BRIEF CLINICAL
involvement of the hypothalamus associated with partial hypopituitarism that improved with ganciclovir and high-dose glucocorticoid therapy. A 40-year-old man with a history of intravenous drug abuse and AIDS had a l-week history of progressive confusion and generalized weakness. His only medications were zidovudine and monthly aerosolized pentamidine. On physical examination, he was a lethargic thin man in no acute distress. His temperature was 38°C rectally with a pulse of loo/minute and blood pressure of 118/90 mm Hg. Examination was remarkable for right parotid swelling, oral thrush, and mild confusion. There were no focal neurologic findings. Laboratory studies revealed a hematocrit of 0.45, white blood cell count of 6.5 X log/L, and platelet count of 160 X log/L. Endocrine testing revealed a serum thyroxine level of 94 nmol/L (normal: 64 to 136 Submitted February 26, 1991, and accepted in nmol/L), thyroid-binding capacirevised form May 21, 1991 ty 521 nmol/L (normal: 270 to 399 ACKNOWLEDGMENT: We thank Ms. Gloria Chan nmol/L), estimated free thyroxand Mr. Lau Kam Shing for performing the endocrine tests and Ms. Venus Yuen for secretarial assisine level 10.3 pmol/L (normal: tance. Reagents for the radioimmunoassay of pitu12.8 to 28.3 pmol/L), and thyitary hormones and steroids were provided by the roid-stimulating hormone level National Institute of Arthritis, Diabetes and Diges0.60 mU/L (normal: 0.10 to 7.0 tive and Kidney Diseases and the World Health Organization Matched Assay Reagents Program. mu/L). Serum free testosterone level was 0.7 nmol/L (normal: 6.9 to 27.7 nmol/L) with serum luteinizing hormone level of 0.8 HYPOPITUITARISM IU/mL (normal: 1.5 to 9.2 ASSOCIATEDWITH A IU/mL) and follicle-stimulating HYPOTHALAMICCMV hormone level of 2.0 IU/mL (norINFECTION IN A PATIENT mal: 1 to 14 IU/mL). An AM cortiWITH AIDS sol level was 579 nmol/L (normal: 193 to 690 nmol/L). Prolactin levCentral nervous system (CNS) el was 50 pg/L (normal: 0 to 20 infection with cytomegalovirus pg/L). A thyrotropin-releasing (CMV) is a common cause of hormone stimulation test remorbidity and mortality in pa- vealed a basal thyroid-stimulattients with the acquired immunoing hormone level of 0.72 mu/L, deficiency syndrome (AIDS) [ 11. with a stimulated value (at 30 Although CMV affects many re- minutes) of 4.61 mu/L. A comgions of the brain, involvement of puted tomographic scan of the the hypothalamic-pituitary axis head with contrast was within has rarely been described [1,2]. normal limits. Lumbar puncture We report here a case of CMV revealed an opening pressure of
tuitarism. N Engl J Med 1965; 272: 771-6. 4. Lam KSL, Wang C, Yeung RTT, eta/. Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma. Clin Endocrinol 1986; 24: 643-51. 5. Oelkers W. Hyponatremia and inappropriate secretion of vasopressin (antidiuretic hormone) in patients with hypopituitarism. N Engl J Med 1989: 321: 492-6. 6. Kleeman CR, Czackes JW, Cutler R. Mechanisms of impaired water excretion in adrenal and pituitary insufficiency. IV. Antidiuretic hormone in primary and secondary adrenal insufficiency. J Clin invest 1964; 43: 1641-S. 7. Emmanuel DS. Lindheimer MD, Katz Al. Mechanisms of impaired water excretion in the hypothyroid rat. J Clin Invest 1974; 54: 926-34. 8. Samaan NA, Vieto R, Schultz PN. et al. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck. Int J Radiat Oncol Biol Phys 1982; 8: 1857-67. 9. Lam KSL. Tse VKC. Wang C, Yeung RTT, Ho JHC. Effects of cranlal irradiation on hypothalamic-pituitary function-a 5-year longitudinal study in patients with nasopharyngeal carcinoma. Q J Med 1991; 78: 165-76. 10. Snyder PJ. Fowble BF, Schatz NJ, Sarino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986; 81: 457-62. 11. Littley MD, Shalet SM, Beardwell CG, Ahmed SR. Appelgate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989: 262: 145-60.
