Orville C. Green

Diabetic ketoacidosis: Induction of hypocalcemia and hypomagnesemia by phosphate therapy

Abstract A nine year old boy with previously undiagnosed diabetes mellitus presented with severe ketoacidosis. His hyperglycemia (plasma glucose=786 mg/dl), acidosis (arterial pH=6.86), dehydration and coma responded well to therapy with intravenous fluids, bicarbonate and insulin. Potassium supplementation was given as a phosphate salt. Despite marked clinical and biochemical improvement, 28 hours after therapy was initiated he was found to have profound hypocalcemia (2.6 meq/liter), hypomagnesemia (0.8 meq/liter) and hyperphosphatemia (9.2 mg/dl). All three electrolyte levels had been normal upon admission, and they were gradually corrected with appropriate supplementation of calcium and magnesium and discontinuation of the intravenous phosphate. We interpret these iatrogenic electrolyte abnormalities in the patient described to have been the result of the massive phosphate load administered, resulting not only in hypocalcemia, but also in hypomagnesemia that inhibited parathyroid hormone release. Current recommendations suggest replacement of the potassium losses in diabetic ketoacidosis with the phosphate salt to compensate for depleted stores of 2,3-diphosphoglycerate. We caution physicians that such a regimen can result in severe electrolyte disturbances which potentially may be life threatening. Judicious use of potassium phosphate as an adjunct to traditional potassium chloride therapy, and close monitoring of serum calcium, magnesium and phosphorus, appears to be a preferable therapeutic regimen than potassium phosphate alone.

Pharmacokinetic studies of prednisolone in children: Plasma levels, half-life values, and correlation with physiologic assays for growth and immunity**

Plasma prednisolone levels have been measured hourly in children receiving a single dose of oral prednisone. Peak prednisolone levels occurred one to two hours after ingestion; half-life studies gave a mean value of 132 minutes in most children. Some children had marked variability in absorption and metabolism of prednisone. Somatomedin activity and cell-mediated immunity were inhibited by plasma prednisolone values which were achieved by single doses of prednisone of 0.5 mg/kg or higher. Monitoring prednisolone levels may be of value in identifying those children who accumulate excessively high levels on moderate dosage regimens.

Somatomedin activity in the Mauriac syndrome

7. Sirinavin S, and McCracken GH: Primary suppurative myositis in children, Am J Dis Child 133:263, 1979. 8. Blair DC, Carroll M, and Silva J: Localization of infectious process with gallium citrate Ga 67, JAMA 230:82, 1974. 9. Hopkins GB, Kan M, and Mende CW: Early 67 Ga scintigraphy for the localization of abdominal abscesses, J Nucl Med 16:990, 1975. 10. Gelrud LG, Arseneau JC, Milder MS, Kramer R J, Swann 11. SJ, Canellas GP, and Johnston GS: The kinetics of 67 gallium incorporation into inflammatory lesions: Experimental and clinical studies, J Lab Clin Med 83:489, 1974. Webster EW, Alper NM, and Brownell GL: Radiation dose in pediatrics nuclear medicine and diagnostic X-ray procedures, in James AE, Wagnon HN, and Cooke RE, editors: Pediatric nuclear medicine, Philadelphia, 1974, WB Saunders Company, p 34.

Studies of growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) secretion in anorexia nervosa.

Abstract (1) Studies of serum thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) responses following TRH administration were performed in 7 subjects with anorexia nervosa (AN). (2) Five patients demonstratod significant increases in circulating GH from a mean of 15.6 ng/ml to a peak of 31.8 ng/ml 30 min after TRH. (3) Basal TSH concentrations were undetectable ( 6 μU/ml) in TSH were identified in 3/7 patients. (4) The largest elevations in TSH occurred in the two subjects in whom no GH rises were found, whereas blunted TSH rises were noted in 4/5 subjects who showed substantial GH secretory responses to TRH. (5) Basal PRL concentrations were normal and rose appropriately after TRH in all subjects. (6) These studies demonstrate that GH secretion can be provoked in AN by TRH similar to patterns in other states (acromegaly, uremia, protein-calorie malnutrition), characterized by elevated basal GH concentrations. (7) It is hypothesized that activated GH secretion may favor TRH responsivity of somatotrophs. (8) Obtundation of TSH secretion in AN, moreover, may be related to the augmented secretion of GH, since TSH secretion can be lowered by exogenous GH administration in man.

Standard Parameters of Diabetic Control: Are They Reliable?

To evaluate the reliability of the tradional methods to assess short-term control of diabetes, 25 children with insulin-dependent diabetes were studied with a 24-h glucose profile in addition to the traditional assessment techniques. Patient compliance was elminated as much as possible from the experimental design. The correlation of the routine methods with the 24-h glucose profile was excellent, and a scoring system for control was empirically derived. The single method of assessment that correlated best with the overall control score was the traditional daily urine test. In 6 of the 25 subjects studied, relative hypoglycemia was observed, occurring asymptomatically at night, and was followed by a hyperglycemic rebound. Traditional assessment techniques did not detect this event. Five additional patients had symptomatic daytime hypoglycemia. We conclude that the traditional daily urine tests are adquate indicators of day-to-day control in most diabetic patients, given adquate compliance. Our data also suggest that asymptomatic nocturnal hypoglycemia occurs frequently in children with diabetes, although clinical proof is difficult in the absence of a 24-h glucose profile.

