Autoimmune (Hashimoto's) thyroiditis associated with Crohn's disease.

We report the occurrence of autoimmune (Hashimoto's) thyroiditis in three patients with Crohn's disease. Previously, thyroid disease has been described only in association with ulcerative colitis. We review the pertinent literature on thyroid disease in inflammatory bowel disease (IBD) and suggest that this association supports the hypothesis that autoimmunity is involved in the pathogenesis of IBD. Early diagnosis and treatment of thyroid dysfunction in patients with IBD is desirable because thyroid dysfunction worsens the symptoms and course of IBD.

The effect of PTH antagonist BIM-44002 on serum calcium and PTH levels in hypercalcemic hyperparathyroid patients.

BIM-44002, a pure competitive antagonist of parathyroid hormone (PTH), has a high affinity for the PTH/PTHrP receptor in vitro, and can completely inhibit the actions of a PTH agonist in rats in vivo. Toxicology studies in rats and dogs showed BIM-44002 to be devoid of any adverse effects. Therefore we undertook an investigation to evaluate the potential utility of BIM-44002 in lowering elevated serum calcium in three patients with primary hyperparathyroidism. BIM-44002 was administered by continuous intravenous infusion at dosages of 100 microg/hour (370 nmol/hour) for 12 hours, followed by 200 microg/hour for 12 hours, followed by 400 microg/hour for 12 hours. Vital signs and serum ionized and total calcium were monitored hourly and for 3 hours after cessation of the infusion. Blood for PTH determinations was obtained at the same time points. Serum calcium and PTH did not change during and after the infusion of the antagonist. No subject experienced any adverse reactions to the infusion of the antagonist. We conclude that although the PTH antagonist BIM-44002 was effective both in vitro and in vivo in animals, and it was safe in humans, it was not able to lower serum calcium in patients with hyperparathyroidism. Possible reasons for lack of clinical efficacy are discussed.

Diagnosis of parathyroid adenomas: efficacy of measuring parathormone levels in needle aspirates of cervical masses.

OBJECTIVE: The purpose of this study was to assess the value of measuring parathormone levels in percutaneous needle aspirates of suspicious cervical lesions in patients with hyperparathyroidism to confirm whether the lesion represents abnormal parathyroid tissue. SUBJECTS AND METHODS: The study group consisted of 66 patients with hyperparathyroidism in whom 80 cervical lesions were aspirated and levels of parathormone in the aspirates were measured. CT guidance was used for two patients and sonographic guidance for the remainder. The lesions selected for aspiration were demonstrated on either sonography or CT and had either an unusual position (separate from the thyroid gland or were intrathyroidal) or configuration (irregular shape or atypical heterogeneous sonographic texture). In 15 patients, an indeterminate, posteriorly located intrathyroidal mass was detected and felt most likely to represent a thyroid nodule by sonographic criteria. These masses were aspirated to rule out atypical parathyroid adenomas. In patients who had been previously explored for hyperparathyroidism and presented with persistent or recurrent hypercalcemia, all indeterminate, cervical, potentially parathyroid masses were aspirated for parathormone determination. The level of parathormone in each aspirate was measured by using an immunoradiometric assay. RESULTS: Levels of parathormone were increased in the aspirates in 37 of the 45 patients in whom sonography showed classic lesions suggestive of parathyroid adenoma. This included the 25 patients who had previously undergone exploratory surgery. At surgery, all 37 had parathyroid adenomas in the indicated locations, for a specificity of 100%. In six patients, the results of the aspiration were false-negative. Parathyroid adenomas were suspected on sonograms and confirmed at surgery, but no parathormone was detected in the aspirate. Results of aspiration of indeterminate lesions were true-negative in two patients who had both characteristic and indeterminate lesions on sonography and in the 15 patients who had indeterminate lesions that were felt to be of thyroid origin. Aspirates contained no parathormone, and surgical findings confirmed the lesions were not of parathyroid origin. CONCLUSION: Our results show that increased levels of parathormone in percutaneous needle aspirates of cervical masses in patients with hyperparathyroidism confirm the mass is a parathyroid adenoma. Although absence or low levels of parathormone in the aspirates usually excludes a parathyroid adenoma, this is not absolute as sometimes the needle may miss the mass, rendering the parathormone value invalid (false-negative).

