Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome.

We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing's syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis.

The relation between skeletal maturation and adiposity in African American and Caucasian children.

OBJECTIVE: African American children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for by their greater adiposity. STUDY DESIGN: We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (BMI SDS), and fat mass by dual energy x-ray absorptiometry (DXA). RESULTS: African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P <.05). Both BA - CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P <.05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P <.05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SDS, and DXA fat mass (all r > 0.46, P <.001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SDS, or DXA fat mass. CONCLUSION: Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity.

Estimation of body fatness by air displacement plethysmography in African American and white children.

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal African American and white children. One hundred nineteen nonoverweight and overweight boys (N = 56) and girls (N = 63), age (mean +/- SD) 9.8 +/- 1.7 y, body mass index 25.9 +/- 7.6 kg/m2 (range, 14.2-47.0 kg/m2), and mean percent body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 +/- 11.7% (range, 12.2-57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and with body fat by several field methods: skinfold thicknesses using the Slaughter et al. equations (Hum Biol 60: 709-723, 1988), bioelectrical impedance analysis (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366-373, 1992), and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et al.: Am J Clin Nutr 63: 299-305, 1996). All methods used to estimate %BF were significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85 (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated %BF by -1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as +/-2 SD) were +/-7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP and DXA did not vary with age, race, or pubertal stage. Application of the age-adjusted Lohman model to ADP significantly increased the magnitude of the underestimation to -6.9% (p < 0.0001). Prediction of %BF by the Slaughter skinfold thickness equation showed no significant mean bias for the overall data, but significantly underestimated %BF in girls (-3.7%) while overestimating %BF in boys (+2.4%) with wide limits of agreement (+/-17.7%, p < 0.01 versus ADP). %BF by the Houtkooper BIA equation or Goran model underestimated %BF to a significantly greater degree than ADP (Houtkooper, -8.1%; Goran, -10.1%; both p < 0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model slightly underestimates %BF as determined by DXA in girls, but appears to be superior to existing field methods both in accuracy and limits of agreement. Because of the ease with which it can be performed, ADP may prove useful for investigations of adiposity in children.