Scintigraphy of incidentally discovered bilateral adrenal masses.

The purpose of this study was to determine the patterns of iodine-131 6 beta-iodomethylnorcholesterol (NP-59) imaging and the correlation with computed tomography (CT)-guided adrenal biopsy and follow-up in patients with bilateral adrenal masses. To this end we investigated a consecutive sample of 29 euadrenal patients with bilateral adrenal masses discovered on CT for reasons other than suspected adrenal disease. Adrenal scintigraphy was performed using 1 mCi of NP-59 injected intravenously, with gamma camera imaging 5-7 days later. In 13 of the 29 patients bilateral adrenal masses were the result of metastatic involvement from lung carcinoma (5), lymphoma (3), adrenocarcinoma of the colon (3), squamous cell carcinoma of the larynx (1), and anaplastic carcinoma of unknown primary (1). Among these cases the NP-59 scan demonstrated either bilaterally absent tracer accumulation (in eight, all with bilateral metastases proven by CT-guided biopsy or progression on follow-up CT) or marked asymmetry of adrenocortical NP-59 uptake (in five). Biopsy of the adrenal demonstrating the least NP-59 uptake documented malignant involvement of that gland in five of five patients. In two patients an adenoma was found simultaneously in one adrenal with a contralateral malignant adrenal mass. In each of these cases, the adenoma demonstrated the greatest NP-59 uptake. In 16 patients diagnosis of adenoma was made on the basis of (a) CT-guided adrenal biopsy of the gland with the greatest NP-59 uptake of the pair (n = 4), or (b) adrenalectomy (n = 2), or (c) absence of change in the size of the adrenal mass on follow-up CT scanning performed 6 months to 3 years later (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes and pregnancy. Factors associated with seeking pre-conception care.

OBJECTIVE: To define sociodemographic characteristics, medical factors, knowledge, attitudes, and health-related behaviors that distinguish women with established diabetes who seek pre-conception care from those who seek care only after conception. RESEARCH DESIGN AND METHODS: A multicenter, case-control study of women with established diabetes making their first pre-conception visit (n = 57) or first prenatal visit without having received pre-conception care (n = 97). RESULTS: Pre-conception subjects were significantly more likely to be married (93 vs. 51%), living with their partners (93 vs. 60%), and employed (78 vs. 41%); to have higher levels of education (73% beyond high school vs. 41%) and income (86% > $20,000 vs. 60%); and to have insulin-dependent diabetes mellitus (IDDM) (93 vs. 81%). Pre-conception subjects with IDDM were more likely to have discussed pre-conception care with their health care providers (98 vs. 51%) and to have been encouraged to get it (77 vs. 43%). In the prenatal group, only 24% of pregnancies were planned. Pre-conception patients were more knowledgeable about diabetes, perceived greater benefits of pre-conception care, and received more instrumental support. CONCLUSIONS: Only about one-third of women with established diabetes receive pre-conception care. Interventions must address prevention of unintended pregnancy. Providers must regard every visit with a diabetic woman as a pre-conception visit. Contraception must be explicitly discussed, and pregnancies should be planned. In counseling, the benefits of pre-conception care should be stressed and the support of families and friends should be elicited.

Hypothalamic atrophy presenting as amenorrhea and sexual infantilism in a female adolescent. A case report.

A 17-year-old girl presented with amenorrhea, sexual immaturity and a remote history of head trauma. Provocative testing of the pituitary with thyrotropin releasing hormone, gonadotropin releasing hormone and insulin-induced hypoglycemia revealed intact pituitary function, with hypothalamic insufficiency. Furthermore, magnetic resonance imaging of the brain demonstrated loss of the hypothalamic infundibulum. To our knowledge, these structural defects have not been found with magnetic resonance imaging in cases of hypothalamic atrophy. This case suggests that the infundibulum or pituitary stalk may be vulnerable to traumatic damage, leading to hypothalamic insufficiency persisting into adulthood.

Scintigraphic evaluation of clinically silent adrenal masses.

