Biomedical subjects
Publications and source records attributed to M L Voorhess.
A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathke's cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.
The hypothalamic-pituitary function of 93 children, who had received central nervous system (CNS) prophylaxis as part of their therapy for acute lymphocytic leukemia (ALL), and who remained in continuous complete remission, was evaluated retrospectively. Treatment regimens included--Group I: 31 subjects, intrathecal methotrexate (IT MTX); Group II: 31 subjects, IT MTX plus 2400 rad cranial irradiation; and Group III: 31 subjects, IT MTX and intravenous intermediate-dose methotrexate. Serum thyroid-stimulating hormone (TSH) and T4 levels were normal. All participants had normal adrenocorticotropic hormone (ACTH) secretion as assessed by plasma cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) excretion of pubertal and postpubertal patients (N = 37) was appropriate, except for one subject from Group I who had an abnormally high output of gonadotropins, and one from Group II who had abnormally low levels. Growth hormone (GH) responses were subnormal after sequential arginine-insulin stimulation as follows--Group 1: 3 of 31 patients; Group II: 6 of 25 patients; and Group III: 2 of 29 patients. Nevertheless, all children had normal linear growth. It was concluded that the three forms of CNS prophylaxis evaluated had no long-term adverse effect on TSH and ACTH secretion. FSH-LH production appears to be normal, but final judgment must await follow-up studies because 60% of the patients were prepuberteral or still receiving chemotherapy. Eleven patients had subnormal GH responses after pharmacologic stimulation of the pituitary, but long-term linear growth was unaffected.
There is a debate whether the fall in plasma cortisol concentrations after the early morning dosing of clonidine represents drug effect or normal diurnal variation. We compared the cortisol patterns of children after a 7:30 AM oral dose of clonidine (0.075 or 0.150 mg/m2) with the cortisol concentrations that resulted from diurnal variation. Some subjects had the diurnal study on day 1 and the clonidine study on day 2, whereas for others the testing sequence was reversed. Our results indicate that clonidine, in either dose, does not cause a fall in plasma cortisol levels greater than that with normal diurnal variation.
This study prospectively evaluated the endocrine function of 11 children treated with cranial irradiation (CRT) for brain tumors. All tumors were remote from the hypothalamic-pituitary axis. Children were studied before treatment and at 3, 6, and 12 months after the completion of CRT. T4, thyroid-stimulating hormone, prolactin, plasma cortisol, and urinary follicle-stimulating hormone and luteinizing hormone values were normal before and after treatment in all patients. Growth hormone (GH) deficiency was identified in 0 of 7 patients before treatment, in 2 of 7 patients 3 months post-CRT, in 9 of 11 patients 6 months post-CRT, and in 7 of 8 patients 12 months post-CRT. Growth deceleration was identified in five of seven prepubertal patients. GH deficiency is an extremely common sequelae of CRT, beginning as early as 3 months after the completion of CRT. The deficit is progressive over time.
Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.
Norepinephrine (NE) is a neurotransmitter of the sympathetic nervous system which is important in GH secretion. It also is a counterregulatory hormone which is released in response to insulin hypoglycemia. We measured the plasma NE, epinephrine, GH, and cortisol responses to insulin-induced hypoglycemia in 29 short healthy children. The 8 patients (5 males and 3 females) which had isolated GH deficiency had no plasma NE response to insulin hypoglycemia, whereas mean plasma NE increased 2-fold in the 21 GH-sufficient children. Plasma epinephrine concentrations increased in both groups, but were lower in the GH-deficient patients. While these findings do not permit us to determine whether the reduced plasma catecholamine responses to acute hypoglycemia are the cause, the consequence, or unrelated to the GH deficiency, we speculate that there is a relationship between the NE and GH deficiencies.
Post-prandial hyperglycemia or meal intolerance has been documented in a majority of patients with Type I Diabetes Mellitus (IDDM) receiving conventional insulin treatment. It is most marked following the breakfast meal. We hypothesized that the abnormality might result from insulin insufficiency because of the short time interval between insulin therapy and meal ingestion. To test this hypothesis a standardized breakfast was fed 30 min. after insulin on one day and 90 min. after insulin on the alternate day. Plasma concentrations of glucose, free insulin and cortisol were measured at 30 min. intervals throughout the study period. A control population consisted of healthy children who were fed the same standardized breakfast. We observed that prolongation of the time period between insulin and meal did not alter the magnitude of the post-meal rise in glucose concentration in the IDDM group. Furthermore, meal intolerance persisted despite the significantly higher pre-meal levels of insulin in the IDDM group compared to the controls. We speculate that a defect in insulin action may be responsible for the phenomenon of meal intolerance in the Type I diabetics given subcutaneous insulin injections once or twice daily.
