Rapid Adrenocorticotropic Hormone Research Articles

Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculosis or MAC pulmonary disease, in a subject with type 2 diabetes mellitus: case report

BackgroundAddison’s disease is primary adrenal dysfunction and is characterized by decrease of cortisol level and increase of adrenocorticotropic hormone (ACTH) level. It is known that infection is one of main causes of Addison’s disease. Among various infections, tuberculous infection accounts for the majority of them. Recently the number of subjects with non-tuberculous mycobacterial infection has been increased, and the infection can also bring about Addison’s disease. Mycobacterium avium complex (MAC) pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection.Case presentationAn 83-year-old female was suspected of having adrenal failure in our outpatient care and hospitalized in our institution. There was pigmentation in her face, hands and legs, especially in auricle and nail beds in her hands and legs. In rapid ACTH load test (0.25 mg of 1–24 ACTH), cortisol level was not increased at all. An abdominal computed tomography (CT) showed swelling of both adrenal glands accompanied by calcification. QuantiFERON test was negative and mycobacterium tuberculosis complex was negative in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of adrenal tuberculosis. It is known that MAC pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. In this subject, however, anti-MAC antibody was negative and MAC-related bacteria were not detected in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of MAC pulmonary disease. Mycobacterium abscessus (Mab) was positive in bronchial lung lavage fluid culture. Based on these data, we diagnosed this subject with Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculous or MAC pulmonary disease. Decreased sodium level and increased eosinophil number were normalized and appetite loss was markedly mitigated after starting hydrocortisone therapy. A chest CT which was taken about 6 months later showed drastic reduction of consolidation in the upper lobe of the left lung although calcification in the adrenal gland was still observed.ConclusionsWe should bear in mind the possibility of Addison’s disease triggered by another type of infection rather than adrenal tuberculosis or MAC pulmonary disease.

Frequency of Adrenal Insufficiency in Patients With Hypoglycemia in an Emergency Department: A Cross-sectional Study.

ContextIn most patients presenting with hypoglycemia in emergency departments, the etiology of hypoglycemia is identified. However, it cannot be determined in approximately 10% of cases.ObjectiveWe aimed to identify the causes of unknown hypoglycemia, especially adrenal insufficiency.MethodsIn this cross-sectional study, we evaluated the etiology of hypoglycemia among patients in our emergency department with hypoglycemia (plasma glucose level < 70 mg/dL (3.9 mmol/L)] between April 1, 2016 and March 31, 2021 using a rapid adrenocorticotropic hormone (ACTH) test.ResultsThere were 528 cases with hypoglycemia included [52.1% male; median age 62 years (range 19-92)]. The majority [389 (73.7%)] of patients were using antidiabetes drugs. Additionally, 33 (6.3%) consumed alcohol; 17 (3.2%) had malnutrition; 13 (2.5%), liver dysfunction; 12 (2.3%), severe infectious disease; 11 (2.1%), malignancy; 9 (1.7%), heart failure; 4 (0.8%), insulin autoimmune syndrome; 3 (0.6%), insulinoma; 2 (0.4%) were using hypoglycemia-relevant drugs; and 1 (0.2%) suffered from non-islet cell tumor. Rapid ACTH tests revealed adrenal insufficiency in 32 (6.1%). In those patients, serum sodium levels were lower (132 vs 139 mEq/L, P < 0.01), eosinophil counts were higher (14 vs 8%, P < 0.01), and systolic blood pressure was lower (120 vs 128 mmHg, P < 0.05) at baseline than in patients with the other etiologies.ConclusionThe frequency of adrenal insufficiency as a cause of hypoglycemia was much higher than what we anticipated. When protracted hypoglycemia of unknown etiology is recognized, we recommend that the patient is checked for adrenal function using a rapid ACTH test.

Association between adrenal function and dialysis vintage in hemodialysis patients.

