244
Brief clinical and laboratory observations
enzymes" and are not likely to be destroyed during preparation of the specimens. We cannot explain the absence of organisms in gastric specimens stained with GMS and PMB, except that the TBO slides contained less extraneous background material. Although the median age of the pneumonitis group was lower than the control group, we do not consider the difference significant for comparison purposes, since the incidence of P. carinii in immunosuppressed patients is not age dependent. The absence of P. carinii organisms from the gastric contents of cancer patients in the control group indicates that this organism is not encountered as a part of the gastric flora in patients without PCP. Therefore, if P. carinff organisms are found in the gastric contents of an immunosuppressed patient with diffuse alveolar disease, the diagnosis of PCP is justified. On the other hand, the absence ofP. carinii organisms in such cases by no means excludes this as the causative agent. Since gastric lavage is a simple method for diagnosis of PCP, it may be useful in cases where lung aspiration or biopsy are not available or the patient is too ill to undergo such procedures. The authors are grateful to Dr. Alvin Mauer, Medical Director, for his critical review of the manuscript.
Hypoglycemia during testing for growth hormone deficiency Stephen H. LaFranchi, M.D., Barbara M. Lippe, M.D.,* and Solomon A. Kaplan, M.D., Los Angeles, Calif. HYPOGLYCEMIA is a frequent complication of hypopituitarism and is often associated with increased sensitivity to insulin? Testing of growth hormone reserve by routine administration of insulin to children with hypopituitarism may be hazardous to those with unrecognized or asymptomatic hypoglycemia. Insulin-induced hypoglycemia, From the Department of Pediatrics, UCLA School of Medicine. Supported in part by United States Public Health Service fellowship training grant 1-F32 A M05039-01. *Reprint address: Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA 90024.
The Journal of Pediatrics February 1977
REFERENCES 1. Dominy DE, and Lucas RN: Pneumocystis carinii infection diagnosed by antemortem lung biopsy, Ann Thoracic Surg 1:305, 1965. 2. Cohen MD, and Weiss EB: Pneumocystis carinii pneumonia: Percutaneous lung biopsy and review of literature. Chest 60:195, 1971. 3. Hodgkin JE, Andersen HA, and Rosenow EC lit: Diagnosis of Pneumocystis carinii pneumonia by transbronchoscopic lung biopsy, Chest 64:551, 1973. 4. Repsher LH, Schroter G, and Hammond WS: Diagnosis of Pneumocystis carinii by means of endobronchial brush biopsy, N Engl J Med 287:340, 1972. 5. Erchul JW, Williams LP, and Meighan PP: Pneumocystis carinii in hypopharyngeal material, N Engl J Med 267:916, 1962. 6. Toth GY, Balogh E, and Belay M: Tracheal smear in pentamidine treated plasma-cell pneumonia, Acta Paediatr Acad Sci Hung 7:339, 1966. 7. Hughes WT, Price RA, Kim HK, Coburn TP, Grigsby D, and Feldman SS: Pneumocystis carinii pneumonitis in children with malignancies, J PEmATR 82:404, 1973. 8. Schwartz R, and Arellano C: Types of Bacillus isolated by gastric lavage and from cerebrospinal fluid, Rev Assoc M ed Argent 57:22, 1943. 9. Smith JW, Hughes WT, and Kim HK: Characterization of Pneumocystis carinii by biophysical and enzymatic methods. Presented to the Am Soc Microbiol, 1971.
however, remains one of the most reliable and potent means for stimulating hGH release and may be invaluable as a definitive test.-' This report describes our experience with six children whose concentrations of blood sugar were approaching or in the hypoglycemia range immediately prior to the scheduled insulin injection. These patients, who were subsequently shown to have hypopituitarism, share common features which should permit their segregation into the category at risk for development of severe hypoglycemia. Abbreviations used hGH: human growth hormone HA: height age WA: weight age PATIENT
POPULATION
AND METHODS
From June, 1970, to October. 1974, 55 children underwent inpatient provocative testing for hGH secretion. Three had a prior history of recurrent episodes of documented hypoglycemia and were, therefore, not scheduled for an insulin tolerance test (all three were subsequently documented to have hGH deficiency by failure to respond
Volume 90 Number 2
Brief clinical and laboratory observations
245
Table I. Patient identification-clinical and laboratory data
Blood sugar (mg/ dl) Patient
A~ (m~
HA (m~
WA (m~
HA/WA (too)
0 rain
1.5 1.0 2.2 1~2 1.8 1.1
43 6 28 28 24 40
l
14
6
4
2 3 4 5 6
21 23 36 61 61
15 9 18 24 38
15 4 15 15 33
,m,nl3omin 12
. . 30
] 45min I 60min
18
. .
