Parathyroid

Question 1

State the location, shape, size, and weight of normal parathyroid glands, and common deviations from normal

Answer 1

Yellow-brown ovoid nodule, weighing 35-40mg each; contain Chief cells which sense Ca & produce PTH; may be ectopic in various places throughout the neck

Question 2

Discuss the normal regulation of the production & release of parathyroid hormone.

Answer 2

NOT dependent on hypothalamo-axis

Releases PTH based on FREE (ionized) Ca levels - when levels are low, it stimulates cleavage and release of PTH (cut from a pre-pro form, with larger active & smaller inactive fractions; both may be detected when determining PTH levels)

Question 3

Summarize the metabolic function of parathyroid hormone in supporting serum calcium levels

Answer 3

PTH binds its 7-TM receptor to activate a G-protein, cAMP pway; this leads to…

1. PTH activation of Osteoclasts
2. Incr in Renal Tubular Ca reab
3. Incr in Renal Tubular Pi excretion
4. Incr in VitD activation at the kidney
5. Incr in GI Ca absorption

Question 4

Discuss the differential diagnosis of hypercalcemia.

Answer 4

Most common cause is malignancy, hyperparathyroidism, hyperthyroidism

Malignancy may present with Sx; while hyperparathyroidism may be silent

Question 5

How does malignancy cause hyperparathyroidism? (3 mechanisms)

Answer 5

1. Osteolytic Metastasis: due to activation of RANK-RANKL pway & Osteoclast axn; Osteoprotegrin inhibits the pway & may be a future treatment
2. PTH Related Protein: assoc w/ non-metastatic cancer; PTHrP mimics PTH, but can’t be regulated
3. PTH secreting neoplasm, either parathyroid or ectopic in origin

Question 6

Identify the typical clinical presentation of parathyroid tumors.

Answer 6

Can be Hyper or Hypo fxn; unlike Thyroid, tumors will create effect due to PTH level, but not Mass Effect

Question 7

Define primary hyperparathyroidism.

Answer 7

It is one of the most common endocrine disorders; due to an incrd prod &/or secretion of PTH assoc w/ Parathyroid dysfxn/hyperfxn

Question 8

Rank 3 etiologies in order of frequency for primary hyperparathyroidism.

Answer 8

Etiology: Adenoma (75-80%) > Primary Hyperplasia (10-15%) > Carcinoma (<5%)

Question 9

Describe the criteria of malignancy for parathyroid carcinoma.

Answer 9

Invasion & Metastasis are the only reliable criteria; cytologic detail is unreliable

Question 10

Describe the skeletal lesions associated with hyperparathyroidism.

Answer 10

incrd osteoclasts, erode bone matrix esp in metaph -> osteoblast activ & formation of new widely spaced trabeculae -> hemorrhage & cyst formation (Osteitis Fibrosa Cystica)

osteoclasts + hemorrhage + giant cells = Brown Tumor

Question 11

Describe the renal lesions associated with hyperparathyroidism.

Answer 11

nephrolithiasis & nephrocalcinosis (tubule stones) due to Metastatic Calcification (systemic hypercalcemia leads to calcification; v. Dystrophic Calcification)

Question 12

What is the most common manifestation of primary hyperparathyroidism?

Answer 12

Asymptomatic Hypercalcemia (associated with elevated serum ionized Ca - easily detected in blood electrolyte even before sx)

Question 13

What is the most common cause of SYMPTOMATIC hypercalcemia?

Answer 13

malignancy

Question 14

What does medullary carcinoma cause?

Answer 14

NOT hypocalcemia but paraneoplastic syndrome due to VIP, SS, 5-HT

Question 15

What’s the serum parathyroid levels in hypercalcemia due to parathyroid disease?

Answer 15

elevated

Question 16

What’s the serum parathyroid levels in hypercalcemia due to non-parathyroidal factors?

Answer 16

low (due to functioning negative feedback pathway)

Question 17

List & discuss the symptoms associated with primary hyperparathyroidism

Answer 17

Painful bones, Renal stones, Abdominal groans, Psychic moans

1. bone pain and fracture due to osteoporosis & osteitis fibrosa cystica, brown tumor
2. kidney stones, also in chronic may see polyuria & polydypsia; pyelonephritis
3. constipation, nausea, peptic ulcer; also pancreatitis and gallstones
4. CNS: depression, lethargy, seizure
5. neuromuscular: weakness & fatigue
6. cardiovascular: aortic & mitral calcifications

Question 18

What’s the etiology of secondary hyperparathyroidism?

Answer 18

anything that leads to apparent reduction in free/ionized serum Ca causing the increased secretion of PTH to normalize

Question 19

What’s the most common cause of secondary hyperparathyroidism?

Answer 19

renal failure causes reduced Pi excretion - Pi binds free Ca giving an appearance of low Ca to parathyroid -> elevated PTH

Question 20

List & discuss 4 causes of hypoparathyroidism

Answer 20

1. surgical: removal of Parathyroid tissue w/ Thyroid Qx, Malignant Neck Mass Qx, Lymph Node Qx, or too much Parathyroid tissue removed to treat primary Hyperparathyroidism
2. congenital agenesis: no glands!
3. familial: no or low functioing gland tissue, associated with APSI
4. idiopathic: most likely auto-immune, auto-Ab to CaS-R (Ca sensing receptor)

Question 21

List and explain the etiology of clinical manifestations of hypoparathyroidism

Answer 21

tetany: (hallmark) neuromuscular irritability due to electrolyte imbalance

mental status changes, intracranial manifestations (Parkinsonisms, increased ICP), ocular disease (calcifications of lens), cardiac conduction defects (~tetany), dental abnormalities esp. during development

Question 22

What’s the hallmark of hypocalcemia?

Answer 22

tetany

Question 23

What’s Chyostek sign?

Answer 23

tapping on the facial nerve elicits contraction of facial mm.

Question 24

What’s Trousseau sign?

Answer 24

carpal spasm following occlusion of forearm and hand circulation

Question 25

What's pseudohypoparathyroidism?

Answer 25

essentially a **PTH resistance syndrome** (similar to TH resistance syndrome) Patients have **low serum calcium and high phosphate and PTH** pathogenesis is linked to dysfunctional G-proteins in the PTH-R pathway