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Biomedical subjects

J L Stock

Publications and source records attributed to J L Stock.

49 records · Page 3Linked to original sources

Multiple endocrine neoplasia, type I. Association with marfanoid habitus, optic atrophy, and other abnormalities.

A patient had a parathyroid adenoma and prolactin-secreting pituitary tumor, suggestive of the multiple endocrine neoplasia (MEN) I syndrome. The presence of a marfanoid habitus--found more typically in MEN III syndrome--as well as mitral valve prolapse, mental retardation, and bilateral optic atrophy suggests a new variant of the MEN syndrome, possibly representing widespread dysplasia of endocrine and other tissues.

Adenoma↗

Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait comprising hypercalcemia, hypophosphatemia, parathyroid hyperplasia, and unusually low renal clearance of calcium. We evaluated the role of parathyroid hormone in the relative hypocalciuria of FHH and characterized the renal transport of calcium in this disorder using three previously hypercalcemic FHH patients with surgical hypoparathyroidism and three controls with surgical hypoparathyroidism. Intravenous infusion of calcium chloride in two patients with FHH and in three controls increased serum calcium from a mean basal of 5.0 to a mean peak of 6.8 meq/liter in two FHH patients and from 4.2 to 5.7 in three control subjects. Urinary calcium in a third FHH patient was studied without calcium infusion during recovery from hypercalcemia of vitamin D intoxication. At all serum concentrations of calcium, calcium clearance was lower in FHH than in controls; at base-line serum calcium, the ratio of calcium clearance to inulin clearance (C(Ca)/C(IN)) in FHH subjects was 32% of that in controls and decreased to 19% during hypercalcemia. Calcium infusion increased the ratio of sodium clearance to inulin clearance in controls from a base line of 0.020 to 0.053 at peak concentrations of calcium in serum, but did not affect this parameter in FHH (0.017 at base-line serum calcium vs. 0.019 at peak). When calcium infusion studies were performed (in two patients with FHH and one control) during administration of acetazolamide, a drug whose principal renal action causes inhibition of proximal transport of solute, C(Ca)/C(IN) in the patients with FHH was 29 and 7% of that of the control at base-line and peak serum calcium, respectively. In contrast, ethacrynic acid, a diuretic that acts in the ascending limb of the loop of Henle, increased C(Ca)/C(IN) more in the FHH patients than in the control subject; C(Ca)/C(IN) was 65% at base-line and 47% at peak serum calcium, compared with that of the control subject. The greater calciuric response to ethacrynic acid than to acetazolamide or calcium infusion alone in FHH indicates that a major renal locus of abnormal calcium transport in this disorder may be the ascending limb of the loop of Henle.Decreased clearance of calcium in patients with FHH and hypoparathyroidism when compared with hypoparathyroid controls indicates that relative hypocalciuria in FHH is not dependent on hyperparathyroidism. Since the parathyroid glands in FHH are not appropriately suppressed by calcium, this implies that FHH represents a disorder of abnormal transport of, and/or response to, extracellular calcium in at least two organs, parathyroid gland and kidney.

Adolescent↗

Human chorionic gonadotropin subunit measurement in primary hyperparathyroidism.

The concentration of subunits of hCG (hCG alpha and hCG beta) was determined in plasma or serum from 70 patients with primary hyperparathyroidism (1 degrees HPT). Two of three patients with parathyroid carcinoma showed elevation in plasma concentrations of both subunits, which fell after surgical removal of the tumor. An extract prepared from the tumor of 1 of these patients contained the subunits in high concentrations, whereas in extracts similarly prepared from tissues removed from 7 patients with benign 1 degrees HPT, the subunits were not detectable or were present in much lower concentrations. In 42 cases of benign 1 degrees HPT, samples from veins containing a 10-fold gradient of parathyroid hormone obtained during selective venous catheterization and peripheral samples from the same patients were analyzed for hCG subunits. Only 1 patient demonstrated a mild elevation of hCG alpha in parathyroid venous effluent alone that may have represented subunit release by apparently benign parathyroid tissue. Thirty patients with multiple endocrine neoplasia type I were tested; 8 evidenced clinically active islet cell tumors, and 6 of these 8 showed high circulating concentrations of hCG alpha (and hCG beta in 1 case). Patients in the multiple endocrine neoplasia type I group with 1 degrees HPT or pituitary tumors, but no evident pancreatic islet disease, did not show elevations in subunit concentrations. Thus, in patients with 1 degrees HPT, determination of subunits of hCG may be helpful in making the diagnosis of parathyroid carcinoma or in screening for associated (and probably malignant) pancreatic islet disease.

