Adrenocorticotropic Hormone Stimulation Research Articles

MON-179 Association Between Long-Term Prednisolone Induced Adrenal Insufficiency and Polymorphisms in the Glucocorticoid Receptor Gene

OBJECTIVE: Several biomarkers for glucocorticoid (GC) sensitivity have been proposed relevant for the inter-individual variation seen in treatment response and side effects to GC treatment. Four single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene have been associated with increased (Bcl1 and N363S) or decreased (9β and ER23/23EK) GC sensitivity. We investigated the influence of these proposed biomarkers for GC sensitivity on GC-induced adrenal insufficiency.SUBJECTS AND METHODS: We included 239 patients receiving long-term prednisolone treatment for rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) / giant cell arteritis (GCA), or after renal transplantation (RTx). Four GR gene SNPs (Bcl1 rs41423247; 9β rs6198; N363S rs56149945; ER22/23EK rs6189 + rs6190) were sequenced by Sanger sequencing. Adrenal function was evaluated by a 250 µg corticotropin stimulation test. To compare allele frequencies with background population, two control groups were generated from two regional whole-genome databases. We downscaled each genome dataset to 239 individuals/group to balance statistical analysis.RESULTS: In total 239 patients were genotyped and 178 of these (RA n=103, PMR/GCA n=47, RTx n=28) treated with a median current dose of 5 mg prednisolone/day (interquartile range 5-7 mg) and a median treatment duration of 48 months (interquartile range 22-111 months) completed the corticotropin test. Seventy-three (41%, CI95%: 34-48%) patients had an insufficient response to the corticotropin test. Neither the risk of adrenal insufficiency, unstimulated nor stimulated P-cortisol levels were directly associated with any of the GR SNPs. However, for both insensitive SNPs 9β and ER23/23EK the effect of current prednisolone dose on stimulated P-cortisol was smaller (higher dose did not suppress the cortisol level as much) in carriers vs. non-carriers (p=0.035 and p=0.0075). The same sensitivity-associated tendency was seen for the N363S, but not the Bcl1 SNP. The Bcl1 SNP occurred more frequently in our cohort compared with control groups (63% vs. 40%, p<0.0001). The same trend was seen for the other sensitive but less frequent SNP N363S. The 9β SNP also occurred more frequently in our cohort (18% vs. 13%, p=0.029), but depending on regional sub cohorts in one control group.CONCLUSION: The GR SNPs did not directly associate to the risk of adrenal insufficiency, unstimulated nor stimulated cortisol levels, respectively. However, the effect of prednisolone dose on stimulated cortisol depended on the GR SNPs: Cortisol was less suppressed with higher current prednisolone dose in patients carrying the insensitive SNPs. The substantially higher frequency of the Bcl1 SNP is remarkable even with modest n=239. It questions whether there is an association between carrying the sensitive GR SNPs and inability to taper GC treatment ending up in this cohort of long-term treated patients.

Bilateral Adrenal Hemorrhage with Adrenal Insufficiency After Dalteparin Use Post HIP Athroplasties

Multiple case reports have implicated the use of heparin for deep vein thrombosis (DVT) prophylaxis with bilateral adrenal hemorrhage. Only 1 previous report has described this with the low molecular weight product, dalteparin. We report a case following bilateral hip arthroplasties. Clinical and laboratory data are presented. A 69-year-old woman underwent bilateral total hip arthroplasties with dalteparin 5,000 international units subcutaneously daily for 30 days postoperatively. The patient's past medical history was unremarkable. She was discharged 5 days post-surgery and required readmission 1 day later for epigastric pain, nausea, and vomiting. Her platelet count was 91 × 109/L (normal, 150 to 400 × 109/L). She was discharged after 4 days with pain resolution. She presented 4 weeks later with nausea and vomiting for several days. Serum sodium was 123 mmol/L (normal, 133 to 145 mmol/L), potassium was 6.0 mmol/L (normal, 3.7 to 5.3 mmol/L), total calcium was 3.37 mmol/L (normal, 2.25 to 2.80 mmol/L), creatinine was 404 μmol/L (normal, 0 to 85 μmol/L), and her platelet count was normal. On short adrenocorticotropic hormone stimulation test, baseline plasma cortisol was 123 nmol/L and the peak was 129 nmol/L. She was treated with hydrocortisone, fludrocortisone, and 0.9% saline with resolution of symptoms and normalization of electrolytes, calcium, and renal function. Computed tomography showed bilateral adrenal masses. Core needle biopsy was consistent with necrosis. There were no bleeding disorders on hematologic work 3 months later. The most likely etiology of bilateral adrenal hemorrhage was heparin-induced thrombocytopenia from dalteparin. This case highlights the importance of vigilance for the complication of bilateral adrenal hemorrhage with adrenal insufficiency in patients receiving dalteparin for DVT prophylaxis.

