Rapid ACTH Stimulation Test Research Articles

7799 Nesidioblastosis Concurrent with Anatomically Confirmed Metastatic Gastric Cancer

Abstract Disclosure: Y. Cho: None. K. Jo: None. J. Han: None. S. Moon: None. E. Kim: None. Background: Nesidioblastosis is a rare condition that should be considered in cases of pancreatogenic hyperinsulinemic hypoglycemia without evidence of insulinoma on imaging. We present the first case of nesidioblastosis concomitant with anatomically confirmed metastatic gastric cancer of the pancreas. Case Report A 57-year-old male presented with recurrent episodes of loss of consciousness and hypoglycemia, with a glucose level of 26 mg/dl upon arrival at the emergency room. Despite a history of advanced gastric cancer and previous chemotherapy, the patient had not been diagnosed with diabetes and was not taking medications associated with hypoglycemia. Four months prior, he underwent total gastrectomy. The fasting plasma glucose levels was 38 mg/dl, accompanied by C-peptide levels of 6.10 ng/mL, insulin levels exceeding 1000 uIU/ml, and proinsulin levels at 8.8 pmol/L. The insulin antibody level was more than 100%, and the highest cortisol level reached 15.60 ug/dL during the rapid ACTH stimulation test. The patient's postprandial 2-hour glucose level reached 233 mg/dl during the 75g glucose tolerance test. Imaging studies, including whole-body PET CT and abdominal CT, showed no evidence of suspected metastatic lesions, and the pancreas appeared normal on MRI. Endoscopic ultrasound could not be performed due to anatomical changes following the surgery. A selective arterial calcium stimulation test demonstrated a substantial over twofold increase in insulin concentrations in the gastroduodenal artery, splenic artery, and superior mesenteric artery. The patient received methylprednisolone 125 mg once daily but insulin levels remained elevated, exceeding 1000 uIU/ml, requiring continuous dextrose infusion. Octreotide therapy was initiated, resulting in an improvement in insulin levels to 589 uIU/ml, although discontinuation of dextrose fluid remained unfeasible. After consultation with the surgeon, a open subtotal pancreatectomy was performed, allowing discontinuation of dextrose on the second post-surgery day, with improved glucose and insulin levels. Histological examination showed three clusters of atypical cells with perineural infiltration. Immunostaining indicated negative synaptophysin and positive CK20, suggesting possible gastric cancer metastasis, consistent with prior gastrectomy findings. Moreover, an increased number of variable-sized Langerhans islets exhibited positive insulin and glucagon immunostaining within the islets, indicative of nesidioblastosis. Conclusion: Nesidioblastosis should be considered in cases of unexplained post-surgery hypoglycemia following metastatic gastric cancer treatment. Furthermore, given the potential link with metastatic gastric cancer, which may elude detection via imaging alone, aggressive surgical intervention should be contemplated as a nesidioblastosis treatment strategy. Presentation: 6/3/2024

PS-BPR01-4: A CASE OF ALDOSTERONE-PRODUCING ADENOMA DIAGNOSED BY ADRENAL ARTERIOGRAPHY AND BRANCH SELECTIVE ADRENAL VENOUS SAMPLING

