The enzyme 17α-hydroxylase (CYP 17) is not present in the outer layer of the cortex and, thus, cortisol and androgens cannot be formed in this layer. Steroids and their metabolic by-products (notably lipid hydroperoxides) are released into the adrenal circulation and inhibit critical enzymes in subsequent layers through which the blood flows. As a result, no aldosterone can be synthesized by cells below the outer glomerulosa layer. In the inner layer, 17α-hydroxyprogesterone cannot be converted to cortisol but is shunted into the formation of androgens. Interestingly high cortisol concentrations reaching the adrenal medulla stimulate the synthesis of phenylethanolamine- N -methyltransferase which catalyzes the conversion of norepinephrine to epinephrine (see Box ). Thus, the structural relationship between the cortex and medulla and its blood supply has additional functional implications within the medulla.
Catecholamines are produced in chromaffin cells in the medulla of the adrenal gland, from tyrosine , a non-essential amino acid derived from food or produced from phenylalanine in the liver. The enzyme tyrosine hydroxylase converts tyrosine to L-DOPA in the first step of catecholamine synthesis. L-DOPA is then converted to dopamine before it can be turned into noradrenaline. In the cytosol , noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and stored in granules. Glucocorticoids produced in the adrenal cortex stimulate the synthesis of catecholamines by increasing the levels of tyrosine hydroxylase and PNMT.  
People experiencing adrenal fatigue normally have lower levels of cortisol, which can often make it more difficult to sustain healthy levels of blood sugar.* When blood sugar levels are low ( hypoglycemia ), people often crave sweets.* But eating sugary foods and carbohydrates can raise blood sugar so quickly that the pancreas responds with a flood of insulin.* Chronic over-consumption of sugar and refined carbohydrates, especially in the absence of increased physical activity, may therefore result in greater insulin resistance in the cells.* In this way, adrenal fatigue with concomitant hypoglycemia may create conditions and induce behaviors that can lead to a greater tendency to develop adult onset diabetes.*