986 In the regimen used in our study, systemic testosterone does not cause an inordinate increase in bone age in relation to chronological age, side-effects are rare and minor, and phallic response in growth is consistent. We therefore advocate early administration of low-dose testosterone, intramuscularly for the treatment of the androgen-sensitive microphallus. The young infant with microphallus should receive a therapeutic trial of low-
dose, intramuscular testosterone. Before surgical sex reversal is considered, androgen-sensitivity to penile
growth should be assessed. S. B. was a trainee in paediatric endocrinology under a programme sponsored by the National Institute of Arthritis, Metabolism and Digestive Diseases.
Requests for reprints should be addressed to M. M. G. .
REFERENCES
Micropenis and its management. In: Blandau Rj, Bergsma D, eds Morphogenesis and Malformation of the Genital System, 3rd International Conference on Morphogenesis and Malformation. Lake Wilderness, Washington, 1976, 147-54. 2. Goodman HG, Grumbach MM, Kaplan SL: Growth and growth hormone II. A comparison of isolated growth-hormone deficiency and multiple pituitary hormone deficiencies in 35 patients with idiopathic hypopituitary dwarfism. N Engl J Med 1968; 278: 56-68. 3. Laron Z, Sarel R. Penis and testicular size in patients with growth hormone insufficiency. Acta Endocrinol 1970; 63: 625-33. 4. Laron Z, Kaushanski A, Josefberg Z. Penile size and growth in children and adolescents with isolated gonadotropin deficiency (IGnD). Clin Endocrinol 1977; 6: 265-70. 5. Lovinger RD, Kaplan SL, Grumbach MM. Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: Four cases secondary to hypothalamic hormone deficiencies. J Pediatr 1975; 87:
1. Smith D.
1171-81. 6. Beam JG. Anencephaly and the development of the male genital tract. Acta Pædiatr Acad Sci Hung 1968; 9: 159-80. 7. Tuchmann-Duplessis H: A study of endocrine glands in anencephalus. Biol
Neonat 1959; 1: 8-32. 8. Caldwell P, Smith DW: The XXY (Klinefelter’s) syndrome in childhood: Detection and treatment. J Pediatr 1972; 80: 250-58. 9. Bergada C, Cleveland WW, Jones HW, et al. Variants of embryonic testicular dysgenesis: Bilateral anorchia and the syndrome of rudimentary testes. Acta Endocrinol 1962; 40: 521-36. 10. Najjar SS, Takla RJ, Hussar VH. The syndrome of rudimentary testes: occurrence in five siblings. J Pediatr 1974; 84: 119-22. 11. Grumbach MM, Barr ML. Cytologic tests of chromosomal sex in relation to
sexual anomalies in man. Rec Prog Horm Res 1958; 14: 255-334. genital defects in patterns of malformation. Birth Defects: Orig Art Ser 1978; 14: 57-61. 13. Conte FA, Grumbach, MM. Pathogenesis classification, diagnosis and treatment of anomalies of sex. In: DeGroot L, et al. eds. Endocrinology. New 12. Smith DW. Male
York: Grunes and Stratton 1979:1317-52.
14.
Aarskog D: Maternal progestins J Med 1979; 300: 75-78.
as a
possible cause
of hypospadias. N Engl
15. Jones HW, Park IJ, Rock JA. Technique of surgical sex reassignment for micropenis and allied conditions. Am J Obstet Gynecol 1978; 132: 870-77. 16. Guthrie RD, Smith DW, Graham CB. Testosterone treatment for micropenis during early childhood. J Pediatr 1973; 83: 247-52. 17. Money J, Ogunro C: Behavioral sexology: ten cases of genetic male intersexuality with impaired prenatal and pubertal androgenization. Arch Sexual Behavior 1974; 3: 181-205. 18. Schonfeld WA, Beebe GW. Normal growth and variation in the male genitalia from birth to maturity. Am J Dis Child 1942; 64: 759-77. 19. Gruelich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Stanford: Stanford University Press, 1959. 20. Burr IM, Sizonenko PC, Kaplan SL, et al. Hormonal changes in puberty. I. Correlation of serum luteinizing hormone and follicle-stimulating hormone with stages of puberty, testicular size and bone age in normal boys. Pediatr Res 1970; 4: 25-35. 21. Aubert ML, Grumbach MM, Kaplan SL. Heterologous radioimmunoassay for plasma prolactin (hPRL); values in normal subjects, puberty, pregnancy and in pituitary disorders. Acta Endocrinol 1974; 77: 460-76. 22. Costom BH, Grumbach MM, Kaplan SL. Effect of thyrotropin releasing factor on serum thyroid-stimulating hormone. An approach to distinguishing hypothalamic from pituitary forms of idiopathic hypopituitary dwarfism. J Clin Invest 1971; 50: 2219-25. 23. Murphy BEP. Some studies of the protein-binding of steroids and their application to routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab 1967; 27: 973-90. 24. Pertzelan A, Blum I, Grunebaum M, et al. The combined effect of growth hormone and methandrostenolone on the linear growth of patients with multiple pituitary hormone deficiencies. Clin Endocrinol 1977; 6: 271-76. 25. Crawford BS. Buried penis. Br J Plastic Surg 1977; 30: 96-99.