UNLABELLED: We studied 229 patients with abnormal adrenal anatomy depicted by CT who were without biochemical evidence of endocrine dysfunction using the presence of 131I-6 beta-iodomethyl-nor-cholesterol (NP-59) adrenal gland uptake as an index of differential adrenal function in the evaluation of the clinically "silent" adrenal mass lesion. METHODS: NP-59 (1 mCi) was injected intravenously with posterior and lateral abdominal images obtained 5-7 days postinjection. RESULTS: One-hundred and fifty-nine of 185 patients with unilateral adrenal enlargement on CT had scintigraphic evidence that the mass represented a functioning (NP-59 avid) but not hypersecretory, (biochemically normal) adrenal cortical adenoma (concordant imaging pattern). Forty-one of 44 patients with intra-adrenal neoplasms were depicted on scintigraphy as decreased or absent NP-59 accumulation on the side of the adrenal mass (discordant imaging pattern). In this study, sensitivity was 71% (41 of 58 patients; 95% confidence interval (CI), 58% to 88%); specificity was 100% (171 of 171 patients; 95% CI, 95% to 100%) and accuracy was 93% (212 of 229 patients; 95% CI, 88% to 96%). CONCLUSIONS: These data confirm our earlier observations that the functional information depicted by scintigraphy complements the morphological evaluation by CT and in the absence of hormonal dysfunction, the presence of concordant CT and 131I-NP-59 scans are characteristic of functioning, but not hypersecretory, benign adrenocortical adenomas. Conversely, discordant CT and 131I-NP-59 scans are suggestive of nonfunctioning, space-occupying, adrenal lesions.

Atrial natriuretic factor in the elderly: diminished response to epinephrine.

We have previously found that epinephrine (EPI) increases plasma immunoreactive atrial natriuretic factor (irANF) in young human subjects. Because elderly humans have decreased sensitivity to adrenergic stimulation, we compared plasma irANF responses to intravenous infusion of EPI, 5 micrograms/min for 80 min in six young (ages 20-29) and nine old (ages 62-75) healthy subjects. In addition, we measured plasma irANF responses of the nine old subjects to 1 liter of normal saline infused over 30 min. Young and old subjects had similar basal EPI levels [108 +/- 18 vs. 106 +/- 10 (SE) pg/ml], but basal irANF levels tended to be higher in the old (32 +/- 7 vs. 50 +/- 8 pmol/l, P = 0.15). The young subjects had a significant increase in irANF levels after the EPI infusion (32 +/- 7 vs. 59 +/- 11 pmol/l, P less than 0.02), but there was no change in irANF in the old (50 +/- 8 vs. 48 +/- 7 pmol/l) despite similar plasma EPI levels in young and old (1,125 +/- 57 vs. 1,183 +/- 52 pg/ml). In contrast, the irANF response of the old subjects to saline infusion was striking: all nine subjects demonstrated a rise in irANF (P less than 0.01); mean levels increased from 54 +/- 4 pmol/l to a peak of 122 +/- 23 pmol/l. We conclude that healthy elderly subjects have a defect in EPI-stimulated ANF secretion, a finding compatible with other evidence for diminished sensitivity to adrenergic stimulation in aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine kinetics in humans: radiotracer methodology.

The use of the plasma epinephrine (EPI) level as an index of adrenomedullary activity in humans is complicated by the rapid removal of EPI from plasma by many tissues. To determine whether the kinetics of distribution and metabolism of EPI could be best quantified using the isotope dilution method or a mathematical modeling technique, eight human subjects received a [3H]EPI infusion for 50-60 min. Analysis of the steady state arterialized plasma levels of EPI and [3H]EPI using the isotope dilution technique showed that the basal plasma EPI appearance rate is 0.87 +/- 0.11 nmol/m2.min, and the basal plasma EPI clearance rate is 1.63 +/- 0.14 L/min.m2. Mathematical modeling of the [3H]EPI levels revealed that a biexponential curve fit was superior to monoexponential and triexponential curve fits. A two-compartment model was the minimal compartment model that accurately described EPI kinetics. The basal plasma EPI appearance (0.82 +/- 0.16 nmol/m2.min) and EPI clearance (1.67 +/- 0.15 L/min.m2) rates that were estimated from this two-compartment model are similar to the results derived from the isotope dilution method. Mathematical modeling revealed a large extravascular mass of EPI. We conclude that the isotope dilution and mathematical modeling techniques similarly describe plasma EPI kinetics in humans. Kinetic analysis using mathematical modeling provides new insights into adrenomedullary function in humans.

