parathyroid path

Question 1

Parathyroid review

Answer 1

The four parathyroid glands are composed of two cell types: chief cells (blue) and oxyphil cells (pink- full of mitochondria)

The function of the parathyroid glands is to regulate calcium homeostasis

Question 2

The metabolic functions of PTH that regulate serum calcium

Answer 2

Increases the renal tubular reabsorption of calcium, thereby conserving free calcium
Increases the conversion of vitamin D to its active dihydroxy form in the kidneys
Increases urinary phosphate excretion, thereby lowering serum phosphate levels
Augments gastrointestinal calcium absorption

Question 3

low serum Ca2+ is sensed through

Answer 3

CaSRs

Question 4

Hyperparathyroidism

Answer 4

Primary hyperparathyroidism: an autonomous overproduction of parathyroid hormone (PTH), usually resulting from an * adenoma or hyperplasia of parathyroid tissue

Secondary hyperparathyroidism: compensatory hypersecretion of PTH in response to prolonged hypocalcemia, most commonly from *chronic renal failure

Tertiary hyperparathyroidism: persistent hypersecretion of PTH even after the cause of prolonged hypocalcemia is corrected, for example after * renal transplant

Question 5

Primary Hyperparathyroidism

Answer 5

one of the most common endocrine disorders, and it is an important cause of hypercalcemia

1. Adenoma: 85% to 95%- arises sporadically
2. Primary hyperplasia (diffuse or nodular): 5% to 10%
3. Parathyroid carcinoma: ~1%

Most pts IDed when hypercalcemia is discovered incidentally on serum electrolyte panel.

most > 50 years

Question 6

sestamibi scan

Answer 6

shows activity of parathyroid glands

Question 7

hyperparathyroidism- Familial syndromes

Answer 7

• distant second to sporadic adenomas. Include MEN types 1 and 2 caused by MEN1 and RET germline mutations.

Question 8

Morphologic changes of hyperparathyroidism in the skeletal system and the urinary tract

Answer 8

osteoporosis, brown tumors and osteitis fibrosa cystica.

Question 9

osteoporosis of hyperparathyroidism

Answer 9

preferential involvement of the phalanges, vertebrae and proximal femur; cortical bone more severely affected

in medullary bone, osteoclasts tunnel –> appearance of railroad tracks –> dissecting osteitis

marrow spaces replaced by fibrovascular tissue

Question 10

brown tumor of hyperparathyroidism

Answer 10

bone loss–> microfractures and 2ndary hemorrhages–> influx of macrophages, ingrowth of reparative fibrous tissue–> mass of reactive tissue = BROWN TUMOR

Question 11

osteitis fibrosa cystica

Answer 11

(von Recklinghausen disease of bone)

The combination of increased osteoclast activity, peritrabecular fibrosis, and cystic brown tumors is the hallmark of severe hyperparathyroidism and is known as generalized osteitis fibrosa cystica

now rarely encountered because hyperparathyroidism is usually diagnosed on routine blood tests and treated at an early, asymptomatic stage.

Question 12

urinary tract stones of PTH-induced hypercalcemia

Answer 12

PTH-induced hypercalcemia favors formation of urinary tract stones (nephrolithiasis) as well as calcification of the renal interstitium and tubules (nephrocalcinosis). Metastatic calcification secondary to hypercalcemia may also be seen in other sites, including the stomach, lungs, myocardium, and blood vessels.

Question 13

Clinical Course of primary hyperparathyroidism

Answer 13

(1) Asymptomatic and identified on routine blood chemistry profile
(2) Associated with the classic clinical manifestations of primary hyperparathyroidism

Question 14

Primary hyperparathyroidism is the most common cause of

Answer 14

asymptomatic hypercalcemia. Hence, many of the classic manifestations, particularly those referable to bone and renal disease, are now seen infrequently in clinical practice.