Adrenal insufficiency in hemodialysis patients is commonly encountered in clinical practice. However, its association with end-stage renal disease is unclear. We investigated the relationship between adrenal function and relevant clinical parameters, focusing on dialysis vintage. Altogether, 100 maintenance hemodialysis patients were enrolled (age: 69.8 ± 11.8years, dialysis vintage: 9.4 ± 9.2years). Basal serum cortisol levels were measured and their associations with relevant clinical parameters were investigated. Subsequently, hormone stimulation tests were performed to assess adrenal function. Basal serum cortisol significantly decreased with an increase in dialysis vintage (< 10years, 11.9 ± 3.7μg/dL; 10-19years, 10.9 ± 2.9μg/dL; ≥ 20years, 9.7 ± 3.8μg/dL). Basal cortisol was negatively correlated with dry weight, β2-microglobulin, creatinine, and lymphocyte count and positively correlated with brachial-ankle pulse wave velocity. Significant negative correlations were observed between basal cortisol and dialysis vintage after adjusting for confounding variables in the multivariate analysis. Standard adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) stimulation tests were performed in 17 patients. Seven patients were diagnosed with adrenal insufficiency and all of them had a long dialysis vintage (≥ 10years). According to the rapid ACTH test, cortisol responses were significantly decreased in patients with long dialysis vintage compared to those with short dialysis vintage (< 10years). Similar findings were observed in ten patients without adrenal insufficiency. The CRH loading test showed similar tendencies, although the differences were not statistically significant. Adrenal function decreased with an increase in dialysis vintage. Long-term dialysis patients might be susceptible to adrenal insufficiency.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98–0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48–4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41–4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

THE CHARACTERISTICS OF PATIENTS SENSITIVE TO MINERALOCORTICOID RECEPTOR ANTAGONISTS

Objective: Primary aldosteronism (PA) is related to various cardiovascular events, thus the treatment of this disease is exceedingly important. From the current guidelines, physicians are encouraged to administrate mineralocorticoid receptor antagonists (MRA) to the patients with bilateral type of this disease, so-called idiopathic hyperaldosteronism (IHA). However, it is recently demonstrated that the benefit of this medicine is only exerted in the patients with enough PRA elevation after MRA treatment. We retrospectively evaluated the predictors for the patients who exceed plasma renin activity (PRA) &gt; 1.0 ng/ml/h at arbitrary chance after MRA administration from baseline characteristics and the result of confirmatory tests. Design and method: Our study protocol was approved by the Ethics Committee of The Jikei University School of Medicine (No. 31-271). 67 patients who received eplerenone for PA are included. We included the patients exceed plasma renin activity (PRA) &gt; 1.0 ng/ml/h at arbitrary chance within a year after MRA administration in Group A, and the patients who did not were included in Group B. Results: The eplerenone dose was comparable in two groups (Group A: 47.7 ± 13.1 v.s. Group B: 46.7 ± 14.4 P = 0.78). The patients in Group A were younger, and baseline PRA was lower in Group A. PRA after furosemide upright test, plasma aldosterone concentration (PAC) after saline infusion test, and PAC and PAC/F (Cortisol) after rapid adrenocorticotropic hormone (ACTH) stimulation test were higher in the Group A. Above all, it is revealed with Receiver operating characteristic curve analyses that PAC/F after rapid ACTH stimulation test at the cut-off value of 12.4 was proved to have the highest Area Under Curve (AUC) among all the indices (AUC 0.770). Conclusions: In conclusion, rapid ACTH stimulation test might be useful for discriminating the patients sensitive to MRA treatment.

Diagnostic value of standard deviation score of log-transformed serum dehydroepiandrosterone sulfate in patients with hypothalamic-pituitary-adrenal axis insufficiency.

Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 μg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 μg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores <-0.853. Thus, this score plays a supportive role in evaluating HPA axis function, particularly in patients with borderline cortisol responses to ACTH.

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.

Comparison of intraoperative cortisol levels after preoperative hydrocortisone administration versus placebo in patients without adrenal insufficiency undergoing endoscopic transsphenoidal removal of nonfunctioning pituitary adenomas: a double-blind randomized trial.