Case report: A 43-year-old man had been followed up for hypertension and hypokalemia, but self-interrupted his hospital visits for the last four years. Based on the serum potassium level of 2.7 mEq/L, plasma aldosterone concentration of 202 pg/mL, and plasma renin activity of 1.1 ng/mL/hr, he was suspected of primary aldosteronism and was admitted to the previous hospital. A saline suppression test and a rapid ACTH stimulation test were both positive, and 24-hr urinary aldosterone level was 19 μg/day under sodium loading of 170 mEq/day, leading to the diagnosis of primary aldosteronism. Since contrast-enhanced CT showed an 8 mm-sized adenoma in the lower portion of the left adrenal gland, an aldosterone-producing adenoma was suspected and a non-segmental adrenal venous sampling (AVS) was performed. However, it yielded apparent bilateral aldosterone suppression in the main trunk of the bilateral adrenal veins, where the aldosterone-to-cortisol (A/C) ratio was lower than that in the inferior vena cava even after ACTH loading. The patient was referred to our hospital for a segmental AVS. Arteriography was first performed from the left inferior adrenal artery to confirm the outflow vessels from the adenoma. Strikingly, there was an aberrant vein which drained into the proximal segment of the left adrenal vein. CT imaging at the time of arteriography revealed, in addition to the known adenoma, a 6 mm-sized micronodule in the lateral region of the left adrenal gland, and the aberrant vein appeared to be the main outflow vessel from the micronodule. A segmental AVS was performed, and blood samples were taken from the bilateral adrenal veins including the aberrant vein and the main trunk of the left adrenal vein proximal to its confluence. The A/C ratio was highest in the aberrant vein, followed by in the main trunk of the proximal left adrenal vein, while it was markedly suppressed in other branches and the main trunk of the left adrenal vein distal to the confluence of the aberrant vein. Based on these results, the presence of aldosterone-producing adenoma in the left adrenal gland was suggested. Laparoscopic partial left adrenalectomy was performed without postoperative complications. Hypertension and hypokalemia were fully resolved afterwards. Conclusions: Adrenal arteriography and segmental AVS should be considered in such cases that apparent bilateral aldosterone suppression is noted in conventional AVS in patients with clinically suspected aldosterone-producing adenoma.

Two Cases of Pembrolizumab-Induced Secondary Adrenal Insufficiency

Title: Two cases of pembrolizumab-induced secondary adrenal insufficiency Background: Although few cases regarding pembrolizumab-induced secondary adrenal insufficiency were reported, it has recently been published that significantly higher prevalence of human leucocyte antigen (HLA)-DR15, B52, and Cw12 was revealed in 11 Japanese patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency as compared with healthy controls and DR15 might be a predictive marker. This is based on the evidence that DR15 has associations with IL-17-mediated autoimmune disease such as Hashimoto’s thyroiditis, and that anti-programmed death 1 (PD-1) inhibitors activate the Th1 and Th17 pathways. We here introduce two Japanese patients with pembrolizumab-induced secondary adrenal insufficiency from a viewpoint of their HLA typing test results. Clinical Case: Case 1. A 52-year old male diagnosed with stage IV lung cancer (squamous non-small cell lung cancer) was treated with chemotherapy consisting of carboplatin, nab-paclitaxel, and pembrolizumab. Six days after the fourth cycle of pembrolizumab, he suffered from hypoglycemia and hyponatremia. Endocrinological examination findings showed ACTH and cortisol deficiency throughout the day, after which a diagnosis of secondary adrenal insufficiency was made based on no response shown in insulin tolerance, anterior pituitary function, and rapid ACTH stimulation tests. Pituitary cell antibody-1 was negative, and no evidence of a swollen/atrophied pituitary gland or space occupying lesion was observed in magnetic resonance imaging (MRI) results. Furthermore, Hashimoto’s thyroiditis was suspected based on anti-thyroid peroxidase antibody positivity. HLA typing test results highly corresponded with the reported results (A24, B52, Cw12, DR4, DR15). Case 2. A 70-year old male was treated with pembrolizumab for recurrence of lung squamous cell carcinoma (stage IV). Two weeks after completion of five cycles, severe diarrhea occurred, suspected to be a side effect of pembrolizumab, which was relieved with temporary use of prednisolone. However, diarrhea recured accompanied with a high fever,eosinophilia, and acute hyponatremia. Based on results showing deficiency of ACTH and cortisol, adrenal insufficiency was suspected. Anterior pituitary function and rapid ACTH stimulation test results supported that diagnosis, while pituitary cell antibody-1 was negative and MRI findings were not remarkable. Notably, completely different HLA typing test results were observed. Conclusion: Similar to the previous report, HLA-A24, B52, Cw12, DR4, and DR15 were found in case 1, whereas all subtypes including HLA-DR15 were lacking in case 2. We think that it should not be given low priority for cases lacking DR15 and the possibility of an association with IL-17 in such cases is required in feature study.