A prospective study of family environments of children hospitalized for nonorganic failure-to-thrive.

Family functioning of nonorganic failure-to-thrive (NOFT) infants was compared with that of physically healthy, normally growing infants of similar socioeconomic status shortly after the time of the diagnosis of this condition (average age of 5 months) and again at 4 years of age. Families of NOFT infants demonstrated less adaptive relationships than did comparison-group infants, as measured by the Family Relationships Inventory (FRI) at both time points, but a comparable number of changes in residence and constellation on follow-up. Contrary to prediction, the quality of family relationships at point of diagnosis did not predict subsequent family relationships, residence, or constellation changes in the NOFT sample. However, more adaptive family relationships in the comparison group at study entry predicted fewer residence and constellation changes and more cohesive relationships 3 years later. The impact of significant discontinuities in family functioning and status should be considered in research and in clinical interventions with NOFT children.

Maternal interactional behavior with nonorganic failure-to-thrive infants: a case comparison study.

Mothers of 47 6-month-old infants with early histories of nonorganic failure to thrive (NOFT) infants and a matched comparison group of physically healthy infants were observed in interactions with their infants in their homes one month following hospitalization. Mothers of NOFT infants were observed to have less adaptive social interactional behavior, less positive affective behavior, and demonstrated more arbitrary termination of feedings. No group differences were found in flexibility or sensitivity of maternal feeding, or in environmental circumstances such as number of persons present, noise level, or level of activity. These salient deficiencies in maternal interactional behavior may continue to disrupt the NOFT child's physical growth and psychological development following initial diagnosis and hospitalization. Additional studies are needed to identify patterns of maternal interactional behavior which influence psychological prognosis and to assess the responsiveness of maternal interactional behavior to intervention.

Arteriographic ablation of cervical parathyroid adenomas.

In some cases of primary hyperparathyroidism, in particular where neck exploration has been unsuccessful, an alternative to surgical therapy may be desirable. We studied the acute and chronic metabolic effects of attempted angiographic destruction by angiographic contrast infusion of solitary parathyroid adenomas in 18 patients with symptomatic disease. Fourteen patients had failed prior surgery; 4 patients had not undergone prior surgery but were extremely high surgical risks. Cervical adenomas were present in 17 of 18 subjects; mediastinal adenoma in 1 of 18. Sixteen patients underwent selective parathyroid venous catheterization, which facilitated subsequent arteriographic localization. Selective arteriographic localization and attempted angiographic ablation were performed in all subjects with standard contrast, renografin-60. Laboratory studies, including serum calcium and PTH, were frequently performed before and after attempted angiographic parathyroid ablation. In all patients serum calcium fell to normal or subnormal levels within 48 h of attempted ablation. Prolonged follow-up (mean, 35.1 months) revealed that ablation was curative in 12 of 18 (sustained normocalcemia) and partially effective in 1 of 18 patients. For the entire group serum calcium fell from 3.14 +/- 0.07 at presentation to 2.42 +/- 0.07 mmol/L at the end of follow-up (or before surgery in unsuccessful cases; P less than 0.001). In 4 of 5 failed cases hypercalcemia recurred within 2 weeks. All 5 failed cases underwent curative surgery, aided by accurate localization achieved during angiographic procedure. Several transient complications and 1 case of permanent hypoparathyroidism were noted. We conclude that angiographic ablation of cervical parathyroid adenomas can be considered as an extension of diagnostic angiographic procedures in selected cases of primary hyperparathyroidism who have failed prior surgery of possibly in rare cases where surgery is contraindicated.

Calcium-dependent release of N-terminal fragments and intact immunoreactive parathyroid hormone by human pathological parathyroid tissue in vitro.

