1361 adrenal
androgen production and, perhaps spontaneous onset of puberty.
no
as a
University Department of Medicine, Royal Infirmary, Glasgow G4 0SF
result,
no
IAN D. HAY
TREATMENT OF CRYPTORCHIDISM BY SYNTHETIC LUTEINISING-HORMONE-RELEASING HORMONE
SIR,-We were interested in the article by Dr Illig and colleagues (Sept. 10, p. 518) and in the letter by Dr Hadziselimovic and co-workers (Nov. 26, p.1125) since we have been using synthetic lutenising-hormone-releasing hormone (L.H.R.H.) in cryptorchidism. 4 boys aged 7i-152 years were given L.H.R.H. subcutaneously; 3 received 500 fLg every 8 h for 3 days and 1 received 100 g every 8 h for 3 days. In 2 boys, 1 aged 15 a with
’
unilateral cryptorchidism and a very retractile testis on 500 g L.H.R.H. and 1 boy aged 7t on 100 pg L.H.R.H. who had one inpalpable testis and one highly retractile testis, there was testicular descent within 3 days of the initiation of therapy and cessation of retractility. Both children had an impaired gonadotrophin response to a standard 100 fLg L.H.R.H. test with no change in L.H. levels and a blunted follicle-stimulating hormone (F.S.H.) response. The 2 other boys, 1 aged 10 years with small inguinal testes and the other aged 13tyears with one impalpable and one retractile testis, showed no improvement after L.H.R.H. Both had a normal gonadotrophin response to 100 g of L.H.R.H., but no testosterone response to stimulation with human chorionic gonadotrophin (H.C.G.). The speed of response in the first 2 boys supports the suggestion that gonadotrophins themselves are responsible for testicular descent, though perhaps only if a testis is potentially fully functional. The descent is unlikely to be due to any systemic rise in androgen production directly relating to the gonadotrophin therapy as gonadotrophins may cause testicular descent in unilateral cryptorchidism where androgen levels are comparatively normal.’ H.C.G. has been the gonadotrophin of choice in the management of crytorchidism but there had been no general agreement about the age at which it should be given. Scorer2 noted in a large prospective series that 3.4% of testes were undescended at birth; half of these were descended at the end of the first month and at the end of the first year only 0.7% were undescended, a figure that remained virtually unchanged into adult life. Ehrlich et al.,3 reviewing management with H.C.G. therapy in 350 undescended testes, found the best response (38% success-rate) in the 2-5-year age-group compared with an overall response of 23% and only 14% in boys aged 6-13. In unilateral cryptorchidism there is evidence that the normal testis undergoes compensatory hypertrophy and normal development through puberty. There is also evidence of testosterone responsiveness to x.c.G.4 but in cases of bilateral cryptorchidism both the baseline testosterone and the response to H.C.G. stimulation are overall significantly lower than normal.l.5.6 This suggests that cryptorchidism itself leads to testicular dysfunction regardless of hypothalamic-pituitarygonadal axis status,7 although histological findings in such cases may be normal. In view of the above findings we suggest that a definite decision on the management of cryptorchidism should be made at the time the condition is first noted, even as early as 12 months of age. Therapy could begin at 12 months as the likelihood of success is probably greatest at this time. Patients who do not respond may have either primary testicular disease or ’
1. Walsh, P. C., and others. J, clin. Endocr. Metab. 1976, 42, 52. 2. Scorer, C. G. Lancet, 1957, ii, 1123. 3. Ehrlich, R. E., and others. J. Urol. 1969, 102, 793. 4. Laron, Z., Silka, E. J. clin. Endocr.Metab. 1969, 29, 1409. 5. Rivarola, M. A., Bergada, C., Cullen, M. ibid. 1970, 31, 526. 6. Cacciari, E., and others Acta endocr. Copenh. 1976, 33, 182. 7. Charny, C. W. J. Urol. 1960, 83, 607.
