James F. Marks

Massive Extraglandular Aromatization of Plasma Androstenedione Resulting in Feminization of a Prepubertal Boy

This report describes the mechanism of origin and the quantity of estrogen produced in a prepubertal boy who developed severe feminization at 8 yr of age as the result of a heretofore undescribed metabolic abnormality. The clinical findings were gynecomastia and accelerated linear growth and bone maturation. At the time feminization developed, there were no signs of growth or development of the otherwise normal prepubertal male external genitalia or any increase of muscle mass that normally accompanies male puberty. The hyperestrogenism was found to be the consequence of massive extraglandular conversion of plasma androstenedione to estrone. During a 6-mo period of study, the plasma production rate of androstenedione ranged from 1.2 to 1.6 mg/day. More than 55% of plasma androstenedione was metabolized by aromatization to estrone which, in turn, was extensively sulfurylated in the tissue sites of aromatization before its entry into the blood. Thus, estrone sulfate was the final product in the aromatizing sites, and the plasma production rate of estrone sulfate derived from plasma androstenedione was 782 mug/24 h. The extent of extraglandular conversion of plasma androstenedione to estrone measured in this boy was 50 times that observed in two normal prepubertal boys. Moreover, 94% of the extraglandular aromatization occurred in extrahepatic sites. The metabolic clearance rate of plasma androstenedione, 2,380 liters/day per m(2), was markedly increased in this boy. Approximately 1,500 liters of plasma androstenedione clearance was accounted for by extrahepatic, extraglandular aromatization. The fractional conversion of testosterone to estradiol, 0.16, was 50 times greater in this boy than that observed in normal young adult men. The total extent of aromatization of plasma prehormones was even greater in this boy inasmuch as evidence was obtained that aromatization of 16-hydroxysteroids, e.g. 16alpha-hydroxy androstenedione and 16alpha-hydroxy dehydroisoandrosterone (sulfate), resulted in estriol formation independent of estrone formation. Thus, extensive extrahepatic, extraglandular aromatization resulted in advanced feminization in this prepubertal boy by a previously undescribed metabolic abnormality.

Systemic carnitine deficiency. Report of a fatal case with multisystemic manifestations

A 14-year-old boy presented with recurrent and intractable hypoglycemia. He developed marked hepatic dysfunction and a severe myopathy. The diagnosis of systemic carnitine deficiency was not made until after his death from acute cardiac arrest. The recognition that systemic carnitine deficiency may present with multisystemic manifestations may allow earlier diagnosis and potentially effective replacement therapy in other patients so afflicted.

Capillary basement membrane width in diabetic children

The effect of juvenile onset diabetes mellitus on quadriceps muscle capillary basement membrane (QCBM) width has been examined by the electron microscopic morphometric method previously developed in this laboratory. The results demonstrate that in this age group QCBM thickening is strongly related to the age of the diabetic subject. As a result, in contrast to the almost constant thickening of QCBM that has consistently been documented in diabetic adults, QCBM hypertrophy is present in only 40 per cent of children with diabetes mellitus. As was previously shown to be the case in adults, in children, too, QCBM thickening is unrelated to the duration of the diabetes. Finally, the finding that QCBM hypertrophy is present at the time of acute onset of juvenile diabetes mellitus in 30 per cent of children, coupled with the fact that this lesion is not affected by duration of hyperglycemia, strongly supports our previous conclusion that diabetic microangiopathy is independent of the hyperglycemia of this disease. On the other hand, barring the possibility that microangiopathy in the pancreas precedes that in muscle, these results represent evidence against the suggestion that basement membrane hypertrophy represents the primary lesion of the diabetic syndrome.

Long term observations in a patient with pseudohypoaldosteronism

AbstractThis paper describes a patient with severe pseudohypoaldosteronism (PHA) for over 12 years. The patient presented at 10 days of age with a serum sodium of 118 mEq/l and potassium of 12 mEq/l. After failing to maintain normal fluid and electrolyte status with standard therapy, including maximal mineralocorticoid stimulation, he was given a special formula containing minimal potassium plus salt supplements which normalized his electrolyte status. However, when he was 4.5 years of age, an acute gastrointestinal illness led to severe volume depletion, hyperkalemia, and cardiopulmonary arrest. This resulted in significant neurological impairment. At 12.5 years of age, the patient continues to require massive sodium supplements and his diet contains less than 0.5 mEq/kg potassium daily; his height and weight are at the 95th percentile, thus demonstrating that normal growth may be achieved with strict dietary manipulation in a patient with persistent, severe PHA. Serial studies to further define the lesion in this patient have demonstrated: (1) normal binding of aldosterone to aldosterone binding globulin (5.1% bound); (2) normal mineralocorticoid “activity”; (2) suppressible renin and aldosterone levels; (4) increased prostaglandin excretion (3.15 μg/g creatinine); (5) lack of benefit of prostaglandin inhibition with indomethacin; (6) normal proximal tubule function (

Increase in Capillary Basement Membrane Width in Parents of Children with Type I Diabetes Mellitus: Association with HLA-DR4

C_{Na} + C_{H_2 O} = 18.0 ml/100

Maternal meiosis II nondisjunction in a case of 47,XXY testicular feminization

ml glomerular filtration rate; (7) impaired distal tubule function

Trisomy 18 with biliary atresia

\left( {C_{H_2 O} /C_{Na} + C_{H_2 O} = 79.8\% } \right)