 hours) respectively, suggesting iatrogenic CS secondary to corticoid steroid injection. Also, given that the patient reported lightheadedness, and decreased libido, cosyntropin stimulation test and free testosterone, FSH and LH were ordered to rule out adrenal insufficiency and hypogonadism respectively. Hypogonadism was ruled out, however, cosyntropin stimulation test showed peak cortisol of 12 and 16 mcg/dL at 30 and 60 minutes (&gt;18 mcg/dL), suggesting adrenal insufficiency, due to suppression of endogenous cortisol production from exogenous glucocorticoid use. Patient was started on hydrocortisone and all glucocoirticoid injections were stopped. Conclusions: Many different non-systemic corticosteroid administrations can cause iatrogenic Cushing’s Syndrome, and therefore, physicians should be thoughtful when prescribing steroids regardless of administration form.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lucinda Gruber ◽  
Sanjeev Nanda ◽  
Todd B Nippoldt ◽  
Alice Y Chang ◽  
Irina Bancos

Abstract Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement. Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol &lt; 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use. Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients achieved hypoglycemia &lt;=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH &lt; 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was &gt;=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment. Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency. 1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506. 2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.


Author(s):  
Didem Turgut ◽  
Serhan Vahit Pişkinpaşa ◽  
Havva Keskin ◽  
Kemal Agbaht ◽  
Ezgi Coşkun Yenigün

Objective: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. Methods: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 μg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. Results: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients’ stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). Conclusion: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.


2005 ◽  
Vol 33 ◽  
pp. A75
Author(s):  
Zachariah Thomas ◽  
Keri Bicking ◽  
Steven A Blau ◽  
Jennifer Bui ◽  
Alicia M Mohr ◽  
...  

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