Senior Report 5.28

Case Presentation by Dr. Brian Junnila

Chief Complaint

Altered mental status

History of Present Illness

57 y/o M sent from his nursing home for evaluation of altered mental status and generalized weakness.  Pt is able to state his name, but is confused with respect to time and location.  Pt acknowledges confusion and generalized weakness, but appears apathetic and withdrawn.   He states that he has not been eating much lately due to lack of appetite; he cannot remember the last time he had a bowel movement.  He denies nausea, vomiting or abdominal pain.  He does state that he is thirsty and asked for ice water to drink.  Pt admits to urinary frequency; denies dysuria, hematuria, fever or chills.

Pt complains of a constant aching pain along his entire spine.  Pt has a PMHx of recently diagnosed metastatic renal cell carcinoma.  He began having back pain 4 months prior, which was associated with a 40lbs weight loss over the same time period.  CT scan showed a mass in the right kidney and pulmonary nodules.  MRI of spine showed suspicious metastatic spread to T4 and T5.  Pt had kyphoplasty of L4 vertebral body.  Biopsy of spine and kidney confirmed metastatic renal cell carcinoma.  Subsequent MRI 2 weeks prior to presentation showed metastatic involvement of T2 through T7 and L2 through L5 with compression fracture deformities, but without spinal cord or nerve root compression.

Past Medical, Family, Social History

Obtained from EMR

PMH: Metastatic Renal Cell Carcinoma, Depression, Chronic Back pain, Constipation

PSH:   Right Renal Biopsy, L4 Biopsy, Kyphoplasty

Meds: Ciprofloxacin 250 mg PO every 12 h,Megestrol 800 mg PO daily, Mirtazapine 15 mg PO twice daily

Acetaminophen 325mg / hydrocodone 10mg 1 tab PO every 4 h PRN pain, Docusate 100 mg PO twice daily

Senna 15 mg PO at bedtime, S/P 1 round of Chemotherapy with temsirolimus

Allergies:  NKDA

Social History: Denies Tobacco, Alcohol, Illicit Drug Use

Physical Exam         Vitals:  BP 138/87, HR 109, RR 20, Temp 36.3, Pulse Ox 96% RA

GENERAL APPEARANCE:  A&O to person, confused on place and time.  Apathetic, withdrawn, slow to answer questions.  Lying in bed in no acute respiratory distress.

HEAD:  Normocephalic, Atraumatic

EYES:  PERRL, EOMI, No nystagmus, Conjunctiva pink, Sclera anicteric

NOSE:  No swollen turbinates.  No septal abnormalities

MOUTH:  Moist mucous membranes.  No central cyanosis.  No intraoral lesions.

NECK:  Supple. No meningismus.  Trachea midline.  No JVD.  No carotid bruis or thrills.  No cervical lymphadenopathy.

RESPIRATORY:  Clear to auscultation bilaterally.  No wheezes, rhonchi, or rales.

CARDIOVASCULAR:  Tachycardic with normal S1,S2, regular rhythm, no murmurs, rubs, or gallops; radial pulses 2+ bilaterally, capillary refill < 2 sec, posterior tibial pulses 2+ bilaterally, no pitting edema to lower extremities.

ABDOMEN:  Soft, nontender, nondistended, no rebound, guarding, or masses palpated, bowel sounds decreased.

BACK:  Pain to palpation along entire spine.  Midline lumbar scar from prior kypoplasty.

EXTREMITIES:  Moving All 4 extremities, strength 4/5.  No bony abnormalities noted.

SKIN:  Pale, dry, cool

NEUROLOGICAL:  A&O x person, PERRL, EOMI, facial muscle intact, protrudes tongue in midline.  Moves all 4 extremities with strength 4/5.  Sensation to intact throughout all distal extremities.  No saddle anesthesia.  Deep tendon reflexes decreased 1+ throughout.  Plantar response is down going bilaterally.

Labs

Electrolytes

Sodium:                        132            (135-147)

Potassium:                   4.3            (3.5-5.3)

Chloride:                        93            (96-112)

Carbon Dioxide:          29            (21-32)

Glucose:                       112            (70-99)

BUN:                              53            (7-20)

Creatinine:                  2.4            (0.4-1.2)

Calcium:                    16.4            (8.0-10.6)

Ionized Calcium:    2.18            (1.13-1.32)

Magnesium:              2.7            (1.6-3.0)

Phosphorus:             4.3            (2.3-5.0)

Abdominal Labs

Albumin          2.0            (3.5-5.2)

Lipase:              67            (73-393)

ALT:                 38            (0-65)

AST:                127            (<37)

Alk Phos:      190            (50-136)

T. Bili:            2.0            (0-1.5)

Cardiac Enzymes

Troponin:     <0.017            (<0.057)

Complete Blood Count

WBC:                   0.6            (3.5-10.6)

Hemoglobin:     8.9          (13.3-17.1)

Hemotocrit:   29.4            (38.9-49.7)

Platelets:         284            (150-450)

Coags

PTT:                 28.9            (23.2-34.1)

PT:                    11.6            (9.6-11.8)

INR:                 1.12            (0.92-1.19)

Urinalysis

Hazy, Yellow,

Glu, Bili, Ketones, Blood, Protein:  neg, Sp. Grav: >1.030, pH 5.0, Urobili 4.0, Nitrate neg, Leuk Esterase 2+,

RBC 5-10, WBC 10-20, Epith Cells < 5,

Casts, Crystals, Mucus:  none

Bacteria 1+

ECG

CXR

Pt refused CXR

Questions

 1)  Which of the following ECG changes is classically attributable to hypercalcemia?