The regulation of PTH secretion by extracellular calcium was studied in parathyroid tissue obtained from patients with hyperparathyroidism (adenoma or hyperplasia) using both an amino (N)-terminal RIA as well as an immunoradiometric assay (intact assay) specific for the intact hormone. The parathyroid glands separated into three major groups when examined in terms of absolute amounts of PTH secreted, degree of suppressibility, and set-point for calcium (the concentration of calcium causing half-maximal inhibition of PTH release). In cell preparations from group A (two different adenomas, two hyperplastic glands from a patient with renal failure, and a hyperplastic gland from a patient with hypophosphatemic rickets), both assays showed comparable PTH release (agreeing within 2-fold), similar degrees of suppressibility and similar, if not identical, set-points. In group B (two adenomas and one hyperplastic gland from a patient with renal failure), PTH secretion, as measured in the N-terminal assay, was 3- to 6-fold more than that measured in the intact assay. The set-points and maximal degrees of suppressibility were, however, still comparable. In group C [two adenomas and one gland from a patient with hypophosphatemic rickets (the sister of the patient in group A)], no suppressibility was observed when PTH release was measured using the intact assay (i.e. less than 50% suppression of PTH release at 2-3 mM Ca2+). In one of these three glands, the N-terminal assay was used in addition to the intact assay, and no suppressibility was present with either assay. Thus, in general, the effects of extracellular Ca2+ on PTH secretion from pathological parathyroid tissue were similar when assessed with both an N-terminal and an intact assay, at least with respect to setpoint and maximal suppressibility. In a few cases, maximal PTH release was greater when measured with the N-terminal assay, consistent with substantial release of N-terminal fragments in addition to intact PTH. In addition, nonsuppressible glands were not uncommon when PTH release was measured by the intact assay, confirming previous studies with less specific assays.

Parathyroid localization, three-dimensional modeling, and percutaneous ablation techniques.

When available, state of the art noninvasive localization studies should be utilized routinely in previously unexplored patients for localizing parathyroid pathology, even when exceptional surgical experience exists. These studies can both minimize the 3 to 20% incidence of missed pathology and promote an approach of limited neck exploration with consequent lowering of morbidity, complications, and costs. Choice of imaging modalities for localizing these small masses is largely dependent on the level of state of the art of available equipment, the interest and experience of the performing physicians, and the attention to technical detail for each of the modalities at an individual institution. In choosing a single test, CT, and most recently cine CT with three-dimensional modeling, is favored because of higher probability of providing the kinds of information most useful to the surgeon. This includes precise anatomic localization and identification of locations likely to be missed by the surgeon (such as mediastinum, deep neck) and the capability for predicting multiple gland disease, for detecting smaller lesions, and for lower incidence of false-positive results. Ultrasound is attractive because of the low cost and noninvasiveness, and it is particularly sensitive in the thyroid region and upper neck. In difficult cases, CT, cine CT, and ultrasound may be augmented by needle aspiration of fluid for PTH assay. Thallium-technetium scanning and MRI are useful alternatives. In the previously explored patient and in patients with difficult diagnostic problems (such as ectopic adenoma, parathyroid carcinoma), the use of multiple noninvasive studies is strongly recommended, preferably CT (particularly, cine CT with three-dimensional imaging) and isotope scanning or MRI. The concurrence of two or more of these studies has a relatively high predictive value (82 to 88%) for localization. However, highly selective venous catheterization and selective magnification arteriography remain the most accurate modalities in these patients (91 to 95% sensitivity with few false-positive results) and may be combined with interventional radiologic techniques for tumor ablation in selected patients without compromising subsequent surgical alternatives. Stereotactic ablation techniques are in development.

Effect of insulin on plasma norepinephrine and 3,4-dihydroxyphenylalanine in obese men.

