10/13- Cases 3: Bone and Mineral Metabolism

Question 1

Case 1)

• You are asked to see a 40-year-old man with dyspepsia, nausea, vomiting and diarrhea for 2 days.
• He reports mild fatigue and anorexia, but denies headaches, nocturia, polyuria, renal colic, hematuria or visual changes.
• He gives his weight as 160 pounds; he weighed 170 pounds 6 months ago

PE:

• BP 145/90 supine; 120/70 upright; P 85 supine and 110 upright; orthostatic hypotension
• R 14; T 98.6; Wt 159.
• HEENT: No hypertensive retinopathy, band keratopathy, decreases in visual fields, oropharyngeal masses, cervical adenopathy or masses.
• Skin, heart, lungs and abdomen are normal, mucus membranes are dry.
• There is no temporal muscle wasting.
• He can remember 5 numbers forward and 4 numbers backward. Possible slight mental deficit. The rest of the neurological examination is normal.

Labs/Imaging:

• Gastroscopy and upper gastrointestinal X-rays were normal.
• Laboratory: Serum calcium 12.0 mg/dL slightly high Ca; phosphorus 2.6 mg/dL, low K; albumin 4.4 g/dL, high albumin (probably due to dehydration)

What additional history would be helpful to narrow the differential diagnoses?

Answer 1

History- ask about causes of hypercalcemia:

• Medications:
• Excess Ca or Vit supplements
• Thiazides
• Lithium
• (but pt says he’s only on Tums)
• Thyroid function:
• Addison’s disease
• (but no change in skin condition; no thyroid symptoms)

Question 2

Case 1 cont’d)

Pt reports family history:

• Mom with 3 kidney stones
• Maternal uncle had peptic ulcer disease and brain tumor (at base; alive 15 years later)

What do these reflect?

Answer 2

Points toward possible MEN 1

• Suspect that maternal uncle had pituitary tumor and pancreatic tumor causing his peptic ulcer disease

Question 3

What are the 3Ps of MEN 1?

Answer 3

1. Pituitary adenoma
2. Parathyroid hyperplasia
3. Pancreatic NE tumor

Question 4

What are characteristics of MEN II?

Answer 4

MEN IIa- Rt proto-oncogene mutation

• Parathyroid
• MTC
• Pheas

MEN IIb

• MTC
• Pheas
• (No parathyroid)

Question 5

Case 1 cont’d)

What additional laboratory tests are likely to give you the diagnosis? (Suspected MEN 1)

Answer 5

• PTH levels (to evaluate for hyperparathyroidism)
• Serum phosphorus levels?

Question 6

High PTH levels with high serum Ca points toward what?

Answer 6

Primary hyperparathyroidism

Question 7

Case 1 cont’d) If abdominal xray shows small fleck of Ca above L kidney, and brain imaging shows enlarged sella turcica.

Diagonsis?

Management?

Answer 7

Pituitary tumor causing primary hyperparathyroidism

• Likely family background history of MEN 1

Need to:

• Genetic testing
• Screen for other possible tumors

Question 8

Case 1 cont’d)

How do you treat this man’s acute symptoms (due to hypercalcemia)?

Answer 8

• Fluids
• Can do thiazide diuretics (e.g. Lasix) after fluid-replete to further lower Ca, but commonly not needed

If extreme hypercalcemia (>12ish)

• Fluids
• Calcitonin: starts acting immediately
• Bisophosphonates (takes 12-24 hrs to start)

Question 9

Probem with using calcitonin to treat hypercalcemia?

Answer 9

Can get tachyphylaxis

• Can’t use for more than a few days (hope bisphosphonates kick in by then)

Question 10

Case 1 cont’d)

How should this pt be managed long term?

Answer 10

Primary hyperparathyroidism and hyperalcemia: remove parathyroid glands

• Tumor must come out if causing symptoms or significant morbidity
• If asymptomatic with mild hypercalcemia:
• Remove if young (lifelong fix)
• Subtle renal (kidney stones) or bone (osteoporosis) manifestations

Pituitary tumor: possibly surgery

• Do pituitary functional panel

Question 11

Case 2)

• You are the internist caring for a 62-year-old Caucasian woman who complains of chronic back pain.
• Two months ago, she began to experience mid-thoracic back pain after riding with her husband on a golf cart over rough terrain.
• She began experiencing menopausal symptoms at age 45 and has had no menses for the past 12 years.
• She smokes one-half pack of cigarettes per day and takes an occasional cocktail. She has never been immobilized in bed for a prolonged period.
• She drinks milk or eats cheese about once a day, and they do not cause abdominal bloating. (if lactose intolerant, would be hinting that she could be dietary Ca deficient)
• She takes a multivitamin and receives some direct sunlight each week. She takes no other medications.
• She has never been obese (lower body weight actually associated with lower bone mass) and has lost about 5 pounds over the past 6 months. She denies any history of fractures or kidney stones.

Physical Exam:

• Vital signs normal
• There is a slight dorsal kyphosis with point tenderness on palpating the spine at L1.
• She has slightly thin skin on the backs of her hands and her face, and a fair complexion.
• HEENT is normal. No breast masses or galactorrhea.
• Chest, heart, and abdomen are normal except for a well healed surgical incision in the midline above the umbilicus.
• Extremities are normal.

Labs:

• CBC normal except for hematocrit 35% (normal >37%) mildly anemic
• Urinalysis normal
• CMP normal

Imaging:

• Her lateral chest X-ray shows wedge-shaped deformities of the 10th and 11th thoracic vertebral bodies and generally osteopenic appearance of her spine.

What is the most likely diagnosis from the patient’s history, and what is her risk factor for that condition?

Answer 11

Osteoporosis causing fragility fracture (riding in golf cart)

Risk factors:

• Age
• Caucasian
• Post-menopausal
• Small stature
• Smoking history
• Alcohol (if being under-reported in the history)
• Want more history about what her surgical scar is from:*
• Gastrectomy/gastric bypass is a risk factor for osteoporosis (affects Ca and Vitamin D absorption)

Question 12

What other diagnoses (non-osteoporosis) should you exclude by additional history and physical examination?

Answer 12

When evaluating primary osteoporosis, also evaluate:

• Lactose intolerance
• Corticosteroid use (prolonged)
• Gastrectomy
• Laxative abuse

Question 13

Treatment?

Answer 13

1st line = bisphosphonates!

Question 14

How should osteoporotic patient be followed up?

Answer 14

• Follow up BMD in 1-2 yrs (ensure improvement)
• Urinary markers for bone turnover allows assessment of treatment (not diagnosis)

Question 15

Why might BMD not improve following bisphosphonate treatment?

Answer 15

Two causes for failure to improve:

• Lack of adherence (fix by giving IV bisphosphonate 1/yr)
• Non-responsive to bisophosphonates (check urine bone turnover marker pre and post treatment