Review Question - QID 109211

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Hyperparathyroidism Treatment Symptomatic patients (e.g., nephrolithiasis) QID: 109211 (M1.EC.17.4798)

QID 109211 (Type "109211" in App Search)

A 64-year-old female with a history of end-stage renal disease presents to her primary care physician complaining of weakness. She reports a six-month history of progressive weakness accompanied by occasional dull aching pain in her arms, legs, and lower back. She has also started to increase her fiber intake because of occasional strained bowel movements. Her past medical history is notable for poorly controlled diabetes, major depressive disorder, and obesity. She takes insulin and sertraline. She has a twenty pack-year smoking history and drinks alcohol socially. Her temperature is 98.5°F (36.9°C), blood pressure is 130/85 mmHg, pulse is 80/min, and respirations are 16/min. Laboratory findings are shown below:

Serum:
Na+: 138 mEq/L
Cl-: 99 mEq/L
K+: 3.9 mEq/L
HCO3-: 26 mEq/L
BUN: 20 mg/dL
Glucose: 140 mg/dL
Creatinine: 2.0 mg/dL
Parathyroid hormone: 720 µU/mL
Ca2+: 11.1 mg/dL
Phosphorus (inorganic): 4.8 mg/dl

A medication with which of the following mechanisms of action is most likely indicated to address this patient’s symptoms?

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Sodium chloride cotransporter antagonist

12%

25/204

Calcimimetic agent

38%

77/204

Osteoprotegerin analog

29%

60/204

Aldosterone receptor antagonist

17/204

Carbonic anhydrase inhibitor

15/204

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This patient with end-stage renal disease presents with fatigue, bone pain, constipation, hyperphosphatemia, and hypercalcemia suggestive of tertiary hyperparathyroidism due to parathyroid dysregulation following chronic renal disease. Hyperparathyroidism can be treated with cinacalcet, a calcimimetic agent.

Cinacalcet activates the calcium sensing receptor (CaSR) in various tissues. Activation of the CaSR on chief cells in the parathyroid gland is the primary regulator of PTH secretion. By increasing the sensitivity of the CaSR in the parathyroid gland, cinacalcet lowers the threshold for activation of feedback inhibition on parathyroid chief cells. This leads to a decrease in PTH secretion and therefore a decrease in serum calcium levels.

Incorrect Answers:
Answer 1: Thiazide diuretics such as hydrochlorothiazide inhibit the sodium chloride cotransporter (NCC) on the distal convoluted tubule. Thiazides are not used in the treatment of hyperparathyroidism.

Answer 3: Denosumab is an osteoprotegerin analog that is used to reduce bone loss in patients with osteoporosis and bone metastasis. Osteoprotegerin is an endogenous RANK-ligand inhibitor that normally serves to decrease activation of RANK by RANK-ligand, thereby decreasing osteoclast maturation and bone catabolism. It is not used in the treatment of hyperparathyroidism.

Answer 4: Aldosterone receptor antagonists such as spironolactone prevent sodium reabsorption in the collecting duct. They are not used in the treatment of hyperparathyroidism.

Answer 5: Carbonic anhydrase inhibitors such as acetazolamide inhibit the activity of carbonic anhydrase in the proximal convoluted tubule, which to a reduction in bicarbonate reabsorption. Carbonic anhydrase inhibitors are not used in the treatment of hyperparathyroidism.

Bullet Summary:
Cinacalcet is a calcium-sensing receptor sensitizer that is used to decrease PTH secretion in patients with secondary and tertiary hyperparathyroidism.

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