Hypercalcemia

Question

I have a patient who presented with severe hypercalcemia at 15.6mg/dl. With rehydration her calcium lowered to 12.3 mg/dl.

Concomitant intact PTH was 15 and 12.7 respectively. D-25 and 1, 25 were 56.3 ng/ml and 95 pg/ml with a gfr of 26 on no vit d supplement for months. 24 hour urine calcium was 438 mg/dl . She had normal thyroid function tests and normal cosyntropin stim test. She had negative malignancy work-up including bone marrow biopsy. ACE level was elevated at 157 so presuming increased 1,25 vitamin d production in sarcoid I placed her on prednisone 10 # 4 a day with taper. Her calcemia normalized in 1week. Pulmonary was consulted and felt that she did not have sarcoid and sent her back to me. I do not see and endocrine problem here and I am not sure where to go from here. Dr. Mary Lynn Kemick

Response

Your patient had increased serum 1,25(OH)2D with a somewhat high 25OHD(especially for someone not taking supplements) and 24 hr urine calcium that was also on the high side. The increased 1,25(OH)2D seemed to be the culprit in causing the hypercalcemia because PTH was low (although not suppressed—but this may be an assay problem) and the patient`s hypercalcemia responded well to steroids. This is all consistent with increased 1,25(OH)2D production either due to a non-infectious granuloma, an infectious granuloma or a lymphoma. (Does she have fever or weight loss?)The increased ACE level is consistent with sarcoid but not diagnostic. Although there is pulmonary involvement in over 90% of cases of sarcoid, there may not be hilar adenopathy and sometimes the alveolitis needs special imaging(eg high resolution CT) for diagnosis. Diagnosing sarcoid therefore may depend on how hard the pulmonary physician looked. Were there any skin or eye manifestations of sarcoid? As you know sarcoid may involve just about any system. I don`t know the age of your patient, but the GFR of 26 is quite low for any age and makes one wonder what the underlying renal pathology is. Interestingly the 1,25(OH)2D was elevated and the PTH was suppressed (presumably by the hypercalcemia) despite the low GFR. You may wish to consult a nephrologist if the low GFR is reproducible, and the nephrologist may decide a biopsy is warranted which could reveal non-caseating granulomas.

Overall therefore the most likely diagnoses, I would say are 1 Sarcoidosis 2 Lymphoma3 Other granulomatous disease. While she is being worked up you might recommend that she not take supplements that contain vitamin D, and stay out of the sun or use sunscreen. If she does have another episode of hypercalcemia, clearly rehydration and prednisone would be indicated until the underlying disease can be treated. David Goltzman, MD

Hypercalcemia

Question

I have a patient who presented with severe hypercalcemia at 15.6mg/dl. With rehydration her calcium lowered to 12.3 mg/dl.

Concomitant intact PTH was 15 and 12.7 respectively. D-25 and 1, 25 were 56.3 ng/ml and 95 pg/ml with a gfr of 26 on no vit d supplement for months. 24 hour urine calcium was 438 mg/dl . She had normal thyroid function tests and normal cosyntropin stim test. She had negative malignancy work-up including bone marrow biopsy. ACE level was elevated at 157 so presuming increased 1,25 vitamin d production in sarcoid I placed her on prednisone 10 # 4 a day with taper. Her calcemia normalized in 1week. Pulmonary was consulted and felt that she did not have sarcoid and sent her back to me. I do not see and endocrine problem here and I am not sure where to go from here. Dr. Mary Lynn Kemick

Response

Your patient had increased serum 1,25(OH)2D with a somewhat high 25OHD(especially for someone not taking supplements) and 24 hr urine calcium that was also on the high side. The increased 1,25(OH)2D seemed to be the culprit in causing the hypercalcemia because PTH was low (although not suppressed—but this may be an assay problem) and the patient`s hypercalcemia responded well to steroids. This is all consistent with increased 1,25(OH)2D production either due to a non-infectious granuloma, an infectious granuloma or a lymphoma. (Does she have fever or weight loss?)The increased ACE level is consistent with sarcoid but not diagnostic. Although there is pulmonary involvement in over 90% of cases of sarcoid, there may not be hilar adenopathy and sometimes the alveolitis needs special imaging(eg high resolution CT) for diagnosis. Diagnosing sarcoid therefore may depend on how hard the pulmonary physician looked. Were there any skin or eye manifestations of sarcoid? As you know sarcoid may involve just about any system. I don`t know the age of your patient, but the GFR of 26 is quite low for any age and makes one wonder what the underlying renal pathology is. Interestingly the 1,25(OH)2D was elevated and the PTH was suppressed (presumably by the hypercalcemia) despite the low GFR. You may wish to consult a nephrologist if the low GFR is reproducible, and the nephrologist may decide a biopsy is warranted which could reveal non-caseating granulomas.

Overall therefore the most likely diagnoses, I would say are 1 Sarcoidosis 2 Lymphoma3 Other granulomatous disease. While she is being worked up you might recommend that she not take supplements that contain vitamin D, and stay out of the sun or use sunscreen. If she does have another episode of hypercalcemia, clearly rehydration and prednisone would be indicated until the underlying disease can be treated. David Goltzman, MD