Altered norepinephrine metabolism in Shapiro's syndrome.

We studied a 66-year-old woman with spontaneous periodic hypothermia (Shapiro's syndrome) to determine the mechanisms that result in increased plasma norepinephrine (NE) levels. In comparison with age-matched control subjects, compartmental analysis of NE kinetics revealed an increased NE release rate into the extravascular compartment and decreases in NE clearance and volume of distribution of NE in the intravascular compartment. Clonidine therapy was associated with an initial dramatic decrease in the frequency of diaphoretic episodes as well as with a fall in NE release rate and increases in NE clearance and volume of distribution. We conclude that increased NE release and decreased plasma NE clearance result in elevated plasma NE levels in Shapiro's syndrome. Clonidine, which was associated with changes in NE kinetics, may provide effective treatment for this disorder.

Effect of sodium-restricted diet and posture on norepinephrine kinetics in humans.

We used compartmental analysis to analyze the kinetics of distribution and metabolism of norepinephrine (NE) and to determine whether the increase in plasma norepinephrine concentration (PNE) during sodium restriction in humans is due to sympathetic nervous system (SNS) activation. [3H]-NE infusion and postinfusion decay were measured in young subjects in the supine position and during 60 min of standing during normal sodium (NS) diet and after 7 days of 10 meq/day sodium-restricted (SR) diet. The mean supine PNE was greater during SR diet compared with NS diet (154 +/- 9 vs. 185 +/- 12 pg/ml, P = 0.02, n = 10). During both NS and SR diets, upright PNE increased (163 +/- 4 vs. 359 +/- 38 pg/ml and 182 +/- 8 vs. 401 +/- 26 pg/ml, respectively, multivariate one-way analysis of variance, P less than 0.001, alpha = 0.05). The increases of PNE with both SR diet and upright posture were accompanied by a fall in NE metabolic clearance rate (MCR1). During SR diet this was due to a fall in the volume of distribution of NE (6.1 +/- 0.4 vs. 5.0 +/- 0.4 liters, P = 0.003, n = 10). In contrast to the effect of upright posture to increase NE release into the extra-vascular compartment (NE2), during SR diet there was no change in NE2 (1.63 +/- 0.09 vs. 1.62 +/- 0.1 micrograms.min-1.m-2, P = 0.97, n = 10). Thus the increase in PNE during SR diet in humans can be explained by a fall in the volume of distribution of NE, resulting in a decrease in MCR1.(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine metabolism in humans. Kinetic analysis and model.

The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steady-state NE specific activity in arterialized plasma during [3H]NE infusion and postinfusion plasma disappearance of [3H]NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [3H]NE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P less than 0.01) and upright (r = 0.90-0.98, all P less than 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87 +/- 0.08 vs. 3.25 +/- 0.2 micrograms/min per m2, P less than 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5 +/- 0.6 vs. 4.7 +/- 0.3 liters, P less than 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80 +/- 0.11 vs. 1.21 +/- 0.08 liters/min per m2, P less than 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.

Age differences in the plasma clearance mechanisms for epinephrine and norepinephrine in humans.

