QUESTION: 193

A 72-year-old man with a diagnosis of prostate cancer was recently seen in the clinic for restaging and re- evaluation. His bone scan showed development of widespread osseous metastases and his PSA was rising. He was started on leuprolide acetate, a gonadotropin releasing-hormone (GnRH) agonist. He now returns to the clinic complaining of new severe mid-thoracic back pain, which is worse with recumbency and worse with Valsalva maneuver. He also reports that he has a brief but intense electric shock sensation in his lower extremities when he bends over to tie his shoes. On physical exam, he had localized tenderness over the mid-thoracic spine, but his motor strength, sensation, and deep tendon reflexes are all intact.

What is the most important prognostic factor regarding this patient's ultimate neurological outcome?

patient's age and co-morbid conditions at time of diagnosis
degree of neurological impairment at time of diagnosis and initiation of therapy
number of vertebral bodies affected by metastatic disease
tumor sensitivity to androgen stimulation or inhibition
patient's overall functional status before the development of the spinal cord injury

Answer(s): B

Explanation:

The patient has symptoms of spinal cord compression and needs an urgent MRI to establish the diagnosis. Spinal cord compression usually develops when patients have metastases to the vertebral body with epidural extension of the tumor, displacing the underlying thecal sac, and causing cord edema and injury. Patients with cord compression usually experience new or worsening pain symptoms days or weeks before the development of motor weakness below the level of compression. Loss of sensation and loss of bowel or bladder control occur even later. Clues that the pain symptoms may represent cord injury include pain that is worse with recumbency or Valsalva and the occurrence of Lhermitte's sign, an electric sensation down the back and into the extremities with extension or flexion of the neck or spine.

Initiation of therapy, such as radiation therapy or neurosurgical intervention, might be necessary later but would be premature before the diagnosis is established with an imaging study. If the patient's history or physical exam suggests spinal cord compression, initiation of corticosteroids should be started immediately while diagnostic imaging is pending. Pain control with adequate narcotic analgesia is important and may be instituted while the appropriate diagnostic studies are being obtained. Delay of 1 week would be inappropriate due to the urgent nature of the problem and risk of neurological compromise. The patient's neurological status at the time of diagnosis is the most important prognostic factor: 7580% of patients who are ambulatory at the time of diagnosis will retain locomotion. But, if already paraplegic, only 10% will regain the ability to walk. While this patient appeared neurologically intact, the development of neurological deficits can progress over a period of days, making rapid diagnosis and institution of appropriate therapy such as corticosteroids and radiotherapy an urgent consideration. Other factors such as age, presence of co-morbid medical conditions, functional status, and tumor androgensensitivity are important to the patient's overall cancer prognosis

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QUESTION: 194

A 72-year-old man with a diagnosis of prostate cancer was recently seen in the clinic for restaging and re- evaluation. His bone scan showed development of widespread osseous metastases and his PSA was rising. He was started on leuprolide acetate, a gonadotropin releasing-hormone (GnRH) agonist. He now returns to the clinic complaining of new severe mid-thoracic back pain, which is worse with recumbency and worse with Valsalva maneuver. He also reports that he has a brief but intense electric shock sensation in his lower extremities when he bends over to tie his shoes. On physical exam, he had localized tenderness over the mid-thoracic spine, but his motor strength, sensation, and deep tendon reflexes are all intact.

What is the most likely explanation for the rapid onset of back pain and neurological difficulty after the initiation of leuprolide?

The patient's tumor was likely androgen-independent and so did not respond to hormonal therapy, with rapid progression of his cancer.
The patient likely experienced vasomotor symptoms such as hot flashes and discontinued the therapy, leading to the tumor progression.
The GnRH agonist produced a transient rise in serum testosterone, causing a "tumor flare."
The patient's response was an unpredictable idiopathic drug reaction.
There is no plausible mechanism by which the medication could cause the development of spinal cord compression, and so it is likely unrelated to the patient's symptoms

Answer(s): C

Explanation:

The patient has symptoms of spinal cord compression and needs an urgent MRI to establish the diagnosis. Spinal cord compression usually develops when patients have metastases to the vertebral body with epidural extension of the tumor, displacing the underlying thecal sac, and causing cord edema and injury. Patients with cord compression usually experience new or worsening pain symptoms days or weeks before the development of motor weakness below the level of compression. Loss of sensation and loss of bowel or bladder control occur even later. Clues that the pain symptoms may represent cord injury include pain that is worse with recumbency or Valsalva and the occurrence of Lhermitte's sign, an electric sensation down the back and into the extremities with extension or flexion of the neck or spine.

