Parathyroid pathalogy

Question 1

What are the 3 predominant cell types of the parathyroid glands

Answer 1

◦ Chief cells
◦ Oxyphil cells
◦ Adipocytes

Question 2

Principle function of the parathyroid gland

Answer 2

calcium homeostasis

Question 3

How does PTH work

Answer 3

◦ Directly releases calcium from bone

◦ Exerts effects on the kidney
◦ Calcium resorption
◦ blocks Phosphate resorption

◦ Conversion of 25(OH)D to 1,25(OH)2D in the
kidney
◦ Further mobilizes calcium from bone and
intestine

Question 4

What regulates the amount of PTH secreted from the parathyroid glands?

Answer 4

The Calcium-sensing receptor (CaSR)

Question 5

What is the most common cause of primary hyperparathyroidism

Answer 5

Adenoma

Question 6

Symptoms of primary hyperparathyroidism

Answer 6

1. Painful bones
   
   • osteoporosis/osteitis fibrosis cystica
2. Renal stones
   
   • nephrolithiasis
3. Abdominal groans
   
   • constipation, gallstones
4. Psychic moans
   
   • depression, lethargy, seizures

Question 7

How does Osteitis Fibrosis Cystica (von Recklinghausen’s disease of bone) start

Answer 7

Starts as a brown tumor

Question 8

Describe Osteitis Fibrosis Cystica

Answer 8

1. osteoclast driven bone destruction
2. small fractures
3. hemorrhage and reactive tissue
4. cystic brown tumors
5. can look like metastatic disease!

Question 9

How is hyperparathyroidism found in real life

Answer 9

Often asymptomatic.

High calcium incidentally found on routine lab work

Question 10

Describe a parathyroid adenoma

Answer 10

Benign neoplasm of parathyroid chief or oxyphil cells

typically solitary

can be surrounded by a rim of normal parathyroid tissue

Question 11

What gene mutation is associated with parathyroid adenomas?

Answer 11

MEN1

sporadic somatic MEN1 mutations are common

Question 12

Is primary or secondary parathyroid hyperplasia more common?

Answer 12

secondary by far

Question 13

How does one distinguish between an adenoma and primary hyperplasia

Answer 13

one gland is affected with adenoma

all glands are affected with hyperplasia

Question 14

Does parathyroid hyperplasia have a normal rim of parathyroid tissue on histology?

Answer 14

no

Question 15

What is the most telltale sign of parathyroid carcinoma?

Answer 15

Metastasis

Question 16

What are highly suggestive features of parathyroid carcinoma

Answer 16

1. Invasion of adjacent tissues
2. Vascular invasion
3. Elevated PTH that doesn’t go down after surgery

Question 17

How does hypercalcemia from hyperparathyroidism present?

From non-parathyroid sources?

Answer 17

1. Most likely to be asymptomatic or have
   subtle symptoms
   ◦ Most commonly due to parathyroid
   adenoma
2. More likely to be overt/symptomatic
   (mental status changes, nausea/vomiting,
   EKG changes – shortened QT interval)

Question 18

Most common cause of symptomatic hypercalcemia

Answer 18

malignancy

Question 19

What are the 2 mechanisms of hypercalcemia in malignancy

Answer 19

1. Humoral hypercalcemia of malignancy (HHM)

2. Local osteolytic hypercalcemia

Question 20

Describe Humoral hypercalcemia of malignancy

HHM

Answer 20

PTHrP (80%)
◦ Analogous to PTH
◦ Squamous carcinomas (and many others)

Vitamin D-mediated
◦ Lymphomas

Question 21

Describe local osteolytic hypercalcemia

Answer 21

Release of calcium - osteoclastic bone resorption
◦ Breast Carcinoma
◦ Myeloma

Question 22

What is the diagnosis when PTH is high but calcium is low?

Answer 22

secondary parathyroid hyperplasia

Question 23

What is the typical endpoint of secondary parathyroid hyperplasia?

Answer 23

4 gland hyperplasia

Question 24

What is renal osteodystrophy

Answer 24

Dissecting osteitis in hyperparathyroidism

Question 25

What can renal osteodystrophy lead to in secondary hyperparathyroidism?

Answer 25

Rugger Jersey Sign on vertebral xray

Question 26

Describe calciphylaxis

Answer 26

Extensive calcification and occlusion of blood vessels with resultant ischemia as a result of Secondary hyperparathyroidism

Question 27

What do calciphylaxis patients die from?

Answer 27

sepsis/gangrene

Question 28

What is the cause of tertiary hyperparathyroidism

Answer 28

prolonged hypocalcemia --> autonomous function of the parathyroid glands

Question 29

Clinical features of hypocalcemia

Answer 29

◦ Behavioral disturbance/stupor ◦ Numbness and parasthesias ◦ Muscle cramps, spasms (tetany) ◦ Convulsions

Question 30

Physical exam finding of hypocalcemia

Answer 30

◦ Trosseau sign positive ◦ Chvostek sign positive ◦ Prolonged QT interval on ECG

Question 31

Describe Chromosome 22q11.2 Deletion Syndrome: | DiGeorge syndrome

Answer 31

``` Facial nomalies cyanosis infection tetany ToF truncus arteriosus thymic hypo/aplasia hypocalcemia ```

Question 32

Describe an inactivating CaSR mutation

Answer 32

Thinks there isn’t enough calcium even when there is Turns on PTH ◦ Hypercalcemia Reduces renal excretion ◦ Hypocalciuria Familial hypocalciuric hypercalcemia

Question 33

Describe an activating CaSR mutation

Answer 33

Thinks there is plenty of calcium even when there isn’t Turns off PTH ◦ Hypocalcemia Increases renal excretion ◦ Hypercalciuria Autosomal dominant hypoPTH (hypercalciuric hypocalcemia)

Question 34

What is pseudohypoparathyroidism

Answer 34

hypocalcemia despite a high serum PTH

Question 35

Why does pseudohypoparathyroidism do what it do?

Answer 35

Resistance to PTH! ◦ Related to G-protein receptor pathways ◦ Can affect other hormone pathways: TSH, LH/FSH

Question 36

Describe Albright’s hereditary osteodystrophy

Answer 36

1. Short stature and obesity 2. Shortened phalanges of upper extremity 3. Shortened phalanges of lower extremity Other findings include dental abnormalities, subcutaneous ossification, cataracts Occasionally, seizures and tetany

Question 37

What is a frequent mutation in Pseudohypoparathyroidism

Answer 37

GNAS