Mild Adrenal Insufficiency Research Articles

SAT283 The Incidence Of Worsening Symptoms Of Adrenal Insufficiency And COVID-19 Infection After Receiving COVID-19 Vaccine In Patients With Adrenal Insufficiency: A Survey-based Study

Abstract Disclosure: K. Al Sibai: None. M.D. Lundholm: None. N. Nachawi: None. J. Baikovitz: None. J. Bena: None. M. Lansang: None. Introduction: There is uncertainty if COVID-19 vaccine administration can induce enough stress to precipitate worsening of adrenal insufficiency (AI) or even adrenal crisis. The aim of the study is to evaluate the incidence of worsening symptoms of AI after receiving the COVID-19 vaccine in patients with AI. Methods: This is a single-center survey study of patients with either primary or secondary AI by ICD code in our electronic medical record. Diagnoses were confirmed with chart review and patients were included if on stable physiologic glucocorticoid replacement doses for at least 3 months prior to COVID-19 vaccination. These patients were sent a survey asking about the date/type of vaccine, the occurrence of AI symptoms, and if they took a higher dose of oral GC, or took injectable GC, or sought a higher level of medical care. Results: There were 340 eligible patients, and 61 patients to date have completed the survey (18% response rate). Responders were 64% female, 41% with primary AI, and 56% with secondary AI. The median age was 57 (IQR 50, 68) years with a median hydrocortisone-equivalent replacement dose used of 20 (IQR 20, 25) mg daily. Each vaccination was treated as a separate event. A total of 194 COVID vaccination events were recorded, which included 35 (18%) vaccination events when higher doses of GC were used, 35% of which were after onset of symptoms. Mild AI symptoms, i.e., fever, weakness, nausea/vomiting, diarrhea, and dizziness, body aches, and weakness occurred in 62% of events. The most reported symptoms were body aches and weakness (48% and 35% respectively). Severe AI symptoms, i.e., low blood pressure and fainting, occurred in 4.6% of events. The need to use injectable GC, seeking medical care or ED visits occurred in 5.7%. There was no significant difference in seeking medical care nor using injectable GC for patients who took stress dose GC vs those who did not (OR 0.69, 95% CI 0.10,4.88, p=0.7). Conclusion: At present analysis, the incidence of worsening AI-related symptoms was high after COVID-19 vaccination (62%). Most reported symptoms were mild and self-limited that did not require a higher level of medical care. About 6% of survey takers used injectable GC or sought a higher level of care. Our preliminary results do not support routine prophylactic stress-dose GC for receiving COVID-19 vaccines in patients with AI. We estimate another 100 patients to complete our survey. Presentation: Saturday, June 17, 2023

Topical clobetasol treatment for oral lichen planus can cause adrenal insufficiency.

Glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, which may lead to glucocorticoid-induced adrenal insufficiency. The study aimed to investigate the prevalence of this state in patients with oral lichen planus treated with topical clobetasol propionate. In this cross-sectional study, 30 patients with oral lichen planus receiving long-term (>6 weeks) clobetasol propionate gel 0.025% were invited to participate. Adrenal function was assessed by measuring morning plasma cortisol after a 48-h withdrawal of clobetasol treatment. In patients with plasma cortisol <280 nmol/L, a cosyntropin stimulation test was performed. Twenty-seven patients were included. Twenty-one (78%) patients presented with plasma cortisol ≥280 nmol/L (range 280-570 nmol/L), and six (22%) <280 nmol/L (range 13-260 nmol/L). Five of these six patients underwent cosyntropin stimulation that revealed severe adrenal insufficiency in two patients (cortisol peak 150 nmol/L and 210 nmol/L) and mild adrenal insufficiency in three patients (cortisol peak 350-388 nmol/L). In this study, approximately 20% of patients receiving intermittent topical glucocorticoid treatment for oral lichen planus had glucocorticoid-induced adrenal insufficiency. It is essential for clinicians to be aware of this risk and to inform patients about the potential need for glucocorticoid stress doses during intercurrent illness.

