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CALCULATION OF PRODUCTION AND METABOLIC CLEARANCE RATES
- May 15, 2018 -

The concept of the production rate of a steroid hormone was introduced to describe the rate at which the hormone enters the circulation de novo, regardless of its origin. Therefore, by definition, the production rate of a steroid hormone is equal to the glandular secretion rate of the hormone plus the secretion rates of any other steroids that are converted extraglandularly to the circulating hormone. In the absence of extraglandular sources of the circulating hormone, the production rate of the hormone is identical to its secretion rate. From the practical point of view, the secretion of a steroid hormone by an endocrine gland can be determined by catheterizing the vein draining the organ and demonstrating a higher concentration of the hormone in the venous effluent of the gland than in the peripheral blood. The concentration gradient (difference between the two concentrations) multiplied by the rate of blood flow from the gland yields a rough approximation of the secretion rate.

It has been shown that the physiologic concentration of a steroid hormone in the circulation is directly proportional to its production rate; therefore,


where PR is the production rate of the hormone, C is its concentration in the circulation, and k is the proportionality constant. This constant was named the metabolic clearance rate (MCR).21

The MCR of a steroid hormone is defined as the volume of blood that is irreversibly cleared of the steroid per unit of time and is usually expressed in liters per day. It is measured by intravenously infusing the radioactive form (usually tritiated) of the steroid, either as a single dose or as a constant rate over a prolonged period (e.g., 2 hours). The radioactive steroid that is infused should have a high specific activity (radioactivity per unit mass), so that only a minute mass of the steroid is administered and the mass does not contribute significantly to the concentration of the endogenous hormone.

The single injection and constant infusion methods yield equivalent MCR for a particular steroid. In the single-dose method, the changes in the concentration of radioactivity (disintegrations per minute [dpm]) associated with the hormone are measured as a function of time. The concentrations of radioactivity are plotted against time, and the areas under the resulting curves are measured. The MCR is then calculated using the following equation: MCR = dose-injected (dpm) divided by area under the radioactivity concentration–time curve (dpm x h/ml).

Because the injected dose is expressed in dpm and the area under the curve as units of dpm per mL multiplied by hours, then the MCR units will be

dpm ÷ (dpm × h)/mL


which can be converted to liters per day. Similarly, if the labeled hormone is infused at a constant rate, a steady state of the radioactive hormone administered will be reached in blood, usually after 1 or 2 hours. A blood sample is taken at this time, and the MCR is calculated using the following equation: MCR = rate of infusion (dpm/h) divided by the concentration of radioactivity associated with the hormone in blood at steady state (dpm/mL).

Because PR ÷ C = MCR, the production rate of a steroid hormone can be readily determined once its MCR and concentration are known. The concentration of the steroid, C, can be measured by radioimmunoassay, whereas the MCR can be determined as described. The following example shows how the production rate of testosterone can be calculated. If the MCR of serum testosterone is found to be 700 L/day in a premenopausal woman and her serum testosterone concentration is measured as 0.35 μg/L, her testosterone production rate can be calculated from the equation, PR = MCR × C. By substituting the values for MCR and C,

PR = 700 L/day × 0.35 μg/L = 245 μg/day