Low-dose Test Research Articles

Normal Short Synacthen Test in Patients with Secondary Adrenal Failure

The short synacthen test (SST), first introduced by Wood et al. 1 in 1965, is widely used to confirm the diagnosis of primary adrenal insufficiency. The optimum method for the diagnosis of secondary adrenal insufficiency remains controversial. The insulin tolerance test (ITT) is accepted by most endocrinologists as the gold standard 2 for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis, but is hazardous at times, with some morbidity and occasional mortality. The short synacthen test is gaining popularity, and by 1994, up to 50% of UK endocrinologists were using it to assess the HPA axis. 3 We describe two cases presenting with hyponatremia in whom hypoadrenalism was suspected, but with normal SST. The secondary adrenal insufficiency was later confirmed in these cases on clinical features, associated hormonal deficiencies, ancillary investigations and most important of all, the therapeutic response to replacement steroids. Case 1 A 63-year-old male presented with a history of six to seven episodes of fainting/loss of consciousness over the previous year-and-a-half. These episodes were never preceded by any palpitations or associated with seizure activity and/or incontinence of urine or feces. He also experienced occasional nausea with vomiting. He was labelled to have ischemic heart disease on the basis of ECG changes, but did not have angina and was taking diltiazem, moduretic (amiloride and hydrochlorothiazide), ranitidine and amitriptyline regularly. He appeared unwell upon admission, and was pale-looking, with a pulse of 90/min. His blood pressure was in the range of 120-140 mm Hg systolic and 70 mm Hg diastolic, but with a significant postural drop of 20 mm Hg. The rest of the examination was unremarkable. Routine investigations revealed serum sodium of 112 mmol/L, potassium of 3.3 mmol/L, and creatinine of 1.0 mg/dL. It was thought that electrolyte imbalance was due to diuretics and associated vomiting. He was rehydrated with normal saline and the

Standard and Low-Dose Short Adrenocorticotropin Test Compared with Insulin-Induced Hypoglycemia for Assessment of the Hypothalamic-Pituitary-Adrenal Axis in Children with Idiopathic Multiple Pituitary Hormone Deficiencies

Standard and Low-Dose Short Adrenocorticotropin Test Compared with Insulin-Induced Hypoglycemia for Assessment of the Hypothalamic-Pituitary-Adrenal Axis in Children with Idiopathic Multiple Pituitary Hormone Deficiencies

Pre-Cushing’s syndrome not recognized by conventional dexamethasone suppression-tests in an adrenal “incidentaloma” patient

Pre-Cushing's syndrome has been recently diagnosed in 6-12% of patients affected with incidentally discovered adrenal masses. Some of these patients have been described to show transient hypoadrenalism after surgery, similarly to those affected with overt Cushing's syndrome. We studied a 70-year-old male patient with a large left adrenal mass, incidentally discovered, who displayed 24-h urinary free cortisol levels at the upper limit of the normal range, normal dexamethasone overnight and low-dose suppression tests and not suppressed ACTH levels, increased 17-hydroxyprogesterone response to ACTH stimulation and low upright plasma renin activity with normal serum aldosterone levels; furthermore, DHEAS level was low and 75 Selenium-cholesterol scintigraphy showed unilateral uptake concordant with the side of the mass. Soon after left adrenalectomy, he complained of acute hypoadrenalism requiring cortisol replacement therapy: ten months after surgery he is still hypoadrenal. Moreover, stimulated 17-hydroxyprogesterone and plasma renin activity in clino- and orthostatic posture have become normal. We propose that conventional dexamethasone suppression-tests may be not enough sensitive in this kind of patients and that in selected cases the absence of controlateral uptake at scintigraphy may be more reliable in predicting post-surgical hypoadrenalism.