Adenoma, Islet Cell↗

Effects of calcium-regulating hormones and drugs on human monocyte chemiluminescence.

Chemiluminescence (CL) associated with phagocytosing monocytes has been used as an index of the oxygen dependent metabolic activity of these cells. Because of the relationships between monocytes and cells involved in bone resorption, we studied the effects on human monocyte CL of hormones and drugs active in mineral metabolism. Two-hour preincubations of monocytes with human PTH-(1-34), bovine PTH, or prostaglandin E2 caused significant decreases in peak CL during phagocytosis stimulated by the addition of latex particles. Similar studies with dichloromethylene diphosphonate, ethane hydroxydiphosphonate, or salmon calcitonin (sCT) caused significant increases in CL, whereas preincubation with human CT at the same molar concentration did not. CL was also decreased after preincubations with methylprednisolone or bacterial endotoxin. The effect of bovine PTH was dose dependent to concentrations as low as 10 ng/ml, was not fully present after a shorter 1-min preincubation with the hormone, and differed in an otherwise identical system using polymorphonuclear leukocytes instead of monocytes. The production of hydrogen peroxide by phagocytosing monocytes was also significantly affected by each of the drugs and hormones. The direction and magnitude of these changes were similar to those in CL experiments, except for the effects of sCT. These studies relate the oxygen-dependent function of phagocytes to mediators of bone resorption and provide a new system for studying the effects of hormones and drugs on the cellular elements of bone and blood.

Bone Resorption↗

The detection of mediastinal parathyroid glands by computed tomography, selective arteriography, and venous sampling: an analysis of 17 cases.

Computed tomography (CT) scans were reviewed in 19 cases of proved mediastinal parathyroid glands. Glands were detected in five of 17 cases (29%) with adequate scans; four of six (67%) anterior mediastinal glands larger than 2 cm were visible. The smallest lesion demonstrated by CT ws 1.6 cm. In the same series, selective arteriography was positive in 10 of 15 cases (67%), with the smallest lesion measuring 0.5 cm. Venous sampling was performed in 15 patients, and a thymic sample obtained in 10; a twofold step-up of parathyroid hormone in thymic veins was noted in eight of 15 cases (53%), but was not localizing, as samples in other veins were elevated in all but one case. Angiography appears more sensitive than second-generation CT for detecting mediastinal glands. However, CT is very useful in patients with previous failed explorations. Scanning must include contiguous sections extending several centimeters below the carina, in order to encompass low-lying mediastinal glands.

Adenoma↗

Maximal urine-concentrating ability: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

Impairment of urine-concentrating ability is common in persons with chronic hypercalcemia. We assessed urine-concentrating ability in 40 patients with typical primary hyperparathyroidism and 10 patients with familial hypocalciuric hypercalcemia, a disorder resembling typical primary hyperparathyroidism but lacking some of its clinical complications. Urine-concentrating ability was determined during a dehydration test of 18-22 h. The two patient groups were comparable with respect to serum calcium concentration and creatinine clearance. In the group with familial hypocalciuric hypercalcemia, the duration of hypercalcemia was probably greater, because it commences during infancy; the urinary excretion rate for calcium was lower [6.6 +/- 5.4 (mean +/- 1 SD) vs. 14.8 +/- 7.5 meq/day; P less than 0.005]. Patients with familial hypocalciuric hypercalcemia showed higher maximal urinary osmolality (800 +/- 150 vs. 664 +/- 130 mosmol/kg; P less than 0.0005). Among the patients with typical primary hyperparathyroidism, there was a negative association between maximal urinary osmolality and urinary cAMP (r = -0.40; P less than 0.05), but there was no significant relation between maximal urinary osmolality and the urinary excretion rate for calcium. Among 18 patients retested within 1 month after surgical correction of typical primary hyperparathyroidism, urine-concentrating ability did not improve. In patients with typical primary hyperparathyroidism, impairment in urine-concentrating ability reflects features of the chronic disease state, as it is not rapidly reversible by correction of that state. However, in patients with familial hypocalciuric hypercalcemia, longstanding hypercalcemia is not associated with obvious impairment of urine-concentrating ability. Complete or partial freedom from impairment of urine-concentrating ability and from calcareous renal disease are expressions of the generally mild course in familial hypocalciuric hypercalcemia.

Calcium↗

Parathyroid imaging after intraarterial injections of [75Se]selenomethionine.

