PARATHYROID DYSFUNCTION

Question 1

It is a generalized disorder of calcium, phosphate, and bone metabolism due to an increased secretion of PTH

Answer 1

PRIMARY HYPERPARATHYROIDISM
* The elevation of circulating hormone usually leads to hypercalcemia and hypophosphatemia.

Question 2

TRUE OR FALSE: A single abnormal gland is the cause of primary hyperparathyroidism in 80% of patients

Answer 2

TRUE.
* the abnormality in the gland is usually a benign neoplasm or adenoma and rarely a parathyroid carcinoma.

Question 3

MEN1 (Wermer’s Syndrome) consists of ____, ______, and ______?

Answer 3

Hyperparathyroidism, tumors of the pituitary, and pancreas
*often associated with gastric hypersecretion and peptic ulcer disease (Zollinger-Ellison syndrome).

Question 4

MEN2A is characterized by________?

Answer 4

Pheochromocytoma and medullary carcinoma of the thyroid, as well as hyperparathyroidism

Question 5

It is a syndrome which occurs in families with parathyroid tumors (often carcinomas) in association with benign jaw tumors and caused by mutations in CDC73 (HPRT2)

Answer 5

HYPERPARATHYROIDISM JAW TUMOR (HPT-JT)

Question 6

It is a distinctive bone manifestation of hyperparathyroidism with an increased in the giant multinucleated osteoclasts in scalloped areas on the surface of the bone and a replacement of the normal cellular and marrow elements by fibrous tissue.

Answer 6

OSTEITIS FIBROSA CYSTICA

Question 7

TRUE OR FALSE: Asymptomatic Hyperparathyroidism is now the most prevalent form of the disease

Answer 7

TRUE.
Asymptomatic primary hyperparathyroidism is defined as biochemically confirmed hyperparathyroidism (elevated or inappropriately normal PTH levels despite hypercalcemia) with the absence of signs and symptoms typically associated with more severe hyperparathyroidism such as features of renal or bone disease.

Question 8

Laboratory or diagnostic parameters to monitor in patients with asymptomatic primary hyperparathyroidism

Answer 8

Serum calcium - annually
Renal - eGFR -annually
Serum creatinine - annually
Skeletal - every 1-2 years (3 sites)

Question 9

Parameters that will warrant surgical intervention in asymptomatic primary hyperparathyroidism

Answer 9

Serum calcium > 1mg/dL
Renal - eGFR <60; 24h urine calcium >400mg/d and increase stone risk; presence of nephrolithiasis or nephrocalcinosis
Skeletal - BMD by DXA: Tscore <-2.5; vertebral fracture
Age - <50

Question 10

The definitive therapy for primary hyperparathyroidism

Answer 10

Surgical excision
* Evidence favoring surgery, if medically feasible, is growing because of concerns about skeletal, cardiovascular, and neuropsychiatric disease, even in mild hyperparathyroidism.

Question 11

_____ is the responsible agent in most solid tumors that cause hypercalcemia

Answer 11

PTHrP
*PTHrP, activates the PTHR1, resulting in a pathophysiology closely resembling hyperparathyroidism, but with normal or suppressed PTH levels.

Question 12

TRUE OR FALSE: Many patients with squamous cell carcinoma of the lung develop hypercalcemia

Answer 12

TRUE

*Many solid tumors associated with hypercalcemia, particularly squamous cell and renal tumors, produce and secrete PTHrP that causes increased bone resorption and mediates the hypercalcemia through systemic actions on the skeleton.

Question 13

TRUE OR FALSE: Chronic ingestion of 40-100 times the normal physiologic requirement of vitamin D (amounts >40,000– 100,000 U/d) is usually required to produce significant hypercalcemia in otherwise healthy individuals.

Answer 13

TRUE

Question 14

Hypercalcemia in vitamin D intoxication is due to an excessive biologic action of the vitamin, perhaps the consequence of increased
levels of _____?

Answer 14

25(OH)D
*These actions lead to both increased intestinal absorption of calcium and increased release of calcium from bone.
**25(OH)D has definite, if low, biologic activity in the intestine and bone.

Question 15

Vitamin D-related hypercalcemia diagnosis is substantiated by documenting what level of 25(OH)D?

Answer 15

> 100 ng/mL

Question 16

TRUE OR FALSE: Hyperthyroidism is associated high bone turn over state

Answer 16

TRUE: The hypercalcemia is due to increased bone turnover, with bone resorption exceeding bone formation
*Hypercalcemia is managed by
treatment of the hyperthyroidism.

Question 17

____ is a potent inhibitor of the renal 1α-hydroxylase.The subsequent reduction in 1,25(OH)2D thus seems to be an important stimulus for the development of secondary hyperparathyroidism.

Answer 17

FGF23

Question 18

Medical therapy to reverse secondary hyperparathyroidism

Answer 18

• reduction of excessive blood phosphate by restriction of
  dietary phosphate
• the use of nonabsorbable phosphate binders
• and careful, selective addition of calcitriol (0.25–2 μg/d) or related
  analogues.