In this double-blind randomized trial, the necessity of preoperative steroid administration in patients without adrenal insufficiency (AI) undergoing endoscopic transsphenoidal surgery (ETSS) for pituitary adenoma was evaluated. Forty patients with and without AI, defined as a peak cortisol level > 18 µg/dl on the insulin tolerance test or rapid adrenocorticotropic hormone (ACTH) test, undergoing ETSS for nonfunctioning pituitary adenomas were randomly allocated to treatment with either 100 mg of preoperative hydrocortisone (group HC, n = 20) or normal saline (group C, n = 20). The patients with pituitary apoplexy, the use of a drug within the last 3 months that could affect the hypothalamic-pituitary-adrenal axis, or a previous history of brain or adrenal surgery were excluded. Intraoperative cortisol and ACTH levels were measured after anesthesia induction, dura incision, and tumor removal, and at the end of surgery. Intraoperative hypotension, early postoperative AI, and postoperative 3-month pituitary function were investigated. Intraoperative serum cortisol levels were significantly higher in the HC group than in the C group after anesthesia induction (median 69.0 µg/dl [IQR 62.2-89.6 µg/dl] vs 12.7 µg/dl [IQR 8.4-18.2 µg/dl], median difference 57.5 µg/dl [95% CI 33.0-172.9 µg/dl]), after dura incision (median 53.2 µg/dl [IQR 44.9-63.8 µg/dl] vs 6.4 [IQR 4.8-9.2 µg/dl], median difference 46.6 µg/dl [95% CI 13.3-89.2 µg/dl]), after tumor removal (median 49.5 µg/dl [IQR 43.6-62.4 µg/dl] vs 9.2 µg/dl [IQR 5.75-16.7 µg/dl], median difference 39.4 µg/dl [95% CI 0.3-78.1 µg/dl]), and at the end of surgery (median 46.9 µg/dl [IQR 40.1-63.4 µg/dl] vs 16.9 µg/dl [IQR 12.1-23.2 µg/dl], median difference 32.2 µg/dl [95% CI -42.0 to 228.1 µg/dl]). Serum ACTH levels were significantly lower in group HC than in group C after anesthesia induction (median 3.9 pmol/L [IQR 1.7-5.2 pmol/L] vs 6.9 pmol/L [IQR 3.9-11.9 pmol/L], p = 0.007). No patient showed intraoperative hypotension due to AI. Early postoperative AI was observed in 3 and 5 patients in groups HC and C, respectively. The postoperative 3-month pituitary hormone outcomes including ACTH deficiency were not different between groups. Preoperative steroid administration may be unnecessary in patients without AI undergoing ETSS for nonfunctioning pituitary adenomas. However, a further large-scale study is needed to determine whether preoperative steroid administration has a significant impact on clinically meaningful events such as perioperative AI and postoperative 3-month ACTH deficiency in these patients.Korean Clinical Trial Registry no.: KCT0002426 (https://cris.nih.go.kr/cris/).

Progression of Hypopituitarism and Hypothyroidism after Treatment with Pembrolizumab in a Patient with Adrenal Metastasis from Non-small-cell Lung Cancer

Pembrolizumab, or anti-programmed death receptor 1 antibody, is an immune checkpoint inhibitor that can cause immune-related adverse events. We herein report for the first time the progression of hypopituitarism and hypothyroidism after treatment with pembrolizumab in a patient with adrenal metastasis of non-small-cell lung cancer. Severe primary hypothyroidism occurred three weeks after the first administration of pembrolizumab. Four months after the discontinuation of pembrolizumab, isolated adrenocorticotropic hormone (ACTH) deficiency was noted. Corticotropin-releasing hormone and rapid ACTH tests performed repeatedly showed that the patient's pituitary and adrenal function had been gradually deteriorating. It is important to diagnose adrenal insufficiency without delay in order to prevent adrenal crisis.

Prognostic Implication of Adrenocortical Response during the Course of Critical Illness.

BackgroundCritical illness-related corticosteroid insufficiency (CIRCI) and adrenocorticotropic hormone (ACTH)-cortisol dissociation are hormonal conditions frequently observed in patients in the intensive care unit (ICU). The aim of this study was to evaluate the association between ACTH-cortisol dissociation and clinical outcomes of critically ill patients. MethodsWe retrospectively reviewed the medical records of 94 ICU patients who underwent two rapid cosyntropin tests during hospital admission and compared the clinical aspects of patients with and without ACTH-cortisol dissociation. ACTH-cortisol dissociation was defined as plasma ACTH and serum cortisol concentrations of <22 pmol/L and >600 nmol/L, respectively. ResultsDissociation was present in 30 of the 94 patients (31.9%). Patients with ACTH-cortisol dissociation in the initial test had significantly higher hospital mortality rate than those in the control group (55% vs. 25.7%, P=0.013) There was no difference in hospital mortality between patients classified as having CIRCI and those who were not. In multivariate adjusted Cox regression analysis, the mortality risk was higher in the group with ACTH-cortisol dissociation (hazard ratio, 2.98; 95% confidence interval, 1.34 to 6.63; P=0.007). Patients with dissociation in two consecutive stimulation tests showed the highest hospital mortality rate among groups classified according to stimulation test results (100% vs. 31.3%). ConclusionsThe hospital mortality was higher in ICU patients diagnosed with ACTH-cortisol dissociation. It is clinically feasible to evaluate the presence of ACTH-cortisol dissociation by analyzing rapid ACTH stimulation test results in critically ill patients.

