Frederic M. Kenny

Improved prognosis in congenital bypothyroidism treated before age three months

The relationship between age at beginning therapy and subsequent intelligence quotient was studied in 31 patients with congenital hypothyroidism. Those patients treated before three months of age had a significantly higher average I.Q. than those treated after three months. Because the clinical symptomatology before three months of age is often obscure, and the diagnosis is often missed, a neonatal screening program could be beneficial.

The syndrome of congenital adrenocortical unresponsiveness to ACTH. Report of six cases

Extract: Six patients with the syndrome of congenital adrenocortical unresponsiveness to ACTH are reported.This syndrome is characterized by feeding problems early in life, hypoglycemic episodes and hyper-pigmentation of the skin (table I). Blood pressure and levels of electrolytes in serum were normal (table II). PPD and histoplasmin skin tests were negative, while antibodies to adrenal, thyroid, and gastric tissues were undetectable. Urinary excretion of 17-hydroxycorticosteroids and cortisol production rates were low and did not respond to administration of ACTH (table III). While receiving a low sodium diet, the patients were able to conserve sodium (figs. 2, 3 and 4) and to increase the rate of aldosterone secretion (tables IV and V).In one case, adrenal pathology showed a normal zona glomerulosa with atrophy of the zonae fasciculata and reticularis.This isolated deficiency in cortisol secretion is not due to a defect in pituitary function or a deficiency of one of the enzymes directly involved in steroid biosynthesis. The most probable pathogenesis is an abnormality at the site (or one of the sites) of ACTH action on cortisol biosynthesis.Speculation: It is probable that some young infants in whom a diagnosis of Addisons disease is made do, in fact, have the syndrome of congenital adrenocortical unresponsiveness to ACTH. Studies of cortisol secretion rates prior to and during ACTH administration and a determination of aldosterone secretion rates while receiving normal and low salt diets will permit differentiation of the two disorders.

Granulocytopenia, lupus-like syndrome, and other complications of propylthiouracil therapy

Thirty-eight patients aged 2 to 18 years with hyperthyroidism were followed with hematologic studies while receiving propylthiouracil. Ten (26 per cent) had one or more episodes of leukopenia (white blood cell count

Endogenous insulin and growth hormone response in children with newly diagnosed diabetes mellitus.

Extract: Forty-five children with newly diagnosed diabetes mellitus were evaluated in terms of endogenous release of insulin and growth hormone using glucose, tolbutamide, arginine and glucagon as stimuli. The mean concentration of insulin in the plasma obtained from fasting diabetic children was found to be 10.0 μU/ml, a value significantly below the mean level of 15.3 μU/ml in the control group. Essentially no increase in the concentration of insulin in plasma resulted from stimulation with the above agents. The mean concentration of growth hormone in the plasma of fasting diabetics was found to be 3.8 mμg/ml, a value higher than but not significantly different from the value of 2.5 mμg/ml in the contrast patients. Following the intravenous infusion of arginine, however, the mean concentration of growth hormone in the plasma of diabetic children rose to 20.8 mμg/ml, a level significantly higher than the mean peak value of 7.4 mμg/ml in the nondiabetics. Although no change in the concentration of growth hormone followed glucagon injection in the nondiabetic children, a prompt, significant elevation to 9.4 mμg/ml occurred in the diabetics. Glucagon administration has not previously been reported to stimulate the release of growth hormone.Speculation: Insulin deficiency alone will not adequately explain the variability in clinical symptomatology and metabolic derangement seen in children with newly diagnosed diabetes mellitus. These data suggest that growth hormone may play an important role. The finding that glucagon administration stimulates release of growth hormone in the juvenile diabetic may indicate the presence of a previously unrecognized interrelation between glucagon-growth hormone and insulin.

Functioning thyroid masses in childhood and adolescence: Clinical, surgical, and pathologic correlations*

Six girls, aged 5 to 15 years, presented with thyroid masses in otherwise nonpalpable thyroid glands and with normal serum thyroxine levels. Scintiscanning before and after TSH stimulation confirmed the presence of autonomous nodules in the four adolescents, of whom two had elevated T3 levels. Surgical exploration revealed adenomatous thyroid hyperplasia in three of the girls and papillary adenocarcinoma in the fourth. Scans in the other two girls revealed absence of the left lobe. One of them proved to have agenesis of the left lobe with enlargement of the right lobe because of lymphocytic thyroiditis. The other girl had an ectopic thyroid with chronic inflammation. A thorough diagnostic evaluation of single or multiple functioning thyroid masses in children and adolescents is essential in establishing the correct diagnosis. The possibility that carcinoma can occur in autonomous nodules as well as in hemiagenesis and ectopic thyroid tissue is discussed. An approach to the management of functioning thyroid masses in the pediatric age group is proposed.

