CASE 1 HYPERCALCEMIA

A 44-year-old woman was hospitalized with hypercalcemic crisis.

Six years before she had total abdominal hysterectomy and oophorectomy.

Four years before she was told of a total calcium of 11.5 mg/dl (8.5-10.3). Subsequently, it varied between 10.7 and 11.5 mg/dl. C-terminal parathyroid hormone was 640 ng/ml (<340) with simultaneous calcium of 11.0 mg/dl. The patient was started on conjugated equine estrogen 0.625 mg. daily. It caused the calcium to decline 0.8 mg/dl.

Three weeks ago she developed anorexia, nausea and began a total seven pound weight loss. She was hospitalized elsewhere with low grade fever and orthostatic hypotension which responded to fluid administration. Laboratory studies at that time included the following results: calcium 17.2 mg/dl; phosphate 2.3 mg/dl (2.5-4.5); chloride 111 meq/l (100-106); glucose 100 mg/dl (70-110); creatinine 1.0 mg/dl (<1.2); free thyroxine 1.2 ng/dl (0.9-1.9), alkaline phosphatase 255 U/l (50-110) and 24 hour urinary calcium excretion 8.5 mg/kg (1.5 to 4.5). Radiographs of the chest and breasts, a protein electrophoresis and renal ultrasound were negative. A dual energy bone mineral density of the lumbar spine had a T score of minus 3.4 (values below 2.5 are considered to be major demineralization).

She was hydrated with 0.9% NaCl solution, ranging from 4.0 to 1.5 liters daily. Pamidronate, 60 mg given intravenously over four hours, caused the calcium to decline to normal over four days. She was dismissed and asked to drink two quarts of Gatorade each day.

Six days later she was admitted to our hospital after a motor vehicle accident caused compound fractures of both tibiae. During the next three days she developed symptoms of severe gastritis, polyuria and lapsed into coma. There was no history of peptic ulcer disease, constipation, fractures, urolithiasis, hypertension or familial endocrinopathy.

Her temperature was 37 degrees C. She was 56 inches tall, weighed 122 pounds, had a blood pressure of 135/90 mm Hg and a pulse of 100 per minute. She was comatose, appeared cachectic and had dry skin. No lymphadenopathy was found. There was a 2.5 cm mass just lateral to the lower pole of the right thyroid lobe. The remaining examination was normal.

Her laboratory studies were as in Table 1. Ultrasonographic exam of the neck showed a well-circumscribed, rounded, homogeneous, hypoechoic mass measuring 2.0 x 4.0 cm inferior and lateral to the inferior aspect of the right lobe of the thyroid gland. Treatment was as outlined in Table 1. An operation was performed.

Table 1

7. Assuming the patient became hypocalcemic shortly postoperatively, to what would you attribute the hypocalcemia? What clues would you have about the cause?

CASE 2 OSTEOPOROSIS

A 52 year old Caucasian woman is referred to you by an orthopedic surgeon. She has acute thoracic back pain associated with rolling over in bed the night before. An x-ray taken in his office shows an acute thoracic 8 (T8) compression fracture. Between ages 20 and 26 she had thyrotoxicosis; it was treated with radioiodine; she has been maintained on l-thyroxine. Menopause occurred at age 49. Her mother and maternal grandmother have osteoporosis. Her grandmother has had a myocardial infarction and the patient has a high-risk lipid profile.

She is 68 inches tall (maximum was 70 inches), weighs 118 pounds, had a blood pressure of 120/80 mm Hg and a regular pulse of 94 per minute. There was new dorsal kyphosis and tenderness to palpation at T8. The thyroid was not palpable.

Review of the outside x-rays confirmed the fracture at T8 and generalized demineralization of the thoracolumbar spine. The dual energy x-ray absorptiometry bone mineral density of the lumbar spine had a T score of minus 3.2 (density is 3.2 standard deviations below the mean of a similar 20 year old woman suggesting bone loss consistent with osteoporosis). Her TSH concentration was undetectable.

Her l-thyroxine maintenance dose was lowered. She was asked to mobilize as pain allowed and to walk 1.5 miles three times per week. Non-steroidal anti-inflammatory agents were recommended for pain. She was instructed on a 1500 mg elemental calcium diet with calcium citrate supplements as needed. After starting this her twenty-four hour urinary calcium excretion was low at 0.5 mg/kgm (1.5 to 4.5). 1,25(OH)2 Vitamin D3, 0.25 mcg per day, was started. This increased her urinary calcium excretion to 1.6 mg/kgm. Because of associated myocardial risk, she was asked to use conjugated equine estrogens, 0.625 mg and medroxyprogesterone acetate, 2.5 mg daily.

She returned in two years. Bone mineral density remained the same. She had taken the estrogen for one year, but stopped it because of fear that it might cause breast carcinoma. Alendronate, 10 mg daily, was prescribed. Two years later her bone mineral density had increased 6%. But during her office visit she mentioned developing esophageal pain related to a bedridden episode of the flu.

CASE 3 PAGET’S DISEASE OF BONE

A 55 year old Caucasian male comes to your office complaining of deep, aching pain in the right tibia and lumbar spine for six months as well as bifrontal headaches for two years. Vital signs were normal. There was a one-half inch increase in hat size and minimal bifrontal enlargement. His right leg was 1/2 inch short and there was 15% lateral bowing and increased warmth in the tibia. The lumbar area was normal to exam. His father had a history of Pagets disease of bone.

His chemistry group was normal except for a four-fold increase of alkaline phosphatase. Bone scan showed increased incorporation of isotope in the head, third lumbar vertebra and the right tibia. Plain radiographs showed: an enlarged Pagetic skull with marked osteoblastic changes; increased cortical and trabecular thickening of the third lumbar vertebra; and lateral bowing and cortical thickening with fissure fractures along the convex surface of the right tibia.

You treated the patient with alendronate, 40 mg p.o. daily which caused elimination of the headaches, lumbar and tibia pain as well as normalization of the alkaline phosphatase in 6 months. During the first month of this treatment he developed perioral numbness and finger tingling which improved when he received eight 650 mg tablets of calcium carbonate in divided doses each day.