February
1992
The American
OBSERVATIONS
250 mm HzO, glucose level of 2.89 mmol/L (normal: 2.8 to 4.4 mmol/L), protein level of 0.42 g/L (normal: less than 0.40 g/L), and cell count of 15 nucleated cells (86% lymphocytes and 14% monocytes). There were no organisms on Gram stain. Cerebrospinal fluid analysis was negative for bacterial culture, acid-fast bacilli (smear and culture), fungus (smear and culture), VDRL, India ink, cryptococcal antigen, bacterial antigen screen, toxoplasmosis antibody, CMV antibody, herpes virus antibody, and cryptococcal antibody. An electroencephalogram revealed moderate generalized slowing consistent with diffuse encephalopathy. During the first week of hospitalization, the patient became increasingly unresponsive and hypothermic (rectal temperature 34.4’C). Administration of intravenous thyroxine (200 pg/day) and hydrocortisone (300 mg/day) was begun for possible myxedema coma. Magnetic resonance imaging (MRI) of the brain with gadolinium revealed increased signal on proton density and T2weighted images in the hypothalamus (Figure 1, top). A stereotactic needle biopsy of the hypothalamic region was performed under general anesthesia. Microscopic examination of the specimen revealed perivascular lymphocytic infiltration and clusters of large cells with basophilic inclusions and giant nuclei consistent with CMV infection. An ophthalmologic consultant found no evidence of CMV retinitis. Goldman visual fields were normal. An acute serum CMV titer was negative, with a convalescent titer (at 4 weeks) positive at 1:16. Intravenous therapy with ganciclovir was initiated at 300 mg twice daily for 2 weeks, then 300 mg daily as a maintenance dose. L-thyroxine was decreased to 100 pg/day orally, after several days Journal
of Medicine
Volume
92
221
BRIEF CLlNlCAL
OBSERVATIONS
Figure 1. Coronal magnetic resonance hypothalamus. Top. Pretreatment study.
images Bottom.
at 200 pglday, and prednisone was gradually tapered to a main222
February
1992
The American
Journal
after gadolinium After 6 weeks
at the level of ganciclovir.
of the
tenance dose of 5 mg in the morning with 2.5 mg in the evening. of Medicine
Volume
92
The patient’s mental status and temperature gradually returned to baseline within 2 weeks. After 5 weeks of ganciclovir therapy, his prolactin level had decreased to 28 pg/L. Subsequent MRI of the brain, after the patient had been receiving ganciclovir for 6 weeks, demonstrated no abnormal enhancement in the hypothalamus (Figure 1, bottom). Although opportunistic CNS infections are common in patients with AIDS, involvement of the hypothalamus has been rarely reported. There has been one case report of toxoplasmosis presenting as panhypopituitarism in a patient with AIDS [3]. In a large autopsy series [2], CMV involvement of the anterior pituitary gland was described in three of 88 patients with AIDS. None of these patients had CMV involvement of the hypothalamus. A previous clinical study [4] has reported abnormal hypothalamicpituitary function in patients with human immunodeficiency virus infection, but results of pituitary imaging studies were normal in those patients. In our patient, ganciclovir therapy, in conjunction with hormonal therapy, resulted in clinical and radiographic improvement. Ganciclovir has previously been shown to have clinical efficacy against CMV retinitis and gastrointestinal CMV infection [5,6]. Although ganciclovir enters the cerebrospinal fluid, it has not been shown to be uniformly effective in CMV encephalitis [5,6]. This case of CMV hypothalamic infection in a patient with AIDS expands the spectrum of CMV infections of the CNS. CMV hypothalamic infection should be considered in patients with AIDS who present with multiple endocrine deficiencies, confusion, and hypothermia. Brain biopsy should be considered if radiographic studies indicate a focal CNS abnormality. Adminis-
BRIEF CLINICAL
tration of ganciclovir and highdose steroids may be useful in the treatment of CMV hypothalamic infection. WILLIAM M. SULLIVAN, M.D. GRANT G. KELLEY, M.D. PATRICK G. O’CONNOR, M.D. PHILIP S. DICKEY, M.D. JUNG H. KIM, M.D. RICHARD ROBBINS, M.D. GERALD I. SHULMAN, M.D., Ph.D.
