parathyroid gland path Flashcards
what are the 2 cell types that make up the parathyroid glands?
Which predominates
- Chief cells (predominate)
- oxyphil cells
Describe the chief cells
- Central, round, uniform nuclei
- light pink cytoplasm
- Sometime they are clear from the glycogen (Water-clear appearance)
- Secretory granules of PTH
Describe the Oxyphil cells
- slightly larger than chief cells
- Acidophilic cytoplasm
- Tightly packed with mitochondria
- Glycogen granules but NOT secretory granules
Describe the amount of stromal fat in parathyroid glands
- increases up to age 25 then plateaus
- up to 30% of the gland
Function of the parathyroid
regulate calcium
What stimulates the synthesis and secretion of PTH
decreased levels of free calcium
Explain what PTH does on different parts of the body
- increases renal tubular reabsorption of Ca
- Increases urinary phosphate excretion
- Increases conversion of vitamin D to its active dihydoxy form in the kidneys . .. augments GI Ca absorption
what are the causes of hypercalcemia associated with increased PTH
- Primary hyperparathyroidism (adenoma > hyperplasia)
- Secondary
- Tertiary
- Familial hypocalciuric hypercalcemia
What are the causes of hypercalcemia associated with decreased PTH
- Hypercalcemia of malignancy
- vitamin D toxicity
- Immobilization
- thiazide diuretics
- Granulomatous disease (Sarcoidosis)
What are the 4 causes of primary hyperparathyroidism
- Autonomous overproduction of parathyroid hormone
- Adenoma
- Hyperplasia
- carcinoma
What are the causes of secondary hyperparathyroidism
- Compensatory hypersecetion of PTH in response to prolonged hypocalcemia
- Chronic renal failure
explain what tertiary hyperparathyroidism is
- hypersecretion of PTH even after the cause of prolonged hypocalcemia is corrected
- ex: after renal transplant
epidemiology of primary hyperparathyroidism
- usually adults
- More common Women . . . 4:1
How are most cases of primary hyperparathyroidism discovered
incidentally on serum electrolyte panel
What is the most common cause of primary hyperparathyroidism
a solitary parathyroid adenoma arising sporadically
What are the 2 molecular defects that play a role in sporadic parathyroid adenomas
- Cyclin D1 gene inversions leading to overexpression of Cyclin D1 . . cell cycle regulator
- MEN1 mutations . . . tumor suppressor gene
what are the genetic syndromes associated with familial hyperparathyroidism
- MEN types 1 and 2 . .. MET1 and RET mutations
- Familial hypocalciuric hypercalcemia . . rare autosomal dominant . . mutations in parathyroid calcium sensing receptor gene (CASR)- LOSS OF FUNCTION
Morphology of parathyroid Adenoma
- solitary
- .5-5 gm
- well circumscribed
- Glands outside the adenoma are usually normal in size or shrunken from feedback inhibition by elevated calcium
- hypercellular with little to no fat
- composed of uniform chief cells
- Few nests of larger oxyphil cells . .. occasionally composed entirely of them (oxyphil adenoma)
- usually a rim of compressed, parathyroid gland, generally separated by a fibrous capsule
Parathyroid hyperplasia occurs sporadically or as a component of _______
MEN syndrome
describe the involvement of the glands in parathyroid hyperplasia
- Classically all 4 involved
- may be Asymmetric which can make distinction from adenoma difficult
- combined weight of all glands rarely >1 gm
Morphology of Parathyroid hyperplasia
- Hypercellular with little to no fat
- Typically see chief cell hyperplasia . . diffusely or multinodular
Describe a parathyroid carcinoma
- enlarge one parathyroid
- sometimes exceeds 10 gm
- rare
- cells can look like normal parathyroid
What do you need for diagnosis of parathyroid carcinoma
-invasion of surrounding tissues and/or metastasis
What scan is used to assess the parathyroid glands?
i.e. location, is it solitary or diffuse
- Sestamibi san
- this is a radionucleotide scan where sestamibi is labeled with the radio-pharmaceutical technetium-99
Symptomatic, untreated primary hyperparathyroidism manifests with what 3 skeletal abnormalities?
- Osteoporosis
- Brown tumors
- Osteitis fibrosa cystica
Describe osteoporosis
-decreased bone mass with preferential involvement of phalanges, vertebrae, and proximal femur
The increased osteoclast activity in hyperparathyroidism affects what part of the bone
cortical bone more severely than medullary
What is it called when, in medullary bone, osteoclasts tunnel into and dissest centrally along the length of the trabeculae
railroad tracks appearance . . . dissecting osteitis
What are brown tumors?
- Microfractures and secondary hemorrhages –>influx in macrophages and reparative fibrous tissue –> mass
- Brown color from vascularity, hemorrhage, and hemosiderin deposition
What is the hallmark of severe hyperparathyroidism and know as generalized osteitis fibrosa cystica?