Hypopituitarism manifesting after invasive dental treatment in a patient with carcinoma of the tongue: a case report

BackgroundThe symptoms of hypopituitarism are not usually discussed in the clinical setting of oral surgery.Case presentationWe herein report a case of hypopituitarism that became evident after biopsy and extraction of several teeth in a 68-year-old man with tongue cancer. Three days after biopsy, the patient developed nausea and vomiting, and his serum sodium had fallen to 124 mEq/L. His serum cortisol concentration was low. Although the plasma concentration of adrenocorticotropic hormone (ACTH) was within the normal range, ACTH stimulation testing showed a lack of cortisol response. Given these findings, we suspected secondary adrenal insufficiency. To investigate the cause of secondary adrenal insufficiency, MRI of the head was performed, which revealed pituitary gland atrophy. The results of pituitary anterior lobe hormone-stimulation tests were compatible with hypopituitarism. Thirty days after biopsy, partial tongue resection was successfully performed under general anesthesia with perioperative hydrocortisone supplementation.ConclusionsWe must be aware of various signs of hypopituitarism when we perform invasive dental treatment.

Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma.

Introduction:Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion.Materials and methods:We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling.Results:Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone–renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests.Conclusions:The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.

Bilateral Aldosterone Suppression in Patients With Right Unilateral Primary Aldosteronism and Review of the Literature.

IntroductionAdrenal vein sampling (AVS) identifies unilateral primary aldosteronism but may occasionally show paradoxically low aldosterone–cortisol ratios bilaterally. Postulated reasons include venous anomalies, fluctuating aldosterone secretion, or superselective cannulation. We report our findings in patients who underwent repeat AVS and reviewed the current literature.MethodsWe performed a retrospective observational study of patients undergoing AVS in an experienced high-volume tertiary center over a 5-year period.ResultsFrom 2015 to 2019, 61 patients underwent sequential cosyntropin-stimulated AVS and all had bilateral successful cannulation (100%). Four of 61 (6.6%) patients had bilaterally low aldosterone–cortisol ratios. Three patients underwent repeat AVS, with all 3 cases demonstrating right-sided lateralization and cure of disease postadrenalectomy. Right-sided disease was also more common in other reports. This may be due to inadvertent superselective cannulation of the short right adrenal vein, resulting in sampling of the adjacent normal gland. Cortisol results cannot detect this problem. In 1 patient, computed tomography venography excluded any accessory right adrenal veins. In another patient, repeat bilateral simultaneous unstimulated AVS was done, and measurements of metanephrines aided in accurately identifying right-sided lateralization.ConclusionIn addition to technical difficulties in cannulating the right adrenal vein, we also have to avoid performing superselective cannulation inadvertently. In cases of inconclusive AVS, repeat sampling may identify patients with potentially curable unilateral primary aldosteronism. The role of corticotropin stimulation and metanephrines measurements during repeat AVS requires further study.

Adrenal Insufficiency in Children With Eosinophilic Esophagitis Treated With Topical Corticosteroids.

