Lawson Wilkins

AN EVALUATION OF SEVENTY-FIVE PATIENTS WITH HYPOPITUITARISM BEGINNING IN CHILDHOOD.

Abstract Seventy-five cases of hypopituitarism were reviewed; forty-five were examples of idiopathic somatotropin deficiency, alone or in combination with other tropin defects, eleven were idiopathic cases of isolated gonadotropin deficiency, and nineteen were cases of central nervous system lesions within or above the pituitary. The presenting complaints for each group, respectively, were growth failure, sexual immaturity, and either neurologic symptoms or diabetes insipidus. Because of characteristic symptoms and almost uniform abnormalities on skull films, the last group was easily separated from the other two. The second group did not show retarded growth, and results of tests of pituitary function were normal except for the persistent absence of gonadotropins. Contrary to previous reports, growth failure was noted by one year of age in 35.9 per cent of patients with idiopathic hypopituitarism. Carbohydrate metabolism abnormalities were common, and two thirds of a small group tested were insulin-sensitive. Serum nonprotein or urea nitrogen levels were frequently elevated; serum calcium, phosphorus and alkaline phosphatase were within normal limits, and serum cholesterol usually varied as expected on the basis of intact or absent TSH in any one patient. In order of decreasing frequency, deficiencies of gonadotropin, ACTH and TSH were noted. A decreased sulfation factor, a diminished metapirone response, and hypoglycemic unresponsiveness accompanying growth failure, are the most characteristic laboratory abnormalities of idiopathic hypopituitarism and are considered the most helpful tools in arriving at a diagnosis in the child.

Further studies on the treatment of congenital adrenal hyperplasia with cortisone. III. The control of hypertension with cortisone, with a discussion of variations in the type of congenital adrenal hyperplasia and report of a case with probable defect of carbohydrate-regulating hormones.

Three cases of congenital adrenal hyperplasia with disturbed electrolyte metabolism, followed for 14 to 20 months, have been reported in detail. The effects of cortisone (compound E) and corticosterone (compound B) on the suppression of the abnormal adrenals and on the electrolyte disturbance have been discussed. Cortisone produces more marked suppression of the adrenal overactivity/mg. (as measured by the urinary excretion of 17-KS), but less sodium retention than corticosterone. Both steroids, however, significantly improve the electrolyte abnormality. The possible mechanism of action of cortisone on the electrolyte metabolism is discussed. Suggestions concerning the therapeutic management of these patients are offered. The use of adequate NaCl without DCA in the initial treatment is emphasized, since suppression of the adrenal with cortisone seems to alter materially DCA requirement. The final combination of therapy, however, must be decided in each patient individually.

THE EFFECT OF PITUITARY GROWTH HORMONE IN DWARFISM WITH OSSEOUS RETARDATION AND HYPOGLYCEMIA AND IN A CRETIN TREATED WITH THYROID

The chemistry and physiology of pituitary growth hormone have recently been reviewed by Li and Evans (1). Pure samples of growth hormone have been prepared by Li and coworkers from bovine pituitary glands (2) and by Wilhelmi and coworkers from a similar source by a somewhat different method (3). This hormone has been prepared and made available to a number of workers for metabolic investigation on human subjects.2 While the recently purified growth hormone causes linear growth, weight gain and nitrogen retention in both rats and dogs (1), no such effect has been reported in humans (4). The increase in inorganic phosphate which is characteristic of growth, has been produced in rats by injection of growth hormone (1) and has been observed in humans with an increased endogenous supply of growth hormone (5), but not in human subjects treated with growth hormone (4). In fact, most individuals who have been treated with growth hormone, have shown an increased excretion of nitrogen, slight elevation of temperature and symptoms of malaise. A dwarf with osseous retardation and hypoglycemia was selected for these studies because it was surmised that such an individual might be more sensitive to the hormone. Since it seemed possible that some of the findings in this case might be attributable to the presence of thyrotropic hormone in the preparation, an athyrotic cretin, rendered euthyroid by the administration

Diagnosis and treatment of congenital virilizing adrenal hyperplasia.

The principle of treatment of congenital virilizing adrenal hyperplasia is to suppress adrenal activity with a cortisonelike steroid, thus preventing formation of precursors which have androgenic and sometimes hypertensive effects. After establishing a depot with initial large doses, the minimal maintenance dose for adequate suppression is determined by the output of urinary 17-ketosteroids. In growing children it is also important to regulate long-range treatment according to rates of growth and osseous development. Cortisone dosage must be greatly increased during periods of stress. In the authors opinion, most of the newer steroids advocated for therapy do not have an advantage over cortisone, desoxycorticosterone acetate or both.

Sexual Infantilism in Females1

IN ANOTHER PAPER we (1) have discussed the failure of normal sexual development resulting from agenesis of the ovary and usually associated with a growth deficiency. There are a number of other conditions which cause failure of sexual maturation in the female. We shall attempt to classify them and shall present a number of cases of different types. CLASSIFICATION As shown in the accompanying table lack of development of the breasts, vagina and uterus and absence of the menarche may result either (a) from primary ovarian deficiency or (b) from a failure of the pituitary to produce the gonadotropic hormones which stimulate the maturation of the ovarian follicles. Primary Ovarian Deficiency. We have reported four cases and have collected eight others from the literature in which there is substantial pathological evidence that the gonads never developed beyond the stage of the genital ridge which is found in the embryo of 5–7 mm.

Sexual Infantilism in Females1: Causes, Diagnosis and Treatment2

IN ANOTHER PAPER we (1) have discussed the failure of normal sexual development resulting from agenesis of the ovary and usually associated with a growth deficiency. There are a number of other conditions which cause failure of sexual maturation in the female. We shall attempt to classify them and shall present a number of cases of different types. CLASSIFICATION As shown in the accompanying table lack of development of the breasts, vagina and uterus and absence of the menarche may result either (a) from primary ovarian deficiency or (b) from a failure of the pituitary to produce the gonadotropic hormones which stimulate the maturation of the ovarian follicles. Primary Ovarian Deficiency. We have reported four cases and have collected eight others from the literature in which there is substantial pathological evidence that the gonads never developed beyond the stage of the genital ridge which is found in the embryo of 5–7 mm.

Sexual Infantilism in FemalesCauses, Diagnosis and Treatment

IN ANOTHER PAPER we (1) have discussed the failure of normal sexual development resulting from agenesis of the ovary and usually associated with a growth deficiency. There are a number of other conditions which cause failure of sexual maturation in the female. We shall attempt to classify them and shall present a number of cases of different types. CLASSIFICATION As shown in the accompanying table lack of development of the breasts, vagina and uterus and absence of the menarche may result either (a) from primary ovarian deficiency or (b) from a failure of the pituitary to produce the gonadotropic hormones which stimulate the maturation of the ovarian follicles. Primary Ovarian Deficiency. We have reported four cases and have collected eight others from the literature in which there is substantial pathological evidence that the gonads never developed beyond the stage of the genital ridge which is found in the embryo of 5–7 mm.