46,XX mosaicism demonstrated only in a streak gonad

46,XX mosaicism demonstrated only in a streak gonad

604 Brief clinical and laboratory observations Gonadal dysgenesis with 45,XO/46,XX mosaicism demonstrated only in a streak gonad David E. Goidstein,...

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604

Brief clinical and laboratory observations

Gonadal dysgenesis with 45,XO/46,XX mosaicism demonstrated only in a streak gonad David E. Goidstein, M.D.,* Thaddeus E. Kelly, M.D., Ph.D.,

The Journal of Pediatrics April 1977

Table I. Chromosomal analyses Chronologic age (yr)

Peripheral leukocytes

16-6/12

46,XX (50 cells) 46,XX (50 cells)

16-11/12 17-6/12 17-7/12

Ann J. Johanson, M.D., and Robert M. Blizzard, M.D., Charlottesville, Va.

GONADAL DYSGENESIS is a disorder characterized by a triad of sexual infantilism secondary to failure of ovarian development, short stature, and unusual somatic abnormalities. 1 Patients with all three features are said to have the Turner syndrome, 2 in which monosomy for the X chromosome was demonstrated in 1959. :~ Since then, the spectrum of clinical and chromosomal findings in gonadal dysgenesis has been greatly expanded with the description of sex chromosomal mosaicism and structural abnormalities? In this report, we describe a patient with features of gonadal dysgenesis in whom multiple cultures of peripheral leukocytes and skin fibroblasts showed 46,XX but with sex chromosomal mosaicism of 45,XO/46,XX in an ovarian streak.

CASE REPORT The patient was referred to the UVAH Pediatric Endocrine Clinic at 16 1/2 years for evaluation of short stature and sexual infantilism. She was the first child of a 22-year-old father and 17year-old mother. There is no family history of infertility, and no adult family members are under 155 cm in height. The patient's early growth and development were normal. Physical examination at chronologic age 16 1/2 years revealed height 145.4 cm, weight 50 kg, blood pressure 100/70 mm Hg, mild obesity with broad shieldlike chest, multiple pigmented nevi, low posterior scalp hairline, cubitus valgus, hyperconvex nails, and sexual immaturity with a small uterus palpable on rectal examination. Laboratory data included a hand-wrist bone age 11 1/2 years, serum concentrations of follicle-stimulating hormone 75 mlU/ ml, luteinizing hormone 30 mlU/ml, thyroxine 11.4 /~g/dl,

From the Department of Pediatrics, University of Virginia School of Medicine. Supported in part by a grant from the National Foundation-The March of Dimes and grants HD 08926 and RR 847. *Reprint address: Universityof Virginia Medical Center, Department of Pediatrics. Charlottesville, VA 22901.

46,XX (50 cells)

Skin fibroblasts

46,XX (50 cells) 46,XX (50 cells)

Ovarian streak OR)

45,XO (15 cells) 46,XX (35 cells)

Peripheral leukocyte cultures on three occasions and fibroblast cultures from two separate skin biopsiesrevealed 46,XXkaryotype. Culture of the right ovarian streak revealed 45,XO/46,XX mosaicism;25% of the cells were 45,XO. At least 50 cells were analyzed for each karyotypicanalysis. Differentialbanding procedures were not performed thyroid-stimulating hormone 5.6 t~U/ml, postexercise growth hormone level of 9 ng/ml, normal skull roentgenogram, and intravenous pyelogram. Culture of peripheral leukocytes revealed 46,XX karyotype. Course. Based on the patient's physical features and the elevated levels of serum gonadotropins, she was believed to have gonadal dysgenesis; treatment with oxandrolone 5 mg daily was begun to promote linear growth. At age 17 1/2 years diagnostic laparoscopy revealed bilateral streak gonads. Biopsy and microscopic examination of the right ovarian streak demonstrated no ovarian follicles. The patient grew 5.1 cm during 13 months of oxandrolone therapy, and, following the laparoscopy, thereapy was started with estrogen and progesterone. Cytogenetic studies. The results of chromosomal analyses are shown in Table I. DISCUSSION Gonadal dysgenesis has been described in phenotypic females with various numerical or structural sex chromosomal abnormalities? Mosaicism has been a frequent finding. Theoretically, examination of many tissues would be required to exclude mosaicism. Only infrequently, however, have peripheral leukocyte chromosomes been normal when abnormalities were demonstrated in other tissues such as skin fibroblasts? In few patients have gonadal tissues been analyzed and in none have discrepancies between blood and streak fibroblast karyotypes been reported. ~ ; A few patients with 46,XX karyotype and features of the Turner syndrome have been described,--' In these patients, routine chromosomal analyses of multiple tissues, including the streak gonads, have not been performed. The patient reported here has gonadal dysgenesis. She did not demonstrate striking short stature and marked somatic abnormalities, but this is not u n c o m m o n in patients with sex chromosomal mosaicism. We suggest

Volume 90 Number 4

Brief clinical and laboratory observations

that in some patients sex chromosomal abnormalities may be demonstrated only by chromosomal study of gonadal streaks.