significant local mechanical obstruction to descent; a worsening of the obstruction or acquired testicular dysfunction may account for the increasing failure of response to gonadotrophins in the older age-group. Surgery should be contemplated for such patients but not later than the age of 10 because of the risk of permanent damage to the spermatogenic epithelium. The use of gonadotrophins after correction of cryptorchidism should not be contemplated until puberty because of the danger of premature androgenisation. Cryptorchid testes exposed to gonadotrophins following7 orchidopexy may show more rapid degeneration and sclerosis. Although L.H.R.H. treatment is a priori more physiological than H.c.G., the latter is favoured now on grounds of cost. However, our use of a 3-day subcutaneous L.H.R.H. regimen (by contrast with a month of snuff) permits speedy decisions about surgery or other investigations, and this treatment could therefore prove cheaper in the long run. Department of Endocrinology, Royal Free Hospital, London NW3 2QG
M. C. WHITE
JEAN GINSBURG
NEEDLE BIOPSY IN OVARIAN CARCINOMA
SIR,-Accurate histological classification of ovarian carcinoma may aid the choice of therapy but has been limited by the absence of a method of obtaining a sufficiently large tumour specimen. Vaginal fine-needle aspiration biopsy is widely used and has few complications1,2 but provides only enough material for cytology. I describe here a procedure in which the tumour biopsy is done first with a fine needle and immediately afterwards with a needle of large gauge similar to that used in percutaneous liver and kidney biopsy,’providing enough material for histological investigation. Before biopsy, the bladder is emptied and the vagina cleaned with antiseptic solution. The tumour should be palpable directly, with no suspicion of visceral interposition. A fine needle (0.8 mm diameter) is inserted into it via the vagina, suction applied with a Franzen syringe, and the needle moved in and out of the tumour. Suction is released when the tip is just below the vaginal mucosa. The material in the needle is ejected on to microscope slides for later cytological investigation. If it is solid and free of blood, urine or fluid from a cyst or the intestine, a second biopsy is done immediately, using a modified Iverson-Roholm needle (length 150 mm, outer diameter 2.0 mm, inner diameter 1.7 mm with a sharp right-angled tip without notches V The trocar is inserted through the vaginal puncture canal, the stylet withdrawn, and suction applied using a syringe with lock. The needle is pushed into the tumour with a rotating movement, one or more times. The needle is withdrawn with sustained suction and the fragments of tissue it contains are placed immediately in fixative. This technique should be used only in patients with advanced tumours where the alternative is a biopsy obtained by laparotomy, a procedure with a significant associated mortality. Laparotomy also has a high risk of disseminating the tumour. With needle biopsies, this risk is probably low even when a large-gauge needle is used. In my experience, the technique is safe and reliable.6 Department of Obstetrics
and Gynaecology, Central Hospital, DK-4800 Nykøbing Falster, Denmark
1. 2.
J. SERUP
Jensen, H. K., Gram, N. C., Francis, D. Ugeskr. Lœg. 1974, 136, 586. Kjellgren, O., Angstrøm, T., Bergman, F., Wiklund, D.-E. Cancer, 1971, 28, 967.
Menghini, G. Gastroenterology, 1958, 35, 190 4. Iversen, P., Brun, C. Am. J. Med. 1951, 11, 324. 5. Brun, C. in Nefro-urologi (edited by S.-E. Bergentz, E. Brodwall, p. 39. Copenhagen, 1973. 6. Serup, J. Ugeskr, Lœg. (in the press). 3.
Fl.
Lund);
androgen production and, perhaps spontaneous onset of puberty.
no
as a
University Department of Medicine, Royal Infirmary, Glasgow G4 0SF
result,
no
IAN D. HAY
TREATMENT OF CRYPTORCHIDISM BY SYNTHETIC LUTEINISING-HORMONE-RELEASING HORMONE
SIR,-We were interested in the article by Dr Illig and colleagues (Sept. 10, p. 518) and in the letter by Dr Hadziselimovic and co-workers (Nov. 26, p.1125) since we have been using synthetic lutenising-hormone-releasing hormone (L.H.R.H.) in cryptorchidism. 4 boys aged 7i-152 years were given L.H.R.H. subcutaneously; 3 received 500 fLg every 8 h for 3 days and 1 received 100 g every 8 h for 3 days. In 2 boys, 1 aged 15 a with
’
unilateral cryptorchidism and a very retractile testis on 500 g L.H.R.H. and 1 boy aged 7t on 100 pg L.H.R.H. who had one inpalpable testis and one highly retractile testis, there was testicular descent within 3 days of the initiation of therapy and cessation of retractility. Both children had an impaired gonadotrophin response to a standard 100 fLg L.H.R.H. test with no change in L.H. levels and a blunted follicle-stimulating hormone (F.S.H.) response. The 2 other boys, 1 aged 10 years with small inguinal testes and the other aged 13tyears with one impalpable and one retractile testis, showed no improvement after L.H.R.H. Both had a normal gonadotrophin response to 100 g of L.H.R.H., but no testosterone response to stimulation with human chorionic gonadotrophin (H.C.G.). The speed of response in the first 2 boys supports the suggestion that gonadotrophins themselves are responsible for testicular descent, though perhaps only if a testis is potentially fully functional. The descent is unlikely to be due to any systemic rise in androgen production directly relating to the gonadotrophin therapy as gonadotrophins may cause testicular descent in unilateral cryptorchidism where androgen levels are comparatively normal.’ H.C.G. has been the gonadotrophin of choice in the management of crytorchidism but there had been no general agreement about the age at which it should be given. Scorer2 noted in a large prospective series that 3.4% of testes were undescended at birth; half of these were descended at the end of the first month and at the end of the first year only 0.7% were undescended, a figure that remained virtually unchanged into adult life. Ehrlich et al.,3 reviewing management with H.C.G. therapy in 350 undescended testes, found the best response (38% success-rate) in the 2-5-year age-group compared with an overall response of 23% and only 14% in boys aged 6-13. In unilateral cryptorchidism there is evidence that the normal testis undergoes compensatory hypertrophy and normal development through puberty. There is also evidence of testosterone responsiveness to x.c.G.4 but in cases of bilateral cryptorchidism both the baseline testosterone and the response to H.C.G. stimulation are overall significantly lower than normal.l.5.6 This suggests that cryptorchidism itself leads to testicular dysfunction regardless of hypothalamic-pituitarygonadal axis status,7 although histological findings in such cases may be normal. In view of the above findings we suggest that a definite decision on the management of cryptorchidism should be made at the time the condition is first noted, even as early as 12 months of age. Therapy could begin at 12 months as the likelihood of success is probably greatest at this time. Patients who do not respond may have either primary testicular disease or ’
1. Walsh, P. C., and others. J, clin. Endocr. Metab. 1976, 42, 52. 2. Scorer, C. G. Lancet, 1957, ii, 1123. 3. Ehrlich, R. E., and others. J. Urol. 1969, 102, 793. 4. Laron, Z., Silka, E. J. clin. Endocr.Metab. 1969, 29, 1409. 5. Rivarola, M. A., Bergada, C., Cullen, M. ibid. 1970, 31, 526. 6. Cacciari, E., and others Acta endocr. Copenh. 1976, 33, 182. 7. Charny, C. W. J. Urol. 1960, 83, 607.