Critical Illness-Related Corticosteroid Insufficiency in Patients with Low Cardiac Output Syndrome after Cardiac Surgery.

BackgroundLow cardiac output syndrome (LCOS) after cardiac surgery usually requires inotropes. In this setting, critical illness-related corticosteroid insufficiency (CIRCI) may develop. We aimed to investigate the clinical features of CIRCI in the presence of LCOS and to assess the efficacy of steroid treatment.MethodsWe reviewed 28 patients who underwent a rapid adrenocorticotropic hormone (ACTH) test due to the suspicion of CIRCI between February 2010 and September 2014. CIRCI was diagnosed by a change in serum cortisol of <9 μg/dL after the ACTH test or a random cortisol level of <10 μg/dL.ResultsTwenty of the 28 patients met the diagnostic criteria. The patients with CIRCI showed higher Sequential Organ Failure Assessment (SOFA) scores than those without CIRCI (16.1±2.3 vs. 11.4±3.5, p=0.001). Six of the patients with CIRCI (30%) received glucocorticoids. With an average elevation of the mean blood pressure by 22.2±8.7 mm Hg after steroid therapy, the duration of inotropic support was shorter in the steroid group than in the non-steroid group (14.1±2.3 days versus 30±22.8 days, p=0.001). Three infections (15%) developed in the non-steroid group, but this was not a significant between-group difference.ConclusionCIRCI should be suspected in patients with LCOS after cardiac surgery, especially in patients with a high SOFA score. Glucocorticoid replacement therapy may be considered to reduce the use of inotropes without posing an additional risk of infection.

Primary aldosteronism in patients with acute stroke: prevalence and diagnosis during initial hospitalization.

BackgroundHypertension is the prime risk factor for stroke, and primary aldosteronism (PA) is the most common cause of secondary hypertension. The prevalence of PA in stroke patients has never been reported. The aim of this study was to elucidate the prevalence of PA.MethodsA total of 427 consecutive patients with acute stroke were prospectively enrolled for this study. The screening tests were performed at the initial visit and a week after admission by measuring plasma aldosterone concentration and plasma renin activity. The rapid adrenocorticotropic hormone (ACTH) test was performed as the confirmatory test when both screening tests were positive. The primary endpoint was a final diagnosis of PA.ResultsThe sensitivity of the dual screening system for the diagnosis of PA was 88.2 %, and PA was finally diagnosed in 4.0 % of acute stroke patients and in 4.9 % of stroke patients with a history of hypertension. Patients with PA were less likely to be male and have diabetes, and they had higher blood pressure at the initial visit, lower potassium concentration, and more intracerebral hemorrhage. The rapid ACTH test was performed safely even in acute stroke patients.ConclusionsThe prevalence of PA is not low among acute stroke patients. Efficient screening of PA should be performed particularly for patients with risk factors.Trial registrationUMIN-CTR; UMIN000011021. Trial registration date: June 23, 2013 (retrospectively registered).

The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome.

BackgroundIn subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.MethodsThirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.ResultsLevels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).ConclusionThe HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

Elevated Levels of Plasma Immunoassayable Aldosterone in a Mild Form of 17 Alpha-Hydroxylase/17,20-lyase Deficiency Diagnosed at the Age of 50

ABSTRACT Objective: 17 Alpha-hydroxylase/17,20-lyase deficiency (17OHD) is a form of congenital adrenal hyperplasia caused by homozygous or compound heterozygous mutations in the CYP17A1 gene. Impaired activities of 17 alpha-hydroxylase and 17,20-lyase typically induce hypertension, hypokalemia, and amenorrhea, with the vast majority of patients with 17OHD are diagnosed in adolescence. Methods: We present a case of 17OHD diagnosed at the age of 50 with complete endocrinologic investigations and genetic analysis. Results: The patient had hypokalemia and a low cortisol level. Her dehydroepiandrosterone sulfate (DHEA-S) and androstenedione levels were undetectable, although her adrenocorticotropic hormone (ACTH) level was elevated. She had markedly elevated pregnenolone, progesterone, deoxycorticosterone, and corticosterone levels. In addition, her plasma renin activity and plasma aldosterone concentration were suppressed and elevated, respectively. Rapid ACTH stimulation increased the hormones upstream of 1...