22
. . 22
Plasma cortisol (ILg/ dl)
. . 24
0 rain
I
[
60 rain
60
60
74
28
22 90 48
56
HA = Heightage; WA = weightage.
to L-dopa and arginine infusion, as well as to lack of sleepinduced hGH secretion). Fifty-two patients were scheduled for the insulin-induced hypoglycemia test and were pretreated with estrogen for three days as previously described? Patients were hospitalized on the day prior to the test and fasted after midnight. Testing was to be started between 8 and 9 AI~ with intravenous insulin (0.075 to 0.1 unit/kg) to be followed in 60 minutes by arginine infusion (0.5 grams/kg/over 45 minutes). The previously described test ~ was modified to begin with insulin injection because this sequence permits simultaneous assessment of ACTH reserve from measurement of cortisol levels in blood obtained prior to and 60 minutes after injection of insulin.:' RESULTS Six of the 52 patients had fasting hypoglycemia prior to scheduled testing (Table I) and were subsequently shown to have hGH deficiency. The hypoglycemia was recognized clinically in four patients (Nos. 2, 3, 4, and 5) and insulin withheld, but in the two whose fasting blood sugars were 40 and 43 mg/dl (Nos. 1 and 6) clinical symptoms were absent and insulin was administered. All were less than 62 months of age and had height age to weight age ratios of 1 or greater. Each of the remaining 46 children was normoglycemic on the morning of testing (fasting blood sugar >45 mg/dl). Six of these children were found to have hGH deficiency. Five of these six patients were older than 62 months and five had HA:WA of less than one. Of the 40 patients tested who were normoglycemic and who had normal hGH responses, only two were less than 62 months of age and neither of these two had HA:WA ratios greater than 1.1. DISCUSSION Patients in whom fasting hypoglycemia was present were under 62 months of age and had HA:WA ratios of 1 or greater, On questioning, a history could be obtained of
poor food intake during the three days of estrogen pretreatment. It appears clear that in some children the estrogen pretreatment resulted in nausea and anorexia which contributed to the hypoglycemia. In contrast, hGHdeficient children who tolerated fasting were older, tended to have HA:WA ratios less than l, and had had good dietary intake. These clinical observations support those made by Hopwood and associates.' Our experience with over one hundred tests in the past eight years has indicated that the insulin-arginine test is a highly reliable means for estimating hGH reserve. In addition, it permits simultaneous assessment of ACTH reserve? We therefore emphasize a careful history of dietary intake over the three days prior to testing and recommend that the AM fasting glucose be documented as normal prior to the insulin tolerance test. Provided the complication of hypoglycemia is appreciated and provided those patients at risk do not receive insulin injection, the combined estrogen, insulin, and arginine stimulatory test remains a most useful means for assessing pituitary hGH and ACTH reserve in most patients. Since the test may be hazardous, however, in children under the age of 60 to 62 months, with high HA:WA ratios (excessive leanness), or with previous symptoms of hypoglycemia, we forego the estrogen pretreatment and insulin tolerance test in them. REFERENCES
1. Hopwood NJ, Forsman PJ, Kenny FM, and Drash AL: Hypoglycemia in hypopituitary children, Am J Dis Child 129:918, 1975. 2. Frasier SD: A review of growth hormone stimulation tests in children, Pediatrics 53:929, 1974. 3. Lippe B, Wong S-LR, and Kaplan SA: Simultaneous assessment of growth hormone and ACTH reserve in children pretreated with diethylstilbestrol, J Clin Endocrinol Metab 33:94, 1971. 4. Penny R, Blizzard RM, and Davis WT: Sequential arginine and insulin tolerance tests on the same day, J Clin Endocrinol Metab 29:1499, 1969.