significant local mechanical obstruction to descent; a worsening of the obstruction or acquired testicular dysfunction may account for the increasing failure of response to gonadotrophins in the older age-group. Surgery should be contemplated for such patients but not later than the age of 10 because of the risk of permanent damage to the spermatogenic epithelium. The use of gonadotrophins after correction of cryptorchidism should not be contemplated until puberty because of the danger of premature androgenisation. Cryptorchid testes exposed to gonadotrophins following7 orchidopexy may show more rapid degeneration and sclerosis. Although L.H.R.H. treatment is a priori more physiological than H.c.G., the latter is favoured now on grounds of cost. However, our use of a 3-day subcutaneous L.H.R.H. regimen (by contrast with a month of snuff) permits speedy decisions about surgery or other investigations, and this treatment could therefore prove cheaper in the long run. Department of Endocrinology, Royal Free Hospital, London NW3 2QG
M. C. WHITE
JEAN GINSBURG
NEEDLE BIOPSY IN OVARIAN CARCINOMA
SIR,-Accurate histological classification of ovarian carcinoma may aid the choice of therapy but has been limited by the absence of a method of obtaining a sufficiently large tumour specimen. Vaginal fine-needle aspiration biopsy is widely used and has few complications1,2 but provides only enough material for cytology. I describe here a procedure in which the tumour biopsy is done first with a fine needle and immediately afterwards with a needle of large gauge similar to that used in percutaneous liver and kidney biopsy,’providing enough material for histological investigation. Before biopsy, the bladder is emptied and the vagina cleaned with antiseptic solution. The tumour should be palpable directly, with no suspicion of visceral interposition. A fine needle (0.8 mm diameter) is inserted into it via the vagina, suction applied with a Franzen syringe, and the needle moved in and out of the tumour. Suction is released when the tip is just below the vaginal mucosa. The material in the needle is ejected on to microscope slides for later cytological investigation. If it is solid and free of blood, urine or fluid from a cyst or the intestine, a second biopsy is done immediately, using a modified Iverson-Roholm needle (length 150 mm, outer diameter 2.0 mm, inner diameter 1.7 mm with a sharp right-angled tip without notches V The trocar is inserted through the vaginal puncture canal, the stylet withdrawn, and suction applied using a syringe with lock. The needle is pushed into the tumour with a rotating movement, one or more times. The needle is withdrawn with sustained suction and the fragments of tissue it contains are placed immediately in fixative. This technique should be used only in patients with advanced tumours where the alternative is a biopsy obtained by laparotomy, a procedure with a significant associated mortality. Laparotomy also has a high risk of disseminating the tumour. With needle biopsies, this risk is probably low even when a large-gauge needle is used. In my experience, the technique is safe and reliable.6 Department of Obstetrics
and Gynaecology, Central Hospital, DK-4800 Nykøbing Falster, Denmark
1. 2.
J. SERUP
Jensen, H. K., Gram, N. C., Francis, D. Ugeskr. Lœg. 1974, 136, 586. Kjellgren, O., Angstrøm, T., Bergman, F., Wiklund, D.-E. Cancer, 1971, 28, 967.
Menghini, G. Gastroenterology, 1958, 35, 190 4. Iversen, P., Brun, C. Am. J. Med. 1951, 11, 324. 5. Brun, C. in Nefro-urologi (edited by S.-E. Bergentz, E. Brodwall, p. 39. Copenhagen, 1973. 6. Serup, J. Ugeskr, Lœg. (in the press). 3.
Fl.
Lund);