Single-institutional outcome-analysis of low-dose stereotactic body radiation therapy (SBRT) of adrenal gland metastases

BackgroundAdrenal gland metastases are a common diagnostic finding in various tumor diseases. Due to the increased use of imaging methods, they are diagnosed more frequently, especially in asymptomatic patients. SBRT has emerged as a new, alternative treatment option in the field of radiation oncology. In the past, it was often used for treating inoperable lung, liver, prostate, and brain tumors. Meanwhile, it is also an established keystone in the treatment of oligometastatic diseases. This retrospective study aims to evaluate the effect of low-dose SBRT in patients with adrenal metastases.MethodsWe analyzed a group of 31 patients with 34 adrenal gland lesions treated with low-dose SBRT between July 2006 and July 2019. Treatment-planning was performed through contrast-enhanced CT, followed by image-guided stereotactic radiotherapy using cone-beam CT. The applied cumulative median dose was 35 Gy; the median single dose was 7 Gy. We focused on local control (LC), progression-free survival (PFS), overall survival (OS), as well as acute and late toxicity.ResultsSeven adrenal gland metastases (20.6%) experienced local failure, 80.6% of the patients faced a distant progression. Fourteen patients were still alive. Median follow-up for all patients was 9.8 months and for patients alive 14.4 months. No treatment-related side-effects >grade 2 occurred. Of all, 48.4% suffered from acute gastrointestinal disorders; 32.3% reported acute fatigue, throbbing pain in the renal area, and mild adrenal insufficiency. Altogether, 19.4% of the patients faced late-toxicities, which were as follows: Grade 1: 12.9% gastrointestinal disorders, 3.2% fatigue, Grade 2: 9.7% fatigue, 6.5% headache, 3.2% loss of weight. The 1-year OS and probability of LF were 64 and 25.9%, respectively.ConclusionLow-dose SBRT has proven as an effective and safe method with promising outcomes for treating adrenal metastases. There appeared no high-grade toxicities >grade 2, and 79.4% of treated metastases were progression-free. Thus, SBRT should be considered as a therapy option for adrenal metastases as an individual therapeutic concept in the interdisciplinary discussion as an alternative to surgical or systemic treatment.

The Changing Face of Adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a rare X-linked disorder of peroxisomal oxidation due to mutations in ABCD1. It is a progressive condition with a variable clinical spectrum that includes primary adrenal insufficiency, myelopathy, and cerebral ALD. Adrenal insufficiency affects over 80% of ALD patients. Cerebral ALD affects one-third of boys under the age of 12 and progresses to total disability and death without treatment. Hematopoietic stem cell transplantation (HSCT) remains the only disease-modifying therapy if completed in the early stages of cerebral ALD, but it does not affect the course of adrenal insufficiency. It has significant associated morbidity and mortality. A recent gene therapy clinical trial for ALD reported short-term MRI and neurological outcomes comparable to historical patients treated with HSCT without the associated adverse side effects. In addition, over a dozen states have started newborn screening (NBS) for ALD, with the number of states expecting to double in 2020. Genetic testing of NBS-positive neonates has identified novel variants of unknown significance, providing further opportunity for genetic characterization but also uncertainty in the monitoring and therapy of subclinical and/or mild adrenal insufficiency or cerebral involvement. As more individuals with ALD are identified at birth, it remains uncertain if availability of matched donors, transplant (and, potentially, gene therapy) centers, and specialists may affect the timely treatment of these individuals. As these promising gene therapy trials and NBS transform the clinical management and outcomes of ALD, there will be an increasing need for the endocrine management of presymptomatic and subclinical adrenal insufficiency. (Endocrine Reviews 41: 1 - 17, 2020).

