Parathyroid Pathology Flashcards

1
Q

In early infancy and childhood, the parathyroid glands are composed almost entirely what type of cell?

A

Chief cells

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2
Q

What are the 3 histological characteristics of the Chief Cells of the parathyroid glands?

A
  • Central round, uniform nuclei
  • Light pink or white cytoplasm (water-clear appearance)
  • Secretory granules
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3
Q

Which cells of the parathyroid gland have an acidophilic cytoplasm and are tightly packed with mitochondria?

A

Oxyphil cells

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4
Q

Which cells of the parathyroid hormone contain large amounts of cytoplasmic glycogen and secretory granules containing PTH?

A

Chief cells

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5
Q

What are 4 specific ways PTH acts to maintain calcium homeostasis?

A
  • ↑ renal tubular reabsorption of Ca2+
  • conversion of Vit D —> active 1,25(OH)2D form in kidneys
  • ↑ urinary phosphate excretion
  • Augments GI calcium absorption
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6
Q

Secondary hyperparathyroidism is a compensatory hypersecretion of PTH in response to prolonged hypocalcemia, most commonly in the setting of what?

A

Chronic renal failure

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7
Q

What are 3 causes of primary hyperparathyroidism; which is most common?

A
  • Adenoma = most common
  • Primary hyperplasia
  • Parathyroid carcinoma
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8
Q

Which 2 molecular defects/mutations have an established role in the development of sporadic parathyroid adenomas?

A
  1. Cyclin D1 gene inversion –> overexpression of cyclin D1
  2. MEN1 mutations
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9
Q

In what 2 ways can MEN1 mutations be associated with parathyroid adenomas and which is more common?

A
  • Germline mutations causing familial MEN1 and can manifest w/ parathyroid adenomas
  • MORE common is sporadic parathyroid adenomas, with somatic MEN1 mutations
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10
Q

Which 2 genetic syndromes are associated with familial parathyroid adenoma; what is the associated gene mutated in each?

A
  • MEN type 1 associated w/ MEN1
  • MEN type 2 associated w/ RET
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11
Q

Familial hypocalciuric hypercalcemia is a rare disorder due to what mutation and how is it inherited?

A
  • Loss-of-function mutation in parathyroid calcium-sensing receptor gene (CASR)
  • Autosomal dominant
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12
Q

What is the typically seen microscopically in parathyroid adenomas; what is the dominant cell type?

A
  • Uniform, polygonal CHIEF cells w/ small, centrally placed nuclei
  • A few nests of larger oxyphil cells are present as well
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13
Q

What is “endocrine atypia” in relation to the morphology of some parathyroid adenomas?

A

Not uncommon to find bizarre and pleomorphic nuclei; this is not a criterion for malignancy

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14
Q

What type of parathyroid adenoma may resemble a Hurthle cell tumor in the thyroid?

A

Oxyphil adenoma (uncommon)

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15
Q

Which morphological feature of the normal parathyroid glands becomes inconspicous in adenomas and hyperplasia?

A

Adipose tissue

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16
Q

How does parathyoid adenoma differ from hyperplasia in terms of glands involved?

A
  • Adenoma are almost always solitary, affecting one lobe
  • Hyperplasia almost always present in multiple glands
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17
Q

What is often seen morphologically surrounding parathyroid adenomas and how does this differ from parathyroid hyperplasia?

A
  • Adenomas have a rim of compressed, normal parathyroid tissue, generally separated by a fibrous capsule
  • Hyperplasia does NOT have a normal rim of parathyroid tissue
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18
Q

What are the only reliable criteria for diagnosis of a parathyroid carcinoma?

A

- Metastasis = most telltale sign!

- Invasion of surrounding tissues or vasculature

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19
Q

Parathyroid carcinomas are often hard to distinguish from what?

A
  • Adenomas
  • Both are solitary and enclosed by fibrous capsule
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20
Q

What 3 interrelated skeletal abnormalities can manifest as a result of symptomatic, untreated hyperparathyroidism?