26. Feldman KW, Smith DW. Fetal phallic growth and penile standards for newborn male infants. J Pediatr 1975; 86: 395-98. 27. Troshev K. Contribution to the anthropometric study of the penis in a group of Bulgarian boys from birth to the age of seven years. Acta Chirgurgiae Plasticæ 1969; 11: 140-48. 28. Flatau E, Josefsburg Z, Reisner SH, et al. Penile size in the newborn infant. J Pediatr 1975; 87: 663-64. 29. Schonfeld WA. Primary and secondary sexual characteristics: study of their development in males from birth through maturity, with biometric study of penis and testes. Am J Dis Child 43; 65: 535-49. 30. Grumbach MM, Kaplan SL. Ontogenesis of growth hormone, insulin prolactin and gonadotropin secretion in the human foetus. In: Fœtal and neonatal physiology. Proceedings of Sir Joseph Barcroft Centenary Symposium. Cambridge University Press: Cambridge 1973: 462-87. 31. Kaplan SL, Grumbach MM. The ontogenesis of human fetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH). Acta
Endocrinologica 1976; 81: 808-29. 32. Cacciari E, Cicognani A, Pirassoli P, et al. Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: effect of GH therapy. Helv Pædiat Acta 1976; 31: 481-85. 33. Amrhein JA, Meyer WJ, III, Danish RK, et al. Studies of androgen production and binding in 13 male pseudohermaphrodites and 13 males with micropenis. J Clin Endocrinol Metab 1977; 45: 732-38. 34. Walsh PC, Wilson JD, Allen TD, et al. Clinical and endocrinological evaluation of patients with congenital microphallus. J Urol 1978; 120: 90-95. 35. Forest MG, Sizonénko PC, et al. Hypophysogonadal function in humans during the first year of life: 1. Evidence for testicular activity in early mfancy. Clin Invest 1974; 53: 819-28. 36. Winter JSD, Hughes IA, Reyes FI, et al. Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from
birth to two years of age. J Endocrinol Metab 1976; 42: 679-86. 37. Forest MG, Cathiard AM. Pattern of plasma testosterone and &Dgr;4-androstenedione in normal newborns: evidence for testicular activity at birth. J Clin
Endocrinol Metab 1975, 41: 977-80. Immergut M, Boldus R, Yannone E, et al. The local application of testosterine cream to the prepubertal phallus. J Urol 1971, 105: 905-06. 39. Jacobs SC, Judd HM, Gittes RF. Penile growth: topical versus systemic testosterone therapy in rats. J Endocrinol 1977; 73: 189-90. 40. Darby CW, Vanderschueren-Lodeweyckx M, Laurance BM. Testosterone cream: use or abuse? Lancet 1974; ii: 598. 41. Jacobs SC, Kaplan GW, Gittes RF. Topical testosteron therapy for penile growth. Urology 1975; 6: 708-10.
38.
INCIDENCE AND SIGNIFICANCE OF ANTIBODIES TO DELTA ANTIGEN IN HEPATITIS B VIRUS INFECTION MARIO RIZZETTO DAVID J. GOCKE GIORGIO VERME
JAMES W.-K. SHIH ROBERT H. PURCELL JOHN L. GERIN
Georgetown University Medical Center, Rockville, Maryland; Rutgers Medical School, Piscataway, New Jersey; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A., and Ospedale S. Giovanni, Torino, Italy A microtitre solid-phase blocking radioimmunoassay (RIA) for antibody to the hepatitis B virus (HBV)-associated &dgr; antigen was specific and detected anti-&dgr; antibody at dilutions of serum of up to 106. Analysis of sera from HBsAg-negative subjects and different categories of HBsAg carriers from different regions confirmed the association of anti-&dgr; antibody with HBV infection. Anti-&dgr; antibody was detected in persistently high titres in 19·1% and 2·6% of sera from patients with chronic hepatitis and symptomatic chronic carriers, respectively, and was not detected in the sera of HBsAg-negative controls. Anti-&dgr; antibody appeared transiently and in low titres (
dose, intramuscular testosterone. Before surgical sex reversal is considered, androgen-sensitivity to penile
growth should be assessed. S. B. was a trainee in paediatric endocrinology under a programme sponsored by the National Institute of Arthritis, Metabolism and Digestive Diseases.
