A case of Turner syndrome with hyperparathyroidism in an adult.

Abstract

Turner syndrome is a hereditary chromosomal anomaly that affects girls and women. A result of gonadal dysgenesis, its primary characteristics are short stature, osteoporosis, neck webbing, and cardiac defects. Turner syndrome may also involve the auditory system and kidneys. We report the case of a woman with Turner syndrome who presented late in adulthood with severe osteoporosis and hypercalcemia. She was subsequently diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma. After excision of the adenoma, the woman's serum calcium level normalized. To the best of our knowledge, only 4 other cases of Turner syndrome with hyperparathyroidism have been reported in the literature.

Introduction

Turner syndrome is a hereditary chromosomal anomaly that leads to gonadal dysgenesis in females. The normal female chromosomal pattern is 46,XX; Turner syndrome occurs when one X chromosome is partly or completely missing (45,XO). Patients with Turner syndrome have a shorter life expectancy because they have a higher incidence of aortic dissection, hypertension, and other cardiovascular conditions. Of all the medical problems that affect these patients, the most noticeable are abnormalities related to the skeletal system: short stature and osteoporosis. Neck webbing may also be present. Hearing impairment is more common in patients with Turner syndrome. (1)

We report a case of Turner syndrome and coexisting hyperparathyroidism that led to severe bone disease. To the best of our knowledge, only 4 other such cases have been previously reported. (2-5)

Case report

A 50-year-old woman presented to our clinic with complaints of primary amenorrhea, chronic low back pain, and hearing loss. On examination, she was short of stature (height: 135 cm [4 ft, 5 in]), her spine was curved (kyphosis), and she had a short webbed neck. The development of her breasts and pubic hair had not progressed beyond Tanner stage 1 (sexual infantilism).

Otologic evaluation identified tympanosclerosis secondary to recurrent middle ear infections. Audiologic assessment revealed that she had a moderately severe mixed hearing loss bilaterally (figure 1). Findings on examination of the cardiovascular system were normal. An initial clinical diagnosis of Turner syndrome with severe osteoporosis was established. The results of dual-energy x-ray absorptiometry of the lumbar spine (table 1) and a karyotype report of 45,XO confirmed the diagnosis.

Laboratory testing revealed elevated levels of serum calcium and parathyroid hormone, which led to a diagnosis of hyperparathyroidism. Results also showed that the patient's follicle-stimulating hormone, luteinizing hormone, and alkaline phosphatase levels were elevated, and the serum total protein, albumin, and creatinine levels were normal (table 2). Technetium Tc 99m sestamibi scintigraphy confirmed the presence of an adenoma of the left inferior parathyroid gland (figure 2).

[FIGURE 1 OMITTED]

Treatment was initiated with hydration and bisphosphonates for correction of the hypercalcemia. Subsequently, the patient underwent cervical exploration and excision of the left inferior parathyroid gland. Histopathologic examination revealed that parts of the tumor contained a lobulated architecture composed of sheets, cords, and follicles of chief cells, oxyphil cells, and clear cells; these findings were consistent with an adenoma. After surgery, the patient's serum calcium level normalized.

Discussion

Turner syndrome in adults poses a number of various risks, so a multidisciplinary approach to treatment is essential? In our patient, the diagnosis was delayed because she had not ever sought medical evaluation for her short stature, amenorrhea, or recurrent ear infections. The workup revealed hyperparathyroidism secondary to a parathyroid adenoma.

To the best of our knowledge, only 4 cases of simultaneous Turner syndrome and hyperparathyroidism have been reported in the literature. (2-5) Chen et al reported a case of Turner syndrome coexisting with thyrotoxicosis and parathyroid adenocarcinoma that resulted in hyperparathyroidism. (2) The other 3 cases included a patient with nephrolithiasis, (3) a patient with necrotizing pancreatitis, (4) and a patient with celiac disease. (5)

Both sensorineural and conductive hearing loss appear to be very severe in patients who lack a short arm of the X chromosome. (1) Deafness can be profound, and it can occur before the patient realizes that gradual hearing loss has taken place. Therefore, a routine audiologic evaluation should be performed in all patients with Turner syndrome. Preliminary data from a U.K. study of the audiologic features of 113 females (age: [greater than or equal to] 16 yr) with Turner syndrome indicate that 17% of them had normal hearing, 19% had a conductive or mixed hearing loss, and 47% had a sensorineural hearing loss (the authors did not account for the other 17% of patients). (7)

Osteoporosis is also common in Turner syndrome. (8) It is caused by the lack of estrogen, and it can be attenuated to some degree in younger women by estrogen replacement therapy. For women who present later in adulthood, as our patient did, the mainstays of treatment are bisphosphonates and calcium supplements. Any patient whose serum calcium level is elevated should undergo measurement of the serum parathyroid hormone level and parathyroid scintigraphy to rule out primary hyperparathyroidism.