TALASEMİ MAJOR TANISI İLE İZLENEN ÇOCUKLARDA ENDOKRİN KOMPLİKASYONLARIN ARAŞTIRLMASI

Background/aim: Thalassemia constitutes the most common disease group in the systemic involvement in hemoglobinopathies. With the development of new treatment methods, the accumulation of possible endocrine complications is observed more frequently, with an increase in the lifetime of cases. The most common cause of endocrine complications is a natural result of hemolytic processes, as well as excessive accumulation of iron in the endocrine organs with transfusions. Southeasthern Anatolia is a region where thalassemia major patients are relatively intense and there is no report on endocrine evaluations of these patients so far. The aim of the study is to evaluate the children who were followed up with the diagnosis of Thalassemia Major in terms of endocrine complications. It is the first study to determine the current situation in our research region. Material and Method: The study included 32 children, ages 1-18, who applied to the Gaziantep University Faculty of Medicine Children's Endocrine Clinic between 2011-2015 years. Children participating in the study were evaluated in terms of growth, pubertal development, adrenal insufficiency, hypothyroidism, diabetes development, and osteroporosis as a scale of the endocrine approach. For evaluation, ACTH, Cortisol, DHEASParathormone, calcium, phosphorus, ALP, Vitamin D, FSH, LH, Estradiol Testesteron, IGF-1, GH, IGFBP, HbA1C, C-peptide fasting glucose, Islet Cell Antibodies, DEXA, pelvic USG, Bone Age, fT4, TSH, anti-TPO, anti TG tests were studied. Standard T test was used for the significance test between variables, and Pearson correlation tests were used for correlation between chi-square, ferrtin and complications. Results: Of the patients were 14 (43.7%) female and 18 (56.3%) male. The average age was 12.33 ± 4.34. The average height was 136.23 ± 25.34 (mean height SDS -2.17 ± 1.44), the average weight was 36.23 ± 13.23 (average weight SDS -2.44 ± 1.30). Short stature in 17 (53.1%) of cases, low weight in 22 (68.7%), regression in pubertal development in 20 (62.5%), mild adrenal insufficiency in 2 (6.2%), 3 (9.3%) hypothyroidism, 2 diabetes, (6.2%), 5 (15.6%) impaired glucose tolerance, and 25 (78%) osteoporosis. DEXA mean was DEXA ortalama -3,12±1,02. A positive correlation was found between the disease duration of the ferritin height and the complications ((rhastalık süresi=863, p&lt;0.001 and (rkomplikasyon= 0.668, p&lt;0.001, respectively). Conclusion: This study reveals that endocrine complications are correlated with disease duration and ferritin level in children with the diagnosis of Thalassemia Major. This result reveals the necessity of monitoring endocrine complications more closely in Thalassemia Major.

Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test.

Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat insufficient stimulated cortisol levels in the setting of MDR-TB.

Adrenal Function Testing Following Hormone Therapy for Infantile Spasms: Case Series and Review of Literature.

Prednisolone and adrenocorticotropic hormone (ACTH) are “hormone” therapies for infantile spasms. There is limited data on the occurrence of decreased adrenal reserve or signs of clinical adrenal insufficiency after hormone therapy. This is a retrospective medical record review of patients referred to our Infantile Spasms Program. Our standardized infantile spasms management guideline began in September 2012 and initially included a post-hormone laboratory assessment of adrenal function. Medical records were assessed for hormone treatments, adrenal function testing, and signs of adrenal insufficiency. Forty-two patients who received one or both hormone therapies met inclusion criteria. A post-hormone laboratory assessment of adrenal function was done in 14 patients. Of these 14 patients, 2 had an abnormal laboratory assessment of adrenal function, both by adrenal stimulation testing – one after ACTH and one after prednisolone. One patient received hydrocortisone replacement and the other received stress dose hydrocortisone as needed; neither patient developed signs of adrenal insufficiency. Another patient treated with both types of hormone therapy in tandem, who did not have a post-hormone laboratory assessment, developed signs of mild adrenal insufficiency and required replacement hydrocortisone. Our study suggests that adrenal suppression can occur after modern hormone therapy regimens. We found two patients with abnormal adrenal function testing after hormone therapy and another patient with signs adrenal insufficiency. Given the seriousness of adrenal crisis, caregiver education on the signs of adrenal insufficiency is critical. Greater vigilance may be indicated in patients receiving both types of hormone therapy in tandem. Although a routine post-hormone laboratory assessment of adrenal function may not be feasible in all patients, replacement or stress dose hydrocortisone is necessary for all patients with suspected adrenal insufficiency.