Insulin resistance and abnormal ovarian responses to human chorionic gonadotropin in chronically anovulatory women

We studied the interrelationships between insulin resistance, obesity, and abnormal ovarian androgen secretion in chronically anovulatory women with clinical or biochemical evidence of hyperandrogenism. Four groups of six subjects each were studied: (1) normal weight (within 10% ideal body weight) anovulatory, (2) obese (greater than 120% ideal body weight) anovulatory, (3) normal weight eumenorrheic, and (4) obese eumenorrheic. After dexamethasone suppression, human chorionic gonadotropin (2000 IU/1.5m2 body surface area intramuscularly) was administered to each subject. Serum testosterone levels were subsequently determined hourly for 17 hours. On a separate occasion, an oral glucose tolerance test was administered to five subjects from each group. Serum glucose and immunoreactive insulin levels were determined before and after the ingestion of a standard 100 gm glucose load. As a group, the anovulatory women had higher (p less than 0.05) basal testosterone levels (1005 +/- 97 pg/ml) than did the ovulatory women (241 +/- 21 pg/ml) (values +/- SE). Obesity per se was not associated with increased basal testosterone levels. Testosterone levels rose in response to human chorionic gonadotropin (p less than 0.005) only in obese anovulatory women, reached maximal levels after 3 hours, and subsequently remained stable. Basal immunoreactive insulin levels were elevated (p less than 0.05) only in obese anovulatory women (52.4 +/- 20 microU/ml) compared with obese eumenorrheic (8.7 +/- 1.0 microU/ml), normal weight anovulatory (5.8 +/- 2.4 microU/ml), and normal weight eumenorrheic (4.6 +/- 0.4 microU/ml) women. Similarly, maximal increases in immunoreactive insulin levels after glucose ingestion were significantly greater (p less than 0.01) in obese anovulatory women compared with other groups. Of note is the observation that maximal changes in testosterone observed within the first 3 hours after human chorionic gonadotropin and maximal changes in insulin were correlated (r = 0.91, p less than 0.01). These data suggest that (1) both insulin resistance and an abnormal acute response to human chorionic gonadotropin are seen only in obese anovulatory women and (2) the degree to which these two abnormalities are manifested is clearly correlated. The mechanism(s) responsible for this interrelationship, as well as the underlying cause(s) of these biochemical defects, remain to be elucidated.

Propranolol-induced hypoglycemia during growth hormone testing

GROWTH HORMON~ D~FICX~NCY has traditionally been confirmed by subnormal responses to at least two standard provocative stimuli, 1 Random unstimulated samples are not satisfactory because of the short half-life (approximately 20 minutes) and fluctUating secretory pattern of GH. 2 Propranolol has been advocated as an adjunct to standard testing methods to ~educe the incidence of false-negative responses? ~ Side effects, specifically hypoglycemia, associated with use of propranolol in this fashion are reported to occur rarely, if at all. This retrospective survey of children receiving growth hormone tests was designed to identify the frequency with which the use of propranolol is associated witb hypoglycemia.

Glucosuria in Children with Diabetes: Advantages of the 2-Drop Clinitest Method

In order to assess the actual and theoretical limitations of using the traditional urinary glucose determinations as an indicator of plasma glucose concentration, we have measured plasma and urine glucose concentrations in 37 children with diabetes mellitus. A constant blood withdrawal system enabled an accurate estimate of the glucose concentration presented to the renal glomerulus over the 30-min period of blood collection and urine formation. The theoretical range of plasma glucose over which the 5-Drop and 2-Drop Clinitest methods are sensitive is 32 mg/dl and 81 mg/dl, respectively. This suggests that the 2-Drop method is the procedure of chioce for most insulin-dependent diabetic patients. Nevertheless, the extremely wide range of plasma glucose corresponding to a given urinary glucose measurement limits the precision with which any single urine test can be interpreted.

Plasma progesterone concentrations in infants: relation to infantile colic.

MINIMAL INFORMATION on normal plasma progesterone concentrations in infants is available; one study of only 14 infants has been reported, 1 and did not examine the reported possible relationship between progesterone deficiency and infantile colic? We determined plasma progesterone concentrations in 57 infants and examined the possible influences of colic, gender, age, and method of feeding on plasma progesterone values. SUBJECTS

Carbohydrate homeostasis in chronic lymphocytic thyroiditis: Increased incidence of diabetes mellitus

Twenty-one patients were seen with the diagnosis of chronic lymphocytic thyroiditis in the Endocrine Clinic during 1965-1972. Three patients developed clinical diabetes mellitus at intervals from one month to three years after the diagnosis of thyroiditis was confirmed. An additional patient, a member of the study group reported here, had asymptomatic glucose intolerance initially and developed insulin-dependent diabetes mellitus six months after the diagnosis of thyroiditis was established. Standard glucose tolerance tests were performed on 12 additional patients. One of these patients had unequivocal evidence of chemical diabetes; one other had a borderline abnormal oral glucose tolerance test. The remaining ten patients had normal glucose and insulin values during the OGTT. These studies indicate that children with chronic lymphocytic thyroiditis are at increased risk of developing diabetes mellitus when compared with the normal childhood population.