One microgram is the lowest ACTH dose to cause a maximal cortisol response. There is no diurnal variation of cortisol response to submaximal ACTH stimulation

There are many suggestions in the literature that the adrenal gland is more sensitive to ACTH in the evening than in the morning. However, all these studies in humans were conducted when the basal cortisol level was not suppressed, and were based on the observation that, after stimulation, the increases in cortisol differed, though the peak values were the same. To examine this, we established the lowest ACTH dose that caused a maximal cortisol stimulation even when the basal cortisol was suppressed, and used a smaller dose of ACTH for morning and evening stimulation. The lowest ACTH dose to achieve maximal stimulation was found to be 1.0 microgram, with which dose cortisol concentration increased to 607.2 +/- 182 nmol/l, compared with 612.7 +/- 140.8 nmol/l with the 250 micrograms test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0.6 microgram) achieved significantly lower cortisol responses (312 +/- 179.4 and 323 +/- 157.3 nmol/l respectively; both P < 0.01 compared with the 1 microgram test). When a submaximal ACTH dose (0.6 microgram) was used to stimulate the adrenal at 0800 and 1600 h, after pretreatment with dexamethasone, no difference in response was noted at either 15 min (372.6 +/- 116 compared with 394.7 +/- 129.7 nmol/l) or 30 min (397.4 +/- 176.6 compared with 403 +/- 226.3 nmol/l; P > 0.3 for both times). These results show that 1.0 microgram ACTH, used latterly as a low-dose test, is very potent in stimulating the adrenal, even when baseline cortisol is suppressed; smaller doses cause reduction of this potency. Our data show that there is probably no diurnal variation in the response of the adrenal to ACTH, if one eliminates the influence of the basal cortisol level and uses physiologic rather than superphysiologic stimuli.

Le test aux androgènes : comparaison d'un test faible et d'un test fort sur le développement du pénis dans les pseudohermaphrodismes masculins

The androgen sensitivity test used in male pseudohermaphroditism for clinical assessment of the androgen sensitivity and prediction of penile development is an important element in choice of gender. However, there is a wide range of testosterone dosage and no standardized test. Two doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18 months). The clinical results were compared with those of the study of androgen receptors. In two cases, both low-dose and high-dose tests resulted in only minimal changes in the penis. In two cases, the low-dose test gave a good result which was confirmed by the high-dose test; on the other hand, in two cases, the low-dose test was considered to be negative whereas the high-dose test led to the development of a normal-sized penis. In all cases except one, there was good concordance between the results of study of androgen receptors and those of the clinical test. The high-dose androgen test is thus useful in both diagnosis and treatment and facilitates the gender assignment.

Use of low- and high-dose dexamethasone tests for distinguishing pituitary-dependent from adrenal tumor hyperadrenocorticism in dogs

Objective To evaluate low- and high-dose dexamethasone suppression tests for differentiating pituitary dependent hyperadrenocorticism (PDH) from adrenal tumor hyperadrenocorticism (ATH) in dogs. Design Prospective study. Animals 181 dogs with PDH and 35 dogs with ATH. Procedure Plasma Cortisol concentrations from dogs with naturally developing hyperadrenocorticism were evaluated before, and 4 and 8 hours after administration of standard low- and high-doses of dexamethasone (0.01 mg/kg of body weight, IV, and 0.1 mg/kg, IV; respectively). Results In response to the low-dose test, all but 3 dogs had an 8-hour post-dexamethasone plasma Cortisol concentration that was consistent with a diagnosis of hyperadrenocorticism, that is, ≥ 1.4 μg/dl. Criteria used to distinguish PDH from ATH in response to low-dose dexamethasone included a 4-hour post-dexamethasone plasma Cortisol concentration &lt; 50% of the basal value or &lt; 1.4 μg/dl, or an 8-hour post-dexamethasone plasma Cortisol concentration &lt; 50% of the basal concentration. Criteria used to distinguish PDH from ATH in response to high-dose dexamethasone included 4- or 8-hour post-dexamethasone plasma Cortisol concentrations &lt; 50% of the basal concentration or &lt; 1.4 μg/dl. In response to the low-dose test, 111 dogs met criteria for suppression (each had PDH). In response to the high-dose test, 137 dogs met criteria for suppression (2 had ATH, 135 had PDH). Twenty-six dogs with PDH (12%) had indications of adrenal suppression in response to high-dose but not low-dose testing. Clinical Implications Low-dose dexamethasone test has value as a discrimination test to distinguish dogs with PDH from those with ATH. The high-dose test need only be considered in dogs with hyperadrenocorticism that do not have adrenal suppression in response to the low-dose test. (J Am Vet Med Assoc 1996;209:772–775)