Unconjugated Estrogens in the Perinatal Period

Extract: High levels of unconjugated estrone ((E1) 3-hydroxyestra-1,3,5(10)-triene-17-one) and estradiol ((E2) estra-1,3,5(10)-triene-3,17β-diol) were found at term in maternal venous, umbilical vein, and umbilical artery plasma. For estrone the respective values in nanograms per milliliter ±SD were 12.8 ± 5.9, 25.1 ± 6.5, and 13.2 ± 7.7. For estradiol the respective values were 17.3 ± 9.2, 8.1 ± 4.0, and 5.1 ± 3.2. For estrone, levels for umbilical vein were higher than those in the paired maternal and umbilical artery; estradiol was higher in maternal vein than in the paired umbilical vessels. Absence of the fetal adrenals was associated with low levels of estrone and estradiol for maternal and umbilical vessels, whereas, in anencephaly, only the maternal levels were markedly diminished. An initially rapid, and then a slower decline in both estrogens was found in normal infants during the first 72 hr of life.Speculation: Despite extensive metabolism of unconjugated estrogen by the fetus, umbilical arterial levels of estrone and estradiol are high. Nevertheless, the neonate shows scant clinical evidence of those high levels. This could be due to incomplete development of estrogen receptors in target tissues, plasma protein binding of estrogen, competition between the biologically most potent estrogen estradiol and the less potent estrone and estriol ((E3) estra-1,3,5(10)-triene-3,16α;,17β-triol), or other factors.

Arginine-induced growthhormone responses in children: Effect of age and puberty

I. Hon, E. H., and Khazin, A. F.: Biochemical studies of the fetus. Part I, Obstet. Gynec. 33: 219, 1969. 2. Hon, E. H., Khazin, A. F., and Paul, R. H.: Biochemical studies of the fetus. Part II, Obstet. Gynec. 33: 237, 1969. 3. Seeds, A. E., and Behrman, R. E.: Acid-base monitoring of the fetus during labor with blood obtained from the scalp, J. P~mAT. 74: 804, 1969. 4. Phillips, L., Lumley, J., Paterson, P., and Wood, C.: Fetal hypoglycemia, Amer. J. Obstet. Gynec. 102: 371, 1968. 5. Hobel, C. J.: The influence of anemia on the acid-base state of the fetus and newborn, Amer. J. Obstet. Gynec. 106: 303, 1970. 6. Saling, E.: Amnioscopy and fetal blood sampiing: Observaffons on foetal acidosis, Arch. Dis. Child. 41: 472, 1966. 7. Wintrobe, M. N.: Clinical hematology, ed. 6, Philadelphia, 1967, Lea & Febiger, Publishers, p. 429. 8. Liley, A. W.: Errors in the assessment of hemolytic disease from amniotic fluid, Amer. J. Obstet. Gynec. 86: 485, 1963. 9. Wu, P. Y. K., and Oh, W.: Evaluation of the newborn, in Charles, A. G., and Friedman, E. A., editors: Rh isoimmunization and erythroblastosis fetalis, New York, 1969, AppletonCentury-Crofts, Inc., p. 168.

Iatrogenic hypopituitarism in craniopharyngioma: Unexplained catch-up growth in three children

Nine consecutive children with craniopharyngiomas were studied who had relatively normal pituitary function prior to operation. Surgical attempts to remove the craniopharyngiomas were frequently followed by a loss of thyroid stimulating hormone, evaluated indirectly by the butanol extractable iodine, and by failure of adrenocorticotrophic hormone as reflected by a fall in urinary 17-hydroxycorticosteroids and a loss of previously normal SU-4885 responsiveness. In addition, diabetes insipidus, which had not been present preoperatively, invariably followed stalk section which was often necessary during surgery. Despite the postoperative appearance of diabetes insipidus and of thyroid-stimulating hormone and adrenocorticotropic hormone failure, three of ten patients showed “catch-up growth” postoperatively. One of the three had a growth spurt which carried him from below the third up to the fiftieth percentile in 1 1/2 years after operation. He showed no increase in serum growth hormone during arginine or insulin provocative tests. The growth spurts in these three patients are difficult to explain in view of the loss of integrity of their hypothalamic-pituitary pathways.

Prevalence of low-titer and “negative” antithyroglobulin antibodies in biopsy-proved juvenile Hashimoto's thyroiditis

Although the finding of antithyroglobulin antibodies has been considered the mostuseful diagnostic procedure for nonbiopsy diagnosis of chronic lymphocytic thyroiditis, we found titers

Reference Standards for Cortisol Production and 17-Hydroxy-Corticosteroid Excretion During Growth: Variation in the Pattern of Excretion of Radiolabeled Cortisol Metabolites

Whereas aldosterone secretion changes little during growth and adrenal androgen excretion rises sharply at adolescence, cortisol production rate (CPR) increases gradually during growth and declines in old age. Previously published data on CPR obtained in our laboratory by an in vivo isotope dilution technique, in 96 subjects from birth to age 20 years, were recorrected for body surface area (/m2), body weight (/Kg.) and creatinine excretion (/Gm. cnne), i.e., muscle mass. The highest CPRs on the basis of /m2, /Kg., and /Gm. cnne were in babies under age 5 days, and the second highest values in the period 5–20 days. There-after in the age groups 20 days-5 years; 5–10 years; 10–15 years; and 15–20 years body surface area was the best predictor of CPR which decreased relative to muscle mass. In contrast to CPR, urinary 17-hydroxycorticosteroid (17-OHCS) excretion, (i.e., β-glucuronidase released Porter-Silber chromogens) was lowest in the age group less than age 5 days, and was still lowest when adjusted /m2. The recovery of 4-14C-cortisol metabolites in a “nonpolar”, conjugated (β-glucuronidase released chloroform extractable) fraction was also lowest in that age group. Nonconjugated “polar” metabolites were significant in the neonatal period. The data fail to elucidate the primary stimulus(i) for the changing rate of CPR from birth to age 20 years. However, they provide guidelines for the interpretation of adrenal function studies based on CPR or 17-OHCS determinations, and therefore are useful from the standpoints of diagnosis and therapy.