There is an age-related increase in plasma norepinephrine (NE) in humans that is due to both an increase in NE appearance into plasma and a decrease in plasma NE clearance. However, previous studies demonstrated no difference in plasma epinephrine (EPI) in young and old subjects, and the effect of aging on plasma EPI appearance and clearance is unclear. To study age differences in basal NE and EPI metabolism we infused eight young (aged 19-26 yr) and eight old (aged 64-74 yr) normal subjects with [3H]NE or [3H]EPI (15 microCi/m2 bolus dose plus 0.35 microCi/m2/min for 50 min) to achieve steady state conditions on separate days. The old subjects had higher arterialized plasma NE levels [mean, 217 +/- 13 (+/- SE) vs. 149 +/- 12 pg/mL; P less than 0.005] and plasma NE appearance. In contrast, neither plasma EPI levels (98 +/- 8 vs. 104 +/- 10 pg/mL; P = NS) nor EPI appearance rates were different in the old and young subjects. The plasma clearance rates of EPI and NE were nearly identical in the young subjects (1.63 +/- 0.14 vs. 166 +/- 0.09 L/min X m2; P = NS). Plasma NE clearance was lower in the old compared to the young subjects (1.38 +/- 0.06 vs. 1.64 +/- 0.10 L/min X m2; P less than 0.05) and was lower than EPI plasma clearance in the same subjects. Although NE and EPI can be removed by both neuronal and nonneuronal uptake mechanisms, and mean plasma clearance values for NE and EPI are the same in the young, the age-related decline in catecholamine clearance is specific for NE. This finding implies a differential effect of age on a catecholamine removal mechanism that is specific for NE.

Epinephrine increases plasma immunoreactive atrial natriuretic hormone levels in humans.

Six normal human subjects each underwent sequential 80-min infusions of saline and epinephrine (EPI) at 0.55 and 2.75 micrograms X min-1 X m-2 to determine the role of EPI in the control of atrial natriuretic hormone (ANH) in humans. Plasma immunoreactive-ANH (IR-ANH) levels nearly doubled in response to the infusion of EPI at 0.55 microgram X min-1 X m-2 (P less than 0.05) and then plateaued; heart rate accelerated significantly (P less than 0.01) with increasing plasma EPI levels, whereas systolic blood pressure increased only with higher plasma EPI levels (P less than 0.05). To determine whether beta-adrenergic mechanisms mediate the EPI-induced increase in IR-ANH, six additional subjects each received infusions on two separate days of saline for 240 min and the beta-adrenergic antagonist propranolol followed by propranolol plus EPI at 2.75 micrograms X min-1 X min-2 each for 80 min. Neither saline nor propranolol plus EPI caused a significant increase in plasma IR-ANH. We conclude that EPI increases plasma IR-ANH through beta-adrenergic mechanisms in humans. beta-Adrenergic-mediated increases in plasma IR-ANH levels appear to be unrelated to changes in the heart rate.

Relationship between plasma and platelet epinephrine concentrations in humans.

Nine healthy humans received sequential 80-min infusions of saline and epinephrine (EPI) at 0.55 and 2.75 micrograms X min-1 X m-2 to determine whether increases in arterialized venous plasma EPI within the physiological range affect platelet EPI levels. The platelet EPI concentration was significantly higher than basal levels only during the 2.75 micrograms X min-1 X m-2 EPI infusion (P less than 0.02). To assess the role of platelets in EPI clearance from plasma, four human subjects underwent a 2.75 micrograms X min-1 X m-2 EPI infusion during beta-adrenergic blockade with propranolol. Propranolol decreased plasma EPI clearance (P less than 0.01) and increased both the plasma and platelet EPI concentrations (P less than 0.01) during the EPI infusion. To determine the changes in plasma and platelet EPI during and after EPI infusion, seven subjects received an 80-min EPI infusion at 2.75 micrograms X min-1 X m-2. After discontinuation of the EPI infusion, plasma EPI levels returned to base line within 30 min, whereas platelet EPI levels were significantly elevated above base line for 120 min (P less than 0.02 vs. base line). Platelets concentrate EPI during increases in plasma EPI, which are similar to the plasma levels seen in physiological and pathophysiological states in humans. The accumulation of catecholamines by platelets may be an additional mechanism in the regulation of plasma catecholamine levels in humans.

The scintigraphic localization of mineralocorticoid-producing adrenocortical carcinoma.

I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.