The aim of the study was to identify practices of gastroenterologists screening for adrenal insufficiency (AI) and report prevalence of AI in children with eosinophilic esophagitis (EoE) treated with topical corticosteroids (TCS); compare serum dehydroepiandrosterone sulfate (DHEA-S) levels to morning serum cortisol (MSC) levels as screening tool for AI. A multipart study was conducted. In part 1, a survey about screening practices for AI in children with EoE on TCS was sent to gastroenterologists belonging to a PedsGI listserv and to EoE consortia. In part 2, children with EoE on TCS for ≥6 months were prospectively screened for AI with MSC levels. For subjects with a MSC level of <10 μg/dL, a repeat MSC level and/or confirmatory adrenocorticotropic hormone (ACTH) stimulation testing was offered. AI was defined by peak serum cortisol level <18 μg/dL. In part 3, DHEA-S levels were drawn with MSC levels. Seven percent (16/238) of gastroenterologists screened for AI. Providers in EoE consortia were more likely to screen than nonconsortia providers [9/21(43%) vs 7/217(3%); P = 0.0001]. Thirty-seven children were prospectively screened for AI, and 51% (19/37) had a low MSC level. Ten patients had a low-dose ACTH stimulation test (LDST) after 1 or more low MSC levels. Five percent (2/37) of patients were diagnosed with AI. DHEA-S and MSC levels had a moderate correlation (rs = 0.44, P = 0.03). Gastroenterologists belonging to EoE consortia were more likely to screen for AI. Prevalence of AI in our prospective cohort was 5%. DHEA-S has a moderate correlation with MSC levels, but more data is required to assess utility as a screening tool for AI.

Adrenal Insufficiency Secondary to Bilateral Adrenal Hemorrhage Associated with Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of AI is critical as this disorder is a life-threatening disease that may lead to fatal outcomes if left untreated. We present a case of AI associated with APS the patient was diagnosed promptly and managed successfully. The diagnosis of APS was based on a combination of clinical features (deep venous thrombosis and pulmonary embolism) and laboratory findings (lupus anticoagulant, anticardiolipin antibody, anti-beta-2 glycoprotein-I antibody), without alternative diagnosis to explain the clinical findings. AI was diagnosed by low morning serum cortisol with elevated adrenocorticotropic hormone (ACTH) level as well as an ACTH stimulation test. A 50-year-old male presented with deep venous thrombosis of the left extremity diagnosed by compressive ultrasound, and was subsequently diagnosed with a pulmonary embolism by computed tomography angiography and treated with heparin. Two days later, he developed hypotension and bilateral flank pain, and an abdominal computed tomography scan revealed bilateral adrenal hemorrhage. Laboratory results showed a serum cortisol of 3.3 mcg/dL (stress normal, 25 to 35 mcg/dL) and ACTH of 319 pg/mL (stress normal, 128 to 218 pg/mL), consistent with primary AI. Symptoms improved quickly with hydrocortisone therapy. The patient still required glucocorticoid therapy for at least 4 years thereafter. In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high-mortality condition allows for appropriate screening and confirmatory tests leading to a prompt diagnosis and timely management.

Clinical and biochemical factors to predict biochemical adrenal insufficiency in hospitalized patients with indeterminate cortisol levels: a retrospective study

BackgroundAdrenal insufficiency (AI) in hospitalized patients is a fatal condition if left undiagnosed. Most patients may require an adrenocorticotropic hormone (ACTH) stimulation test to facilitate AI diagnosis. We aim to identify simple biochemical and clinical factors and derive a predictive model to help identify hospitalized patients with biochemical AI who have indeterminate 0800 h serum cortisol levels.MethodsA seven-year retrospective study was performed in a tertiary care medical center. We identified 128 inpatients who had undergone low-dose or high-dose ACTH stimulation tests. The association between biochemical AI and other factors was evaluated using a logistic regression model clustering by ACTH dose. Stepwise regression analysis was used to demonstrate the predictive model. Diagnostic performance was evaluated using ROC analysis.ResultsOf the 128 patients, 28.1% had biochemical AI. The factors associated with biochemical AI were serum random cortisol < 10 μg/dL (OR = 8.69, p < 0.001), cholesterol < 150 mg/dL (OR = 2.64, p = 0.003), sodium < 140 mmol/L (OR = 1.73, p = 0.004)). Among clinical factors, cirrhosis (OR = 9.05, p < 0.001), Cushingoid appearance in those with exogenous steroid use (OR = 8.56, p < 0.001), and chronic kidney disease (OR = 2.21, p < 0.001) were significantly linked to biochemical AI. The AUC-ROC of the final model incorporating all factors was 83%.ConclusionsThese easy-to-perform biochemical tests and easy-to-assess clinical factors could help predict biochemical AI in hospitalized patients with high accuracy. The physician should therefore have a high index of suspicion to perform dynamic tests for AI diagnosis in those who meet the proposed model criteria.