A CASE OF ACROMEGALY COMPLICATED BY PRIMARY ALDOSTERONISM DIAGNOSED DURING THE COURSE OF HEART FAILURE

Objective: [Case] A 32-year-old male was admitted to the Department of Cardiology of our hospital complaining of weight gain, exertional chest pain, dyspnea, and palpitation. He was pointed out hypertension at the age of 18 and started taking oral antihypertensive drugs at the age of 27. Although his high blood pressure was well-controlled with calcium channel blocker, angiotensin receptor blocker, and alpha-and beta-blocker, he had stopped taking medicines since the age of 30. He was diagnosed as congestive heart failure due to hypertensive heart disease and was transferred to our department for the further examination of suspected secondary hypertension after his heart failure was improved. Design and method: Aldosterone / renin activity ratio (ARR) was >= 200, and primary aldosteronism (PA) was suspected. In consideration of his impaired cardiac function, a captopril challenge test and a rapid ACTH stimulation test were conducted. Since both were positive, the diagnosis of PA was made. Although computed tomography (CT) scans revealed a left adrenal adenoma, adrenal venous sampling showed overproductions of aldosterone from both adrenal glands, and thus he was treated with eplerenone, a mineral corticoid receptor blocker. Results: He was also suspected to have acromegaly because he had protruded chin, thickened lips, enlarged nose, and enlarged hands and feet. Brain magnetic resonance (MR) imaging detected a macroadenoma in the pituitary gland. Endocrinological examinations showed high concentrations of serum GH of 7.78 ng/ml and insulin-like growth factor 1 (IGF-1) of 824 ng/ml (+8.8SD), and 75 g oral glucose tolerance test (OGTT) showed a nadir of GH as 5.22 ng/ml, indicating a failure of suppression of GH. Acromegaly was diagnosed and transsphenoidal sinus pituitary surgery was done after monthly intramuscular injections of octreotide 20 mg four times. Conclusions: [Discussion] We experienced a case of acromegaly complicated by PA diagnosed during the course of heart failure. Both acromegaly and PA may be involved in the development of heart failure, however, the combination of acromegaly and PA is rare. We will discuss Its pathophysiology with a literature review.

Malnutrition prevalence in adrenal insufficiency among hospitalized elderly patients: limitations of the body mass index in the assessment of malnutrition.

This study aimed to evaluate malnutrition prevalence and usefulness of the body mass index (BMI) in the assessment of malnutrition in hospitalized elderly patients with adrenal insufficiency (AI). 318 hospitalized AI patients were diagnosed by a rapid ACTH stimulation test with a history of steroid treatment and compared with 374 control patients. Nutrition was assessed using the Malnutrition Universal Screening Tool (MUST). Nutritional status was evaluated using the Mini Nutritional Assessment short form (MNA-SF) and BMI. There was no difference in nutritional screening between the AI and control groups. Nutritional assessments indicated that 31.2% of all elderly patients suffered from malnutrition and 33.8% of patients were at risk of malnutrition. Less than half of the patients (34.9%) were identified as well nourished. In this study, 33.6% vs 29.1% of patients were malnourished in the AI and control group, respectively. Overall, prevalence of malnutrition was higher in the AI group than the control group. In the AI group, patients with low basal cortisol had a higher incidence of malnutrition than those with high basal cortisol. The BMI of patients in the AI group was higher than in the control group. According to BMI criteria, 64.3% of malnourished patients were overweight or obese in the AI group. Elderly AI patients are prone to develop malnutrition despite being overweight or obese. Therefore, more extensive nutritional assessment of elderly patients with AI is required regardless of BMI.