- increased osteoclast activity
- Peritrabecular fibrosis
- cystic brown tumors
What is another word for generalized osteitis fibrosa cystica
-Recklinghausen disease of bone
What are other organ pathologies that occur in primary hyperparathyroidism
- Nephrolithiasis: urinary tract stones
- Nephrocalcinosis: calcification of the renal interstitium and tubules
- Calcification may also be seen in the stomach, lungs, myocardium, and blood vessels
what are the 2 clinical courses of primary hyperparathyroidism
- Asympsotmatic and identified on routine blood chemistry
- or classic symptoms
What is the most common cause of symptomatic hypercalcemia
-malignancy
What malignancies can cause hypercalcemia
- Solid tumors: lung, breast, head and neck, and renal
- Hematologic: multiple myeloma
What do osteolytic tumors secrete to induce hypercalcemia?
What is the other way they can cause hypercalcemia
PTH-related peptide (PTHrP)
-metastasis . . cytokine induced bone resorption
Labs in primary hyperparathyroidism
- elevated Ca
- Elevated PTH: this is low if hypercalcemia is caused by non parathyroid disease
- low phosphate
What is the phrase used to describe the symptoms of primary hyperparathyroidism aka hypercalcemia
Bones, stones, abdominal groans and psychic moans
GI symptoms of hypercalcemia
- constipation
- nausea
- peptic ulcers
- pancreatitis
- gallstones
CNS symptoms of hypercalcemia
- depression
- lethargy
- eventually seizures
Neuromuscular symptoms of hypercalcemia
-weakness and fatigue
Cardiac symptoms of hypercalcemia
Aortic and/or mitral valve calcifications
Secondary hyperparathyroidism is caused by any condition that gives rise to what?
chronic hypocalcemia, which in turn leads to compensatory overactivity of the parathyroid glands
What is by far the most common cause of secondary hyperparathyroidism?
Give the other causes also
-Renal failure
- inadequate dietary intake of calcium
- steatorrhea
- vitamin D deficiency
Mechanism by which chronic renal failure induces secondary hyperparathyroidism
- decreased phosphate excretion . . elevated phosphate levels directly depress serum calcium levels
- Also, loss of renal substance reduces the availability of a-1-hydroxylase which is necessary for the synthesis of the active form of vitamin D which in turn reduces intestinal absorption of calcium
Morphology of secondary hyperparathyroidism
- hyperplastic parathyroid glands (decreased fat) . . can be asymmetric
- Increased number of chief cells (diffuse or mutinodular)
- “metastatic” calcifications can be seen in lungs, heart, stomach and blood vessels
Describe the clinical course of secondary hyperparathyoidism
- usually dominated by the inciting chronic renal failure
- the hyperparathyroidism per se is usually not as severe or as prolonged as primary
- Calciphylaxis: vascular calcifications –> ischemic changes to skin and other organs
Treatment of secondary hyperparathyroidism
- Vitamin D supplements
- phosphate binders
If a patient with secondary hyperparathyroidism, the parathyroids become autonomous and excessive
tertiary hyperparathyroidism
Treatment for tertiary hyperparathyroidism
parathyroidectomy
What are the causes of hypoparathyroidism
- SURGICALLY INDUCED
- autoimmune
- autosomal dominant hypoparathyroidism
- Familial isolated hypoparathyroidism
- Congenital absence of parathyroid glands
Autoimmune hypoparathyroidism is associated with what?
chronic mucocutaneous candidiasis and primary adrenal insufficiency ( autoimmune polyendocrine syndrome type 1: APS1)
Congenital absence of parathyroid glands is also called what if present with thymic defects
DiGeorge syndrome
Autosomal recessive familial isolated hypoparathyroidism (FIH) is caused by loss of function mutations in what
glial cells missing-2 (GCM2)
Describe the Tetany changes found with hypocalcemia
- Circumoral or parestesias (tingling) of the distal extremeities and carpopedal spasm
- When severe: life threatening laryngospasm and generalized seizures
- Chvostek sign: tap area of facial nerve to induce contractions of the muscles of the eye, mouth and nose
- Trousseau sign: carpal spasms produced by occlusion of the circulation of the forarm and hand with a blood pressure cuff for several minutes
What are the mental status changes associated with hypocalcemia
- emotional instability
- anxiety
- depression
- confusion
- hallucinations
- frank psychosis
what are the paradoxical calcifications from hypocalcemia
- likely from increased phosphate levels
- Basal ganglia: parkinsonian like movement disorders
- Lens and cataract formation
Cardio symptoms of hypocalcemia
conduction defect: prolongation of QT interval in electrocardiogram
What occur when hypocalcemia is present during early development and are highly characteristic of hypoparathyroidism
dental abnormalities
occurs because of end organ resistance to actions of PTH . . . serum PTH levels are normal or elevated
pseudohypoparathyroidism
What does pseudohypoparathyroidism present as
hypocalcemia and hyperphosphatemia
in pseudohypoparathyroidism, there can also be end organ resistance to what?
PTH, TSH, and FSH/LH . . . genetic defects in G protein coupled receptors