Abstract #126: Complete Quick Resolution of Chronic Gastroparesis in a Male with Mild Adrenal Insufficiency Heterozygous Positive for the CYP2D6*41 Reduced Activity Variant by Treating with an Extremely Low Dosage of Dextroamphetamine Sulfate and Low Dosage Hydrocortisone

Abstract #126: Complete Quick Resolution of Chronic Gastroparesis in a Male with Mild Adrenal Insufficiency Heterozygous Positive for the CYP2D6*41 Reduced Activity Variant by Treating with an Extremely Low Dosage of Dextroamphetamine Sulfate and Low Dosage Hydrocortisone

Reactive Hypoglycemia Associated with Mild Adrenal Dysfunction, So-called Adrenal Fatigue

We here described a case of a 38-year-old woman who was referred to our hospital for general malaise, slight fever, and palpitations after a meal for the past several years. She became hungry at approximately 3:00 or 4:00 p.m. every day, and simultaneously felt the urge to eat something sweet. During a five-hour 75g OGTT test, her blood glucose level dropped sharply twice (79 mg/dL at 60 min and 76 mg/dL at 300 min) due to the excessive secretion of insulin (29.9 µU/mL at 30 min and 43.1 µU/mL at 120 min). She was diagnosed with a mild adrenal insufficiency due to a decrease in her serum cortisol value in the early morning and an insufficient response to the rapid ACTH stress test. We speculated that the reactive hypoglycemic symptoms observed in this patient may have developed due to the inadequate secretion of serum cortisol as a counterregulation against insulin, which resulted in a relative excess of serum insulin after a meal. Her clinical manifestations and laboratory data were similar to a state called adrenal fatigue. Since the presentation of mild adrenal insufficiency is often insidious and difficult to recognize, careful

Erratum: Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder

Erratum: Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder

Mild adrenal insufficiency due to a NROB1 (DAX1) gene mutation in a boy presenting an association of hypogonadotropic hypogonadism, reduced final height and attention deficit disorder

Mutation on NROB1 (DAX1) gene can cause different phenotypes of adrenal insufficiency in infancy. Long-term evolution of these patients shows that it is possible to have an association with hypogonadotropic hypogonadism. In this article we describe the evolution of a patient with NROB1 gene mutation, diagnosed with a mild form of adrenal insufficiency, and we highlight the presence of hypogonadotropic hypogonadism and short stature, besides the presence of attention deficit disorder. Such associations should make physicians aware during the follow-up of patients with this disease.

Treating Adrenal Insufficiency and Hypotension with Glycyrrhiza

Glycyrrhiza&nbsp;may be appropriate as an adjunctive therapy for a variety of disorders involving mild adrenal insufficiency, low aldosterone output, or hyperkalemia due to effects on 11-β-HSD enzymes, direct effects at mineralocorticoid receptors, and downstream effects on aldosterone as well as fluid and electrolyte balance.&nbsp;Glycyrrhiza&nbsp;has also been shown to help correct hyperkalemia that may result from spirolactone therapy in PCOS. Patients with orthostatic hypotension may respond to&nbsp;Glycyrrhiza&nbsp;therapy due to its ability to improve blood volume and potassium levels and reduce activation of baroreceptors.

Bilateral adrenal abscesses and skin lesions in an immunocompetent patient

A 45-year-old non-diabetic man presented with a 4-month history of fever accompanied by 5 kg weight loss. Examination revealed multiple non-itchy papules with central umbilication distributed over face, neck, and trunk (figure, A). Contrast enhanced computed tomography (CECT) of the abdomen revealed bilateral adrenal abscesses (figure, B). Adrenal function was preserved. Skin biopsy from one of the papules over the chest revealed dermal histiocytic infilteration, containing numerous Histoplasma capsulatum organisms. ELISA for HIV was negative and serum immunoglobulin levels were normal. The patient was treated with intravenous amphotericin B for 18 days with a cumulative dose of 586 mg, and showed marked improvement, with disappearance of fever and skin lesions. The size of the adrenal glands and the morphology of adrenal lesions remained unaltered. The patient was discharged on oral itraconazole 200 mg twice a day. There was no recurrence of symptoms. A repeat CECT of the abdomen, done 6 weeks later, revealed an increase in the size of the bilateral adrenal abscesses. Cytopathological examination of pus aspirated from right adrenal gland showed numerous H capsulatum organisms. Low-dose (1 μg) adrenocorticotrophic hormone stimulation test revealed evidence of mild adrenal insufficiency at this stage. He was treated with intravenous amphotericin B (total dose 2 g) and repeated aspirations of adrenal abscesses with intralesional instillation of amphotericin B (350 mg over seven sittings). The size of the adrenal abscesses remained the same. Open drainage was then done where large amount of pus was drained, which again showed the presence of H capsulatum. Subsequently the patient showed clinical and radiological improvement. The patient is currently on maintenance itraconazole therapy with no new lesions, or progression of old lesions. Bilateral adrenal abscesses and skin lesions in an immunocompetent patient

Inherited adrenal hypoplasia: not just for kids!