Diagnosis and Management of Addison's Disease in a Nulliparous Woman followed by Successful Pregnancy Outcome in a Rural Tertiary Hospital: A Case Report

Introduction: Addison's disease is a relatively rare endocrine condition requiring life-long glucocorticoid and mineralcorticoid replacement therapy. Women with Addison's disease may have a reduced parity. Addisonian crises, a rare but life-threatening event in pregnant women, may accompany stressful conditions such as labor, puerperium, infection, hyperemesis gravidarum or surgery.Case Presentation: This is a case report of previously healthy 24-year-old nulliparous woman presented with a history of fatigue, fever, diarrhoea and skin darkening. She had pale conjunctiva, low blood pressure, tachycardia, some dehydration, hyperpigmentation of palmer creases, knuckles, buccal mucosa and face. Her serum cortisol was low and rapid ACTH stimulation test with Synacthen showed a poor cortisol response. Patient was immediately managed with IV steroid and later dicharged with oral steroid. After 6 months she became pregnant and the steroid therapy was regulated to avoid adrenal crisis during pregnancy. The patient underwent to caesarean section at 38th week and gave birth to a normal baby.Conclusion: Addisonian crisis represents an endocrine emergency that requires a correct diagnosis with prompt and appropriate salt and steroid replacements to save the patient. Though Addison's disease in women is a risk factor for an adverse pregnancy outcome, it is believed that appropriately treated patients can expect to have uneventful pregnancies of normal duration and without fetal compromise.KYAMC Journal Vol. 7, No.-2, Jan 2017, Page 814-817

Secondary Adrenal Insufficiency Is Associated with Poor Survival Outcomes in Multiple Myeloma

Background: Glucocorticoids has been a backbone of various treatment regimens for multiple myeloma (MM). The repeated and chronic use of high doses of glucocorticoids is associated with development of secondary adrenal insufficiency (AI), and AI could be a major problem in critically-ill patients. However, there has been no specialized data about incidence and clinical significance of secondary AI in hospitalized patients with MM.Purpose: The objective of this retrospective study is to evaluate incidence, predictive factors, and clinical significance of secondary AI in hospitalized patients with MM.Methods: We retrospectively evaluated medical records of MM patients who were hospitalized in Chonnam National University Hwasun Hospital, South Korea from December 2014 to December 2015. The definite AI was diagnosed when the peak cortisol concentration was less than < 500 nmol/L (18 mcg/dL) after ACTH administration.Results: Between December 2014 and December 2015, 77 patients were hospitalized, and 58 underwent rapid ACTH stimulation test. The most frequent cause of hospitalization was infection (70.7%), followed by weakness (24.1%), and the others (5.3%). The definite AI was confirmed in 19 patients (32.7%). To evaluate the predictive factors of AI, all variables including clinical characteristics, laboratory results, cumulative steroid dose, and treatment duration at hospitalization were analyzed, but there were no significant predictors for AI. In addition, the patients with AI had a significantly poor survival outcomes compared to those without AI (the median overall survival of 42.3 months vs. 82.7 months; P = 0.037) (Figure 1).Conclusions: This study showed that the secondary AI is not a rare condition among hospitalized patients with MM, and there was no specific predictable symptoms or signs. In addition, development of AI in the treatment period is associated with a poor prognosis. This study suggests that evaluation of AI is routinely needed in hospitalized patients with MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Disseminated Tuberculosis Causing Addison’s Disease in an Adult Diabetic Patient

Tuberculosis may affect many of the endocrine glands including the hypothalamus, pituitary, thyroid with adrenal gland being the commonest. We describe a patient presented with recurrent spontaneous hypoglycemia, hypotension, fever, weight loss and cough. Along with this clinical picture, high ACTH in the face of low cortisol was compatible with diagnosis of Addison’s disease. Rapid ACTH stimulation test affirmed the diagnosis. Disseminated TB affecting adrenal glands was supported by CXR, USG, CT Abdomen and FNAC. Adrenal Crisis was led by add-on bacterial pneumonia. Patient made good recovery with treatment for adrenal crisis and subsequently with standard antitubercular regimen and steroid replacement therapy. Tuberculosis, although uncommon but potentially devastating cause of adrenal failure, merits consideration when fever, weight loss, gastrointestinal symptoms, hyponatremia, hyperkalemia are observed in patients with features of active tuberculosis or past history of tuberculosisJ Bangladesh Coll Phys Surg 2015; 33(1): 44-47

