The Endocrine System
also called calcitriol), the active
form of vitamin D. It should be clear from this description that
D is synthesized in the body, so it is a hormone.
The major action of 1,25-(OH)
D is to stimulate the
intestinal absorption of calcium. Thus, the major event in vita-
min D defi ciency is decreased intestinal calcium absorption,
resulting in decreased plasma calcium.
The blood concentration of 1,25-(OH)
D is subject to
physiological control. The major control point is the second
hydroxylation step that occurs in the kidney (1-hydroxylase),
which is stimulated by parathyroid hormone. Because a low
plasma calcium concentration stimulates the secretion of para-
thyroid hormone, the production of 1,25-(OH)
D is increased.
Both hormones work together to restore plasma calcium to
is a peptide hormone secreted by cells (called para-
follicular cells) that are within the thyroid gland but are dis-
tinct from the thyroid follicles. Calcitonin decreases plasma
calcium concentration, mainly by inhibiting osteoclasts,
thereby reducing bone resorption. Its secretion is stimulated
by an increased plasma calcium concentration, just the oppo-
site of the stimulus for parathyroid hormone secretion. Unlike
parathyroid hormone and 1,25-(OH)
D, however, calcitonin
plays no role in the normal day-to-day regulation of plasma
calcium regulation in humans. It may be a factor in decreasing
bone resorption when plasma calcium is very high.
Metabolic Bone Diseases
Various diseases refl ect abnormalities in the metabolism of
(in children) and
(in adults) are
conditions in which mineralization of bone matrix is defi cient,
causing the bones to be soft and easily fractured. In addition,
a child suffering from rickets is typically severely bowlegged
due to weight-bearing on the developing leg bones. A major
cause of rickets and osteomalacia is defi ciency of vitamin D.
In contrast to these diseases, in
both matrix
and minerals are lost as a result of an imbalance between
bone resorption and bone formation. The resulting decrease
in bone mass and strength leads to an increased incidence of
fractures. Osteoporosis can occur in people who are immobi-
lized (“disuse osteoporosis”), in people who have an excessive
plasma concentration of a hormone that favors bone resorp-
tion, and in people who have a defi cient plasma concentration
of a hormone that favors bone formation (see Table 11–7). It
is most commonly seen, however, with aging. Everyone loses
bone as he or she ages, but osteoporosis is more common in
elderly women than in men for several reasons: women have
a smaller bone mass to begin with, and the loss that occurs
with aging occurs more rapidly, particularly after menopause
removes the bone-promoting infl uence of estrogen.
Prevention is the focus of attention for osteoporo-
sis. Treatment of postmenopausal women with estrogen or
its synthetic analogs is very effective in reducing the rate of
bone loss. A regular weight-bearing exercise program, such
as brisk walking and stair-climbing, is also helpful. Adequate
dietary calcium (1000 to 1500 mg/day) and vitamin D intake
throughout life are important to build up and maintain bone
mass. Several agents also provide effective therapy once osteo-
porosis is established. Most prominent is a group of drugs,
that interfere with the resorption of
bone by osteoclasts. Other antiresorptive agents include calci-
tonin and
selective estrogen receptor modulators (SERMs),
which, as their name implies, act by interacting with estro-
gen receptors, thus compensating for the low estrogen after
Hyper- and Hypocalcemia
There are a variety of pathophysiological disorders that lead
to abnormally high
or low
calcium levels in the blood.
A common cause of hypercalcemia is
This is usually caused by a benign
tumor (adenoma) of one of the four parathyroid glands.
These tumors are composed of abnormal cells that are
not adequately suppressed by extracellular calcium. As a
result, the adenoma secretes parathyroid hormone (PTH)
in excess, leading to an increase in calcium resorption
from bone, increased kidney reabsorption of calcium
and the increased production of 1,25-(OH)
D from the
kidney. This results in an increase in calcium absorption
in the GI tract. Primary hyperparathyroidism is most
effectively treated by surgical removal of the parathyroid
Certain types of cancer can lead to
hypercalcemia of malignancy
The cause of the hypercalcemia
is often the release of a molecule that is chemically similar to
PTH, called
PTH-related peptide (PTHrp)
and that has
effects similar to those of PTH. This chemical is produced
by certain types of cancerous cells (for example, breast cancer
cells). However, authentic PTH release from the normal
parathyroid glands is decreased due to the hypercalcemia
caused by PTHrp released from the cancer cells. The most
effective treatment of humoral hypercalcemia of malignancy is
to treat the cancer that is releasing PTHrp. In addition, drugs
(like bisphosphonates) that decrease bone resorption can also
provide effective treatment.
Finally, excessive ingestion of vitamin D can lead to
hypercalcemia despite the fact that PTH levels will be very low.
Regardless of the cause, hypercalcemia causes signifi cant
symptoms primarily from its effects on excitable tissues.
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