Hyperparathyroidism Week 6

Question 1

What is hyperparathyroidism?

Answer 1

it is the result of excessive parathyroid hormone (PTH) secretion, PTH-induced bone resorption, and hypercalcemia. 3 types- primary, secondary, tertiary

Question 2

Primary HPT is characterized by?

Answer 2

abnormal regulation of PTH secretion by calcium, resulting in excessive PTH secretion and hypercalcemia.

Question 3

causes of primary HPT?

Answer 3

a single parathyroid adenoma mostly (85%)
four-gland hyperplasia (10%)
multiple adenomas (5%)
parathyroid carcinomas- rare (<5%).

Question 4

How do you diagnose primary HPT?

Answer 4

Persistent hypercalcemia with increased or high-normal serum PTH levels confirms the diagnosis of primary HPT.
diagnosis primarily on laboratory studies since sx usually non- specific or absent

Question 5

normal lab values- PTH and calcium

Answer 5

PTH 10-65 pg/mL- increase with age- unknown why

calcium 8.5-10.5 mg/dL

Question 6

How might you make the diagnosis of primary HPT more certain before recommending parathyroidectomy?

Answer 6

Get at least 3 fasting serum calcium levels, ideally with no venous occlusion, and 2 PTH measurements at least several weeks apart. Ensure that the patient has normal renal function. Discontinue any thiazide diuretics for at least 1 week before measurement. Discontinue lithium if safe to do so.

Question 7

2 major hormones modulating calcium and phosphate homeostasis

Answer 7

PTH and calcitrol (1,25-dihydroxyvitamin D)

Question 8

diagnostic of primary hyperparathyroid

Answer 8

elevated PTH and elevated serum calcium (because of hyper secretion of PTH relative to the serum calcium concentration)

Question 9

a decrease in serum calcium would do what to the PTH?

Answer 9

stimulates the release of PTH from the parathyroid gland

Question 10

PTH increases the activity of ____ leading to _____.

Answer 10

1α-hydroxylase in the kidney; increased activation of

vitamin D

Question 11

PTH increases _____ and decreases_____.

Answer 11

the reabsorption of calcium (into blood); the reabsorption of inorganic phosphate (Pi)

Question 12

Elevations in plasma Pi levels stimulate what?

Answer 12

the release of PTH

Question 13

In bone, PTH stimulates ? Which leads to what?

Answer 13

bone resorption. which leads to an increase in plasma calcium levels

Question 14

clinical manifestations of primary hyperparathyroidism

Answer 14

elevated intact PTH levels
increased plasma calcium levels (hypercalcemia)
increased urinary calcium excretion (hypercalciuria) which may lead to kidney stones (urolithiasis)
and decreased plasma phosphate

Question 15

symptoms and signs of excess PTH secretion/ hyperparathyroid

Answer 15

s/s of hypercalcemia
bone disease
nephrolithiasis
hypophosphotemia
increased production of calcitrol
proximal renal tubular acidosis
hypomagnesemia
hyperuricemia and gout
anemia

Question 16

most patients with primary hyperthyroid present with calcium levels of?

Answer 16

10- 11mg/dL, often discovered on routine testing

Question 17

SX: Renal: hypercalciuria, nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, renal insufficiency probable cause in hyperparathyroid ?

Answer 17

Parathyroid hormone (PTH) stimulates bone resorption, hypercalcemia, bicarbonaturia, and phosphaturia, causing decreased tubular responsiveness to antidiuretic hormone (ADH), polyuria, calcium oxalate 
and phosphate crystallization, nephrocalcinosis, and renal insufficiency

Question 18

SX: Neuromuscular: weakness, myalgia probable cause in hyperparathyroid?

Answer 18

Prolonged excessive PTH arguably causes direct neuropathy with abnormal nerve conduction velocities (NCVs) and characteristic electromyographic changes and myopathic features on muscle biopsy

Question 19

SX: Neurologic and psychiatric: memory loss, depression, psychoses, neuroses, confusion, lethargy, fatigue, paresthesias probable cause in hyperparathyroid?

Answer 19

PTH and calcium cause peripheral neuropathy with abnormal NCVs and central nervous system damage with abnormal electroencephalographic changes

Question 20

SX: Skeletal: bone pain, osteitis fibrosa, osteoporosis, and subperiosteal skeletal resorption probable cause in hyperparathyroid?

Answer 20

PTH increases bone resorption and acidosis with subsequent bone buffering and bone loss of calcium and phosphate

Question 21

SX: Gastrointestinal: abdominal pain, nausea, peptic ulcer, constipation, and pancreatitis probable cause in hyperparathyroid?

Answer 21

Hypercalcemia stimulates gastrin secretion, decreases peristalsis, and increases the calcium-phosphate product with calcium-phosphate deposition in and obstruction of pancreatic ducts

Question 22

SX: Hypertension probable cause in hyperparathyroid?