Yale University School of Medicine New Haven, Connecticut 1. Vinters HV, Kwok MK, Ho HW. eta/. Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 1989; 112: 245-68. 2. Ferreiro J, Vinters HV. Pathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS). Pathology 1988; 20: 211-5. 3. Milligan SA, Katz MS, Craven PC, Strandberg DA, Russell IJ, Becker RA. Toxoplasmosis presenting as panhypopituitarism in a patient with the acquired immune deficiency syndrome. Am J Med 1984; 77: 760-4. 4. Dobs AS, Dempsey MA, Ladenson PW, et al. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988; 84: 61 l-6. 5. Jacobson MA, Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome. Ann Intern Med 1988; 108: 585-94. 6. Laskin OL, Stahl-Bayliss CM, Kalman CM, Rosecan LR. Use of ganciclovir to treat serious cytomegalovirus infections in patients with AIDS. J Infect Dis 1987; 155: 323-7. Submitted
October
4, 1990, and accepted in revised form June 7, 1991
IMMOBILIZATION-INDUCED HYPERCALCEMIAIN A RENAL TRANSPLANT RECIPIENTWITH PERSISTENT HYPERPARATHYROIDISM We report a case of symptomatic hypercalcemia following traumarelated immobilization in a renal transplant recipient with documented persistent hyperparathyroidism due to parathyroid hyperplasia. After failure of a variety of conservative therapies, parathyroidectomy effectively established normocalcemia despite continued immobilization. This case represents a special form of immobilization-induced hypercalcemia in the presence of an increased parathyroid mass. In distinction to other forms of
immobilization-induced hypercalcemia, parathyroidectomy is a rational and effective treatment in the context of parathyroid hyperplasia and immobilization. A 32-year-old man was admitted to the hospital after a highspeed motor vehicle accident. His multiple injuries included spinal fractures, which resulted in a spastic paraparesis. Four years prior to the accident, the patient had received a cadaveric renal transplant for end-stage renal disease secondary to Alport’s syndrome. Before the transplantation, he had been undergoing hemodialysis for only 1 month followed by 5 months of longterm ambulatory peritoneal dialysis. The function of the renal allograft was excellent (creatinine clearance 115 ml/minute, serum creatinine concentration 0.9 mg/dL). Long-term maintenance therapy consisted of prednisolone (15 mg every day) and azathioprine (100 mg every day). The only other medication was propranolol (80 mg twice a day) for mild hypertension. Since the transplantation, the patient had been followed in the mineral metabolism clinic for persistent secondary hyperparathyroidism. Two months before the accident, a serum parathyroid hormone (PTH) concentration of 133 pg/mL (immunoradiometric [IRMA] assay, normal 10 to 65 pg/mL) and a 1,25-dihydroxyvitamin D concentration of 54 pg/mL (normal 20 to 50 pg/ mL) were measured, with a serum calcium concentration of 10.8 mg/dL (total) and a urinary calcium excretion of 295 mg/24 hours. The patient had no symptoms of hypercalcemia, the serum phosphorus concentration was in the normal range, and his radial bone density as measured by photon absorptiometry had remained stable since the transplantation, albeit at the lower range of normal. February
1992
The American
OBSERVATIONS
During immobilization after the accident, the patient developed severe hypercalcemia with predominantly gastrointestinal symptoms. Despite vigorous oral and intravenous hydration, the serum calcium concentration rose to 13.6 mg/dL (serum albumin concentration 3.1 g/dL). The serum concentration of phosphorus was 3.4 mg/dL. Figure 1 shows the total serum calcium concentration during the hospital course and the various therapeutic measures that were employed: in addition to hydration therapy, the patient was treated with salmon calcitonin (4 and 8 IJ, respectively/kg subcutaneously twice a day), cautious oral phosphorus supplementation (with close monitoring of the calcium/ phosphorus product in the serum to minimize the risk of metastatic calcification), and four intravenous doses of mithramycin. The patient did not develop metastatic calcifications or frank renal failure, but the creatinine clearance decreased to 80 ml/minute. The urinary excretion of calcium was 705 mg/24 hours. During the severe hypercalcemia, the serum concentration of PTH was 90 pg/mL (IRMA assay, normal 10 to 65 pg/mL) with a 1,25-dihydroxyvitamin D concentration of 39 pg/mL (normal 20 to 50 pg/ mL). An extensive search for an occult tumor remained negative. After conservative management failed, the patient was referred for parathyroidectomy as soon as the neurologic risk of neck exploration after his spinal injury was considered acceptable. At surgery, four hyperplastic parathyroid glands were identified and 3.5 g of hyperplastic tissue was removed, leaving about 30 mg of one gland intact. After a short period of postoperative hypocalcemia, the patient has remained normocalcemic with a serum calcium concentration of 9.5 mg/dL, phosphorus concentraJournal