Question 19

This drug is no longer effective in lower calcium after 24 hours from its first use due to tachyphylaxis

Answer 19

Calcitonin
**Therefore, in life-threatening hypercalcemia, calcitonin can be used effectively within the first 24h in combination with rehydration and saline diuresis while waiting for more sustained effects from a simultaneously
administered bisphosphonate such as pamidronate.
**Usual doses of calcitonin are 2–8 U/kg of body weight IV, SC, or IM every 6–12 h.

Question 20

TRUE OR FALSE: Glucocorticoids have utility, especially in hypercalcemia complicating certain malignancies.

Answer 20

TRUE
**They increase urinary calcium excretion and decrease intestinal calcium absorption
***The malignancies in which hypercalcemia responds to glucocorticoids include multiple myeloma, leukemia, Hodgkin’s disease, other lymphomas, and
carcinoma of the breast, at least early in the course of the disease.

Question 21

The treatment of choice for severe hypercalcemia complicated by renal failure, which is difficult to manage medically

Answer 21

Dialysis
**the serum inorganic phosphate concentration should be measured after dialysis, and phosphate supplements should be added to the diet or to dialysis fluids if necessary.

Question 22

The strongest anti-resorptive therapy for hyperclacemia with onset of action 1-2 days and duration of action >3weeks

Answer 22

Denosumab
**a monoclonal antibody that
binds to RANK ligand (RANKL) and prevents it from binding to
the receptor RANK on osteoclast precursors and mature osteoclasts.

Question 23

Which hormone is the primary regulator of calcium physiology?
A) Calcitonin
B) Parathyroid hormone (PTH)
C) Vitamin D
D) Estrogen

Answer 23

Correct Answer: B) Parathyroid hormone (PTH)
Rationale: PTH is the primary hormone that regulates calcium levels in the extracellular fluid. It acts on bone, kidneys, and indirectly on the intestine to maintain calcium homeostasis.

Question 24

What is the primary effect of PTH on the kidney?
A) Increases phosphate reabsorption in the proximal tubules
B) Enhances calcium reabsorption in the distal tubules
C) Decreases production of 1,25(OH)2D
D) Promotes calcium excretion in urine

Answer 24

Correct Answer: B) Enhances calcium reabsorption in the distal tubules
Rationale: PTH reduces calcium excretion by enhancing its reabsorption in the distal tubules. Additionally, it increases phosphate excretion in the proximal tubules and stimulates the production of 1,25(OH)2D.

Question 25

What is a hallmark feature of humoral hypercalcemia of malignancy (HHM)?
A) Elevated PTH levels
B) Production of PTH-related peptide (PTHrP)
C) Increased 1,25(OH)2D synthesis
D) Hypocalcemia

Answer 25

Correct Answer: B) Production of PTH-related peptide (PTHrP)
Rationale: HHM is commonly caused by tumors that produce PTHrP, which mimics the effects of PTH without elevating actual PTH levels.

Question 26

What is the most common cause of primary hyperparathyroidism?
A) Parathyroid carcinoma
B) Solitary adenoma
C) Multiple endocrine neoplasia (MEN) syndrome
D) Chronic kidney disease

Answer 26

Correct Answer: B) Solitary adenoma
Rationale: Approximately 80% of cases of primary hyperparathyroidism are caused by a solitary parathyroid adenoma, which is typically benign.

Question 27

Which imaging feature is pathognomonic for osteitis fibrosa cystica?
A) Bone marrow edema
B) Subperiosteal bone resorption
C) Osteophyte formation
D) Sclerotic bone lesions

Answer 27

Correct Answer: B) Subperiosteal bone resorption
Rationale: Subperiosteal bone resorption, particularly in the phalanges, is a hallmark radiographic feature of osteitis fibrosa cystica seen in hyperparathyroidism.

Question 28

In hypocalcemia following parathyroid surgery, which deficiency should be investigated as a potential cause?
A) Vitamin B12 deficiency
B) Magnesium deficiency
C) Phosphate deficiency
D) Potassium deficiency

Answer 28

Correct Answer: B) Magnesium deficiency
Rationale: Severe magnesium deficiency can impair PTH secretion, leading to hypocalcemia. Postoperative hypocalcemia may require magnesium supplementation if levels are low.

Question 29

What is the primary mechanism of action of bisphosphonates in treating hypercalcemia?
A) Increase calcium excretion in the kidneys
B) Inhibit osteoclast-mediated bone resorption
C) Enhance intestinal calcium absorption
D) Stimulate PTH secretion

Answer 29

Correct Answer: B) Inhibit osteoclast-mediated bone resorption
Rationale: Bisphosphonates inhibit osteoclast activity, reducing bone resorption and lowering serum calcium levels. They are commonly used in hypercalcemia management.