Answer 22

Hypercalcemia causes vasoconstriction, and parathyroid hypertensive factor (PHF) may raise blood pressure

Question 23

SX: Arthralgia, synovitis, arthritis probable cause in hyperparathyroid?

Answer 23

HPT is associated with increased crystal deposition from calcium phosphate (para-articular calcification), calcium pyrophosphate (pseudogout), and uric acid/urate (gout)

Question 24

SX: Band keratopathy probable cause in hyperparathyroid? (classic but unusual sign of HPT)

Answer 24

Calcium-phosphate precipitation in medial and limbic margins of cornea

Question 25

SX: Anemia probable cause in hyperparathyroid?

Answer 25

unknown

Question 26

Primary hyperparathyroidism (HPT) is associated with what? (major things)

Answer 26

hypercalcemia, osteoporosis, nephrolithiasis, and symptoms associated with these conditions

Question 27

The new recommendations for surgery in patients with asymptomatic HPT are ?

Answer 27

serum calcium more than 1 mg/dL above the upper normal limit, decreased estimated GFR to less than 60 mL/min, reduced bone density with T-score less than –2.5, age less than 50 years, and calcium nephrolithiasis

Question 28

Advantages of parathyroid surgery include ?

Answer 28

cure of HPT and hypercalcemia in most cases with a single operation, no need for regular prolonged follow-up, decreased fracture rate, and increased bone mass in most patients.

Question 29

What are the classic radiographic findings in HPT?

Answer 29

often no radiographic findings related to HPT (since pts diagnosed early). If HPT is prolonged, osteopenia or osteoporosis develops. However, the classic radiographic finding is subperiosteal bone resorption along the radial aspect of the middle and distal phalanges and distal clavicles. Salt-and-pepper skull is another classic finding.

Question 30

differential diagnosis of primary HPT?

Answer 30

Because the main abnormality in primary HPT is hypercalcemia, the differential diagnosis initially is that of hypercalcemia- 2 most common causes of hypercalcemia are primary HPT and malignancy.

Question 31

What lab tests help to distinguish the three types of HPT?

Answer 31

``` primary= PTH normal or high and calcium high secondary= PTH high and calcium low or normal tertiary= PTH very high and calcium high ```

Question 32

What pathophysiologic changes occur in secondary HPT? most common cause?

Answer 32

Secondary HPT is excessive PTH secretion occurring as a compensatory response to absolute or relative hyperphosphatemia, hypocalcemia, or low calcitriol levels. Renal failure is the most common cause of secondary HPT, often producing PTH hypersecretion by means of all three of these stimuli. In renal failure, phosphorus increases because of decreased renal function. The increased phosphorous stimulates PTH secretion and decreases calcium and 1,25(OH) 2 D levels. The lower calcium and vitamin D levels also increase PTH synthesis and secretion. Thus, controlling phosphorus levels with diet and phosphate binders and appropriate calcitriol supplementation may delay onset of the secondary HPT of renal failure.

Question 33

What pathophysiologic changes occur in tertiary HPT?

Answer 33

Tertiary HPT results from progression of secondary HPT. In tertiary HPT, prolonged hyperphosphatemia and/or hypocalcemia cause further parathyroid hyperplasia with eventual development of autonomous parathyroid function and hypercalcemia. (most common in chronic renal failure) PTH levels usually approximately 15- 30 times normal

Question 34

early manifestation of surgical removal of parathyroid glands?

Answer 34

hypocalcemic tetany

Question 35

classic sign for hypocalcemic tetany

Answer 35

Chvostek sign= twitching or contraction of the facial muscles in response to tapping the facial nerve at a point anterior to the ear and above the zygomatic bone

Question 36

pseudohypoparathyroidism

Answer 36

not bc of decreased PTH levels but because of an abnormal response to the PTH because of a congenital defect in the G protein associated with PTHR1

Question 37

pseudohypoparathyroidism type 1a

Answer 37

Characterized by a generalized hormone resistance to PTH, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone, is associated with abnormal physical features including short stature and skeletal anomalies

Question 38

pseudohypoparathyroidism type 1b

Answer 38

Characterized by renal resistance to PTH and normal appearance. The PTHR1 has decreased Gαs activity, and this can be tested by measuring the increase in urinary cAMP in response to PTH administration (which should be low in patients with defective Gαs activity).

Question 39

In pseudohypoparathyroidism type 1b pts present with?

Answer 39

- low plasma calcium (bc of inability of PTH to increase calcium rabsorption) - high phosphate levels (bc of inability to excrete phosphate) - elevated PTH (bc the parathyroid gland is trying to respond to low calcium levels/ high phosphate levels by making more PTH but it won't work)