Increasing evidence relates serum insulin level and blood pressure in obese individuals. Although the connection between these two factors is not established, a common presumption is that the sympathetic nervous system is somehow involved, in part, because laboratory studies demonstrate insulin stimulation of sympathetic and cardiovascular activity. Because the obese may exhibit altered responsiveness to insulin action, the current investigation compared cardiovascular and neurohumoral responses to euglycemic insulin infusion (200 mU/m2/min) in obese and lean men. At baseline, obese men displayed higher glucose and insulin levels, faster pulse rates, and elevated mean arterial pressures (MAP) than lean controls; plasma norepinephrine (NE) and 3,4-dihydroxyphenylalanine (DOPA) concentrations, however, did not differ. During insulin infusion, pulse rate increased equally in obese and lean subjects (from 69 to 78 min-1 in obese and from 56 to 66 min-1 in lean subjects), while MAP remained unchanged in both groups. Elevations in plasma NE (+85 pg/mL in obese and +109 in lean pg/mL) and reductions in plasma DOPA (-233 pg/mL in obese and -376 pg/mL in lean) did not differ between groups. Sodium excretory rate decreased during insulin infusion in lean subjects by 2.2 mEq/h but increased in obese by 5.3 mEq/h (difference in response between groups, P = .024). Thus, in these obese men, cardiovascular and sympathetic responses to insulin persist despite evidence of moderate insulin resistance; increased sympathetic activity, as a cause for the resting tachycardia and borderline hypertension at baseline, seems unlikely.

Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells.

Alterations in parathyroid glandular sensitivity to calcium may contribute to the hypersecretion of PTH in hyperparathyroidism. Since the cytosolic calcium concentration may mediate the effects of extracellular calcium on PTH release, we have employed the calcium-sensitive intracellular dye QUIN-2 to examine the relationship between extracellular calcium, cytosolic calcium, and PTH secretion in adult, neonatal, and cultured bovine as well as pathological human parathyroid cells. PTH release was measured using C- and N-terminal radioimmunoassays. Neonatal bovine parathyroid cells showed a greater set-point for secretion (the Ca++ concentration causing half of the maximal inhibition of PTH release) than adult cells (1.27 +/- 0.11 vs. 1.06 +/- 0.11 mM extracellular calcium, P less than 0.01), and a slightly higher extracellular calcium was necessary to raise the cytosolic calcium concentration to a given level in neonatal than in adult bovine parathyroid cells. In individual neonatal and adult cell preparations, there was a close correlation between the set-point for secretion and the "set-point" for cytosolic calcium (r = 0.832, P less than 0.001). In cells from five human parathyroid adenomas, which had an increase in set-point for secretion, the extracellular calcium concentration necessary to raise the cytosolic calcium concentration to a given level was slightly greater than in the neonatal cells. In four preparations of human parathyroid cells there was a significant correlation between the set-points for secretion and cytosolic calcium (r = 0.856, P less than 0.01). Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells. Cellular proliferation, estimated by 3H-thymidine incorporation, increased significantly in culture from 104 +/- 10.1 counts/well on day 1 (first 24 h in culture) to 588 +/- 188 and 6,156 +/- 649 counts/well on days 2 and 4, respectively. In cultured cells on day 1, highly Ca++ (2-3 mM) inhibited maximal PTH release by 58.8 +/- 3.2%, which decreased significantly (P less than 0.001) to 38.2 +/- 1.9 and 17.1 +/- 3.7% on days 2 and 4, respectively. The cytosolic calcium observed at 3 mM calcium on day 1 was 701 +/- 43 nM, which declined to 466 +/- 60 and 314 +/- 14 nM on days 2 and 4 (P less than 0.05). There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001). Thus, during active proliferation of cultured cells, there is an alteration in the regulation of cytosolic calcium at a given extracellular calcium concentration, and changes in the regulation of PTH release and cytosolic calcium by extracellular calcium may be related to enhanced cellular proliferation.

Characterization of the insulin resistance of aging.