Question 30

Which of the following conditions is characterized by elevated FGF23 levels and secondary hyperparathyroidism?
A) Hyperparathyroidism jaw tumor syndrome
B) Chronic kidney disease (CKD)
C) Primary hyperparathyroidism
D) Vitamin D intoxication

Answer 30

Correct Answer: B) Chronic kidney disease (CKD)
Rationale: Elevated FGF23 in CKD reduces 1,25(OH)2D production, leading to hypocalcemia and secondary hyperparathyroidism.

Question 31

What is the most appropriate initial treatment for severe hypercalcemia (>3.7 mmol/L)?
A) Subcutaneous denosumab
B) Intravenous hydration with saline
C) Oral calcium supplements
D) Intravenous magnesium

Answer 31

Correct Answer: B) Intravenous hydration with saline
Rationale: Hydration with IV saline is the first-line treatment for severe hypercalcemia to restore fluid balance and promote calcium excretion through diuresis.

Question 32

Which therapy has the strongest antiresorptive effect and is effective for over three weeks?
A) Pamidronate
B) Denosumab
C) Calcitonin
D) Phosphate oral

Answer 32

Correct Answer: B) Denosumab
Rationale: Denosumab is noted in the table to have the strongest antiresorptive effect and a duration of action of more than three weeks. Its disadvantages include rare jaw necrosis and hypocalcemia.

Question 33

What is the most appropriate therapy for a patient with severe hypercalcemia who requires rapid action but has a short duration of effect (1–2 days)?
A) Glucocorticoids
B) Calcitonin
C) Dialysis
D) Forced diuresis

Answer 33

Correct Answer: B) Calcitonin
Rationale: Calcitonin works within hours and has a short duration of 1–2 days. It is particularly useful in severe hypercalcemia as an adjunct therapy.

Question 34

Which therapy for hypercalcemia may result in hypophosphatemia, hypocalcemia, and jaw necrosis, despite its high potency?
A) Zoledronate
B) Pamidronate
C) Hydration with saline
D) Denosumab

Answer 34

Correct Answer: B) Pamidronate
Rationale: Pamidronate, a bisphosphonate, is highly potent and acts in 1–2 days. Its disadvantages include hypophosphatemia, hypocalcemia, and rare occurrences of jaw necrosis.

Question 35

What is the best treatment option for a patient with renal failure and life-threatening hypercalcemia?
A) Dialysis
B) Pamidronate
C) Glucocorticoids
D) Normal saline hydration

Answer 35

Correct Answer: A) Dialysis
Rationale: Dialysis is effective for patients with renal failure and life-threatening hypercalcemia. It can immediately reverse the condition but is reserved for extreme or special circumstances due to its complexity.

Question 36

Which therapy is limited in use to certain malignancies, sarcoidosis, and vitamin D excess and is not typically a first-line treatment for hypercalcemia?
A) Glucocorticoids
B) Zoledronate
C) Phosphate oral
D) Calcitonin

Answer 36

Correct Answer: A) Glucocorticoids
Rationale: Glucocorticoids are effective in reducing calcium levels in specific conditions like sarcoidosis, malignancies, and vitamin D toxicity. They are not a general treatment for hypercalcemia.

Question 37

Which therapy combines hydration with the use of a loop diuretic and requires intensive monitoring due to potential complications?
A) Forced diuresis
B) Calcitonin
C) Denosumab
D) Glucocorticoids

Answer 37

Correct Answer: A) Forced diuresis
Rationale: Forced diuresis involves hydration with normal saline plus a loop diuretic, providing rapid action but requiring intensive monitoring for complications like electrolyte disturbances and cardiac decompensation.

Question 38

How often should serum calcium levels be monitored in patients with asymptomatic primary hyperparathyroidism?
A) Monthly
B) Annually
C) Every 5 years
D) Only if symptoms develop

Answer 38

Correct Answer: B) Annually
Rationale: According to the table, serum calcium levels should be monitored annually in patients with asymptomatic primary hyperparathyroidism to assess for progression or worsening of the condition.

Question 39

Which of the following is part of the renal monitoring guideline for asymptomatic primary hyperparathyroidism?
A) eGFR annually, serum creatinine annually
B) eGFR every 5 years, renal imaging annually
C) eGFR monthly, renal imaging as needed
D) Renal monitoring is not required

Answer 39

Correct Answer: A) eGFR annually, serum creatinine annually
Rationale: The table indicates that renal function should be monitored annually through eGFR and serum creatinine. If renal stones are suspected, further investigations such as a 24-hour biochemical stone profile and renal imaging are recommended.

Question 40

What is the recommended frequency of skeletal monitoring (e.g., bone density) in asymptomatic primary hyperparathyroidism?
A) Every 6 months
B) Every 1–2 years
C) Every 10 years
D) Only if bone pain is present

Answer 40

Correct Answer: B) Every 1–2 years
Rationale: Skeletal monitoring, including assessment at three sites, should be performed every 1–2 years. Additional imaging, such as x-rays or vertebral fracture assessment (VFA), is recommended if clinically indicated (e.g., height loss or back pain).