Mary L. Voorhess

Iron Deficiency Anemia and Increased Urinary Norepinephrine Excretion.

Chronic iron deficiency in rats resulted in decreased MAO activity both in vitro and in vivo. Since MAO is an important enzyme in inactivation of catecholamines, urinary excretion of DA, NE, E, MN-NMN, and VMA was measured in 24-hour samples from 11 iron-deficient children before and after treatment with intramuscular iron. Pretreatment NE excretion was abnormally high and returned to normal (P=0.001) within one week of therapy. VMA excretion also was higher before than after treatment (P greater than 0.05), but most values were within the normal range for healthy children of comparable size. There was no significant difference between DA, E, and MN-NMN excretion before and after iron therapy. Anemic, non-iron-deficient children had normal urinary NE, E, and VMA excretion before and after transfusion. These findings suggest that the irritability, lack of attentiveness, and low performance scores of iron-deficient children may be related to alterations in catecholamine metabolic pathways secondary to dependence of MAO on adequate iron stores.

Acute Diabetic Ketoacidosis in Children: Role of the Stress Hormones

Summary: Twenty-five cases of acute ketoacidosis, occurring in insulin-treated diabetic children in previous good health, were studied close to the onset of illness and throughout the first 24 hr of therapy. In most patients, symptoms of illness and ketonuria had been present for less than 12 hr; in 9 subjects, they had been present for less than 4 hr. Initial plasma glucose concentrations ranged from 252 to 849 mg/dl. The first pH values in 21 cases were less than 7.27, and in the remaining 4 studies, the CO2 was less than 14 mEq/liter. Identifiable sources of stress, such as infections or emotional arousal, preceded the development of ketoacidosis in 20 cases.Serial measurements were made of plasma glucocorticoid, growth hormone, and glucagon concentrations as well as urinary excretion of epinephrine and norepinephrine to assess the role of these hormones in acute ketoacidosis and to evaluate their relationship to the abnormalities in glucose and electrolyte homeostasis. Excessive urinary excretion of epinephrine was a frequent and striking phenomenon. Output was greater than 4 S.D. above the mean in 20 of 23 cases in the first 2 hr of the study. In 15 cases, the values fell into the normal range by approximately 14.5 hr, but in seven patients, epinephrine overproduction persisted for the entire study. Cortisol hypersecretion was present in 24 of 25 patients and persisted for 6 to 8 hr or longer before gradually subsiding. Initial growth hormone concentrations were elevated in seven patients (20 ng/ml or above), but the highest values (20 to 160 ng/ml) were observed after insulin administration. At the outset, plasma glucagon concentrations were less than 200 pg/ml in 11 patients; in 11 others, it ranged between 250 and 1250 pg/ml. The elevated values usually were transient. Of 22 cases in whom all five hormones were measured at the start of the study, 21 exhibited increased production of at least three of the stress hormones.We conclude that some diabetic children who have received their usual dose of insulin develop hyperglycemia, dehydration, and acidosis within a few hr of experiencing stress because large amounts of counterregulatory hormones, especially catecholamines and cortisol, are released.Speculation: Acute onset of ketoacidosis in previously healthy insulin-treated diabetic children occurs because their daily dose of insulin is insufficient to offset the effects of the counterregulatory hormones produced in response to stress (catecholamines, cortisol, glucagon, and growth hormone). Hyperglycemia, dehydration, and acidosis result from the glycogenolytic, lipolytic, and ketogenic action of the stress hormones.

Trisomy 18 syndrome with absent radius, varus deformity of hand, and rudimentary thumb: Report of a case***

Summary The patient described in this report had the characteristic findings of trisomy 18 syndrome. In addition, there was absence of the left radius, severe varus deformity of the left hand on the forearm, and a rudimentary left thumb. To our knowledge these findings have not previously been reported.

Outcome of Lower L-Thyroxine Dose for Treatment of Congenital Hypothyroidism

The appropriateness of the recommended L-thyroxine dose (10-15 μg/kg/day) for the treatment of congenital hypothyroidism has been questioned because of the risk of iatrogenic hyperthyroidism. We report the outcome of 23 newborns with congenital primary hypothyroidism treated with 25 μg L-thyroxine per day (5.3-9.2 μg/kg/day) and followed for an average of 59 months. Serum thyroxine (T4) values increased (X = 11.4 ± 2.7 μg/dL) within 4 weeks posttherapy; eight infants had T4 levels ≥13 μg/dL on only half the currently recommended dose. Thyroid-stimulating hormone (TSH) values remained elevated in 18 of 21 patients for 2-21 months despite a high-normal T4. Psychometric tests were performed in 19 of the 23 patients. The mean Full Scale IQ for the congenital hypothyroid group (n = 16 ) was 101.4 ± 13.2 with comparable Verbal and Performance IQ scores. Patients with a bone age (BA) of ≤32 weeks or T4 <2 μg/dL at initial evaluation had significantly Lower Verbal IQ scores. A standardized parent-report assessment of behavioral and emotional functioning revealed subgroup scale scores that were indistinguishable from nonclinical norms. We conclude that (1) average range IQ scores and positive behavioral adaptation are observed in congenitally hypothyroid children treated with L-thyroxine doses lower than currently recommended; (2) the L-thyroxine dose should be individualized to prevent iatrogenic hyperthyroidism; (3) TSH normalization should not be a primary objective of treatment, and (4) a prospective study comparing the advantages and risks of different doses of L-thyroxine is needed.

