parathyroid gland path Flashcards
1
Q
what are the 2 cell types that make up the parathyroid glands?
Which predominates
A
- Chief cells (predominate)
- oxyphil cells
2
Q
Describe the chief cells
A
- Central, round, uniform nuclei
- light pink cytoplasm
- Sometime they are clear from the glycogen (Water-clear appearance)
- Secretory granules of PTH
3
Q
Describe the Oxyphil cells
A
- slightly larger than chief cells
- Acidophilic cytoplasm
- Tightly packed with mitochondria
- Glycogen granules but NOT secretory granules
4
Q
Describe the amount of stromal fat in parathyroid glands
A
- increases up to age 25 then plateaus
- up to 30% of the gland
5
Q
Function of the parathyroid
A
regulate calcium
6
Q
What stimulates the synthesis and secretion of PTH
A
decreased levels of free calcium
7
Q
Explain what PTH does on different parts of the body
A
- 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
8
Q
what are the causes of hypercalcemia associated with increased PTH
A
- Primary hyperparathyroidism (adenoma > hyperplasia)
- Secondary
- Tertiary
- Familial hypocalciuric hypercalcemia
9
Q
What are the causes of hypercalcemia associated with decreased PTH
A
- Hypercalcemia of malignancy
- vitamin D toxicity
- Immobilization
- thiazide diuretics
- Granulomatous disease (Sarcoidosis)
10
Q
What are the 4 causes of primary hyperparathyroidism
A
- Autonomous overproduction of parathyroid hormone
- Adenoma
- Hyperplasia
- carcinoma
11
Q
What are the causes of secondary hyperparathyroidism
A
- Compensatory hypersecetion of PTH in response to prolonged hypocalcemia
- Chronic renal failure
12
Q
explain what tertiary hyperparathyroidism is
A
- hypersecretion of PTH even after the cause of prolonged hypocalcemia is corrected
- ex: after renal transplant
13
Q
epidemiology of primary hyperparathyroidism
A
- usually adults
- More common Women . . . 4:1
14
Q
How are most cases of primary hyperparathyroidism discovered
A
incidentally on serum electrolyte panel
15
Q
What is the most common cause of primary hyperparathyroidism
A
a solitary parathyroid adenoma arising sporadically
16
Q
What are the 2 molecular defects that play a role in sporadic parathyroid adenomas
A
- Cyclin D1 gene inversions leading to overexpression of Cyclin D1 . . cell cycle regulator
- MEN1 mutations . . . tumor suppressor gene
17
Q
what are the genetic syndromes associated with familial hyperparathyroidism
A
- 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
18
Q
Morphology of parathyroid Adenoma
A
- 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
19
Q
Parathyroid hyperplasia occurs sporadically or as a component of _______
A
MEN syndrome
20
Q
describe the involvement of the glands in parathyroid hyperplasia
A
- Classically all 4 involved
- may be Asymmetric which can make distinction from adenoma difficult
- combined weight of all glands rarely >1 gm
21
Q
Morphology of Parathyroid hyperplasia
A
- Hypercellular with little to no fat
- Typically see chief cell hyperplasia . . diffusely or multinodular
22
Q
Describe a parathyroid carcinoma
A
- enlarge one parathyroid
- sometimes exceeds 10 gm
- rare
- cells can look like normal parathyroid
23
Q
What do you need for diagnosis of parathyroid carcinoma
A
-invasion of surrounding tissues and/or metastasis
24
Q
What scan is used to assess the parathyroid glands?
i.e. location, is it solitary or diffuse
A
- Sestamibi san
- this is a radionucleotide scan where sestamibi is labeled with the radio-pharmaceutical technetium-99
25
Symptomatic, untreated primary hyperparathyroidism manifests with what 3 skeletal abnormalities?
- Osteoporosis
- Brown tumors
- Osteitis fibrosa cystica
26
Describe osteoporosis
-decreased bone mass with preferential involvement of phalanges, vertebrae, and proximal femur
27
The increased osteoclast activity in hyperparathyroidism affects what part of the bone
cortical bone more severely than medullary
28
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
29
What are brown tumors?
- Microfractures and secondary hemorrhages -->influx in macrophages and reparative fibrous tissue --> mass
- Brown color from vascularity, hemorrhage, and hemosiderin deposition
30
What is the hallmark of severe hyperparathyroidism and know as generalized osteitis fibrosa cystica?
- increased osteoclast activity
- Peritrabecular fibrosis
- cystic brown tumors
31
What is another word for generalized osteitis fibrosa cystica
-Recklinghausen disease of bone
32
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
33
what are the 2 clinical courses of primary hyperparathyroidism
- Asympsotmatic and identified on routine blood chemistry
| - or classic symptoms
34
What is the most common cause of symptomatic hypercalcemia
-malignancy
35
What malignancies can cause hypercalcemia
- Solid tumors: lung, breast, head and neck, and renal
| - Hematologic: multiple myeloma
36
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
37
Labs in primary hyperparathyroidism
- elevated Ca
- Elevated PTH: this is low if hypercalcemia is caused by non parathyroid disease
- low phosphate
38
What is the phrase used to describe the symptoms of primary hyperparathyroidism aka hypercalcemia
Bones, stones, abdominal groans and psychic moans
39
GI symptoms of hypercalcemia
- constipation
- nausea
- peptic ulcers
- pancreatitis
- gallstones
40
CNS symptoms of hypercalcemia
- depression
- lethargy
- eventually seizures
41
Neuromuscular symptoms of hypercalcemia
-weakness and fatigue
42
Cardiac symptoms of hypercalcemia
Aortic and/or mitral valve calcifications
43
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
44
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
45
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
46
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
47
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
48
Treatment of secondary hyperparathyroidism
- Vitamin D supplements
| - phosphate binders
49
If a patient with secondary hyperparathyroidism, the parathyroids become autonomous and excessive
tertiary hyperparathyroidism
50
Treatment for tertiary hyperparathyroidism
parathyroidectomy
51
What are the causes of hypoparathyroidism
- SURGICALLY INDUCED
- autoimmune
- autosomal dominant hypoparathyroidism
- Familial isolated hypoparathyroidism
- Congenital absence of parathyroid glands
52
Autoimmune hypoparathyroidism is associated with what?
chronic mucocutaneous candidiasis and primary adrenal insufficiency ( autoimmune polyendocrine syndrome type 1: APS1)
53
Congenital absence of parathyroid glands is also called what if present with thymic defects
DiGeorge syndrome
54
Autosomal recessive familial isolated hypoparathyroidism (FIH) is caused by loss of function mutations in what
glial cells missing-2 (GCM2)
55
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
56
What are the mental status changes associated with hypocalcemia
- emotional instability
- anxiety
- depression
- confusion
- hallucinations
- frank psychosis
57
what are the paradoxical calcifications from hypocalcemia
- likely from increased phosphate levels
- Basal ganglia: parkinsonian like movement disorders
- Lens and cataract formation
58
Cardio symptoms of hypocalcemia
conduction defect: prolongation of QT interval in electrocardiogram
59
What occur when hypocalcemia is present during early development and are highly characteristic of hypoparathyroidism
dental abnormalities
60
occurs because of end organ resistance to actions of PTH . . . serum PTH levels are normal or elevated
pseudohypoparathyroidism
61
What does pseudohypoparathyroidism present as
hypocalcemia and hyperphosphatemia
62
in pseudohypoparathyroidism, there can also be end organ resistance to what?
PTH, TSH, and FSH/LH . . . genetic defects in G protein coupled receptors