Requests for reprints should be addressed to M. M. G. .
REFERENCES
Micropenis and its management. In: Blandau Rj, Bergsma D, eds Morphogenesis and Malformation of the Genital System, 3rd International Conference on Morphogenesis and Malformation. Lake Wilderness, Washington, 1976, 147-54. 2. Goodman HG, Grumbach MM, Kaplan SL: Growth and growth hormone II. A comparison of isolated growth-hormone deficiency and multiple pituitary hormone deficiencies in 35 patients with idiopathic hypopituitary dwarfism. N Engl J Med 1968; 278: 56-68. 3. Laron Z, Sarel R. Penis and testicular size in patients with growth hormone insufficiency. Acta Endocrinol 1970; 63: 625-33. 4. Laron Z, Kaushanski A, Josefberg Z. Penile size and growth in children and adolescents with isolated gonadotropin deficiency (IGnD). Clin Endocrinol 1977; 6: 265-70. 5. Lovinger RD, Kaplan SL, Grumbach MM. Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: Four cases secondary to hypothalamic hormone deficiencies. J Pediatr 1975; 87:
1. Smith D.
1171-81. 6. Beam JG. Anencephaly and the development of the male genital tract. Acta Pædiatr Acad Sci Hung 1968; 9: 159-80. 7. Tuchmann-Duplessis H: A study of endocrine glands in anencephalus. Biol
Neonat 1959; 1: 8-32. 8. Caldwell P, Smith DW: The XXY (Klinefelter’s) syndrome in childhood: Detection and treatment. J Pediatr 1972; 80: 250-58. 9. Bergada C, Cleveland WW, Jones HW, et al. Variants of embryonic testicular dysgenesis: Bilateral anorchia and the syndrome of rudimentary testes. Acta Endocrinol 1962; 40: 521-36. 10. Najjar SS, Takla RJ, Hussar VH. The syndrome of rudimentary testes: occurrence in five siblings. J Pediatr 1974; 84: 119-22. 11. Grumbach MM, Barr ML. Cytologic tests of chromosomal sex in relation to
sexual anomalies in man. Rec Prog Horm Res 1958; 14: 255-334. genital defects in patterns of malformation. Birth Defects: Orig Art Ser 1978; 14: 57-61. 13. Conte FA, Grumbach, MM. Pathogenesis classification, diagnosis and treatment of anomalies of sex. In: DeGroot L, et al. eds. Endocrinology. New 12. Smith DW. Male
York: Grunes and Stratton 1979:1317-52.
14.
Aarskog D: Maternal progestins J Med 1979; 300: 75-78.
as a
possible cause
of hypospadias. N Engl
15. Jones HW, Park IJ, Rock JA. Technique of surgical sex reassignment for micropenis and allied conditions. Am J Obstet Gynecol 1978; 132: 870-77. 16. Guthrie RD, Smith DW, Graham CB. Testosterone treatment for micropenis during early childhood. J Pediatr 1973; 83: 247-52. 17. Money J, Ogunro C: Behavioral sexology: ten cases of genetic male intersexuality with impaired prenatal and pubertal androgenization. Arch Sexual Behavior 1974; 3: 181-205. 18. Schonfeld WA, Beebe GW. Normal growth and variation in the male genitalia from birth to maturity. Am J Dis Child 1942; 64: 759-77. 19. Gruelich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Stanford: Stanford University Press, 1959. 20. Burr IM, Sizonenko PC, Kaplan SL, et al. Hormonal changes in puberty. I. Correlation of serum luteinizing hormone and follicle-stimulating hormone with stages of puberty, testicular size and bone age in normal boys. Pediatr Res 1970; 4: 25-35. 21. Aubert ML, Grumbach MM, Kaplan SL. Heterologous radioimmunoassay for plasma prolactin (hPRL); values in normal subjects, puberty, pregnancy and in pituitary disorders. Acta Endocrinol 1974; 77: 460-76. 22. Costom BH, Grumbach MM, Kaplan SL. Effect of thyrotropin releasing factor on serum thyroid-stimulating hormone. An approach to distinguishing hypothalamic from pituitary forms of idiopathic hypopituitary dwarfism. J Clin Invest 1971; 50: 2219-25. 23. Murphy BEP. Some studies of the protein-binding of steroids and their application to routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab 1967; 27: 973-90. 24. Pertzelan A, Blum I, Grunebaum M, et al. The combined effect of growth hormone and methandrostenolone on the linear growth of patients with multiple pituitary hormone deficiencies. Clin Endocrinol 1977; 6: 271-76. 25. Crawford BS. Buried penis. Br J Plastic Surg 1977; 30: 96-99.