REFERENCES 1. Grumbach MM, and Van Wyk JJ: Disorders of sex differentiation, in Williams RH, editor: Textbook of endocrinology, ed 5, Philadelphia, 1974, WB Saunders Company, pp 423-501. 2. Turner HH: A syndrome of infantilism, congenital webbed neck and cubitus valgus, Endocrinology 23:566, 1938. 3. Ford CE, Jones KW, Polani PE, et al: A sex chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome), Lancet 1:711, 1959.

Hypernatremia associated with pineal tumor Farahnak Khomami-Asadi, M.D.,

605

4. Simpson JL: Gonadal dysgenesis and abnormalities of the human sex chromosomes: Current status of phenotypickaryotype correlations, Birth Defects 11:23, 1975. 5. Simpson JL, Christakos AC, Horwith M, et al: Gonadal dysgenesis in individuals with apparently normal chromosomal complements: Tabulation of cases and compilation of genetic data, Birth Defects 7:215, 1971. 6. Schlegel R J. Neu RL, Le~io JL, et al: XX sex chromosomes in cells cultured from "streak gonads" and in peripheral leukocytes, J Clin Endocrinol 27:1588, 1967. 7. Landau B, Ber D, Eckerling B, et al: Rare gonadal dysgenesis with an XX chromosomal pattern in streak gonads, Ann Intern Med 70:421, 1969.

Serum electrolytes (mEq/1) were as follows: Na 9 160; K 9 3.6; CI- 110; HCO3- 25. BUN was 19 mg/dl; serum calcium 10.6 mg/ dl; serum phosphorus 4.1 mg/dl; serum glucose 83 mg/dl; serum osmolality 339 mOsm/kg/H20; urine osmolality 240 mOsm/kg/ H~O; creatinine clearance 98 ml/min/1.73 M-'. Fluid intake in the hospital was 2.0 to 2.5 l/day with a urine output of 1.0-1.5 1/day. Sustained but fluctuating hypernatremia was noted (Na + 155-170 mEq/l) on a 2 gm/day sodium intake.

Michael E. Norman, M.D.,* John S. Parks, M.D., Ph.D., and M. William Schwartz, M.D., Philadelphia, Pa. DESTRUCTIVE LESIONS of the hypothalamic-hypophyseal area may lead to central diabetes insipidus with hypernatremia.":' Primary and persistent hypernatremia as an initial manifestation of intracranial lesions, not associated with dehydration but secondary to impaired osmoregulation o f A D H secretion, has been infrequently r e p o r t e d / a n d rarely in the pediatric literature.:' A 13-year-old boy with a pineal tumor developed persistent hypernatremia before evidence of neurologic disturbance, leading to subsequent neurologic evaluation and the correct diagnosis. C A S E REPORT The patient was admitted with a one-year history of anorexia, weight loss, nocturia, and poor school performance. There was no history of polydipsia. Blood pressure was 100/55, pulse rate 75/ minute, temperature 37~ height 145 cm (10%), and weight 28.6 kg (<3%). There was no dehydration, and results of neurologic and funduscopic examinations were normal. Secondary sexual development was absent. From the Department of Pediatrics, University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia. Supported in part by Clinical Research Grant RR00240. *Reprint address: The Children's Hospital of Philadelphia 34th St. and Civic Center Bird, Philadelphia, Pa. 19104.

Abbreviations used ADH: antidiuretic hormone BUN: blood urea nitrogen

The initial diagnosis of diabetes insipidus seemed unlikely because of the absence of dehydration, increased thirst, or azotemia. The following physiologic studies were performed: Water deprivation resulted in a 5% weight loss over 16 hours, urine volume diminished from 60 ml/hr to 20 ml/hr, urine osmolality rose from 180 to d94 mOsm/kg/H20 , and plasma osmolality rose from 320 to 330 mOsm/kg/H~O. Intramuscular aqueous pitressin increased urine osmolality to 618 mOsm/kg/ H~O after one hour. These results were compatible with partial central diabetes insipidus" and impaired thirst mechanisms. Since defective osmoregulation of ADH release could result in hypernatremia, the interaction between volume regulation and osmoregulation of ADH release was further evaluated by measuring the renal response to volume expansion with water and saline. Twenty milliliters per kilogram of water was given orally over 30 minutes followed by an intravenous infusion of 5% dextrose in water at a rate of 0.3 ml/kg/min, until steady-state conditions were achieved for three consecutive hourly periods. Weight increased by 5%, serum osmolality fell to 320 mOsm/kg/ H~O, but serum sodium was unchanged (150 mEq/l). Urine volume rose from 75 to 150 ml/hr while urine osmolality fell from 400 to 178 mOsm/kg/H~O. Free-water clearance rose from --0.1 to + 1.05 ml/minute. Intravenous 3% saline (0.2 ml/kg/ min) did not change urine flow rate, but urine osmolality fell to 67 mOsm/kg/H20 and free-water clearance rose to +2.0 ml/ minute, despite increased serum sodium (162 mEq/1) and osmolality (337 mOsm/kg/H~.O).