43-jähriger Patient mit Wesensveränderung, rezidivierenden Bewusstseinsstörungen und retrograder Amnesie

A 43-year-old male patient with recurring impaired consciousness and retrograde amnesia was admitted to the department of neurology. During the neurological evaluation no pathological findings could initially be revealed but one day the patient was confused again and presented with inadequate behavior: at this time a blood glucose value of 40 mg/dl was measured. For further evaluation the patient was transferred to our department. As the reason for the impaired consciousness was suspected to be of neuroglucopenic origin a rapid adrenocorticotropic hormone (ACTH) stimulation test was first performed to rule out adrenal insufficiency. For further evaluation a fasting test was conducted: after 48 h an episode with neuroglucopenic symptoms occurred again which disappeared after intravenous administration of glucose. The laboratory results of glucose, insulin and c-peptide determined at this point in time led to the diagnosis of an insulinoma. By ultrasound examination a hypoechogenic lesion 1.5 cm in size could be shown in the head of the pancreas and was confirmed by magnetic resonance imaging (MRI). After duodenum-preserving partial pancreatic head resection with enucleation of the insulinoma no further neuroglucopenic symptoms occurred.

Intravenous Immunoglobulin Therapy for Persistent Pemphigoid Gestationis with Steroid Induced Iatrogenic Cushing's Syndrome

Dear Editor: A 30-year-old woman developed pemphigoid gestationis (PG) after 20 weeks of gestation during her first pregnancy. Initially, she was treated with prednisone (10~30 mg/d), but she had a miscarriage in the 26th week of pregnancy. After the miscarriage, she was treated with prednisone (30~40 mg/d) and azathioprine (100 mg/d). However, her PG did not show clinical remission and new blisters continued to develop until the 12th post-partum week. Therefore, she was referred to our clinic for further treatment. She had erythematous patches, plaques and tense bullae on both the upper extremities and trunk (Fig. 1A). Histopathological examination of the skin samples showed the presence of subepidermal vesicles with perivascular lymphocytes and eosinophils (Fig. 2A, B). Direct immunofluorescence examination revealed positive, linear deposition of IgG and C3 in the basement membrane zone (Fig. 2C, D). Therefore, we confirmed the diagnosis of PG and started her on high-dose systemic corticosteroids; however, after receiving the treatment, she rapidly gained weight and developed moon face. Therefore, we performed a rapid adrenocorticotropic hormone stimulation test and measured her 24-hour urine cortisol level; on the basis of the test results, she was diagnosed with iatrogenic Cushing's syndrome. Therefore, she was started on prednisone (40~60 mg/d) and azathiprine (100 mg/d), but the symptoms persisted. After considering further treatment options, we decided to administer intravenous immunoglobulin (IVIG) therapy at a dose of 0.5 g kg-1 day-1 for 2 consecutive days. Fig. 1 (A) Large tense bullae and erythematous pruritic plaques on the arm. (B) Improved skin lesions with postinflammatory hyperpigmentation after intravenous immunoglobulin combination treatment. Fig. 2 (A) Subepidermal blister with superficial inflammatory infiltrate. (B) Superficial perivascular lymphohistiocytic infiltration, with moderate infiltration of eosinophils. Linear staining for (C) IgG, (D) C3 at the basement membrane zone. (A) H&E, ... After receiving the IVIG therapy, her skin lesions quickly subsided (Fig. 1B), so prednisone was tapered down to 10 mg/day. She was also administered a steroid at a low dose for 8 weeks for treating her Cushing's syndrome. At the follow-up after 3 months, no lesions were found on the patient. PG is a rare autoimmune-mediated blistering disease, usually occurring in the late pregnancy and immediate postpartum period. Many patients experience spontaneous resolution during the latter part of gestation only to experience a flare at the time of delivery. However, the persistence of disease activity for many years postpartum has been reported. Numerous immunosuppressive treatments have been reported for PG1. If the disease persists, treatment options are limited because they have potential side-effects, e.g. development of Cushing's syndrome, as seen in our patient. IVIG has been used to treat various autoimmune blistering diseases2. Many authors reported the use of IVIG for treating PG. The immunomodulatory actions of IVIG are mediated via several immune-mediated mechanisms, such as complement blockade and degradation, Fc receptor blockade and induction of immunomodulatory Fc receptors, inhibition of B cells, and alteration of T-cell function, cytokine modulation, and cellular migration3. IVIG therapy is relatively safe, and severe adverse events associated with the use of IVIG are rare. Headache and acute cutaneous reactions are the most common adverse effects of the therapy, while renal failure, thromboembolic events, and anaphylaxis have rarely been reported in association with IVIG therapy3. It is difficult to differentiate refractory PG from epidermolysis bullosa acquisita using only clinical, histological and direct immunofluorescence findings. Therefore, the findings of enzyme-linked immunosorbent assay and indirect immunofluorescence performed on sodium chloride-split skin are helpful in the differentiation4. We confirmed the diagnosis of PG in the case of our patient, as PG manifests itself during pregnancy, moreover, the patient achieved remission after one-cycle treatment2,3. PG is a rare disease and only 4 cases of PG treated with IVIG have been reported to date. We presented a case of persistent PG treated with IVIG combination therapy. IVIG should be considered as a therapeutic option in patients that fail to respond to conventional immunosuppressive treatment.

