Calcium Metabolism (PTH, Vitamin D, and Calcitonin)

Overall calcium homeostasis:

40% of calcium is bound to plasma proteins
60% is unbound, and is either complexes to anions such as phosphate or is free
Free calcium is biologically active
Serum calcium is determined by:
a. Intestinal absorption
b. Renal excretion
c. Bone remodeling
*Each of which is hormonally regulated
To maintain calcium BALANCE- net absorption must be balanced by urinary
excretion
*Positive calcium balance:
Seen in growing children
Intestinal calcium absorption exceeds urinary excretion, and the excess is deposited
in the growing bones
*Negative calcium balance:
Seen in women during pregnancy or lactation
Intestinal calcium absorption is less than calcium excretion, the deficient comes
from maternal blood

Parathyroid hormone:
1. Major hormone for the regulation of serum calcium
2. Made and secreted by the chief cells of the parathyroid gland

Both sets of glands are supplied by the inferior thyroid arteries with venous
drainage through the thyroid plexus of the veins (superior and inferior sets)

The parathyroid glands are connective tissue encapsulated structures that contain
two population of cells: chief cells and oxyphil cells
Chief cells are predominant- they are small, polygonal cells with secretory
granules containing PTH
Oxyphil cells have unknown function-are large cells containg abundant
acidophilc mitochondria

Secretion of PTH:

Controlled by the serum calcium binding to calcium sensing receptors in the

parathyroid cell membrane
Decreased serum calcium increases PTH, whereas increased serum calcium
decreases PTH
Decreased serum calcium causes decreased binding to the calcium sensing
receptor, which stimulates PTH secretion
Mild decreases in serum magnesium stimulate PTH secretion
Severe decreases in serum magnesium inhibit PTH secretion and product
symptoms of hypoparathyroidism (hypocalcemia)
The secondary messenger for PTH secretion of the PT gland is cAMP

Actions of PTH:
Increase serum calcium and decrease serum phosphatase
The second messenger for PTH action on its target tissues is cAMP
a. PTH increases bone resorption
a. Brings both calcium and phosphate from bone mineral into ECF.
i. Alone this effect on bone would not increase the serum ionized
calcium because phosphate complexes calcium
ii. Resorption of the organic matrix of bone is reflected in increased
hydroxyproline excretion
b. PTH inhibits renal phosphate reabsorption in the proximal tubule, and
therefore increase phosphate excretion. The phosphate resorbed from bone is
excreted in the urine, allowing the serum ionized calcium to increase
a. cAMP generated as a result of the action of PTH on the proximal tubule
is excreted in the urine (urinary cAMP)
c. PTH increases calcium reabsorption in the distal tubule which also
increases serum
d. PTH increases intestinal calcium absorption indirectly by stimulating the
production of 1,25 dihydroxycholcalciferol in the kidney (via a
second hydroxylation reaction catalyzed by 1 alpha-hydroxylase)

Pathophysiology of Primary Hyperparathyroidism:

Two to three times more common in women than men
Most commonly caused by parathyroid adenoma (>80% of cases); sporadic
parathyroid hyperplasia and parathyroid carcinoma are less common causes
Parathyroid adenoma is a BENIGN neoplasm, usually involves ONE gland
Results in asymptomatic hypercalcemia; however may present with consequences
of increased PTH and hypercalcemia such as
1. Nephrolithiasis (calcium oxalate stones)
2. Nephrocalcinosis-metastatic calcification of the renal tubules potentially
leading to renal insufficiency and polyuria > decreased GFR and renal failure
3. CNS disturbances (depression and seizures)
4. Constipation, peptic ulcer disease, and acute pancreatitis
5. Osteitis fibrosa cystica-resorption of bone leading to fibrosis and cystic
spaces
(calcified supporting structures are replaced with fibrous tissue and the
formation of cyst-like brown tumors in and around the bone)
a. Causes bone pain and sometimes pathologic fractures
b. hyperparathyroidism often results in the preferential loss of cortical bone
c. There is an increase in the number of bone-resorbing osteoclasts, marrow fibrosis,
and cystic lesions that may contain fibrous tissue (brown tumors)
d. Bone cysts or brown tumors may present as osteolytic lesions. Dental films may
disclose loss of the lamina dura of the teeth, but this is a nonspecific finding also
seen in periodontal disease.
e. The first bones to be affected are fingers, facial bones, ribs and pelvis

85% of patients presenting today have neither bone nor renal manifestations of
hyperparathyroidism and are regarded as asymptomatic or at most minimally
symptomatic

Is characterized by the following:

1.
2.
3.
4.
5.
6.
7.

Increased serum calcium

Decreased serum phosphate
Increased urinary phosphate excretion
Increased urinary calcium excretion
Increased urinary cAMP
Increased bone resorption
Increased serum alkaline phosphatase
Treatment involves surgical removal of affected gland

Medical treatment for those who are not good surgical candidates or decline
surgery includes encouragement of adequate hydration and physical activity
Loop diuretics such as furosemide can be given to enhance calcium excretion
Avoid thiazide diuretics as they can exacerbate hypercalcemia
Can also give bisphosphonates to inhibit bone loss or calcintonin
The surgical strategy (ie, minimally invasive vs bilateral neck exploration) depends on the
ability of localizing studies such as sestamibi scanning to identify one clearly abnormal gland
and the availability of intraoperative PTH determinations to verify that the disease-producing
lesion has been removed during surgery. If multiple enlarged glands are suspected, the likely
diagnosis is parathyroid hyperplasia or double adenoma. In patients with hyperplasia, the
preferred operation is a 3 gland parathyroidectomy, leaving a remnant sufficient to prevent
hypocalcemia. Double parathyroid adenomas are both removed in affected patients.

Secondary Hyperparathyroidism:
a. Excess production of PTH due to a disease process extrinsic to the PTH gland
b. Most common cause is chronic renal failure
1. Renal insufficiency leads to decreased phosphate excretion
2. Increased serum phosphate binds to free calcium
3. Decreased in free calcium stimulates all four PTH glands
4. Increased PTH leads to bone resorption (contributing to renal
osteodystrophy)
5. Lab findings include increased PTH, decreased serum calcium, increased
serum phosphate and increase alkaline phosphatase

Hypoparathyrodism:
a. Low PTH
b. Causes include autoimmune damage to the parathyroids, surgical excision
and DiGeorge syndrome
c. Presents with symptoms related to low serum calcium
1. Numbness and tingling (particularly circumoral)
2. Muscle spasms (tetany) may be elicited with filling of a blood
pressure cuff (Trousseau sign) or tapping of the facial nerve
d. Pseudohypoparathyroidism is due to end-organ resistance to PTH
e. Labs reveal hypocalcemia with increased PTH levels
f. Autosomal dominant form is associated with short stature and short 4 th and
6th digits
Multiple endocrine neoplasia type 1 (MEN-1 syndrome)
Wermer's syndrome is part of a group of disorders that affect the endocrine system through
development of neoplastic lesions in pituitary, parathyroid gland and pancreas.[1]
Multiple endocrine neoplasia involves tumors in at least two endocrine glands