Brief clinical and laboratory observations
enzymes" and are not likely to be destroyed during preparation of the specimens. We cannot explain the absence of organisms in gastric specimens stained with GMS and PMB, except that the TBO slides contained less extraneous background material. Although the median age of the pneumonitis group was lower than the control group, we do not consider the difference significant for comparison purposes, since the incidence of P. carinii in immunosuppressed patients is not age dependent. The absence of P. carinii organisms from the gastric contents of cancer patients in the control group indicates that this organism is not encountered as a part of the gastric flora in patients without PCP. Therefore, if P. carinff organisms are found in the gastric contents of an immunosuppressed patient with diffuse alveolar disease, the diagnosis of PCP is justified. On the other hand, the absence ofP. carinii organisms in such cases by no means excludes this as the causative agent. Since gastric lavage is a simple method for diagnosis of PCP, it may be useful in cases where lung aspiration or biopsy are not available or the patient is too ill to undergo such procedures. The authors are grateful to Dr. Alvin Mauer, Medical Director, for his critical review of the manuscript.
Hypoglycemia during testing for growth hormone deficiency Stephen H. LaFranchi, M.D., Barbara M. Lippe, M.D.,* and Solomon A. Kaplan, M.D., Los Angeles, Calif. HYPOGLYCEMIA is a frequent complication of hypopituitarism and is often associated with increased sensitivity to insulin? Testing of growth hormone reserve by routine administration of insulin to children with hypopituitarism may be hazardous to those with unrecognized or asymptomatic hypoglycemia. Insulin-induced hypoglycemia, From the Department of Pediatrics, UCLA School of Medicine. Supported in part by United States Public Health Service fellowship training grant 1-F32 A M05039-01. *Reprint address: Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA 90024.
The Journal of Pediatrics February 1977
REFERENCES 1. Dominy DE, and Lucas RN: Pneumocystis carinii infection diagnosed by antemortem lung biopsy, Ann Thoracic Surg 1:305, 1965. 2. Cohen MD, and Weiss EB: Pneumocystis carinii pneumonia: Percutaneous lung biopsy and review of literature. Chest 60:195, 1971. 3. Hodgkin JE, Andersen HA, and Rosenow EC lit: Diagnosis of Pneumocystis carinii pneumonia by transbronchoscopic lung biopsy, Chest 64:551, 1973. 4. Repsher LH, Schroter G, and Hammond WS: Diagnosis of Pneumocystis carinii by means of endobronchial brush biopsy, N Engl J Med 287:340, 1972. 5. Erchul JW, Williams LP, and Meighan PP: Pneumocystis carinii in hypopharyngeal material, N Engl J Med 267:916, 1962. 6. Toth GY, Balogh E, and Belay M: Tracheal smear in pentamidine treated plasma-cell pneumonia, Acta Paediatr Acad Sci Hung 7:339, 1966. 7. Hughes WT, Price RA, Kim HK, Coburn TP, Grigsby D, and Feldman SS: Pneumocystis carinii pneumonitis in children with malignancies, J PEmATR 82:404, 1973. 8. Schwartz R, and Arellano C: Types of Bacillus isolated by gastric lavage and from cerebrospinal fluid, Rev Assoc M ed Argent 57:22, 1943. 9. Smith JW, Hughes WT, and Kim HK: Characterization of Pneumocystis carinii by biophysical and enzymatic methods. Presented to the Am Soc Microbiol, 1971.
however, remains one of the most reliable and potent means for stimulating hGH release and may be invaluable as a definitive test.-' This report describes our experience with six children whose concentrations of blood sugar were approaching or in the hypoglycemia range immediately prior to the scheduled insulin injection. These patients, who were subsequently shown to have hypopituitarism, share common features which should permit their segregation into the category at risk for development of severe hypoglycemia. Abbreviations used hGH: human growth hormone HA: height age WA: weight age PATIENT
POPULATION
AND METHODS
From June, 1970, to October. 1974, 55 children underwent inpatient provocative testing for hGH secretion. Three had a prior history of recurrent episodes of documented hypoglycemia and were, therefore, not scheduled for an insulin tolerance test (all three were subsequently documented to have hGH deficiency by failure to respond
Volume 90 Number 2
Brief clinical and laboratory observations
245
Table I. Patient identification-clinical and laboratory data
Blood sugar (mg/ dl) Patient
A~ (m~
HA (m~
WA (m~
HA/WA (too)
0 rain
1.5 1.0 2.2 1~2 1.8 1.1
43 6 28 28 24 40
l
14
6
4
2 3 4 5 6
21 23 36 61 61
15 9 18 24 38
15 4 15 15 33
,m,nl3omin 12
. . 30
] 45min I 60min
18
. .