Thirteen patients with persistent hyperparathyroidism after unsuccessful neck surgery were given up to 250 microCi [75Se]selenomethionine intraarterially during parathyroid arteriography, gamma-Camera images of the neck and mediastinum localized abnormal parathyroids in four of five patients receiving complete injections, despite very small glands or unsuccessful arteriograms in some of the patients. Correctly localizing images were obtained in three patients receiving incomplete injections. However, images in five of eight of the remaining patients receiving incomplete injections showed areas of false positive uptake, and there was no way preoperatively to distinguish these from the true positive studies. We conclude that intraarterial injection of radioselenomethionine is a simple supplementary procedure in patients undergoing arteriography that may, with proper technique, be useful in identifying small foci of abnormal parathyroid tissue.

Humans↗

Adenosine 3',5'-monophosphate response to parathyroid hormone: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

We investigated cAMP metabolism during and after a 15-min infusion of parathyroid hormone (PTH) in 7 normals, 13 patients with typical primary hyperparathyroidism (1HPT), and 6 patients with familial hypocalciuric hypercalcemia (FHH). Nephrogenous urinary cAMP excretion rate reached a peak during the first or second 30 min urine collection interval after the start of the PTH infusion in all subjects. cAMP concentration in plasma reached a peak within 5--20 min of the start of the infusion and then decreased with an initial half-time of 15 min. The peak value of nephrogenous urinary cAMP excretion rate was lower in the group with 1HPT than in the group with FHH or in normals (119 vs, 275 vs. 204 nmol/100 ml glomerular filtrate; P less than 0.0 5 for both comparisons). Similarly, the peak value of plasma cAMP concentration was less in 1HPT subjects than in FHH patients or in normals (11.1 vs. 17.1 vs. 16.6 nmol/100 ml, respectively; P less than 0.05 for both comparisons). For purposes of diagnostic classification, the two hypercalcemia groups could be more completely separated by the values of either the renal calcium to creatinine clearance ratio or the plasma PTH concentration than by the values of inidices of cAMP response to PTH. The differences in cAMP response to PTH between FHH and 1HPT patients could be secondary to differences in circulating PTH concentrations (these are lower in subjects with FHH) or could reflect a renal lesion more closely related to the underlying etiology of FHH.

Cyclic AMP↗

Familial hypocalciuric hypercalcemia: recognition among patients referred after unsuccessful parathyroid exploration.

Of 67 patients referred after unsuccessful surgery for presumed primary hyperparathyroidism, six were shown to be members of kindreds with familial hypocalciuric hypercalcemia. This diagnosis had not been recognized in any of the six previosuly. Most of the remaining 61 cases had proven or probable typical primary hyperparathyroidism, and a subgroup of four had hypercalcemia with suppression of the parathyroid glands. Urine calcium excretion expressed as the calcium:creatinine clearance ratio provided an easily measurable and effective index to separate the groups with familial hypocalciuric hypercalcemia, typical primary hyperparathyroidism, and suppressed parathyroids. Thus, at least 9% of patients referred after unsuccessful parathyroidectomy had familial hypocalciuric hypercalcemia. The assessment of urine calcium excretion by indices such as the calcium:creatinine clearance ratio should facilitate recognition of this condition, which responds poorly to standard subtotal parathyroidectomy.

Adult↗

Urinary cyclic 3',5'-adenosine monophosphate (cAMP): an index of the action of parathyroid hormone on the kidney.

Quantitation of cAMP in plasma and urine allows derivation of indices or renal responsiveness to PTH, indices of steady-state circulating PTH bioactivity, and indices of rapid changes in circulating PTH bioactivity. For each of these three applications, we have cited examples, primarily from our clinical experience, of abnormally high and abnormally low values of the measured indices.

Calcium↗

Adolescent pregnancy and sexual risk-taking among sexually abused girls.

Data on 3,128 girls in grades eight, 10 and 12 who participated in the 1992 Washington State Survey of Adolescent Health Behaviors were used to analyze the association of a self-reported history of sexual abuse with teenage pregnancy and with sexual behavior that increases the risk of adolescent pregnancy. In analyses adjusting for grade level, respondents who had been sexually abused were 3.1 times as likely as those who had not been abused to say they had ever been pregnant; in multivariate analyses, respondents who had experienced abuse were 2.3 times as likely as others to have had intercourse but were not more likely than other sexually active respondents to have been pregnant. However, those with a history of sexual abuse were more likely to report having had intercourse by age 15 (odds ratio, 2.1), not using birth control at last intercourse (2.0) and having had more than one sexual partner (1.4). Thus, an association between sexual abuse and teenage pregnancy appears to be the result of high-risk behavior exhibited by adolescent girls who have been abused.

Adolescent↗