parathyroid path Flashcards
Parathyroid review
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
The metabolic functions of PTH that regulate serum calcium
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
low serum Ca2+ is sensed through
CaSRs
Hyperparathyroidism
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
Primary Hyperparathyroidism
one of the most common endocrine disorders, and it is an important cause of hypercalcemia
- Adenoma: 85% to 95%- arises sporadically
- Primary hyperplasia (diffuse or nodular): 5% to 10%
- Parathyroid carcinoma: ~1%
Most pts IDed when hypercalcemia is discovered incidentally on serum electrolyte panel.
most > 50 years
sestamibi scan
shows activity of parathyroid glands
hyperparathyroidism- Familial syndromes
- distant second to sporadic adenomas. Include MEN types 1 and 2 caused by MEN1 and RET germline mutations.
Morphologic changes of hyperparathyroidism in the skeletal system and the urinary tract
osteoporosis, brown tumors and osteitis fibrosa cystica.
osteoporosis of hyperparathyroidism
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
brown tumor of hyperparathyroidism
bone loss–> microfractures and 2ndary hemorrhages–> influx of macrophages, ingrowth of reparative fibrous tissue–> mass of reactive tissue = BROWN TUMOR
osteitis fibrosa cystica
(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.
urinary tract stones of PTH-induced hypercalcemia
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.
Clinical Course of primary hyperparathyroidism
(1) Asymptomatic and identified on routine blood chemistry profile
(2) Associated with the classic clinical manifestations of primary hyperparathyroidism
Primary hyperparathyroidism is the most common cause of
asymptomatic hypercalcemia. Hence, many of the classic manifestations, particularly those referable to bone and renal disease, are now seen infrequently in clinical practice.
Causes of hypercalcemia
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
hypercalcemia by raised vs lowered PTH
raised: hyperparathyroidism (primary- adenoma > hyperplasia, secondary, tertiary); familial hypocalciuric hypercalcemia
decreased PTH: hypercalcemia of malignancy,
Vitamin D toxicity
immobilization
thiazide diuretics granulomatous disease (sarcoidosis)
mnemonic for symptomatic primary hyperparathyroidism
stones, abdominal groans, painful bones, psychiatric moans
Secondary Hyperparathyroidism
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
Clinical Course of the secondary hyperparathyroidism
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
Tertiary hyperparathyroidism
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.
signs of low calcium levels
chvostek sign
tetany - trousseau’s sign
tetany,
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.
Chvostek sign
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.
key concepts - hyperparathyroidism
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
Hypoparathyroidism
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
Clinical Features of hypoparathyroidism
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.