Inherited adrenal hypoplasia: not just for kids!

A race to the lab

A 35-year-old man was admitted in October, 2000, with an elevated serum potassium: 7·3 mmol/L (NR: 3·5–5·0) on routine blood test following a venesection. 4 years previously, he had been diagnosed with haemochromatosis. A liver biopsy showed micronodular cirrhosis and grade 4 iron overload. His serum ferritin was more than 5000 μg/L (NR: 41–480), and he had a homozygous mutation in the haemochromatosis gene (HFE). He had weekly venesections, and his ferritin level had returned to normal range. 6 months before admission, tests had shown evidence of hypogonadotrophic hypogonadism and mild adrenal insufficiency.

Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy.

Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.

Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay.

Although delayed puberty is relatively common and often familial, its molecular and pathophysiologic basis is poorly understood. In contrast, the molecular mechanisms underlying some forms of hypogonadotropic hypogonadism (HH) are clearer, following the description of mutations in the genes KAL, GNRHR, and PROP1. Mutations in another gene, DAX1 (AHC), cause X-linked adrenal hypoplasia congenita and HH. Affected boys usually present with primary adrenal failure in infancy or childhood and HH at the expected time of puberty. DAX1 mutations have also been reported to occur with a wider spectrum of clinical presentations. These cases include female carriers of DAX1 mutations with marked pubertal delay and a male with incomplete HH and mild adrenal insufficiency in adulthood. Given this emerging phenotypic spectrum of clinical presentation in men and women with DAX1 mutations, we hypothesized that DAX1 might be a candidate gene for mutation in patients with idiopathic sporadic or familial HH or constitutional delay of puberty. Direct sequencing of DAX1 was performed in 106 patients, including 85 (80 men and 5 women) with sporadic HH or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified (T114C, G498A). This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency.

The Neuroendocrinology of Chronic Fatigue Syndrome

Since the introduction of operationalized criteria, there has been considerable interest in the pathophysiology of chronic fatigue syndrome (CFS). There is an increasing volume of evidence to support the view that patients with this syndrome have unique neuroendocrinology patterns. Central to this endocrine dysfunction is altered hypothalamic-pituitary-adrenal axis (HPA) activity. The cardinal findings include attenuated adrenocorticotrophic hormone (ACTH) responses to corticotropin-releasing hormone (CRH) and low 24-hour urinary cortisol. These are compatible with a mild central adrenal insufficiency. Adrenal steroids have widespread impact in the brain, and of particular importance is their dense concentration on serotonergic and noradrenergic neurotransmitter pathways. Using a variety of different challenge drugs, a supersensitivity of the serotonergic 5-HT 1A receptor has been demonstrated although the results have not been entirely consistent. A blunting of dexamethasone-induced growth hormone releas...

Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids.

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

Adrenal Insufficiency After Operative Removal of Apparently Nonfunctioning Adrenal Adenomas

We describe a woman who developed adrenal insufficiency after removal of an apparently nonfunctional adrenal adenoma. She displayed no stigmata of Cushing's syndrome and had normal plasma and urinary cortisol levels. A second patient without clinical findings of Cushing's syndrome also had normal basal steroid levels. This patient displayed partial suppressibility with dexamethasone, had low-normal levels of serum corticotropin, and excreted a low concentration of urinary 17-ketosteroids. She also developed mild adrenal insufficiency after the operation. We believe the adrenal adenomas in these patients secreted enough cortisol to suppress the contralateral adrenal gland but not enough hormone to elevate basal steroid levels. Therefore, we suggest that all patients with adrenal masses be studied with the overnight dexamethasone suppression test rather than basal steroid hormone measurements to detect low levels of autonomous cortisol secretion. In addition, patients with adrenal masses that are not removed surgically should have serial adrenal function tests performed.