Carolyn A. Romshe

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subjects bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

Intraoperative identification of parathyroid gland pathology: A new approach

Technetium 99m-sestamibi, a radiopharmaceutical used for the diagnostic imaging of abnormal parathyroid tissue, and the Neoprobe 1000, a hand-held, gamma-detecting probe, were used concurrently, during surgical exploration, in three children with hyperparathyroidism. This novel combination assisted with the identification of an ectopic mediastinal parathyroid adenoma and with the localization of multiple hyperplastic parathyroid glands. 99mTc-sestamibi combined with the Neoprobe 1000 may prove to be a useful adjunctive technique for the intraoperative localization of abnormal parathyroid tissue in selected patients.

Dominant inheritance of cerebral gigantism

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

The combined effect of growth hormone and oxandrolone in patients with growth hormone deficiency

Twenty patients with growth hormone deficiency ranging in age from 5 5/12 to 15 8/12 years were treated for 12 months with a combination of human growth hormone and oxandrolone, followed by a period of six months off both medications. Eight of the patients received the combined therapy during the first year of hGH treatment, and 12 during either the second or fourth years of hGH administration. In considering growth velocity alone, the addition of anabolic steroid was beneficial. The bone age advanced rapidly when oxandrolone was added during the first year of hGH treatment, and less rapidly in subsequent years. The increased growth velocity, however, compensated for the acceleration of bone maturation and the overall effect of the combined treatment was beneficial, particularly when used after the first year of hGH treatment. We conclude that there is no advantage to using oxandrolone during the first year of hGH therapy, that oxandrolone in the appropriate dose is of benefit in subsequent years of hGH treatment, and that because of the individual variation in bone maturation, bone age should be frequently assessed.

INTRACRANIAL PRESSURE IN REYE'S SYNDROME

During the past 3 years the intracranial pressure(ICP)of 17 children with Reyes Syndrome(RS)has been monitored. The epidural monitor was placed in patients whose level of coma was III or deeper(Sherard Stages I-VI). The cerebrospinal fluid pressure or ICP was measured on 15 patients on admission to the hospital. The pressure was 200mm H2O or less in 7 patients and 300mm H2O or less in 13 patients. In survivors maximum ICP was recorded at 8-24 hours after admission and correlated with the level of coma. An ICP of 400-800 mm H2O was associated with coma level of IV or deeper. In one child the ICP was greater than 1300mm H2O. In 8 patients abrupt increases in ICP to 700mm HpO or greater occurred and preceded any clinical evidence of increasing ICP. These episodes lasted 20-30 minutes, and were treated with hyperventilation and/or mannitol. In 4 patients these episodes were repetitive, being separated by intervals of 2-12 hours. Most of our patients were admitted to the hospital during the early hours of their illness and were in Stage II or III coma. During this phase, the level of consciousness does not appear to be directly related to the ICP, however if the level of coma deepens during the next 24 hours after admission the ICP correlates with the stage of coma. Continuous ICP monitoring is essential for the optimal management of intracranial hypertension associated with RS and serves as an objective criteria for the administration of hyperosmolar agents in patients with coma Stage III or deeper.

Successful spleno-renal shunt and splenectomy in two patients with alpha-1-antitrypsin deficiency

Recent evidence suggests that the cirrhosis of alpha-1-antitrypsin deficiency is not invariably fatal as it was previously thought. Portal hypertension is often the major determinant of survival. The few reports of porta-systemic venous anastomosis in this disorder have shown poor results or uncertain outcome. Thus, doubts exist as to whether porta-systemic shunts should be performed in alpha-1-antitrypsin deficiency. Two patients with alpha-1-antitrypsin deficiency (PiZZ) and associated portal hypertension, cirrhosis, and hypersplenism underwent splenorenal shunt and splenectomy 8 yr ago, and both have done well. One of the patients has chronic severe headaches, diarrhea, exudative enteropathy, sinusitis, and hematuria, all uncommon in alpha-1-antitrypsin deficiency but possibly related to the antienzyme deficiency. She also has a higher trypsin inhibitory capacity than is generally reported in ZZ individuals. Based on the experience with these 2 patients, it appears that alpha-1-antitrypsin deficiency with cirrhosis is not a valid contraindication to the performance of a portasystemic shunt.

