Parathyroid Gland Pathology

Question 1

3 predominant cell types of parathyroid gland

Answer 1

Chief cells — central round, uniform nuclei; light pink or white cytoplasm, secretory granules

Oxyphil cells — smaller darker nuclei, eosinophilic granular material, less endocrinologically active

Adipocytes

Question 2

2 major functions of parathyroid hormone released from parathyroid glands

Answer 2

Directly releases calcium from bone

Promotes synthesis of 1,25-dihydroxyvitamin D in kidney (further mobilizes calcium from bone and intestine)

Question 3

3 major causes of primary hyperparathyroidism

Answer 3

Adenoma (85-95%)

Primary hyperplasia (5-10%)

Parathyroid carcinoma (1%)

Question 4

Parathyroid adenomas are benign neoplasms of parathyroid ______ or ______ cells. They are typically solitary and can be surrounded by a rim of normal parathyroid tissue

Answer 4

Chief; oxyphil

Question 5

Germline mutations in the tumor suppressor gene ______ can manifest with parathyroid adenomas

Answer 5

MEN1

Question 6

T/F: sporadic parathyroid adenomas with somatic MEN1 mutations are less common than parathyroid adenomas in the setting of familial MEN1

Answer 6

False, they are more common

Question 7

T/F: Parathyroid hyperplasia almost always presents in multiple glands and may be caused by MEN syndromes, but secondary hyperplasia is MUCH more common

Answer 7

True

Question 8

T/F: in cases of parathyroid hyperplasia, NO normal rim of parathyroid tissue is present

Answer 8

True

Question 9

Intraoperative monitoring of ____ predicts a successful outcome in parathyroidectomy

Answer 9

PTH

Question 10

Most telltale sign of parathyroid carcinoma

Answer 10

Metastasis

Question 11

The most telltale sign of parathyroid carcinoma is metastasis. However, what are some highly suggestive features?

Answer 11

Invasion of adjacent tissues

Vascular invasion

Elevated PTH that doesn’t go down after surgery

Question 12

Symptoms of primary hyperparathyroidism

Answer 12

Symptoms largely derive from hypercalcemia — bones, stones, groans, psychic moans —

Osteoporosis/osteitis fibrosis cystica
Nephrolithiasis
Constipation, gallstones
Depression, lethargy, seizures

Others: weakness, fatigue, heart valve calcifications

Question 13

Although you may see/diagnose primary hyperparathyroidism based on symptoms of hypercalcemia, what is the far more common way it is diagnosed?

Answer 13

Hypercalcemia discovered as incidental finding on routine lab work

Question 14

Brown “tumor” (although not technically a neoplasm) that forms d/t osteoclast-driven bone destruction leading to small fractures, hemorrhage, and reactive tissue

Answer 14

Osteitis fibrosis cystica

[note osteitis fibrosis cystica is rarely the initial presentation; it also may look like metastatic disease]

Question 15

In the setting of asymptomatic hypercalcemia, it is important to consider _____________

In the setting of symptomatic hypercalcemia, it is important to consider __________

Answer 15

Primary hyperparathyroidism

Malignancy

Question 16

How is hypercalcemia due to primary hyperparathryoidism differentiated from hypercalcemia due to malignancy (based on labs)

Answer 16

Primary hyperparathyroidism = hypercalcemia with raised [PTH] (similar presentation to familial hypocalciuric hypercalcemia)

Malignancy = hypercalcemia with decreased [PTH] (similar presentation to people on thiazide diuretics or with granulomatous disease like sarcoidosis)

Question 17

What is secondary hyperparathyroidism?

Answer 17

Hypocalcemia due to renal failure, vitamin D deficiency, or pseudohypoparathyroidism —> increased parathyroidal volume as an adaptive process

Question 18

What causes tertiary hyperparathyroidism?

Answer 18

Prolonged hypocalcemia —> autonomous function of parathyroid glands

Question 19

What is Rugger Jersey sign?

Answer 19

Dissecting osteitis in hyperparathyroidism — specifically secondary hyperparathyroidism in which there is renal osteodystrophy

Question 20

Condition in secondary hyperparathyroidism characterized by extensive calcification and occlusion of blood vessels with resultant ischemia; patients are susceptible to necrosis leading to infection and sepsis

Answer 20

Calciphylaxis

Question 21

2 major mechanisms of hypercalcemia of malignancy

Answer 21

Humoral hypercalcemia of malignancy (HHM) [d/t PTHrP release (often in squamous carcinoma) or Vitamin D-mediated (often in lymphoma)]

Local osteolytic hypercalcemia [release of calcium d/t osteoclastic bone resorption]

Question 22

Causes of acquired hypoparathyroidism

Answer 22

Iatrogenic (surgical)

Autoimmune

Question 23

Causes of congenital hypoparathyroidism

Answer 23

DiGeorge Syndrome — developmental defects in 3rd to 4th pharyngeal pouches [parathyroid glands may be absent or underdeveloped]

CASR germline mutations — familial hypocalcemic hypercalciuria [hyperactive calcium-sensing receptors]

Familial isolated hypoparathyroidism [precursor PTH can’t get all the way to functional PTH]

Question 24

Signs/symptoms of hypocalcemia

Answer 24

Muscle cramps and spasms (tetany)
Trousseau sign positive
Chvostek sign positive

[others include behavioral disturbance and stupor, numbness and parasthesias, laryngeal stridor, cataracts, basal ganglia calcification, papillaedema, prolonged QT interval on ECG]

Question 25

What is pseudohypoparathryoidism?

Answer 25

Hypoparathyroidism that occurs because of end-organ resistance to the actions of PTH (related to GPCR pathways)

Serum PTH is typically elevated; presents with hypocalcemia and hyperphosphatemia

Can affect other hormone pathways: TSH, LH/FSH