Page 62 - Clinical Small Animal Internal Medicine

30 Section 2 Endocrine Disease

Steroids Hormones in Circulation
VetBooks.ir Steroid hormones include the adrenocortical hormones Concentrations of hormones in circulation may vary sig­

(e.g., cortisol, aldosterone), reproductive steroids (e.g.,
estrogen, testosterone), and vitamin D. They are manu­ nificantly depending on a variety of circumstances.
factured in their tissues of origin from cholesterol. In Specific hormones show characteristic secretory pat­
turn, most of the cholesterol used for synthesis is trans­ terns in blood. For example, ACTH and cortisol show
ported in blood, taken up, and stored in the endocrine periodic and, to some degree, irregular spikes and
tissue. Each endocrine cell expresses a unique set of troughs throughout the day (Figure 4.1). Stressful condi­
enzymes used in the conversion of cholesterol to final tions elevate levels of both of these hormones. In addi­
product. These cells typically possess large amounts of tion, ACTH and cortisol levels may also vary with time of
smooth endoplasmic reticulum and enzymatic conver­ day. In humans, ACTH and cortisol levels in circulation
sions occur in this location as well as other intracellular are higher in the early morning hours. This circadian
sites (e.g., mitochondria). The final products accumu­ variation is significantly less (or absent) in dogs and cats.
late and simply diffuse out of the cell because of their By contrast, T4 levels in blood do not change as dramati­
hydrophobic nature. cally and instead are relatively steady, varying by approxi­
Steroids are relatively insoluble in water and are mately 15–20% during the day (see Figure 4.1). Growth
found in circulation bound to carrier proteins, includ­ hormone is secreted in bursts or pulses and in humans,
ing globulins and albumin. Because of this protein greatest levels are observed shortly after going to sleep.
binding, steroids generally have longer half‐lives in These patterns of secretion and resultant normal fluc­
blood than proteins/polypeptides. While the free or tuations have practical consequences. For example, rest­
unbound portion is available to enter and act in target ing cortisol measurement is of little value in the diagnosis
cells, the loosely bound albumin fraction is available to of hyperadrenocorticism. Overall, cortisol levels are
deliver steroid to targets as well. The globulin‐bound greater in dogs with hyperadrenocorticism but because
portion serves as a reservoir, buffering steroids in cir­ of the normal fluctuating nature of its secretion, values
culation and also assisting in delivery to tissues by overlap when comparing single baseline levels between
releasing bound steroid as the complex permeates dogs with normal adrenals and dogs with hyperadreno­
through tissues. Steroids act on target cells primarily corticism. An additional confounding factor in evaluat­
by binding to intracellular receptors; the receptor hor­ ing baseline cortisol concentrations is that stress
mone complex then binds to specific DNA sequences associated with blood sample collection may result in an
and affects rates of gene transcription. Steroids are elevated cortisol level. The fact that T4 concentrations
removed by the liver and kidney. Active hormones are are more stable throughout the day permits the use of
inactivated by processes including removal of double resting or baseline T4 determination as a screening test
bonds, conjugation to glucuronic acid and sulfate, and for hypothyroidism in dogs and hyperthyroidism in cats.
excretion in urine and feces.
Hormone Receptors
Hormones Made from Amino Acids
Receptors for the majority of protein/polypeptide
The principal hormones in this chemical class are the hormones (and catecholamines) reside on the target cell
catecholamines and thyroid hormones, which are
derived from the amino acid tyrosine by different 150
means. Catecholamines (epinephrine and norepineph­ Cortisol
rine) are made by a series of enzymatic events involv­ 125 T4
ing hydroxylation, decarboxylation, and methylation 100
in adrenal medullary cells. Catecholamines have short
half‐lives in blood and bind to receptors on the cell Hormone concentration 75
surface. By contrast, thyroid hormones (T4 and T3) 50
are made in thyroid follicles (colloid) by iodination
and coupling of iodinated tyrosines and are stored in 25
thyroglobulin until colloid is taken up into the thyroid 0
follicular cells, broken down, and T4 and T3 are 0 4 8 12 16 20 24
secreted. Thyroid hormones behave much like ster­ Hours
oids; they are carried in blood primarily in protein‐ Figure 4.1 Fluctuations in levels of cortisol and T4 in a healthy
bound form and act on target cells by binding to dog during the day. Levels of cortisol show significant random
intracellular receptors. variation, while levels of T4 are relatively stable.