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation.

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15–98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n = 14) or non-cold exposure (controls; n = 191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissues samples were stained for cortisol using a rabbit anti-human polyclonal antibody. Cell culture: AtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other cases of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels of ACTH after 10–15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15–20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

Correlation Between Size and Function of Unilateral and Bilateral Adrenocortical Nodules: An Observational Study

OBJECTIVE. Adrenal incidentalomas occur in 5% of adults and can produce autonomous cortisol secretion that increases the risk of metabolic syndrome and cardiovascular disease. The objective of our study was to evaluate the relationship between adrenal nodule size measured on CT and autonomous cortisol secretion. SUBJECTS AND METHODS. In a prospective study of 73 patients 22-87 years old with incidentalomas, unilateral in 52 patients and bilateral in 21 patients, we measured maximum nodule diameter on CT and serum cortisol levels at 8:00 am, 60 minutes after the adrenocorticotropic hormone stimulation test, and after the dexamethasone suppression test. We also studied 34 age-, sex-, and body mass index-matched control subjects. Statistics used were Spearman correlation coefficients, t tests, ANOVA test, and multivariate analysis. RESULTS. The mean maximum diameter of unilateral nodules measured on CT was larger on the right (2.47 ± 0.98 [SD] cm) than on the left (2.04 ± 0.86 cm) (p = 0.01). In the bilateral cases, the mean diameter of the right nodules was 2.69 ± 0.93 cm compared with 2.13 ± 0.89 cm on the left (p = 0.06). Mean baseline serum cortisol level was significantly higher in the patients with incidentalomas (bilateral, 13.1 ± 4.5 mcg/dL [p < 0.001]; unilateral, 9.7 ± 3.2 mcg/dL [p = 0.019]) than in the control subjects (7.5 ± 3.6 mcg/dL). After dexamethasone suppression test, serum cortisol levels were suppressed to less than 1.8 mcg/dL in 100% of control subjects, 33% of patients with bilateral incidentalomas, and 62% of patients with unilateral incidentalomas (p < 0.001). There were significant correlations between maximum nodule diameter on CT and serum cortisol levels after the dexamethasone suppression test (ρ = 0.500; p < 0.001) and at baseline (ρ = 0.373; p = 0.003). CONCLUSION. Increasing size of adrenal nodules is associated with more severe hyper-cortisolism and less dexamethasone suppression; these cases need further evaluation and possibly surgery because of increased risks of metabolic syndrome and cardiovascular mortality.

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach.

Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA. We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided. Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises. Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.

Ectopic Cushing\u2019s syndrome associated with a pheochromocytoma in a dog: a case report

BackgroundEctopic Cushing’s syndrome (ECS) associated with malignant tumors, such as small cell lung carcinoma, bronchial carcinoids, and pheochromocytoma, has been reported in human medicine. However, ECS related to pheochromocytoma has not been reported in dogs.Case presentationAn 11-year-old castrated, male Scottish terrier was diagnosed with a left adrenal mass. Cushing’s syndrome was suspected based on clinical signs, including pot belly, polyuria, polydipsia, bilateral alopecia, recurrent pyoderma, and calcinosis cutis. Cushing’s syndrome was diagnosed on the basis of consistent clinical signs and repeated adrenocorticotropic hormone (ACTH) stimulation tests. In addition, tests for fractionated plasma metanephrine/normetanephrine suggested a pheochromocytoma. Unilateral adrenalectomy was performed after medical management with trilostane and phenoxybenzamine. Histopathology confirmed a diagnosis of pheochromocytoma without cortical lesions. After surgery, fractionated metanephrine/normetanephrine and the findings of low-dose dexamethasone suppression and ACTH stimulation tests were within the normal ranges without any medication. There were no clinical signs or evidence of recurrence and metastasis on thoracic and abdominal X-rays and ultrasonography up to 8 months after surgery.ConclusionsPheochromocytoma should be considered a differential diagnosis for dogs with Cushing’s syndrome with an adrenal tumor. A good prognosis can be expected with prompt diagnosis and surgical intervention.

