Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B.

CONTEXT: Pseudohypoparathyroidism type 1B (PHP1B) patients have PTH resistance at the renal proximal tubule and develop hypocalcemia and secondary hyperparathyroidism. Hyperparathyroid bone disease also develops in some patients. PHP1B patients are at theoretical risk of developing tertiary hyperparathyroidism. SETTING: Patients were studied in a clinical research center. PATIENTS: Five female PHP1B patients presented with hypercalcemia and elevated PTH. INTERVENTION: Patients either underwent parathyroidectomy (n = 4) or received cinacalcet (n = 1). MAIN OUTCOME MEASURES: Serum calcium and PTH were serially measured before and after intervention. RESULTS: Five PHP1B patients developed concomitantly elevated serum calcium and PTH levels (range, 235-864 ng/liter) requiring termination of calcium and vitamin D therapy (time after diagnosis, 21-42 yr; median, 34 yr), consistent with tertiary hyperparathyroidism. Four patients underwent parathyroidectomy with removal of one (n = 2) or two (n = 2) enlarged parathyroid glands. Calcium and vitamin D therapy was reinstituted postoperatively, and at 93-month median follow-up, PTH levels ranged between 56 and 182 (normal, <87) ng/liter. One patient was treated with cinacalcet, resulting in resolution of hypercalcemia. CONCLUSIONS: PHP1B patients are at risk of developing tertiary hyperparathyroidism and/or hyperparathyroid bone disease and should therefore be treated with sufficient doses of calcium and vitamin D to achieve serum calcium and PTH levels within or as close to the normal range as possible. Surgery is the treatment of choice in this setting. Cinacalcet may be a useful alternative in those who do not undergo surgery.

Orbital inflammatory disease in a patient treated with zoledronate.

OBJECTIVE: To increase awareness of orbital inflammatory disease as a rare adverse effect of bisphosphonates. METHODS: We present a case report and a review of the relevant literature. RESULTS: A 57-year-old woman with history of esophageal, breast, and lung cancers was diagnosed with postmenopausal osteoporosis. She initially received intravenous ibandronate for a total of 6 infusions. Later, she was changed to zoledronate infusion because of its yearly dosing schedule. Several hours after her initial infusion of zoledronate, she developed a painfully swollen left eye with photophobia. Ophthalmologic exam showed edema of the left upper lid. No exophthalmos was noted. Slit-lamp exam showed conjunctival injection in the left eye with an elevated intraocular pressure. An orbital computed tomographic scan showed inflammation of the left orbital, preseptal, and retroseptal spaces. She was started on 2 methylprednisolone dose packs and the swelling and erythema disappeared completely in 2 weeks. Subsequent orbital magnetic resonance imaging showed no mass within either the left or right orbit, and no abnormal enhancement following contrast administration. CONCLUSION: Physicians should be aware of this rare complication of zoledronate. It should be used with caution in patients with a history of inflammatory eye disease or mild ocular symptoms following use of a bisphosphonate.

Symptomatic and scintigraphic improvement after intravenous pamidronate treatment of Paget's disease of bone in patients with normal serum alkaline phosphatase levels.

OBJECTIVE: To describe three patients with symptomatic Paget's disease of bone who presented with normal levels of serum alkaline phosphatase. METHODS: We present three cases of Paget's disease of bone and chronicle the laboratory, scintigraphic, and clinical findings relative to treatment with intravenously administered pamidronate. RESULTS: Although measurement of serum total alkaline phosphatase usually provides a general indication of bone turnover in Paget's disease, about 15% of patients present with normal serum alkaline phosphatase levels. Nonetheless, these patients may have active Paget's disease when assessed with bone scintigraphy or urinary markers of bone resorption. All three study patients had xray findings characteristic of Paget's disease of bone, increased uptake of radiotracer material on bone scans, and elevated levels of urinary markers of bone resorption but normal alkaline phosphatase levels. They were treated with intravenously administered pamidronate, 60 mg once weekly for 2 to 3 consecutive weeks. After treatment, the serum alkaline phosphatase level decreased by 19 to 36%, markers of bone resorption normalized, bone scans showed improvement, and bone pain resolved. CONCLUSION: Pagetic activity in bone and related clinical manifestations may be present in the setting of a normal serum alkaline phosphatase level. Appropriate therapy should not be withheld because of the normal alkaline phosphatase.

Central diabetes insipidus due to cytomegalovirus infection of the hypothalamus in a patient with acquired immunodeficiency syndrome: a clinical, pathological, and immunohistochemical case study.

We report a case of central diabetes insipidus (CDI) in a patient with AIDS due to cytomegalovirus (CMV) infection of the vasopressin-producing areas of the hypothalamus. The clinical diagnosis is established by definitive clinical and laboratory evidence of CDI. Detailed histopathological and immunohistochemical studies establish CMV as the causative agent and demonstrate the deficit of vasopressin in the synthesizing neurons. Physicians caring for patients with AIDS should be aware of CDI and adipsic hypernatremia as potential complications of CMV infection. The case also demonstrates that patients with diabetes insipidus do not have polyuria when glucocorticoid deficiency coexists.

Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient.

Bone marrow transplantation is now an established successful treatment for several hematologic malignancies. Bone loss is among the long-term adverse effects of this procedure. The underlying pathophysiology is believed to be multifactorial. We report a case of osteoporosis in a young patient who underwent allogenic bone marrow transplantation for acute lymphoblastic leukemia that was complicated by intestinal graft-versus- host disease. Her bone density measurement showed T-scores of -3.46 and -2.47 in the lumbar spine and femoral neck respectively. On evaluation, she had low normal serum calcium, low urine calcium, low 25- hydroxyvitamin D, elevated total and bone specific alkaline phosphatases, and elevated parathyroid hormone. Following treatment with calcifediol, the biochemical markers normalized and the bone mineral density increased by 88% in the lumbar spine and almost 60% in the femoral neck, both of which were above the mean for her age group. We believe that the graft-versus-host disease caused a malabsorptive state that led to vitamin D deficiency and possible resistance and consequent osteomalacia.