A pilot study of adrenal suppression after dexamethasone therapy as an antiemetic in cancer patients

Dexamethasone has a high therapeutic index when used to prevent chemotherapy-induced nausea and vomiting. However, the chronic use of glucocorticoids has been associated with suppression of the hypothalamic-pituitary-adrenal axis. Therefore, the authors designed this pilot study to assess the incidence of adrenal insufficiency after dexamethasone therapy as an antiemetic in cancer patients receiving chemotherapy. The rapid adrenocorticotropic hormone (ACTH) stimulation test was performed in 103 cancer patients, who had been treated with high-dose dexamethasone as an antiemetic for more than 3 months. When response to the rapid ACTH stimulation test was abnormal, the patient received corticosteroid replacement by prednisolone 7.5 mg daily for 1-2 weeks and after prednisolone replacement, changes in symptoms associated with adrenal insufficiency were investigated using a visual analog scale. Forty-five of the 103 patients (43.7%) showed a suppressed adrenal response to the rapid ACTH stimulation test, and the incidence of adrenal suppression was found to be significantly affected by megestrol acetate use (P = 0.035). Thirty-three patients with a suppressed adrenal function achieved an improvement in quality of life after prednisolone replacement, as determined using a self-report questionnaire (22.9 ± 14.7 to 14.8 ± 11.0, P < 0.001). We suggest that suppression of adrenal response is common after antiemetic dexamethasone therapy in cancer patients receiving chemotherapy.

A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene

Antley-Bixler syndrome (ABS) is a skeletal malformation syndrome primarily affecting the skull and limbs. Although causal mutations in the FGFR2 gene have been found in some patients, mutations in the electron donor enzyme P450 oxidoreductase gene (POR) have recently been found to cause ABS in other patients. In addition to skeletal malformations, POR deficiency also causes glucocorticoid deficiency and congenital adrenal hyperplasia with ambiguous genitalia in both sexes. Here, we report on a 7-month-old Korean girl with ABS and ambiguous genitalia who was confirmed by POR gene analysis. Our patient showed typical skeletal findings with brachycephaly, mid-face hypoplasia, and radiohumeral synostosis. She also had partial labial fusion and a single urogenital orifice, as well as increased 17alpha-hydroxyprogesterone levels, suggesting a 21-hydroxylase deficiency. Cortisol and DHEA-sulfate response to rapid adrenocorticotropic hormone (ACTH) stimulation was inadequate. Direct sequencing of the POR gene revealed compound heterozygous mutations (I444fsX449 and R457H). This is the first report of a Korean patient with ABS caused by POR gene mutations.

Relationship between Cortisol Increment and Basal Cortisol: Implications for the Low-Dose Short Adrenocorticotropic Hormone Stimulation Test

We analyzed the low-dose (1 microg) rapid adrenocorticotropic hormone test (LDST) in 17 patients with a normal hypothalamic-pituitary-adrenal axis to determine reference intervals for the LDST on the basis of poststimulation cortisol increments. We analyzed test results for 17 patients (14 females and 3 males; age range, 18-46 years) who had received a 2-mL aliquot of low-dose (1 microg) adrenocorticotropic hormone prepared from one 250-microg vial of Synacthen diluted in 500 mL of sterile normal saline solution. Sampling took place at 0, 20, 30, and 60 min post stimulation. The cortisol increment was plotted against basal cortisol. We observed a marked interdependence of the basal cortisol concentration with the increase in cortisol concentration. The relationship was inverse and linear with the best fit observed at 30 min post stimulation. The lower 95% prediction limit for basal cortisol at the zero increment was 400 nmol/L with a mean concentration of 600 nmol/L. We propose that a peak cortisol concentration <400 nmol/L is a sufficient single criterion for abnormal adrenal function as assessed by the LDST. Concentrations of 400-600 nmol/L are in the gray area, and those >600 nmol/L confirm normal adrenal function. Repeat analyses with larger sample sizes are warranted to confirm these observations.