A
  • Osteoporosis
  • Brown tumors
  • Osteitis fibrosa cystica
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21
Q

The osteoporosis associated with symptomatic, untreated hyperparathyroidism preferentially involves which bones?

A

Phalanges + vertebrae + prox. femur

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22
Q

The osteoclast activity associated with hyperparathyroidism affects what type of bone more severly?

A

Cortical bone (i.e., subperiosteal and endosteal surfaces)

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23
Q

In untreated hyperparathyroidism, what do the osteoclasts due in medullary bone; create what appearance?

A
  • Tunnel into and dissect centrally along the length of the trabeculae
  • Create appearance of rail-road tracks aka dissecting osteitis
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24
Q

What are the 3 hallmarks of severe hyperparathyroidism and is known as generalized osteitis fibrosa cystica (von Recklinghausen disease of bone)?

A
  • Osteoclast-driven bone destruction –> microfractures + hemorrhage
  • Peritrabecular fibrosis
  • Cystic brown tumors (STARTS as a brown tumor)
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25
Q

What is the pathophysiological process underlying the development of brown tumors?

A

Bone loss predisposes to microfractures and 2’ hemorrhages, which elicits influx of macrophages and ingrowth of reparative fibrous tissue creating a mass

26
Q

PTH-induced hypercalcemia leads to the formation of what in the urinary tract/kidneys?

A
  • Urinary tract stones (nephrolithiasis)
  • Nephrocalcinosis (calcification of the renal interstitium and tubules)
27
Q

The cystic brown tumors of osteitis fibrosis cystica can resemble what?

A

Metastatic disease

28
Q

What is the most common cause of asymptomatic hypercalcemia?

A

Primary hyperparathyroidism

29
Q

What is the most frequent cause of symptomatic hypercalcemia in adults?

A

Malignancy (i.e., breast, lung, head/neck and renal cancers)

30
Q

Most common mechanism through which osteolytic tumors induce hypercalcemia is by secretion of what?

A

PTH-related peptide (PTHrP)

31
Q

What are the levels of PTH and Ca2+ like in primary hyperparathyroidism?

A
  • ↑ PTH + ↑Ca2+
  • When Ca2+ levels are ↑, levels of PTH should be ↓ due to negative feedback
32
Q

Other than Ca2+ and PTH, what other lab values can point to PTH excess?

A
  • Hypophosphatemia
  • ↑ urinary excretion of both calcium and phosphate
33
Q

What are 5 GI manifestations which may result from increased PTH secretion and hypercalcemia (aka 1’ hyperparathyroidism)?

A
  • Constipation
  • Nausea
  • Peptic ulcers
  • Pancreatitis
  • Gallstones
34
Q

What are 3 CNS alterations which may result from increased PTH secretion and hypercalcemia (aka 1’ hyperparathyroidism)?

A
  • Depression
  • Lethargy
  • Eventually seizures
35
Q

What are 2 neuromuscular abnormalities which may result from increased PTH secretion and hypercalcemia (aka 1’ hyperparathyroidism)?

A
  • Weakness
  • Fatigue
36
Q

What are 2 cardiac manifestations which may result from increased PTH secretion and hypercalcemia (aka 1’ hyperparathyroidism)?

A
  • Aortic calcification
  • Mitral calcification
  • Or BOTH
37
Q

Nephrolithiasis and bone disease are abnormalities most directly related to what in the setting of primary hyperparathyroidism?

A

↑↑↑ PTH (hyperparathyroidism)

38
Q

Fatigue, weakness, pancreatitis, metastatic calcifications, and constipation are abnormalities most directly attributable to what in the setting of primary hyperparathyroidism?

A

Hypercalcemia

39
Q

What is the most common cause of secondary hyperparathyroidism and list 3 other causes?

A
  • Renal failure = most common
  • Inadequate dietary intake of Ca2+
  • Steatorrhea (malabsorption of ADEK)
  • Vit D deficiency
40
Q

What are 5 causes of hypercalcemia which are associated with ↓ [PTH]?