With respect to the cardiovascular complications, patients with Turner syndrome may have a bicuspid rather than tricuspid aortic valve, which places them at increased risk of infective endocarditis. It is therefore important to identify those women who do have a bicuspid valve and start them on prophylactic antibiotics prior to any surgical procedure. Other cardiovascular manifestations of Turner syndrome include coarctation of the aorta (which causes hypertension) and aortic root dilation. (9) Both of these conditions can lead to dissection of the aorta, a potentially lethal complication that requires urgent surgical repair. Therefore, aggressive management of hypertension is essential in these patients.

Other medical problems experienced by these patients include primary hypothyroidism secondary to Hashimoto thyroiditis, renal disorders, and infertility, which require evaluation and periodic monitoring while patients are receiving therapy. (1)

[FIGURE 2 OMITTED]

References

(1.) Elsheikh M, Dunger DB, Conway GS, Wass JA. Turner's syndrome in adulthood. Endocr Rev 2002;23(1): 120-40.

(2.) Chen JF, Chen JY, Huang HS. Primary hyperparathyroidism with parathyroid adenocarcinoma in a patient with Turner's syndrome complicated with thyrotoxicosis [in Chinese]. Changgeng Yi Xue Za Zhi 1993;16(2):133-9.

(3.) Francois I, Proesmans W, de Zegher E Case of the month: A girl with Ullrich-Turner syndrome, nephrolithiasis and hypercalcemia. Eur J Pediatr 1996;155(7):615-16.

(4.) Kishida M, Otsuka F, Mimura Y, et al. A lethal complication, acute necrotizing pancreatitis, of Turner's Syndrome with primary hyperparathyroidism. Endocr J 2003;50(6):835-6.

(5.) Sleiman I, Godi D, Villanacci V, et al. Osteitis fibrosa cystica, coeliac disease and Turner syndrome. A case report. Dig Liver Dis 2004;36(7):486-8.

(6.) Ostberg JE, Conway GS. Adulthood in women with Turner syndrome. Horm Res 2003;59(5):211-21.

(7.) Beckman A, Conway GS, Cadge B. Audiological features of Turner's syndrome in adults. Int J Audiol 2004;43(9):533-44.

(8.) Bakalov VK, Axelrod L, Baron J, et al. Selective reduction in cortical bone mineral density in Turner syndrome independent of ovarian hormone deficiency. J Clin Endocrinol Metab 2003;88(12): 5717-22.

(9.) Sybert VP, McCauley E. Turner's syndrome. N Engl J Med 2004; 351(12):1227-38.

Thomas V. Paul, MD; James Dinakar, MBBS; Nihal Thomas, MD, FRACP; Suma Susan Mathews, MS; Nylla Shanthly, MBBS, DRM; Aravindan Nair, MS

From the Department of Endocrinology (Dr. Paul, Dr. Dinakar, and Dr. Thomas), the Department of Otolaryngology (Dr. Mathews), the Department of Nuclear Medicine (Dr. Shanthly), and the Department of Surgery (Dr. Nair), Christian Medical College, Vellore, India.

Reprint requests: Nihal Thomas, MD, Department of Endocrinology, Christian Medical College, Vellore 632 004, India. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

Table 1. Results of dual-energy x-ray absorptiometry

             BM D *
Region   (g/[cm.sup.2])   T score

L1           0.286         -5.8
L2           0.335         -6.3
L3           0.348         -6.7
L4           0.371         -6.8

Total        0.338         -6.4

* BMD = bone mineral density.

Table 2. Results of blood testing

Analyte                            Level      Range of normal

Above normal
  Calcium                        10.8 mg/dl     8.3 to 10.4
  Parathyroid hormone            418 pg/ml        8 to 74
  Follicle-stimulating hormone   105 mU/ml      2.8 to 11.3
  Luteinizing hormone            23.1 mU/ml     1.1 to 11.6
  Alkaline phosphatase            238 U/L        40 to 125

Normal
  Total protein                   6.8 g/dl       6 to 8.5
  Albumin                         3.8 g/dl      3.5 to 5.0
  Creatinine                     0.5 mg/dl      0.5 to 1.4