Initiation of therapy, such as radiation therapy or neurosurgical intervention, might be necessary later but would be premature before the diagnosis is established with an imaging study. If the patient's history or physical exam suggests spinal cord compression, initiation of corticosteroids should be started immediately while diagnostic imaging is pending. Pain control with adequate narcotic analgesia is important and may be instituted while the appropriate diagnostic studies are being obtained. Delay of 1 week would be inappropriate due to the urgent nature of the problem and risk of neurological compromise. The patient's neurological status at the time of diagnosis is the most important prognostic factor: 7580% of patients who are ambulatory at the time of diagnosis will retain locomotion. But, if already paraplegic, only 10% will regain the ability to walk. While this patient appeared neurologically intact, the development of neurological deficits can progress over a period of days, making rapid diagnosis and institution of appropriate therapy such as corticosteroids and radiotherapy an urgent consideration. Other factors such as age, presence of co-morbid medical conditions, functional status, and tumor androgensensitivity are important to the patient's overall cancer prognosis

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QUESTION: 195

A 48-year-old woman with metastatic breast cancer presents to the Emergency Center complaining of a 4- day history of nausea, anorexia, and generalized weakness. Her husband reports that she has been more somnolent, sleeping 1214 hours per day, and at times she seems confused. CT scan of the brain reveals no abnormalities. Initial laboratory evaluation reveals a normal CBC, but her BUN is elevated at 32 mg/dL with a slight elevation of serum creatinine above her baseline. Her serum calcium is elevated at 15 mg/dL.

What is the most appropriate initial therapy for the patient's hypercalcemia?

volume resuscitation with normal saline
administration of furosemide every 6 hours
subcutaneous calcitonin
intravenous zoledronate
treatment of the patient's underlying malignancy with chemotherapy

Answer(s): A

Explanation:

The patient is hypercalcemic and has laboratory features suggesting dehydration, as do most patients with symptomatic hypercalcemia. Initial management would include saline rehydration, which replaces volume deficits, dilutes the elevated serum calcium, and promotes urinary calcium excretion. The addition of loop diuretics such as furosemide can also increase calciuresis, but should only be added after the patient has had adequate volume repletion. Administration of bisphosphanates, such as pamidronate or zoledronate, provide more powerful reduction of serum calcium by inhibiting bone resorption and liberation of calcium. Their effects may last for several weeks, but their onset of action does not occur for 12 days. Subcutaneous calcitonin can provide a faster onset of action to inhibit bone resorption within a few hours, but patients develop tachyphylaxis and become unresponsive to the drug effect within 2448 hours. Most cancer patients with hypercalcemia develop this problem as a paraneoplastic phenomenon, due to the production of a parathyroid hormone-related protein (PTHrP).

This problem, called humoral hypercalcemia of malignancy (HHM), is very common, affecting 510% of all cancer patients. The diagnosis is usually straightforward, as there is a readilyavailable laboratory assay for PTHrP. Other cancer patients develop HHM due to the production of an enzyme that converts 25- hydroxyvitamin D to the more active 1,25- hydroxyvitamin D, similar to the hypercalcemia seen in patients with granulomatous diseases. Severe hypercalcemia solely due to the presence of osteolytic metastases is much less common. Hyperparathyroidism and medications such as thiazide diuretics can also cause elevations of serum calcium, but usually not to the severe levels seen in HHM.

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QUESTION: 196

A 48-year-old woman with metastatic breast cancer presents to the Emergency Center complaining of a 4- day history of nausea, anorexia, and generalized weakness. Her husband reports that she has been more somnolent, sleeping 1214 hours per day, and at times she seems confused. CT scan of the brain reveals no abnormalities. Initial laboratory evaluation reveals a normal CBC, but her BUN is elevated at 32 mg/dL with a slight elevation of serum creatinine above her baseline. Her serum calcium is elevated at 15 mg/dL.
What is the most likely cause of her hypercalcemia?

widespread osteolytic metastases
ectopic production of a parathyroid hormone-related protein
excessive administration of oral calcium and Vitamin D supplementation to prevent osteoporosis
undiagnosed primary hyperparathyroidism
side effect of medications such as thiazide diuretics

Answer(s): B

Explanation:

The patient is hypercalcemic and has laboratory features suggesting dehydration, as do most patients with symptomatic hypercalcemia. Initial management would include saline rehydration, which replaces volume deficits, dilutes the elevated serum calcium, and promotes urinary calcium excretion. The addition of loop diuretics such as furosemide can also increase calciuresis, but should only be added after the patient has had adequate volume repletion. Administration of bisphosphanates, such as pamidronate or zoledronate, provide more powerful reduction of serum calcium by inhibiting bone resorption and liberation of calcium. Their effects may last for several weeks, but their onset of action does not occur for 12 days. Subcutaneous calcitonin can provide a faster onset of action to inhibit bone resorption within a few hours, but patients develop tachyphylaxis and become unresponsive to the drug effect within 2448 hours. Most cancer patients with hypercalcemia develop this problem as a paraneoplastic phenomenon, due to the production of a parathyroid hormone-related protein (PTHrP).

This problem, called humoral hypercalcemia of malignancy (HHM), is very common, affecting 510% of all cancer patients. The diagnosis is usually straightforward, as there is a readilyavailable laboratory assay for PTHrP. Other cancer patients develop HHM due to the production of an enzyme that converts 25- hydroxyvitamin D to the more active 1,25- hydroxyvitamin D, similar to the hypercalcemia seen in patients with granulomatous diseases. Severe hypercalcemia solely due to the presence of osteolytic metastases is much less common. Hyperparathyroidism and medications such as thiazide diuretics can also cause elevations of serum calcium, but usually not to the severe levels seen in HHM.

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QUESTION: 193

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