Question 15

Causes of hypercalcemia

Answer 15

Malignancy stands out as the most frequent cause of symptomatic hypercalcemia in adults

Solid tumors, such as lung, breast, head and neck, and renal cancers, and with hematologic malignancies, notably multiple myeloma

The most common mechanism (in ~80% of cases) through which osteolytic tumors induce hypercalcemia is by secretion of PTH-related peptide (PTHrP), whose functions are similar to PTH in inducing osteoclastic bone resorption and hypercalcemia

Question 16

hypercalcemia by raised vs lowered PTH

Answer 16

raised: hyperparathyroidism (primary- adenoma > hyperplasia, secondary, tertiary); familial hypocalciuric hypercalcemia

decreased PTH: hypercalcemia of malignancy,
Vitamin D toxicity
immobilization

thiazide diuretics
granulomatous disease (sarcoidosis)

Question 17

mnemonic for symptomatic primary hyperparathyroidism

Answer 17

stones, abdominal groans, painful bones, psychiatric moans

Question 18

Secondary Hyperparathyroidism

Answer 18

caused by any condition that gives rise to chronic hypocalcemia, which in turn leads to compensatory overactivity of the parathyroid glands

Renal failure is by far the most common cause of secondary hyperparathyroidism

inadequate dietary intake of calcium, steatorrhea, and vitamin D deficiency, may also cause this disorder

Question 19

Clinical Course of the secondary hyperparathyroidism

Answer 19

usually dominated by chronic renal failure

not as severe or prolonged as primary hyperparathyroidism, so skeletal issues milder

vascular calcification –> ischemic damage to skin/ organs: calciphylaxis

Vitamin D supplementation and phosphate binders can help

Question 20

Tertiary hyperparathyroidism

Answer 20

In a minority of patients, parathyroid activity may become autonomous and excessive, with resultant hypercalcemia, a process that is sometimes termed tertiary hyperparathyroidism.

Parathyroidectomy may be necessary to control the hyperparathyroidism in such patients.

Question 21

signs of low calcium levels

Answer 21

chvostek sign

tetany - trousseau’s sign

Question 22

tetany,

Answer 22

The hallmark of hypocalcemia is tetany, which is characterized by neuromuscular irritability, resulting from decreased serum calcium levels. The symptoms range from circumoral numbness or paresthesias (tingling) of the distal extremities and carpopedal spasm, to life-threatening laryngospasm and generalized seizures.

Question 23

Chvostek sign

Answer 23

is elicited in subclinical disease by tapping along the course of the facial nerve, which induces contractions of the muscles of the eye, mouth, or nose. Trousseau sign refers to carpal spasms produced by occlusion of the circulation to the forearm and hand with a blood pressure cuff for several minutes.

Question 24

key concepts - hyperparathyroidism

Answer 24

primary- most common cause of asymptomatic hypercalcemia

mostly sporadic parathyroid adenoma (solitary)
hyperplasia- multiglandular process

skeletal manifestations: bone resorption, osteitis fibrosa cystica, brown tumors.

renal: stones, nephrocalcinosis

painful bones, renal stones, abdominal groans, psychic moans

2ndary- caused by renal failure (usually) –> decreased serum calcium, –> reactive hyperplasia of parathyroid glands

malignancies also –> hypercalcemia, from osteolytic metastases or release of PTH-related protein from nonparathyroid tumors

Question 25

Hypoparathyroidism

Answer 25

is far less common than is hyperparathyroidism.

Acquired hypoparathyroidism is almost always an inadvertent consequence of surgery

inadvertent removal of all the parathyroid glands during thyroidectomy, excision of the parathyroid glands in the mistaken belief that they are lymph nodes during radical neck dissection for some form of malignant disease, or removal of too large a proportion of parathyroid tissue in the treatment of primary hyperparathyroidism

Question 26

Clinical Features of hypoparathyroidism

Answer 26

Mental status changes: emotional instability, anxiety and depression, confusional states, hallucinations, and frank psychosis.

Intracranial manifestations: calcifications of the basal ganglia, parkinsonian-like movement disorders, and increased intracranial pressure with resultant papilledema. The paradoxical association of hypocalcemia with calcifications may be because of an increase in phosphate levels, resulting in tissue deposits with calcium that exists in local extracellular milieu.

Ocular disease takes the form of calcification of the lens and cataract formation.

Cardiovascular manifestations: prolongation of the QT interval .

Dental abnormalities occur when hypocalcemia is present during early development. These findings are highly characteristic of hypoparathyroidism and include dental hypoplasia, failure of eruption, defective enamel and root formation, and abraded carious teeth.