Free cortisol/cortisone ratio in pooled urine was increased after rapid-ACTH stimulation test under dexamethasone suppression

We employ rapid-ACTH stimulation test under dexamethasone (DEX) suppression to assess the adrenal function in daily clinic. However, we have little knowledge about the excretion of urinary free cortisol (FF) and cortisone (FE) in pooled urine in this setting. The purpose was to examine the changes of FF and FE as well as FF/FE ratio in pooled urine after rapid-ACTH stimulation test under DEX suppression using stable isotope dilution-gas chromatography/mass spectrometry (SID-GC/MS). Pooled urine samples were collected from 8 patients (age 33-71 years) who were suspected to have primary aldsteronism. They all were finally diagnosed as having normal glucocorticoid secretion. We performed rapid-ACTH stimulation test with DEX suppression for consecutive 4 days as follows. (1) 24 hour urine samples were serially collected from 2300 h on day 1 for 72 hours (Basal, DEX1mg, and DEX8mg-ACTH). (2) 1 and 8 mg DEX was given at 2300 h on day 2 and 3, respectively. (3) 250 µg of ACTH was given at 0900 h on day 4. Urine free steroids were delivered with bismethylenedioxy-heptafluorobutyric anhydride and analyzed by SID-GC/MS (µg/day). From DEX1mg to DXE8mg-ACTH, (1) FF and FE were significantly increased (3.9±1.3 to 21.3±14.6 and 12.4±4.8 to 26.1±11.0 µg/day, respectively), but (2) FF/FE ratio significantly increased (0.32±0.05 to 0.77±0.23). These data suggested that newly synthesized cortisol by ACTH stimulation was not efficiently metabolized to cortisone.

A Case Report of Bilateral Adrenocortical Carcinoma Complicated by Adrenal Insufficiency

Adrenocortical carcinoma is often functional and presents with signs and symptoms of adrenal steroid hormone excess. Adrenal insufficiency secondary to bilateral adrenocortical carcinoma is a particularly rare complication. We recently encountered a case of bilateral adrenocortical carcinoma complicated by adrenal insufficiency. A 52-year-old male was transferred to this hospital com plaining of general weakness and weight loss. A bilateral adrenal mass was detected on abdomen CT. Plasma cortisol and aldosterone failed to rise during the rapid ACTH stimulation test. The CT-guided adrenal biopsy revealed findings consistent with adreno cortical carcinoma. Left hemiparesis was developed and brain metastasis was detected via brain MRI. Despite the application of gamma knife surgery and chemotherapy, the disease progressed and the patient died. (Endocrinol Metab 26:243-247, 2011)

Significance of Corticosteroids and Their Relationship with Other Parameters in Patients with Sepsis

Background: Corticosteroids are known to be significant prognostic parameters in sepsis. Recently, an absolute and relative insufficiency of the corticosteroids system has often been reported to often develop particularly in severe sepsis. Degree of such an adrenal insufficiency not only has prognostic implications but also can be used to guide corticosteroids replacement therapy. The 24-hour urinary cortisol levels as well as serum cortisol concentrations were measured to assess the clinical significance and their relationship with the other parameters of sepsis, and also evaluated the clinical implications of the relative adrenal insufficiency. Methods: 26 consecutive patients with sepsis were enrolled. The basal random serum cortisol, ACTH, ADH, lactate levels and 24-hour urinary free cortisol amount were measured. The rapid ACTH (250 μg) stimulation test was also performed. Results: Basal serum cortisol levels were higher in the non-survivors than in the survivors. The 24-hour urinary free cortisol levels were higher in the patients with severe sepsis than in those without. The serum cortisol levels strongly correlated with the serum ADH and lactate levels. The 24-hour urinary free cortisol levels strongly correlated with the serum cortisol and lactate levels. The fractional changes in the cortisol levels after the rapid ACTH stimulation tests correlated with the serum cortisol, ADH, and lactate levels. Conclusion: Both the serum cortisol and 24-hour urinary cortisol were found to be significant prognostic factors in sepsis, and showed a strong correlation with the other parameters. The relative adrenal insufficiency might also be an important clinical parameter. (Tuberc Respir Dis 2006; 61: 356-365)

