Parathyroids

Question 1

Hypercalcemia with a raised PTH

Answer 1

1. Primary (Adenoma > hyperplasia)
2. secondary and tertiary hyperparathyroidism
3. familial hypercalciuric hypercalcemia

Question 2

hypercalcemia with low PTH

Answer 2

1. malignancy
2. vit D toxicity
3. immobilization
4. granulomatous diz

Question 3

primary hyperparathyroidism, most common cause. associated defects.

Answer 3

parathyroid adenoma (~80% of the time).

1. CyclinD1
2. Germline muts Men 1 and 2
3. RET
4. AD FHH muts in PTH-R
5. Cyclin D1 gene inversions leading to overexpression of cyclin D1: major regulator of the cell cycle
6. MEN1 mutations: tumor suppressor gene
7. Familial syndromes: Multiple Endocrine Neoplasia (MEN), types 1 and 2
   
   1. Germline mutations of MEN1 and RET
8. Familial syndromes: Familial hypocalciuric hypercalcemia
   
   1. Rare autosomal‐dominant
   2. Mutations in the parathyroid calcium‐sensing receptor gene

Question 4

morphology parathyroid adenoma

Answer 4

1. Solitary
2. 0.5‐5 gm
3. Well‐circumscribed
4. •Glands outside the adenoma are usually normal in size or shrunken from feedback inhibition by elevated calcium
5. Hypercellular with little to no fat
6. Composed of uniform chief cells
7. Few nests of larger oxyphil cells
   
   1. Occasionally composed entirely of them
8. Usually a rim of compressed, parathyroid gland, generally separated by a fibrous capsule

Question 5

occurances of PTH and what you see classically

Answer 5

1. Occurs sporadically or as a component of MEN syndrome
2. Classically all four glands are involved
   
   1. there can be asymmetry
      
      1. Can make distinction from adenoma difficult
3. Combined weight of all glands rarely > 1 gm
4. Hypercellular with little to no fat
5. Typically see chief cell hyperplasia
6. Diffusely or multinodular

Question 6

parathyroid carcinoma: distinguish from parathyroid adenoma

Answer 6

Rare

Parathyroid Carcinoma: Cells can look like normal parathyroid

Need invasion of surrounding tissues and/or metastasis for dx

Question 7

clinical symptoms of parathyroid neoplasia

Answer 7

1. Clinical Course
2. Either:
   
   1. Asymptomatic and identified on routine blood
   2. Associated with the classic clinical sx
      
      1. Malignancy most common cause

Question 8

hypercalcemia of malignancy: why its significant, how it presents and where, forms of it, and why it causes hypercalcemia.

Answer 8

Most common cause of symptomatic hypercalcemia

Solid tumors: Lung, breast, head and neck, and renal cancers

Hematologic malignancies: Multiple myeloma

Typically caused by tumor secretion of PTH‐related peptide (PTHrP): acts like PTH

Can also be from metastases to the bone and subsequent cytokine‐induced bone resorption

Question 9

Symptoms of Primary Hyperparathyroidsm

Answer 9

Symptoms of Primary Hyperparathyroidsm

1. “bones, stones, (abdominal) groans, and (psychic) moans”
2. Bone disease and bone pain secondary to fractures of bones weakened by osteoporosis or osteitis fibrosa cystica
3. Nephrolithiasis (renal stones) in 20% of newly diagnosed patients
4. Pain and obstructive uropathy
5. Chronic renal insufficiency and abnormalities in renal function
6. Polyuria and secondary polydipsia
7. GI sx:
   
   1. constipation
   2. nausea
   3. peptic ulcers
   4. pancreatitis
   5. gallstones
8. CNS sx:
   
   1. depression
   2. lethargy
   3. eventually seizures
9. Neuromuscular: weakness and fatigue
10. Cardiac: aortic and/or mitral valve calcifications

Question 10

secondary hyperparathyroidism: causes, morphology

Answer 10

Caused by any condition that leads to chronic hypocalcemia → overac ve parathyroid glands

Usually renal failure
Also inadequate dietary intake of calcium, steatorrhea, and vitamin D deficiency

Hyperplastic parathyroid glands (decreased fat)

Can be asymmetric
Increased number of chief cells

Diffuse or multinodular

“Metastatic” calcifications can be seen in lungs, heart, stomach, and blood vessels

Question 11

cliniclal symptoms of secondary hyperparathyroidism

Answer 11

1. Symptoms are typically not as severe or as prolonged as primary hyperparathyroidism
2. Calciphylaxis:
   
   1. Vascular calcifica on → ischemic damage to skin and other organs
3. Tx: vitamin D supplements and phosphate binders

Question 12

tertiary hyperparathyroidism

Answer 12

1. Occasionally in pt with secondary hyperparathyroidism
   
   1. Parathyroids become autonomous and excessive
   2. Tx: removal of parathyroids

Question 13

CASR gene mutations

Answer 13

1. can be seen with
   
   1. autosomal dominant mutations in primary hyperparathyroidism
   2. gain of function mutations in hypoparathyroidism

Question 14

causes of hypoparathyroidism

Answer 14

Hypoparathyroidsm

1. surgical removal of hyperparathyroids
2. APS1: Associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency (called autoimmune polyendocrine syndrome type 1 (APS1))
3. Autosomal‐dominant hypoparathyroidism
   
   1. Gain‐of‐function mutations in the calcium‐sensing receptor
      
      1. (CASR) gene
4. Familial isolated hypoparathyroidism
5. Congenital absence of parathyroid glands: DiGeorge syndrome

Question 15

symptoms of hypocalcemia

Answer 15

Tetany

1. Circumoral numbness or paresthesias (tingling) of the distal extremities and carpopedal spasm
2. When severe: life‐threatening laryngospasm and generalized seizures
3. Chvostek sign: tap area of the facial nerve to induce contractions of the muscles of the eye, mouth, or nose
4. Trousseau sign: carpal spasms produced by occlusion of the circulation to the forearm and hand with a blood pressure cuff for several minutes
5. Mental status changes
   
   1. Emotional instability, anxiety and depression,
   2. confusional states, hallucinations, and frank psychosis

Question 16

non tetany manifestations of hypocalcemia

Answer 16

1. Paradoxical calcifications (likely from increased phosphate levels)
   
   1. Basal ganglia → parkinsonian‐like movement disorder
2. Lens and cataract formation
3. Heart Conduction defect
4. prolongation of the QT interval in the electrocardiogram
5. Dental abnormalities when hypocalcemia is present during early development

Question 17

pseudoparathyroidism

Answer 17

1. Pseudohypoparathyroidism
   
   1. End‐organ resistance to PTH
   2. Serum PTH levels are normal or elevated
   3. Presents as hypocalcemia and hyperphosphatemia
   4. Can also have end‐organ resistance to TSH and FSH/LH
      
      1. From genetic defects in G‐protein–coupled receptors