Predictive Factors of Adrenal Insufficiency in Outpatients with Indeterminate Serum Cortisol Levels: A Retrospective Study.

Background and Objectives: To diagnose adrenal insufficiency (AI), adrenocorticotropic hormone (ACTH) stimulation tests may need to be performed, but those tests may not be available in some institutions. In addition, they may not be necessary for some patients. The objective of this study was to identify clinical and biochemical factors that could facilitate AI diagnosis in outpatient departments and decrease the number of unnecessary dynamic tests. Materials and Methods: This seven-year retrospective study was performed in a tertiary care medical center. A total of 517 patients who had undergone ACTH stimulation tests in the outpatient department were identified. AI was described as a peak serum cortisol level of <18 µg/dL at 30 or 60 min after stimulation. The associations between clinical factors, biochemical factors, and AI were analyzed using the Poisson regression model and reported by the risk ratio (RR). Results: AI was identified in 128 patients (24.7%). Significant predictive factors for the diagnosis of AI were chronic kidney disease (RR = 2.52, p < 0.001), Cushingoid appearance (RR = 3.44, p < 0.001), nausea and/or vomiting (RR = 1.84, p = 0.003), fatigue (RR = 1.23, p < 0.001), serum basal cortisol <9 µg/dL (RR = 3.36, p < 0.001), serum cholesterol <150 mg/dL (RR = 1.26, p < 0.001), and serum sodium <135 mEq/L (RR = 1.09, p = 0.001). The predictive ability of the model was 83% based on the area under the curve. Conclusion: The easy-to-obtain clinical and biochemical factors identified may facilitate AI diagnosis and help identify patients with suspected AI. Using these factors in clinical practice may also reduce the number of nonessential dynamic tests for AI.

Left-right differences in adrenal vein sampling for primary aldosteronism.

In adrenal venous sampling (AVS) for patients with primary aldosteronism (PA), adrenocorticotropic hormone (ACTH) stimulation generally increased the success rate. The effect of ACTH stimulation on the left-right differences of laterality diagnosis in AVS remains unclear. A total of 167 patients with PA underwent successful AVS were examined. Patients with autonomous cortisol secretion were excluded. The proportion of dominant side in AVS was compared before and after ACTH stimulation. Unilateral disease on AVS was defined as a lateralization index of more than 4, both before and after ACTH stimulation. Before ACTH stimulation, unilateral disease was more frequently observed on the right side than the left side (right 33.5% vs. left 13.8%, p < 0.01). After ACTH stimulation, unilateral disease was more frequently observed on the left side than the right side, without statistical significance (left 15.6% vs. right 10.8%, p = 0.20). Among the 56 patients who had right unilateral disease before ACTH stimulation, 17 patients (30.0%) also had right unilateral disease after ACTH stimulation. The affected side of AVS was changed from right unilateral to bilateral after ACTH stimulation in 34 (60.7%) out of 56 patients. These patients had milder PA and CT scans showed no nodular lesions on the right side. In AVS, ACTH stimulation not only decreased unilateral results but also shifted to the dominant side. Overestimation should be carefully considered when the surgical indication for the right adrenal gland was decided based on AVS results without ACTH stimulation.

Serum Morning Cortisol as A Screening Test for Adrenal Insufficiency

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI). Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC. Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value. Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol.