26. Feldman KW, Smith DW. Fetal phallic growth and penile standards for newborn male infants. J Pediatr 1975; 86: 395-98. 27. Troshev K. Contribution to the anthropometric study of the penis in a group of Bulgarian boys from birth to the age of seven years. Acta Chirgurgiae Plasticæ 1969; 11: 140-48. 28. Flatau E, Josefsburg Z, Reisner SH, et al. Penile size in the newborn infant. J Pediatr 1975; 87: 663-64. 29. Schonfeld WA. Primary and secondary sexual characteristics: study of their development in males from birth through maturity, with biometric study of penis and testes. Am J Dis Child 43; 65: 535-49. 30. Grumbach MM, Kaplan SL. Ontogenesis of growth hormone, insulin prolactin and gonadotropin secretion in the human foetus. In: Fœtal and neonatal physiology. Proceedings of Sir Joseph Barcroft Centenary Symposium. Cambridge University Press: Cambridge 1973: 462-87. 31. Kaplan SL, Grumbach MM. The ontogenesis of human fetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH). Acta
Endocrinologica 1976; 81: 808-29. 32. Cacciari E, Cicognani A, Pirassoli P, et al. Congenital hypopituitarism associated with neonatal hypoglycemia and microphallus: effect of GH therapy. Helv Pædiat Acta 1976; 31: 481-85. 33. Amrhein JA, Meyer WJ, III, Danish RK, et al. Studies of androgen production and binding in 13 male pseudohermaphrodites and 13 males with micropenis. J Clin Endocrinol Metab 1977; 45: 732-38. 34. Walsh PC, Wilson JD, Allen TD, et al. Clinical and endocrinological evaluation of patients with congenital microphallus. J Urol 1978; 120: 90-95. 35. Forest MG, Sizonénko PC, et al. Hypophysogonadal function in humans during the first year of life: 1. Evidence for testicular activity in early mfancy. Clin Invest 1974; 53: 819-28. 36. Winter JSD, Hughes IA, Reyes FI, et al. Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from
birth to two years of age. J Endocrinol Metab 1976; 42: 679-86. 37. Forest MG, Cathiard AM. Pattern of plasma testosterone and &Dgr;4-androstenedione in normal newborns: evidence for testicular activity at birth. J Clin
Endocrinol Metab 1975, 41: 977-80. Immergut M, Boldus R, Yannone E, et al. The local application of testosterine cream to the prepubertal phallus. J Urol 1971, 105: 905-06. 39. Jacobs SC, Judd HM, Gittes RF. Penile growth: topical versus systemic testosterone therapy in rats. J Endocrinol 1977; 73: 189-90. 40. Darby CW, Vanderschueren-Lodeweyckx M, Laurance BM. Testosterone cream: use or abuse? Lancet 1974; ii: 598. 41. Jacobs SC, Kaplan GW, Gittes RF. Topical testosteron therapy for penile growth. Urology 1975; 6: 708-10.
38.
INCIDENCE AND SIGNIFICANCE OF ANTIBODIES TO DELTA ANTIGEN IN HEPATITIS B VIRUS INFECTION MARIO RIZZETTO DAVID J. GOCKE GIORGIO VERME
JAMES W.-K. SHIH ROBERT H. PURCELL JOHN L. GERIN
Georgetown University Medical Center, Rockville, Maryland; Rutgers Medical School, Piscataway, New Jersey; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, U.S.A., and Ospedale S. Giovanni, Torino, Italy A microtitre solid-phase blocking radioimmunoassay (RIA) for antibody to the hepatitis B virus (HBV)-associated &dgr; antigen was specific and detected anti-&dgr; antibody at dilutions of serum of up to 106. Analysis of sera from HBsAg-negative subjects and different categories of HBsAg carriers from different regions confirmed the association of anti-&dgr; antibody with HBV infection. Anti-&dgr; antibody was detected in persistently high titres in 19·1% and 2·6% of sera from patients with chronic hepatitis and symptomatic chronic carriers, respectively, and was not detected in the sera of HBsAg-negative controls. Anti-&dgr; antibody appeared transiently and in low titres (