A.      Prolongation of ST segment

B.      Supraventicular dysrhythmias

C.      Shortening of the QRS complex

D.     Shortening of QT interval

E.      Shortening of PR interval

 2)  Calculate the patient’s corrected serum calcium.

A      14

B.      15

C.      16

D.      17

E.      18

3)  What is the most appropriate initial therapy for the patient with hypercalcemia of malignancy?

A.  0.9% Normal Saline at 200-300ml/hr

B.  Calcitonin, 4–8 units/kg IM or Sub Cu

C.  Furosemide 80-100mg IVP

D.  Miramycin 25mCg/kg IM

E.   Pamidronate 60-90mg IVPB over 2-4h

F.   Prednisone 60-80mg IVP

4)   What is the most common cause of humoral hypercalcemia of malignancy in Renal Cell Carcinoma?

A.  1, 25(OH)2 vitamin D

B.  Interleukin-1 (IL-1)

C.  Parathyroid hormone-related protein (PTHrP)

D.  Transforming growth factor-alpha (TGF-α)

E.  Tumor necrosis factor (TNF)

 

 5)  What is the name of the following formula?  QTc = QT/√RR

A.  Bazett

B.  Framingham

C.  Fredericia

D.  Hodges

 

Answers

  1. D
  2. E.
  3. A
  4. C
  5. A

 

 

 

Hypercalcemia of Malignancy

 

Hypercalcemia occurs in 20-40% of all cancer patients, and is more commonly seen in pts with advanced disease.  In general a calcium level > 14mg/dL constitutes a medical emergency.  Hypercalcemia is the most common life threatening metabolic disorder associated with malignancy.

Pathophysiology

Normal physiologic calcium regulation is through an interaction between parathyroid hormone, calcitonin and 1, 25(OH)2 vitamin D.  In all cases of hypercalcemia of malignancy disruption of physiologic calcium regulation leads to increased bone resorption and increased renal reabsorption of calcium

Hypercalcemia of malignancy is attributed to two mechanisms.  Primary malignancies arising in bone, such as leukemia and multiple myeloma, and metastatic bone involvement from other primary malignancies both cause direct destruction of bone.  Increased osteoclastic activity liberates calcium and phosphate stores resulting in hypercalcemia.  It is important to note that bony metastases are not a requirement for, and when present do not necessarily lead to, the development of hypercalcemia.

Humoral-like substances produced by tumors are associated with the development of hypercalcemia.  Parathyroid hormone-related protein (PTHrP) appears as the major causative agent in humoral hypercalcemia of malignancy (HHM).  PTHrP is associated with a broad range of tumors including squamous cell carcinoma of lung, breast carcinoma, renal cell carcinoma, adult T-cell leukemia/lymphoma and ovarian carcinoma.  PTHrP binds to PTH receptors which mobilize calcium from bone and increase the renal reabsorption of calcium.  PTHrP has also been shown to be involved in complex cell growth signaling and is a potential target for therapeutic intervention.

 

Clinical Presentation

Stones, Bones, Moans, Psychiatric Groans

Hypercalcemia affects every organ system.  Severity of symptoms depends on the level of plasma calcium, the rate of rise and the general medical condition of the patient.

General

CNS

Cardiac

GI

Renal

Dehydration

-Itching

-Weakness

-Fatigue

-Weight loss

-Weakness

-Hypotonia

-Hyporeflexia

-AMS

-Apathy

-Disturbances of perception

-Seizure

-Coma

 

-Hypertension

-Dig Toxicity

-Bradycardia

-Prolonged PR

-Prolonged QRS

-Short QT

-Wide T wave

-High grade AV Block

-Ventricular Dysrhythmias

Anorexia

Dyspepsia

Nausea Vomiting

Ileus

Pancreatitis

-Polydypsia

-Polyuria

-Nephrocalcinosis

 


Diagnosis

Elevated serum calcium

Corrected Calcium = [ 0.8 * ( Normal Albumin – Pts Albumin) ] + Pts Calcium

 

 

Treatment

Depends on the patient’s clinical presentation and the serum calcium level.

General principles of treatment include…

Correcting dehydration

Increasing urinary calcium excretion

Inhibiting osteoclastic activity

Reducing calcium intake

Continue underlying treatment of the malignancy

Encouraging ambulation

 

*Isotonic Saline:      0.9% Normal Saline bolus and then @ 200-300 ml/h

Most important initial therapeutic intervention for hypercalcemia.

Mechanism:                Restores intravascular volume.  Dilution of serum calcium levels.  Promotes renal excretion

Onset:                         Immediate

Duration:                     While Infusing

Benefit:                       Reduction of serum calcium 1.6-2.4 mg/dL

Caution:                      Monitor urine output for goal of 100-150 ml/hr, monitor serum electrolytes, use with caution in CHF

 

References

 

-Marx JA. Rosen’s Emergency Medicine Concepts and Clinical Practice 7th Ed. © 2010 Saunders

– Sourbier C., Massfelder T;  Parathyroid hormone-related protein in human renal cell carcinoma.  Cancer Letters 240 (2006) 170-182

-Tintinalli, J.E.; Emergency Medicine:  A Comprehensive Study Guide – 6th Ed. © 2004 The McGraw Hill Companies Inc.

-http://lifeinthefastlane.com/ecg-library

-http://www.emergency-medicine-tutorials.org/Home/medical-3/cardiovascular/ecgs-1/short-qt

-Brunton LL;  Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition.  © 2011 The McGraw Hill Companies Inc.