22
. . 22
Plasma cortisol (ILg/ dl)
. . 24
0 rain
I
[
60 rain
60
60
74
28
22 90 48
56
HA = Heightage; WA = weightage.
to L-dopa and arginine infusion, as well as to lack of sleepinduced hGH secretion). Fifty-two patients were scheduled for the insulin-induced hypoglycemia test and were pretreated with estrogen for three days as previously described? Patients were hospitalized on the day prior to the test and fasted after midnight. Testing was to be started between 8 and 9 AI~ with intravenous insulin (0.075 to 0.1 unit/kg) to be followed in 60 minutes by arginine infusion (0.5 grams/kg/over 45 minutes). The previously described test ~ was modified to begin with insulin injection because this sequence permits simultaneous assessment of ACTH reserve from measurement of cortisol levels in blood obtained prior to and 60 minutes after injection of insulin.:' RESULTS Six of the 52 patients had fasting hypoglycemia prior to scheduled testing (Table I) and were subsequently shown to have hGH deficiency. The hypoglycemia was recognized clinically in four patients (Nos. 2, 3, 4, and 5) and insulin withheld, but in the two whose fasting blood sugars were 40 and 43 mg/dl (Nos. 1 and 6) clinical symptoms were absent and insulin was administered. All were less than 62 months of age and had height age to weight age ratios of 1 or greater. Each of the remaining 46 children was normoglycemic on the morning of testing (fasting blood sugar >45 mg/dl). Six of these children were found to have hGH deficiency. Five of these six patients were older than 62 months and five had HA:WA of less than one. Of the 40 patients tested who were normoglycemic and who had normal hGH responses, only two were less than 62 months of age and neither of these two had HA:WA ratios greater than 1.1. DISCUSSION Patients in whom fasting hypoglycemia was present were under 62 months of age and had HA:WA ratios of 1 or greater, On questioning, a history could be obtained of
poor food intake during the three days of estrogen pretreatment. It appears clear that in some children the estrogen pretreatment resulted in nausea and anorexia which contributed to the hypoglycemia. In contrast, hGHdeficient children who tolerated fasting were older, tended to have HA:WA ratios less than l, and had had good dietary intake. These clinical observations support those made by Hopwood and associates.' Our experience with over one hundred tests in the past eight years has indicated that the insulin-arginine test is a highly reliable means for estimating hGH reserve. In addition, it permits simultaneous assessment of ACTH reserve? We therefore emphasize a careful history of dietary intake over the three days prior to testing and recommend that the AM fasting glucose be documented as normal prior to the insulin tolerance test. Provided the complication of hypoglycemia is appreciated and provided those patients at risk do not receive insulin injection, the combined estrogen, insulin, and arginine stimulatory test remains a most useful means for assessing pituitary hGH and ACTH reserve in most patients. Since the test may be hazardous, however, in children under the age of 60 to 62 months, with high HA:WA ratios (excessive leanness), or with previous symptoms of hypoglycemia, we forego the estrogen pretreatment and insulin tolerance test in them. REFERENCES
1. Hopwood NJ, Forsman PJ, Kenny FM, and Drash AL: Hypoglycemia in hypopituitary children, Am J Dis Child 129:918, 1975. 2. Frasier SD: A review of growth hormone stimulation tests in children, Pediatrics 53:929, 1974. 3. Lippe B, Wong S-LR, and Kaplan SA: Simultaneous assessment of growth hormone and ACTH reserve in children pretreated with diethylstilbestrol, J Clin Endocrinol Metab 33:94, 1971. 4. Penny R, Blizzard RM, and Davis WT: Sequential arginine and insulin tolerance tests on the same day, J Clin Endocrinol Metab 29:1499, 1969.