A
  • Hypercalcemia of malignancy
  • Vit D toxicity
  • Immobilization
  • Thiazide diuretics
  • Granulomatous disease (sarcoidosis)
41
Q

What is the morphology of the parathyroid glands in secondary hyperparathyroidism?

A

Are hyperplastic as a result of reactive hyperplasia

42
Q

The skeletal abnormalities of secondary hyperparathyroidism are usually not as severe or as prolonged as primary hyperparathyroidism and are known as what?

A

Renal osteodystrophy

43
Q

Renal osteodystrophy associated w/ secondary hyperparathyroidism may be seen as what “sign” on imaging?

A

Rugger Jersey Sign”

44
Q

What is Calciphylaxis in the setting of secondary hyperparathyroidism?

A

Extensive calcification and occlusion of blood vessels w/ resultant ischemia

45
Q

Vitamin D mediated causes of humoral hypercalcemia of malignancy are seen with what type of tumors?

A

Lymphomas

46
Q

Local osteolytic hypercalcemia due to the release of calcium as a result of osteoclastic bone resorption is associated with what 2 types of tumors?

A
  • Breast carcinoma
  • Myeloma
47
Q

Acquired hypoparathyroidism is almost always a consequence of what?

A

Surgery

48
Q

Autoimmune hypoparathyroidism is often associated with what underlying condition?

A

Auto-immune polyendocrine insufficiency syndrome type 1 (APS1)

49
Q

Auto-immune polyendocrine insufficiency syndrome type 1 (APS1) is due to mutations in what gene?

A

Autoimmune regulator (AIRE) gene

50
Q

When does Auto-immune polyendocrine insufficiency syndrome type 1 (APS1) typically present and what are the manifestations of this disease?

A
  • During childhood w/ onset of candidiasis
  • Followed several years later by hypoparathyroidism
  • Then adrenal insufficiency during adolescence
51
Q

Autosomal-dominant hypoparathyroidism is caused by gain-of-function mutations in which gene?

A

Calcium-sensing receptor (CASR) gene

52
Q

Inappropriate CASR activity in autosomal-dominant hypoparathyroidism leads to what serum and urine calcium levels?

A

HYPOcalcemia and HYPERcalciuria

53
Q

Familial isolated hypoparathyroidism (FIH) can be inherited via AD or AR patterns; how does each differ and which mutation is seen?

A
  • AD = due to mutation in gene encoding PTH precursor peptide, which impairs its processing to the mature hormone
  • AR = due to loss-of-function mutations in the transcription factor gene glial cells missing-2 (GCM2), essential for parathyroid development
54
Q

Congenital absence of parathyroid glands can occur in conjunction with what?

A
  • Thymic aplasia
  • Cardiovascular defects
  • Part of 22q11 deletion syndrome (i.e., DiGeorge Syndrome)
55
Q

What is the hallmark of hypocalcemia?

A

Tetany (aka neuromuscular irritability)

56
Q

What are 3 intracranial manifestations which may result from chronic hypocalcemia?

A
  • Calcifications of the basal ganglia
  • Parkinsonian-like movement disorders
  • ↑ ICP —> papilledema
57
Q

What are 2 disease manifestations of the eye which may occur in the setting of hypocalcemia?

A
  • Calcification of the lens
  • Cataract formation
58
Q

What is a cardiovascular manifestation of hypocalcemia?

A

Conduction defect –> prolongation of the QT interval on ECG

59
Q

What is the pathophysiology of Pseudohypoparathyroidism?

A

Due to end-organ resistance to the actions of PTH

60
Q

Due to PTH acting through a GPCR, one form of Pseudohypoparathyroidism also shows resistance to what other hormones?

A

TSH and FSH/LH

61
Q

What are the serum levels of PTH, calcium, and phosphate like in Pseudohypoparathyroidism?

A
  • Normal or ↑ PTH
  • HYPOcalcemia
  • HYPERphosphatemia
62
Q

Which condition presents with hypocalcemia despite a high serum PTH?

A

Pseudohypoparathyroidism