Neuroblastoma with normal urinary catecholamine excretion

Summary Previous reports have suggested that neural crest cells which give rise to spinal nerve roots and ganglia have suppressed tyrosine metabolism and that neuroblastomas arising from these structures are nonsecretors of catecholamines. This paper describes 2 infants who had paresis from spinal cord compression by primary neuroblastoma orignating in the cervical dorsal nerve roots and ganglia and normal urinary excretion of catecholamines and metabolites.

NEUROBLASTOMA‐PHEOCHROMOCYTOMA: PRODUCTS AND PATHOGENESIS

Neuroblastornas and pheochromocytomas are embryologically related tumors of neural crest origin that have the capacity to synthesize and metabolize catecholamines. The intriguing characteristics of these neoplasms have been the object of numerous investigations during the past decade. I will summarize some of the vagaries of neuroblastomas and pheochrornocytornas, present data that depict the relationship between urinary catecholamine excretion and tumor catecholamine content, and attempt to correlate the results of electron microscopic and biochemical studies by various investigators with the clinical findings in patients with these tumors.

The adrenomedullary and glucagon responses of hypopituitary children to insulin-induced hypoglycemia.

Summary: The activity of phenyl-N-methyl transferase (PNMT), the adrenomedullary enzyme which catalyzes the N-methylation of norepinephrine (NE) to epinephrine (E) is induced by endogenous glucocorticoid hormones secreted by the adrenal cortex. We quantitated the urinary output of NE and E before, during, and after insulin-induced hypoglycemia in patients with pituitary dysfunction. Plasma concentrations of cortisol, growth hormone, and glucagon were measured simultaneously. The study population was comprised of nine healthy controls (group 1), eight children with growth hormone deficiency (group 2), and eight children with combined growth hormone and cortisol deficiencies (group 3). Recovery from acute hypoglycemia was similar in all groups. Mean plasma glucagon values reached a maximum at 30 min after insulin injection, and no significant differences were observed among the groups. Plasma cortisol levels were similar in groups 1 and 2, maximum values ocurring at 45 min after insulin. Patients in group 3 did not increase their cortisol concentrations above 5.5 μg/d despite a greater than 50% drop in blood glucose. Mean urinary E output of all groups increased significantly above pretest values (groups 1 and 2, P < 0.001; and group 3, P < 0.01), whereas NE levels were unchanged. After hypoglycemia, the mean E increments in the control and cortisol-deficient groups were not significantly different.The data can be interpreted in two ways. Endogenous cortisol production in ACTH-deficient bypopituitary children is sufficient to maintain PNMT activity at a level needed for synthesis of E from NE. Alternatively, cortisol may not be essential for E release during acute hypoglycemia because hypothalamic regulatory mechanisms supervene, and direct neural stimulation promotes PNMT activity and synthesis of E.We conclude that patients with cortisol and growth hormone deficiencies are able to recover from acute hypoglycemia when hepatic glycogen stores are adequate because there is sufficient release of E or because other adrenergic mechanisms stimulate glucagon release and hepatic glycogenolysis.Speculation: Although children with cortisol and growth hormone deficiencies are able to recover from acute hypoglycemia, many do not tolerate a prolonged fast because of diminished gluconeogenesis and depletion of hepatic glycogen.

CARDIOVASCULAR EFFECTS OF THERAPY IN CONGENITAL HYPOTHYROIDISM.

Cardiovascular changes have long been known to occur during the early treatment of hypothyroidism. The responsible factors have not been clearly elucidated. In this study heart rate changes in three cretins were studied in a constant-environment laboratory. Within ten days after the initiation of therapy, cardiac rate increased in the three subjects as did cardiac responsivity to exteroceptive stimuli in two of the infants. Transient, potentially serious arrhythmias were also noted during therapy.

Disorders of the adrenal medulla and multiple endocrine adenomatoses.

This article reviews the structure and development of the adrenal medulla, and the principal pathways of synthesis and metabolism of the catecholamines. The clinical manifestations and current treahnent regimens for pheochromocytoma, neuroblastoma, and multiple endocrine adenomatoses are also discussed.

XX/XO mosaicism in a girl: Report of the youngest patient+

A phenotypic female child was first seen at 2 10/12 years of age because of growth and behavioral retardation. She had an odd facies with prominent epicanthi and low-set ears. There was no webbing of the neck or lymphedema. The nipples appeared to be widely spaced. There was a soft systolic murmur over the precordium. No abnormalities of the external genitals were apparent. Less than 2 per cent of the cells from the buccal mucosa were chromatin positive although many drumstick forms were seen in the polymorphonuclear leukocytes. Chromosomal analysis of cultured peripheral leukocytes revealed XX/XO mosaicism.