Reye syndrome in siblings.

Reye syndrome in siblings was seen in three of 85 families; the incidence of RS in these family groups appears to exceed that of the general population. The interval between development of RS in the first and second siblings was two to 11 days and related to the incubation period of the initial viral infection. In five of the children this infection was chickenpox and in two, an unspecified upper respiratory illness. To assess the role of genetic factors, HLA typing was performed on these siblings; a common genetic marker indicating susceptibility to RS was not identified. All families resided in rural and suburban areas; exposure to a common environmental toxin was not identified.

519 SUCCESSFUL SPLENO-RENAL SHUNT AND SPLENECTOMY IN TWO PATIENTS WITH ALPHA-1-ANTITRYPSIN DEFICIENCY

The hepatitis associated with AlAT deficiency is no longer considered an invariably fatal disorder. For some patients portal hypertension may be the major determinant of survival. The few reports of porta-systemic venous anastomoses have shown poor results or uncertain outcome, and doubts exist as to whether such shunts should be performed. Two patients with AlAT deficiency (PiZZ) and associated portal hypertension, cirrhosis (proven by biopsy) and hypersplenism underwent spleno-renal shunt and splenectomy six years ago, and both are doing well, attending school, and have practically normal liver function. One of the patients has chronic severe headaches, diarrhea, exudative enteropathy (20% of Cr51-labelled albumin recovered in stools in 4 days), sinusitis and hematuria, all uncommon in A1AT deficiency but likely related to the primary disorder. She also has a higher trypsin inhibitory capacity (0.45 mg trypsin inhibited/ml serum) than is generally reported in ZZ individuals. Based on the experience with these two patients, we conclude that AlAT deficiency is not a valid contraindication to the performance of a porta-systemic shunt.Supported in part by the John W. Champion Center.

337 INTERACTION OF GROWTH HORMONE AND GASTRIC INHIBITORY POLYPEPTIDE IN HYPOPITUITARY PATIENTS

Gastric Inhibitory polypeptide (GIP) given intravenously with glucose potentiates insulin secretion and improves glucose tolerance. Since patients with growth hormone (GH) deficiency frequently show alterations in oral glucose tolerance (GTT) and may have low insulin levels, the secretion of GIP in hypopituitary patients before and after GH administration for 6 months was studied. Glucose, insulin and GIP levels were obtained during an oral GTT. The results are expressed as ± the standard error of mean.There was no significant difference in the response of GIP, insulin, or glucose to an oral GTT before and after 6 months of GH administration (2 units Im 3 times weekly). The levels of GIP are comparable to normal controls suggesting no impaired secretion of GIP in growth hormone deficiency. It does not appear that GIP plays a role in the carbohydrate abnormalities in growth hormone deficiency.(Supported in part by the John W. Champion Center.)

A FAMILIAL THYRO-CEREBRAL-RENAL SYNDROME: A NEWLY REC-ognized disorder

A brother and sister had renal, neurological and thyroid disease; both with normal mentality. The sister presented at one year of age with evidence of renal disease (BUN 35 mg/dl). At age 9 neurological deterioration, muscle wasting, ataxia and myoclonus developed. Diffuse goiter was present (T4 RIA 5.0 μg/dl; thyroid microsomal antibodies 1:100; I131 uptake 8% at 2 hours. Perchlorate discharge was 50%, indicating a possible organification defect). Sensorineural deafness was demonstrated. Platelets were low (20,000) and serum zinc was high (570 μg/dl). Hyperuricemia persisted (10.3 mg/dl). The condition progressed with generalized muscular weakness, hemiparesis, clonic-tonic seizures and increasing renal insufficiency. BUN was 120 mg/dl and serum creatinine 1.5 mg/dl. The discrepancy between BUN and creatinine persisted. Kidney biopsy and poat-mortem examination showed interstitial and tubular nephropathy with secondary glomerular sclerosis with negative immunofluorescence, simple colloid goiter and degenerative and focal demyelination of the cerebral white matter and extensive neuronal loss and demyelination of the cerebellum.The brother is 13 years old and has interstitial nephritis (two biopsies), slurred speech, headaches, thrombocytopenia, an abnormal EEC and goiter.Supported in part by The John W. Champion Center.