Влияние пептидов АКТГ 6–9 -PGP и АКТГ 4–7 -PGP на уровень тревожности у крыс при наказуемом и ненаказуемом поведении

One of the currently studied classes of regulatory peptides is melanocortins (MCs), which include biologically active substances such as adrenocorticotropic hormone (ACTH), α-, β- and γ-melanocyte stimulating hormones (MSH). ACTH fragments, like other peptides of the MC family, have pronounced neurotropic effects aimed, in particular, at stimulating the processes of learning, memory and attention. Moreover, the active ACTH center necessary for the activation of all types of melanocortin receptors is the His-Phe-Arg-Trp sequence corresponding to the ACTH6-9 fragment. In the present work, we studied a synthetic peptide, ACTH6-9-PGP, which contains a natural fragment ACTH6-9-PGP stabilized from the C-terminus with the amino acid sequence prolyl-glycyl-proline (PGP) to increase resistance to the action of carboxypeptidases. The effects of intraperitoneal administration of ACTH6-9-PGP at doses of 0.5; 5; 50; 150 and 450 µg/kg were studied once 15 minutes before the start of the experiment on studying the level of anxiety in rats using the Vogel conflict test (punished behavior) and the elevated plus maze test (unpunished behavior). The effects of ACTH6-9-PGP and its structural analogue, ACTH4-7-PGP at doses of 50, 150 and 450 µg/kg were compared using these tests. It was found that ACTH6-9-PGP in the Vogel conflict test led to an increase in the level of anxiety in rats, which manifested itself in a reduction in drinking time (in all doses) and a decrease in the number of licks (at doses of 0.5 and 150 μg/kg (p <0.01)). In the elevated plus maze test, ACTH6-9-PGP did not significantly affect rat behavior. In models of punished behavior and unpunished behavior, no effects of ACTH4-7-PGP were detected. Thus, it was found that ACTH6-9-PGP, in contrast to ACTH4-7-PGP, affects the level of anxiety in rats depending on the dose of the peptide and the model of behavior studied.

Variations in Morning Serum Cortisol Levels Based on Sex and Pubertal Status

Introduction: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency. Methods: A retrospective chart review was conducted using electronic medical records of patients seen at Children’s Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males – both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation. Results: Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2–5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2–5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001). Conclusions: These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the ­pediatric population.

Effects of breed, management and personality on cortisol reactivity in sport horses.

Sport horses need to fulfill high physical and psychological requirements during training and competition. These as well as certain conditions of modern husbandry may affect their wellbeing. Here we aimed to (1) evaluate effects of demographic and management factors as well as personality traits on stress reactivity of sport horses, (2) investigate if elite sport horses have elevated stress levels compared to amateur sport horses, and (3) assess whether different equestrian disciplines differentially influence equine adrenal cortex responsiveness. For this purpose, we visited 149 healthy elite (n = 94) and amateur (n = 54) sport horses in Switzerland and performed an adrenocorticotropic hormone (ACTH) stimulation test. Additionally, a person who was familiar with the horse completed a questionnaire about demographic and management factors and their horses’ personality traits. Linear models were calculated to assess associations between the questionnaire data and salivary cortisol 60 (T60) and 90 (T90) minutes after ACTH stimulation. While the model at T90 was not significant, post-stimulatory cortisol after 60 minutes appears most informative in line with a previous study and was significantly affected by the breed and by three management factors: “number of riders”, “hours spent outside” and “group housing” (adjusted r2 = 15%, p<0.001). Thoroughbred and Warmblood horses displayed an increased adrenal response compared to Franches-Montagnes horses. Horses with several riders had a less pronounced reaction than horses with one rider, and horses that spent more time outside had a decreased response compared to horses that were stabled most of the time. Horses living in groups showed higher post-stimulatory cortisol values than horses that were housed singly. However, no significant associations of cortisol responsiveness with personality traits were found, and neither the use as elite or as amateur sport horses nor the discipline had an effect on the cortisol response. This suggests that optimizing husbandry conditions may be more important for improving equine welfare than changing their use.

Atypical hypoadrenocorticism in a dog with chronically elevated serum alanine aminotransferase (ALT) activity

A 10-year-old male, castrated, Beagle dog was presented for subclinical, chronic elevated serum alanine aminotransferase activity on serial serum biochemistry profiles. Additionally, mild hypocholesterolaemia, hypoalbuminaemia and hyperammonaemia were identified. Microhepatica...

Seated saline infusion test in predicting subtype diagnosis of primary aldosteronism.

Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series. This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT). Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms). Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT. The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P=.023). ROC curve analysis predicted optimal cut-off PACs of 13.1ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT. Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.