To clarify the nature of the insulin resistance of aging we studied the dose response for insulin-induced glucose disposal and the binding of insulin to circulating monocytes in healthy young and old men. A total of 49 two-hour euglycemic insulin clamp studies were performed in 17 young and 10 old healthy nonobese subjects. While the old group had lower estimates of lean body mass and greater estimates of total body fat than the young group, these differences did not exceed 5% and did not reach statistical significance. Insulin was infused at 20 mU/m2 per min (young = 8, old = 5); 80 mU/m2 per min (young = 13, old = 9); 200 mU/m2 per min (young = 9, old = 5). Increasing levels of hyperinsulinemia were associated with dose-dependent increases in steady-state glucose infusion rates in young and old. The maximal glucose infusion rates (milligrams per kilogram body weight per minute) were the same for young and old. However, the dose-response curve was shifted to the right in the old subjects. In the four individuals in each age group in whom studies were performed at each dose level, the Km was 54 +/- 14 microU/ml in the young and 113 +/- 11 microU/ml in the old (P less than 0.02). Correction of glucose infusion rate for lean body mass had no effect on comparisons between age groups. These data indicate an age-associated decline in sensitivity of peripheral tissues to insulin without a change in maximal tissue responsiveness. Studies of insulin binding with 14 young and 9 old subjects indicated no effect of age on the insulin binding to receptors on circulating monocytes (young = 5.25 +/- 0.35; old = 6.22 +/- 0.53% of 125I-insulin bound/10(7) cells). These studies suggest that aging may be associated with a postreceptor defect in insulin action manifested by decreased whole-body tissue sensitivity to insulin without a change in tissue responsiveness.

Effect of age on insulin stimulation of sympathetic nervous system activity in man.

Previous studies have shown that oral glucose increases plasma norepinephrine (NE) in man, an effect which is more pronounced in the elderly. Recently we have shown that hyperinsulinemia results in a dose-dependent increase in sympathetic nervous system (SNS) activity in young men independent of changes in blood glucose. We now report studies of the influence of hyperinsulinemia on SNS activity in healthy elderly. Euglycemic glucose clamp studies were performed at 2 insulin infusion rates, 2 mU/kg/min (young 22-37 yr, n = 7; old 63-77 yr, n = 9) and 5 mU/kg/min (young 22-36 yr, n = 7; old 64-75 yr, n = 5) nonobese men. Control studies were performed in 5 young and 3 old subjects. In control studies there were no significant changes in NE or cardiovascular measures in either group. Insulin infusion at 2 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) pulse (p less than 0.05), pulse pressure (p less than 0.005) and double product (pulse x systolic pressure) (p less than 0.01). In contrast 2 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to an increase in pulse pressure (p less than 0.01). The changes in NE at this insulin infusion dose were greater in the young than in the old (p less than 0.005). Insulin infusion at 5 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) mean arterial blood pressure (MABP) (p less than 0.001), pulse pressure (p less than 0.001) and double product (p less than 0.001). In contrast 5 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to a decrease in MABP (p less than 0.001) only. The change in NE and MABP at this insulin infusion dose were greater in the young than in the old (p less than 0.001) for each). In the young group the increases in NE were greater during the 2 mU/kg/min studies than in the control studies (p less than 0.001) and the increases in NE during the 5 mU/kg/min studies were greater than during the 2 mU/kg/min studies (p less than 0.001). In the old group there were no differences in NE or cardiovascular measures between the control, 2 mU or 5 mU insulin infusions. These studies indicate diminished insulin-induced SNS activation in the elderly. The disparity in the elderly between the enhanced SNS response to oral glucose and the blunted response to intravenous insulin and glucose suggests that splanchnic factors may mediate the SNS activation after oral glucose.

Influence of age on clearance of insulin in man.

With advancing age, glucose-induced insulin release is decreased in vitro, yet circulating insulin levels after glucose challenge are not decreased in the elderly. Age-related changes in insulin clearance may contribute to this discrepancy. We employed the 2-h euglycemic clamp technique to examine insulin clearance (C1) during steady-state insulin infusions (N = 53) at rates of 20, 80, and 200 mU/m2/min in healthy young (N = 16, age range 22-37 yr, relative weight 1.07 +/- 0.03) and old (N = 10, age range 63-77 yr, relative weight 1.14 +/- 0.03) men. Steady-state insulin levels were statistically significantly higher (P less than 0.01) in the elderly at each infusion rate. C1 was 40% lower (p less than 0.01) in the infusion rate. There was no effect of increasing relative weight on C1 within age groups. Within each age group, C1 was similar in insulin infusion rates of 20 and 80 mU/m2/min (young P less than 0.05, old P less than 0.001), implying a saturable system for insulin clearance. Alterations in C1 contribute to changes in insulin levels with age and may reconcile the discrepancy between in vivo and in vitro studies of glucose-induced insulin release. These results indicate the value of evaluating C1 as one determinant of circulating insulin level in states of abnormal insulin physiology.

Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.

The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.

Effect of hyperparathyroidism and hypercalcemia on lower esophageal sphincter pressure.

Heartburn is a frequent and sometimes initial complaint in hyperparathyroidism, and it is often relieved by successful parathyroid surgery. Four of five patients with primary hyperparathyroidism and heartburn obtained relief of symptoms and had an increase in lower esophageal sphincter pressure after successful operative treatment. Four of five volunteers undergoing calcium infusion exhibited a decrease in lower esophageal sphincter pressure after about 2.5 to 3 hours of infusion. Calcium infusion in a treated patient who had an increase in lower esophageal sphincter pressure postoperatively resulted in a transient return of lower esophageal sphincter pressure to preoperative levels.

Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure.

Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean +/- SEM, 8.48 +/- 1.9 , 8.1 +/- 3, and 10.1 +/- 0.78 ng/10(5) cells. h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2-3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (p less than 0.01 and P less than 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hyperplasia), but may occur in secondary hyperplasia as well.

Effect of isocaloric fat or glucose on albumin synthesis and nitrogen balance in patients receiving amino acid infusion.

Twelve patients who had undergone colon operations were randomized prospectively in the postoperative recovery room. Seven received a hypocaloric intravenous solution consisting of 3.5% amino acids plus 2.5% glucose and five received 3.5% amino acids plus 10% fat. Nitrogen balance data indicated that isocaloric amounts of glucose and fat seem equally effective when combined with amino acids. Although the albumin synthesis rates (measured by the 14C technique on the fourth postoperative day) were not significantly different between the two groups, when the results were included with pooled data from previous similar studies, there was a statistically significant difference which indicated a higher rate of albumin synthesis in patients who received the combination of amino acids and fat compared with those who received amino acids and glucose P < 0.05). In this clinical setting, fat may favor the uptake and synthesis of amino acids into visceral proteins, while glucose may have a more direct role in the synthesis of skeletal muscle protein.

Parathyroid adenomas: cinearteriography.

Parathyroid adenomas in an ectopic location, either the mediastinum or high in the neck, can be relatively easily identified arteriographically because the lesions are separate from the thyroid gland and therefore are not confused with it. However, in most cases in which the adenoma is situated adjacent to thyroid tissue (85%-90%), arteriographic identification, particularly when the lesion is small, may be extremely difficult. Cineangiography during parathyroid arteriography has been found extremely helpful in positive identification of these juxtathyroidal adenomas. Movement of the head from side to side and swallowing maneuvers during cine recording of a selective arteriogram allow determination of the location of a suspicious "blush" in relation to the thyroid gland. As a rule, parathyroid adenomas stain densely in the tissue phase, are nearly always posterior to the thyroid, and separate from thyroid tissue on swallowing. In 10 of 14 parathyroid arteriographic examinations, cinearteriography was useful in confirming or excluding a parathyroid adenoma.

Carbohydrate metabolism in phenylketonuria.

Carbohydrate metabolism was studied in 6 adult patients with phenylketonuria both on a low phenylalanine and an unrestricted institutional diet. Tolerance tests included PO glucose, PO phenylalanine, and combined glucose phenylalanine loading. Glucose, insulin, pyruvate, lactate, and phenylalanine were sampled at 0, 1/2, 1, 2, 3, and 4 hr. Fasting glucose levels were normal as were mean glucose values after challenge. Basal insulin secretion, as well as insulin response, to glucose challenge and to combined phenylalanine and glucose loading appeared normal. Insulin response to phenylalanine alone, however, was lower than expected in the phenylketonuria patients. Both off and on low phenylalanine diet, blood pyruvate and lactate were also normal. Thus, our data from blood did not show evidence of the abnormalities in glucose and pyruvate metabolism which have been proposed to occur in phenylketonuric patients but did not suggest that the potency of phenylalanine as an insulin secretagogue is diminished by chronic hyperphenylalaninemia.