Summary. A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-131I and albumin-1251 allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-125I can be used to represent the expansion of the thyroxine-13I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-""1I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-'81I and albumin-125I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-'31I. The thesis is advanced that the distribution of thyroxine,

Endocrinologic evaluation of 39 patients with trisomy 21 and associated hypogonadism demonstrated elevations of follicle-stimulating hormone and luteinizing hormone; consequently, it can be concluded that both germinal and Leydig cell function are affected. A negative correlation between testicular size and plasma follicle-stimulating hormone was documented. Plasma testosterone levels were found to be normal in male patients as were estradiol levels in female patients with trisomy 21. On the basis of these findings, the simplest and most practical diagnostic approach to evaluate germinal cell function appears to be a single plasma follicle-stimulating hormone determination supplemented by an accurate measurement of testicular volume in males.