Effect of β-blockade on dobutamine stress echocardiography

Dobutamine is an effective pharmacologic stress used in conjunction with echocardiography because of its β-agonist properties. Concurrent β-blockade might after this effectiveness; however, current clinical experience has been variable. The purpose of this study is to determine whether concurrent β-blockade alters the ability of a dobutamine stress echocardiogram to detect a fixed coronary stenosis by preventing the onset of a wall motion abnormality or by altering the dose at which the wall motion abnormality appears. Paired dobutamine stress tests with and without β-blockade (esmolol 500 μg/kg initial bolus, 100 μg/kg/min infusion) were performed in a canine model ( n = 8) with a fixed single-vessel coronary stenosis. Heart rate, systolic pressure, proximal left anterior descending coronary flow, myocardial thickening (by sonomicrometry), and left ventricular area change (by epicardial echocardiography) were monitored. Simultaneous β-blockade resulted in (1) a delayed and diminished increase in hemodynamic parameters (peak heart rate 164.1 ± 22.3 without β-blockade vs 110.1 ± 28.9 beats/min with β-blockade, p < 0.001, and peak systolic blood pressure 137.9 ± 26.8 mm Hg without β-blockade vs 107.3 ± 15.3 mm Hg with β-blockade, p = 0.01), (2) an elimination of the physiologic effects of low-dose (5 and 10 μg/kg/min) dobutamine (−0.7% ± 16.7% change in myocardial thickening from baseline with β-blockade, p = NS), and (3) an elimination or alteration in timing of inducible wall motion abnormalities caused by severe coronary artery stenoses (mean termination dose 28.8 ± 9.9 with β-blockade vs 15.6 ± 6.1 μg/kg/min without β-blocker, p < 0.01). The findings in this canine model suggest that the competitive antagonist markedly attenuates the ability of dobutamine stress echocardiography to detect a significant coronary lesion and may alter its ability to detect viable myocardium at low-dose testing. Further clinical studies to determine the sensitivity of dobutamine stress echocardiography in the presence of β-blockers and to establish protocol standards are necessary.

Prognostic significance of low-dose dobutamine test in patients with advanced congestive heart failure due to dilated cardiomyopathy

Prognostic significance of low-dose dobutamine test in patients with advanced congestive heart failure due to dilated cardiomyopathy

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests. ARBD was considered to be present when > 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive (> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was > 15 micrograms/g wet weight and/or the Aluminon staining was positive (> 0%). Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH > 650 ng/l had a positive staining (> 0%) even when the bone aluminium level was elevated (> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively. The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.

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.

Enhanced pharmacological testing in patients with erectile dysfunction.

This study was designed to evaluate the practical use of the combination of a low-dose intracavernous injection test (ICI) and visual erotic stimulation (VES) in the assessment of patients with erectile dysfunction. Additionally, a postinvestigation questionnaire (PIQ) was used to rate the erection following the investigation when the patient had left the office. It was hypothesized that the combination (ICIVES) and the PIQ would yield a higher erectile response rate than ICI or VES alone and would minimize the occurrence of prolonged erection. Of the 90 patients studied, 17 (19%) showed adequate erections to VES, 10 (11%) to ICI, and 60 (67%) to ICIVES. Of the 30 non-responders, 7 (23%) reported adequate erections on the PIQ. Overall, in 75% of the patients adequate erections were achieved. No prolonged erections were encountered. It is concluded that the combination of a low-dose ICI and VES, and the application of a postinvestigation questionnaire, is a powerful and safe test to select patients for autoinjection therapy.