of Medicine
Volume
92
223
involvement of the hypothalamus associated with partial hypopituitarism that improved with ganciclovir and high-dose glucocorticoid therapy. A 40-year-old man with a history of intravenous drug abuse and AIDS had a l-week history of progressive confusion and generalized weakness. His only medications were zidovudine and monthly aerosolized pentamidine. On physical examination, he was a lethargic thin man in no acute distress. His temperature was 38°C rectally with a pulse of loo/minute and blood pressure of 118/90 mm Hg. Examination was remarkable for right parotid swelling, oral thrush, and mild confusion. There were no focal neurologic findings. Laboratory studies revealed a hematocrit of 0.45, white blood cell count of 6.5 X log/L, and platelet count of 160 X log/L. Endocrine testing revealed a serum thyroxine level of 94 nmol/L (normal: 64 to 136 Submitted February 26, 1991, and accepted in nmol/L), thyroid-binding capacirevised form May 21, 1991 ty 521 nmol/L (normal: 270 to 399 ACKNOWLEDGMENT: We thank Ms. Gloria Chan nmol/L), estimated free thyroxand Mr. Lau Kam Shing for performing the endocrine tests and Ms. Venus Yuen for secretarial assisine level 10.3 pmol/L (normal: tance. Reagents for the radioimmunoassay of pitu12.8 to 28.3 pmol/L), and thyitary hormones and steroids were provided by the roid-stimulating hormone level National Institute of Arthritis, Diabetes and Diges0.60 mU/L (normal: 0.10 to 7.0 tive and Kidney Diseases and the World Health Organization Matched Assay Reagents Program. mu/L). Serum free testosterone level was 0.7 nmol/L (normal: 6.9 to 27.7 nmol/L) with serum luteinizing hormone level of 0.8 HYPOPITUITARISM IU/mL (normal: 1.5 to 9.2 ASSOCIATEDWITH A IU/mL) and follicle-stimulating HYPOTHALAMICCMV hormone level of 2.0 IU/mL (norINFECTION IN A PATIENT mal: 1 to 14 IU/mL). An AM cortiWITH AIDS sol level was 579 nmol/L (normal: 193 to 690 nmol/L). Prolactin levCentral nervous system (CNS) el was 50 pg/L (normal: 0 to 20 infection with cytomegalovirus pg/L). A thyrotropin-releasing (CMV) is a common cause of hormone stimulation test remorbidity and mortality in pa- vealed a basal thyroid-stimulattients with the acquired immunoing hormone level of 0.72 mu/L, deficiency syndrome (AIDS) [ 11. with a stimulated value (at 30 Although CMV affects many re- minutes) of 4.61 mu/L. A comgions of the brain, involvement of puted tomographic scan of the the hypothalamic-pituitary axis head with contrast was within has rarely been described [1,2]. normal limits. Lumbar puncture We report here a case of CMV revealed an opening pressure of
tuitarism. N Engl J Med 1965; 272: 771-6. 4. Lam KSL, Wang C, Yeung RTT, eta/. Hypothalamic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma. Clin Endocrinol 1986; 24: 643-51. 5. Oelkers W. Hyponatremia and inappropriate secretion of vasopressin (antidiuretic hormone) in patients with hypopituitarism. N Engl J Med 1989: 321: 492-6. 6. Kleeman CR, Czackes JW, Cutler R. Mechanisms of impaired water excretion in adrenal and pituitary insufficiency. IV. Antidiuretic hormone in primary and secondary adrenal insufficiency. J Clin invest 1964; 43: 1641-S. 7. Emmanuel DS. Lindheimer MD, Katz Al. Mechanisms of impaired water excretion in the hypothyroid rat. J Clin Invest 1974; 54: 926-34. 8. Samaan NA, Vieto R, Schultz PN. et al. Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck. Int J Radiat Oncol Biol Phys 1982; 8: 1857-67. 9. Lam KSL. Tse VKC. Wang C, Yeung RTT, Ho JHC. Effects of cranlal irradiation on hypothalamic-pituitary function-a 5-year longitudinal study in patients with nasopharyngeal carcinoma. Q J Med 1991; 78: 165-76. 10. Snyder PJ. Fowble BF, Schatz NJ, Sarino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986; 81: 457-62. 11. Littley MD, Shalet SM, Beardwell CG, Ahmed SR. Appelgate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 1989: 262: 145-60.