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A diagnosis of congenital adrenal hypoplasia was established in a male child at 3 years of age. Although there was biochemical evidence of mineralocorticoid deficiency when he was 2 months old, no definite glucocorticoid deficiency was demonstrated. The child thrived well without replacement hormone therapy until he contracted an illness associated with vomiting. Subsequent tests confirmed the existence of both glucocorticoid and mineralocorticoid deficiencies due to adrenal hypoplasia. This case and the other reported in the literature point out that the glucocorticoid deficiency in congenital adrenal hypoplasia may become progressively more severe with time. Congenital adrenal hypoplasia may be the correct diagnosis in cases mistakenly diagnosed as acquired adrenal insufficiency.
Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.
Nine of 12 girls diagnosed consecutively as having severe and longstanding primary hypothyroidism were found to have multicystic ovaries when evaluated by pelvic ultrasound examination. The cysts resolved rapidly with thyroid replacement therapy. The patients had either elevated or high normal plasma luteinizing hormone levels which decreased markedly after thyroid therapy. Five of seven patients tested with luteinizing hormone-releasing hormone had attenuated gonadotropin responses; the other two reacted normally. The pathogenesis of the cysts remains uncertain. Use of pelvic ultrasound scan has documented a high frequency of multicystic ovaries in girls with primary hypothyroidism.
Ovarian function was evaluated in eight adolescent women 1-90 months after completion of treatment for non-Hodgkin's lymphoma, which included a cyclophosphamide-containing combination chemotherapy protocol and radiation therapy. Two women received whole abdomen irradiation and both had ovarian failure. In contrast, none of six women who received combination chemotherapy and radiation therapy which did not include the abdomen had evidence of ovarian failure. These findings suggest that both the prepubertal and postpubertal ovary are relatively unaffected by this combination chemotherapy program which included cyclophosphamide and methotrexate.
Teratomas of the cervical area are relatively rare tumors--only 132 cases have been reported. This paper adds two more cases to the literature and reviews the important clinical aspects of the disease. This tumor commonly presents in early infancy with increasing respiratory distress; polyhydramnios is commonly associated with tumors greater than 10 cm in diameter. They are always benign in infants and are believed to arise from the thyroid gland. Prompt surgical removal is mandatory. Thyroid function studies should be initiated preoperatively, if feasible, and definitely postoperatively to avoid the possible complication of hypothyroidism in the young infant.
The Verner-Morrison syndrome has been described in 19 previous patients with ganglioneuroma and ganglioneuroblastoma but never neuroblastoma. Its occurrence following treatment of a neuroblastoma with chemotherapy with maturation of the tumor has only been reported on one previous occasion. Our case suggests that vasoactive intestinal polypeptide may be used not only as a diagnostic indicator for the presence of a neural crest tumor but also as a marker to monitor maturation of the tumor and indicate an improving prognosis.
Plasma beta-hydroxybutyrate (beta-OHB) concentrations and simultaneous urine tests for ketonuria (nitroprusside reaction) were evaluated every 4 h throughout a 24-h study in 10 healthy insulin-dependent diabetics who had poor control based on home urine tests and elevated hemoglobin A1C. Concurrent measurements of the major carbohydrate regulatory hormones were made in the diabetic group and in a control population of 20 age-matched subjects. In the diabetics, 73% of the beta-OHB measurements were elevated. Only 43% of the abnormal beta-OHB values were associated with ketonuria. The diabetic subjects also showed exaggerated diurnal patterns for plasma beta-OHB and cortisol. There were no significant differences for the other regulatory hormones in the diabetic and normal groups. We conclude that 1) abnormal plasma beta-OHB levels without ketonuria are prevalent in poorly controlled diabetics; 2) negative nitroprusside tests for ketonuria underestimate the presence of ketonemia due to increased beta-OHB concentrations; 3) both insulin deficiency and glucocorticoid excess may influence ketone body metabolism in insulin-dependent diabetic patients.
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A 26-month-old boy with Stage III abdominal ganglioneuroblastoma had tachycardia and hypertension. The hypertension increased following the institution of chemotherapy and necessitated the use of both alpha and beta adrenergic blocking agents to control the effects of the marked catecholamine production. After excision of the residual tumor, the blood pressure and urinary catecholamine excretion returned to normal. Histologic examination of this tissue under light microscopy revealed some sections of ganglioneuroblastoma as well as large areas of ganglioneuroma. Examination by electron microscopy demonstrated a moderate number of dense core neurosecretory-type granules in the cell bodies of the ganglion-like cells and an abundance of the same type of granules in the bundles of the interwoven cytoplasmic neural processes. To data, 32 months after diagnosis and 20 months off chemotherapy, the patient remains free of tumor and is in excellent general health. We postulate that the large number of secretory granules in this tumor permitted storage and release of markedly increased quantities of norepinephrine and resulted in a clinical profile similar to that associated with pheochromocytoma.
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