Hemophagocytic Syndrome Associated with Bilateral Adrenal Gland Tuberculosis

We report a case of a patient who presented with hemophagocytic syndrome (HPS) and adrenal crisis associated with bilateral adrenal gland tuberculosis, and resulted in a poor outcome. A 50-year-old man was transferred to our hospital from a local clinic due to fever, weight loss, and bilateral adrenal masses. Laboratory findings showed leukopenia, mild anemia, and elevated lactate dehydrogenase. Computed tomography (CT) of the abdomen revealed bilateral adrenal masses and hepatosplenomegaly. CT-guided adrenal gland biopsy showed numerous epithelioid cells and infiltration with caseous necrosis consistent with tuberculosis. Bone marrow aspiration and biopsy showed significant hemophagocytosis without evidence of malignancy, hence HPS associated with bilateral adrenal tuberculosis was diagnosed. During anti-tuberculosis treatment the patient showed recurrent hypoglycemia and hypotension. Rapid ACTH stimulation test revealed adrenal insufficiency, and we added corticosteroid treatment. But pancytopenia, especially thrombocytopenia, persisted and repeated bone marrow aspiration showed continued hemophagocytosis. On treatment day 41 multiple organ failure occurred in the patient during anti-tuberculous treatment and steroid replacement.

Effect of Inhaled Fluticasone Propionate on Hypothalamic-Pituitary-Adrenal Axis in Bronchial Asthma Patient

Background : Inhaled glucocorticoids are the medical treatment of choice in asthma patients. Fluticasone propionate is one of the most effective inhaled corticosteroids and has been reported to have minimal effect on the hypothalamic-pituitary-adrenal axis at the recommended dose. However, reports of long-term trials characterizing their systemic safety with chronic use are rare. This study was designed to evaluate the long-term safety of inhaled fluticasone propionate to the hypothalamic-pituitary-adrenal axis. Method : This study was conducted on 21 patients to evaluate the adrenal response to rapid ACTH stimulation test after 6 months of treatment with fluticasone propionate from to daily. The serum cortisol levels was measured to assess its effect on the hypothalamic-pituitary-adrenal axis just prior to the injection, at 30 minutes and 60 minutes after an intramuscular injection of synthetic ACTH. Result : The mean dose of inhaled fluticasone propionate was per day(SD=, range= to ). The mean serum cortisol levels of the patients was (SD=) prior to the injection, (SD=) after 30 minutes, and (SD=) after 60 minutes. Sixteen patients of the 21 patients had a normal response(> ), and 5 out of the 21 patients had serum cortisol levels below the normal range after the rapid ACTH stimulation test. Conclusion: Adrenal suppression occurred in 5 out of 21 patients with 6 months treatment with inhaled fluticasone propionate.

Reproducibility of the cortisol response to stimulation with the low dose (1 microg) of ACTH.

Previous studies have shown that the rapid ACTH stimulation test using a low dose of 1 microg is more sensitive than that using 250 microg ACTH for detecting subtle cases of adrenal insufficiency. However, there are controversies for the reproducibility of the 1 microg-test. To evaluate the reproducibility of the 1 microg-test, we assessed both day-to-day and diurnal variations of cortisol responses to 1 microg ACTH injection. In addition, optimum sampling time for the 1 microg-test was also determined. AND DESIGN Eight healthy volunteers and five patients with secondary adrenal insufficiency were recruited. Healthy subjects were given 1 microg ACTH 3 times in the morning (0800 h) and 2 times in the afternoon (1600 h). Patients with adrenal insufficiency had 2-tests in the morning and 2 in the afternoon. Serum cortisol levels were measured every 10 minutes for 1 h after the injection. In healthy subjects, basal and peak serum cortisol levels were significantly higher in the morning (P < 0.05), whereas maximum cortisol increments were higher in the afternoon (P < 0.001). In patients with adrenal insufficiency, basal and peak serum cortisol levels in the morning were not different from corresponding values in the afternoon. Intra-individual coefficient of variation (CV) of peak serum cortisol response to 1 microg ACTH ranged from 3.0 to 16.4% in healthy subjects and 10.0-34. 4% in patients. Also, there was a significant correlation between peak morning or afternoon cortisol levels after 1 microg ACTH injection given in different days in both healthy subjects and patients. Twenty-six of the 40 studies in healthy subjects showed peak response at 20 minutes, while nine showed it at 30 minutes Using the data acquired at 20 and 30 minutes, all 40 studies in healthy subjects showed normal results while none of 20 studies in patients was normal. We conclude that the cortisol response to 1 microg ACTH stimulation was reproducible in both healthy subjects and patients with secondary adrenal insufficiency. In order to assess adrenal function more accurately with the 1 microg ACTH stimulation test, serum cortisol should be measured before and 20 and 30 minutes after ACTH injection.