February
1992
The American
OBSERVATIONS
250 mm HzO, glucose level of 2.89 mmol/L (normal: 2.8 to 4.4 mmol/L), protein level of 0.42 g/L (normal: less than 0.40 g/L), and cell count of 15 nucleated cells (86% lymphocytes and 14% monocytes). There were no organisms on Gram stain. Cerebrospinal fluid analysis was negative for bacterial culture, acid-fast bacilli (smear and culture), fungus (smear and culture), VDRL, India ink, cryptococcal antigen, bacterial antigen screen, toxoplasmosis antibody, CMV antibody, herpes virus antibody, and cryptococcal antibody. An electroencephalogram revealed moderate generalized slowing consistent with diffuse encephalopathy. During the first week of hospitalization, the patient became increasingly unresponsive and hypothermic (rectal temperature 34.4’C). Administration of intravenous thyroxine (200 pg/day) and hydrocortisone (300 mg/day) was begun for possible myxedema coma. Magnetic resonance imaging (MRI) of the brain with gadolinium revealed increased signal on proton density and T2weighted images in the hypothalamus (Figure 1, top). A stereotactic needle biopsy of the hypothalamic region was performed under general anesthesia. Microscopic examination of the specimen revealed perivascular lymphocytic infiltration and clusters of large cells with basophilic inclusions and giant nuclei consistent with CMV infection. An ophthalmologic consultant found no evidence of CMV retinitis. Goldman visual fields were normal. An acute serum CMV titer was negative, with a convalescent titer (at 4 weeks) positive at 1:16. Intravenous therapy with ganciclovir was initiated at 300 mg twice daily for 2 weeks, then 300 mg daily as a maintenance dose. L-thyroxine was decreased to 100 pg/day orally, after several days Journal
of Medicine
Volume
92
221
BRIEF CLlNlCAL
OBSERVATIONS
Figure 1. Coronal magnetic resonance hypothalamus. Top. Pretreatment study.
images Bottom.
at 200 pglday, and prednisone was gradually tapered to a main222
February
1992
The American
Journal
after gadolinium After 6 weeks
at the level of ganciclovir.
of the
tenance dose of 5 mg in the morning with 2.5 mg in the evening. of Medicine
Volume
92
The patient’s mental status and temperature gradually returned to baseline within 2 weeks. After 5 weeks of ganciclovir therapy, his prolactin level had decreased to 28 pg/L. Subsequent MRI of the brain, after the patient had been receiving ganciclovir for 6 weeks, demonstrated no abnormal enhancement in the hypothalamus (Figure 1, bottom). Although opportunistic CNS infections are common in patients with AIDS, involvement of the hypothalamus has been rarely reported. There has been one case report of toxoplasmosis presenting as panhypopituitarism in a patient with AIDS [3]. In a large autopsy series [2], CMV involvement of the anterior pituitary gland was described in three of 88 patients with AIDS. None of these patients had CMV involvement of the hypothalamus. A previous clinical study [4] has reported abnormal hypothalamicpituitary function in patients with human immunodeficiency virus infection, but results of pituitary imaging studies were normal in those patients. In our patient, ganciclovir therapy, in conjunction with hormonal therapy, resulted in clinical and radiographic improvement. Ganciclovir has previously been shown to have clinical efficacy against CMV retinitis and gastrointestinal CMV infection [5,6]. Although ganciclovir enters the cerebrospinal fluid, it has not been shown to be uniformly effective in CMV encephalitis [5,6]. This case of CMV hypothalamic infection in a patient with AIDS expands the spectrum of CMV infections of the CNS. CMV hypothalamic infection should be considered in patients with AIDS who present with multiple endocrine deficiencies, confusion, and hypothermia. Brain biopsy should be considered if radiographic studies indicate a focal CNS abnormality. Adminis-
BRIEF CLINICAL
tration of ganciclovir and highdose steroids may be useful in the treatment of CMV hypothalamic infection. WILLIAM M. SULLIVAN, M.D. GRANT G. KELLEY, M.D. PATRICK G. O’CONNOR, M.D. PHILIP S. DICKEY, M.D. JUNG H. KIM, M.D. RICHARD ROBBINS, M.D. GERALD I. SHULMAN, M.D., Ph.D.