Loperamide to Diagnose Cushing's Syndrome

To the Editor. —We read with great interest the article by Yanovski et al. 1 Yanovski et al report that the dexamethasone— corticotropin-releasing hormone (CRH) test is a useful test to distinguish patients with Cushing's syndrome from those with a pseudo-Cushing's state. In fact, in the experience of Yanovski et al, the evaluation of cortisol levels 15 minutes after CRH injection, performed after the low-dose dexamethasone test, yields 100% sensitivity, specificity, and diagnostic accuracy. Therefore, Yanovski et al recommend its use as a more accurate procedure to distinguish Cushing's syndrome. In recent years, we proposed the use of loperamide hydrochloride for screening patients with suspected hypercortisolism. Loperamide is a drug that acts as an opiate agonist and is able to inhibit corticotropin levels in normal subjects and in patients with Addison's disease, but not in patients with Cushing's syndrome. 2 In fact, the opioidergic control of corticotropin secretion is operating

Inhibitory effect of circulating insulin on glucagon secretion during hypoglycemia in type I diabetic patients.

To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.

Consider Magnesium Homeostasis

All physicians must learn about magnesium (Mg) balance. If the serum Mg or red cell Mg is low, the patient is in a state of negative Mg balance. Even if they are both normal, Mg deficiency or negative Mg balance may be present. In such cases, a low-dose Mg load test needs to be done. Childbearing females and premature neonates are at risk for Mg deficiency. Oral repletion can be accomplished with Mg gluconate, and a technique is suggested.

Intravenous dexamethasone and subsequent ACTH test in comparison with dexamethasone oral test in the diagnosis of Cushing’s syndrome: A report of 20 cases

Dexamethasone inhibits ACTH secretion in the pituitary corticotropic cells of normal subjects; this ability is variously affected in Cushing's syndrome. The iv infusion of dexamethasone is not time consuming, nor it is influenced by the variability of intestinal absorption or hepatic metabolism, as occurs with oral administration. Iv dexamethasone (1.5 mg/h) over 7 h and an ACTH bolus at the 6th h were administered to 17 patients with Cushing's disease, 3 patients with Cushing's syndrome (2 with adrenal adenoma, 1 with ectopic ACTH secretion) and 13 normal subjects. After 4 days the 20 patients were also given the standard oral low-dose and high-dose dexamethasone test. Two h after starting the drug infusion, cortisol concentrations were inhibited by more than 50% in each control subject. In contrast, in all but one patient they remained higher than 50% over the baseline. At the 6th heach control subject and 15 of the 17 patients with Cushing's disease showed an inhibition of plasma cortisol concentration which was greater than 50%. Inhibition was less than 50% in 2 patients with Cushing's disease and in the 3 patients with non-pituitary dependent Cushing's syndrome. The sensitivity and specificity of this test are comparable with those of the dexamethasone oral test. Although statistically significant, results obtained from ACTH bolus were not sufficiently discriminating. If studies conducted on a larger population confirm these preliminary data, the rapidity and reliability of the dexamethasone infusion test could make it an important new tool in diagnosing Cushing's syndrome.

Geometrical properties of a digital beam attenuator system.

A digital beam attenuator system has been developed to automatically generate patient-specific compensating filters for chest radiography. An initial low-dose test image is used to generate the attenuator, which is fabricated by overprinting multiple layers of a heavy-metal material onto a nonattenuating substrate. The attenuator is subsequently inserted into the x-ray beam for a final compensated radiograph. The effects of focal spot blurring and limited attenuator resolution result in the final compensated image containing only high-spatial frequency information. The frequency response of the process is not strictly describable by a modulation transfer function, but an approximation of the frequencies remaining in the compensated image is obtained for low-contrast conditions. It is found that a 4 X 4 blurring function on the original 64 X 64 test image is required for the attenuator to give appropriate compensated image appearance. A proposed attenuator printing scheme prints the attenuator in a 16 X 16 matrix, staggering successively printed layers to achieve the required 64 X 64 sampling with appropriate blurring. The resulting compensated image has good anatomical definition and contains a frequency response similar to that obtained by compensation techniques being investigated by Plewes and Sorenson.

Digital beam attenuator technique for compensated chest radiography.

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.