The Low Dose (1-μg) Adrenocorticotropin Stimulation Test in the Evaluation of Patients with Suspected Central Adrenal Insufficiency

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 microg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 microg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-microg test performs significantly better than the 250-microg test compared to the gold standard, insulin tolerance test. We suggest that the 1-microg ACTH stimulation test replace the conventional 250-microg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-microg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-microg vials.

Prevalence of cortisol deficiency in late HIV disease

In order to determine the prevalence of cortisol deficiency in advanced HIV disease and to examine whether it may be predicted by clinical features or biochemical abnormalities, we conducted a prospective study which assessed responses to a rapid ACTH stimulation test (short-duration synthetic corticotrophin test, synacthen test) in HIV-positive patients with a CD4 count of < or = 50 x 10(6)/l. Subjective fatigue, postural drop in blood pressure, electrolyte changes, presence of concurrent opportunist infection and drug treatment were recorded. Cortisol responses were defined as 'normal' (a post stimulation cortisol level > or = 450 nmol/l), 'abnormal' (post stimulation cortisol level < 350 nmol/l) or 'impaired' (an intermediate response). Of 49 patients tested (42 male, seven female), a suboptimal response (abnormal or impaired) was found in 14 (29%) and frank insufficiency in eight (16%). Cortisol deficiency was not predicted by postural drop in blood pressure, biochemistry or symptoms of fatigue. Patients with an impaired/abnormal test were not more likely to have cytomegalovirus or mycobacterial disease but were more likely to be taking megestrol acetate (P = 0.05, Fisher's exact test). Two of three patients with initially normal tests developed impaired/abnormal cortisol responses on re-testing 6-9 months later. Cortisol deficiency is common in late stage HIV disease, but symptoms of fatigue and postural hypotension, as well as biochemical findings, are poor predictors of cortisol deficiency. We found good subjective response to therapy. Routine screening by a rapid ACTH stimulation test is recommended in HIV-positive patients with CD4 count < or = 50 x 10(6)/l. Re-testing at regular intervals may be necessary. The interaction between megestrol acetate, cortisol metabolism and synacthen testing requires further investigation.

Menopause Related Changes of Adrenocortical Steroid Production

To elucidate changes of adrenocortical steroid production with age, reproductive age (n = 14), peri-menopausal (n = 12) and post-menopausal (n = 13) women were studied using basal hormone levels and the results of a rapid ACTH stimulation test. Peripheral serum levels of pregnenolone, 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone and androstenedione were measured by RIA. The basal levels of all steroids except pregnenolone decreased with age. A significant increase in the levels of all steroids after ACTH stimulation was observed in all subjects. Although, there was an age related decrease in the response of C19-steroids to ACTH, the response of pregnenolone and 17 alpha-hydroxyprogesterone to ACTH did not alter with age. The preserved response of 17 alpha-hydroxyprogesterone to ACTH in post-menopausal women suggests that 17 alpha-hydroxyprogesterone production plays a role in the age independency of cortisol. In the present paper, the changes in the capacity of the post-menopausal adrenal cortex to produce androgens and C21-steroids were demonstrated.