Yale University School of Medicine New Haven, Connecticut 1. Vinters HV, Kwok MK, Ho HW. eta/. Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 1989; 112: 245-68. 2. Ferreiro J, Vinters HV. Pathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS). Pathology 1988; 20: 211-5. 3. Milligan SA, Katz MS, Craven PC, Strandberg DA, Russell IJ, Becker RA. Toxoplasmosis presenting as panhypopituitarism in a patient with the acquired immune deficiency syndrome. Am J Med 1984; 77: 760-4. 4. Dobs AS, Dempsey MA, Ladenson PW, et al. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988; 84: 61 l-6. 5. Jacobson MA, Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome. Ann Intern Med 1988; 108: 585-94. 6. Laskin OL, Stahl-Bayliss CM, Kalman CM, Rosecan LR. Use of ganciclovir to treat serious cytomegalovirus infections in patients with AIDS. J Infect Dis 1987; 155: 323-7. Submitted
October
4, 1990, and accepted in revised form June 7, 1991
IMMOBILIZATION-INDUCED HYPERCALCEMIAIN A RENAL TRANSPLANT RECIPIENTWITH PERSISTENT HYPERPARATHYROIDISM We report a case of symptomatic hypercalcemia following traumarelated immobilization in a renal transplant recipient with documented persistent hyperparathyroidism due to parathyroid hyperplasia. After failure of a variety of conservative therapies, parathyroidectomy effectively established normocalcemia despite continued immobilization. This case represents a special form of immobilization-induced hypercalcemia in the presence of an increased parathyroid mass. In distinction to other forms of
immobilization-induced hypercalcemia, parathyroidectomy is a rational and effective treatment in the context of parathyroid hyperplasia and immobilization. A 32-year-old man was admitted to the hospital after a highspeed motor vehicle accident. His multiple injuries included spinal fractures, which resulted in a spastic paraparesis. Four years prior to the accident, the patient had received a cadaveric renal transplant for end-stage renal disease secondary to Alport’s syndrome. Before the transplantation, he had been undergoing hemodialysis for only 1 month followed by 5 months of longterm ambulatory peritoneal dialysis. The function of the renal allograft was excellent (creatinine clearance 115 ml/minute, serum creatinine concentration 0.9 mg/dL). Long-term maintenance therapy consisted of prednisolone (15 mg every day) and azathioprine (100 mg every day). The only other medication was propranolol (80 mg twice a day) for mild hypertension. Since the transplantation, the patient had been followed in the mineral metabolism clinic for persistent secondary hyperparathyroidism. Two months before the accident, a serum parathyroid hormone (PTH) concentration of 133 pg/mL (immunoradiometric [IRMA] assay, normal 10 to 65 pg/mL) and a 1,25-dihydroxyvitamin D concentration of 54 pg/mL (normal 20 to 50 pg/ mL) were measured, with a serum calcium concentration of 10.8 mg/dL (total) and a urinary calcium excretion of 295 mg/24 hours. The patient had no symptoms of hypercalcemia, the serum phosphorus concentration was in the normal range, and his radial bone density as measured by photon absorptiometry had remained stable since the transplantation, albeit at the lower range of normal. February
1992
The American
OBSERVATIONS
During immobilization after the accident, the patient developed severe hypercalcemia with predominantly gastrointestinal symptoms. Despite vigorous oral and intravenous hydration, the serum calcium concentration rose to 13.6 mg/dL (serum albumin concentration 3.1 g/dL). The serum concentration of phosphorus was 3.4 mg/dL. Figure 1 shows the total serum calcium concentration during the hospital course and the various therapeutic measures that were employed: in addition to hydration therapy, the patient was treated with salmon calcitonin (4 and 8 IJ, respectively/kg subcutaneously twice a day), cautious oral phosphorus supplementation (with close monitoring of the calcium/ phosphorus product in the serum to minimize the risk of metastatic calcification), and four intravenous doses of mithramycin. The patient did not develop metastatic calcifications or frank renal failure, but the creatinine clearance decreased to 80 ml/minute. The urinary excretion of calcium was 705 mg/24 hours. During the severe hypercalcemia, the serum concentration of PTH was 90 pg/mL (IRMA assay, normal 10 to 65 pg/mL) with a 1,25-dihydroxyvitamin D concentration of 39 pg/mL (normal 20 to 50 pg/ mL). An extensive search for an occult tumor remained negative. After conservative management failed, the patient was referred for parathyroidectomy as soon as the neurologic risk of neck exploration after his spinal injury was considered acceptable. At surgery, four hyperplastic parathyroid glands were identified and 3.5 g of hyperplastic tissue was removed, leaving about 30 mg of one gland intact. After a short period of postoperative hypocalcemia, the patient has remained normocalcemic with a serum calcium concentration of 9.5 mg/dL, phosphorus concentraJournal
of Medicine
Volume
92
223
