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AUTOIMMUNE THYROIDITIS AND HASHIMOTO'S DISEASE
585 ASSESSMENT OF OVARIAN FUNCTION BY SALIVARY PROGESTERONE
SIR,-Salivary cortisol concentrations can be used to assess adrenal function.’ Further investigations have shown the value of a salivary 17-OH-progesterone assay in monitoring therapy in patients with congenital adrenal hyperplasia.2 Our studies have now been extended to include the determination of salivary progesterone for assessing ovarian function. Previous experience showed that salivary steroid concentrations rarely exceeded 3% of the usual plasma concentration. A sensitive, specific radioimmunoassay was therefore developed for measuring progesterone in saliva, based on that for plasmaprogesterone.3 The sensitivity of the saliva assay, defined as the least amount of steroid distinguishable from zero at the 95% confidence limit, was 7 pg/tube.4 This sensitivity allowed determination of progesterone concentrations in small volumes of saliva (400.1) collected during the luteal phase of the menstrual cycle. The intra-assay and interassay coefficients of variation of high, medium, and low quality control saliva samples were <10.6% and 7.2%, respectively. Seven normal women, aged 20-40 years provided daily samples of saliva (2 ml) for one complete menstrual cycle. A 25-year-old patient with primary amenorrhoea and a 46-yearold perimenopausal woman were studied daily for 46 and 28 days, respectively. In normal women, the length of the menstrual cycle varied from 21 to 34 days. It was not possible to establish by independent means the timing of ovulation in these women. To overcome this difficulty, the length of the menstrual cycle in each subject was adjusted to 28 days and the progesterone concentration (mean ± S.D.) in successive 3-day periods was calculated. During the follicular phase, progesterone concentrations in saliva were usually too low for accurate determination and rarely exceeded 40 pg/ml. After ovulation, progesterone levels increased rapidly, reaching peak values of 100-200 pg/ml (figure). Progesterone concentrations declined rapidly during the late luteal phase and rarely exceeded 40 pg/ml at the onset of menses. The pattern observed for salivary progesterone concentrations throughout the menstrual cycle closely reflected those well documented for plasma progesterone.5 The patient with primary amenorrhoea had consistently low salivary progesterone concentrations, whereas the perimenopausal woman had widely fluctuating progesterone levels which exceeded 80 1. 2. 3.
Walker, R. F., Fahmy, D. R., Llewelyn, D. E. H. J. Endocr. 1978, 77, 26P. Walker, R. F., Fahmy, D. R. ibid. (in the press). DeVilla, G. O., Roberts, K. Wiest, W. G., Mikhail, G., Fhckinger, G.J. clin. Endocr. Metab. 1972, 35. 4. Kaiser, H., Specker, H. Z. Anal. Chem. 1956, 46, 149. 5. Ross, G. T., Cargille, C. M., Lipsett, M. B., Rayford, P. L., Marshalle, J. R., Strott, C. A., Rodbard, D. Recent Prog. Hormone Res. 1970, 26,
on four occasions during the 28-day study. This illusthe need for serial sampling if ovarian function is to be assessed accurately. Daily venepunctures are obviously impractical in routine clinical practice. Daily samples of saliva, however, can be collected with ease at home, stored deepfrozen in a domestic refrigerator, and then brought to the laboratory at weekly or monthly intervals for determination of progesterone concentrations. The availability of a salivary progesterone radioimmunoassay will greatly facilitate the investigation of women with disorders of ovarian function. RICHARD F. WALKER IEUAN A. HUGHES Tenovus Institute for DIANA RIAD-FAHMY Cancer Research, Cardiff CF4 4XX GRAHAM F. READ
pg/ml trates
AUTOIMMUNE THYROIDITIS AND HASHIMOTO’S DISEASE
SiR,—Bastenie* described the variants of autoimmune thyroiditis. We confirmed2 his earlier observation3 of a high incidence of "asymptomatic atrophic thyroiditis" at necropsy; all the patients were clinically euthyroid and only 5 of 13 patients showed atrophic thyroiditis less than 15 g. This form of autoimmune thyroiditis was found in 4-2% of adult males and in 8.5% of adult females of general population in Japan.4 Serum-thyrotropin in this condition was usually norrnal.4 Therefore we prefer to use the term "subclinical autoimmune thyroiditis" instead of "asymptomatic atrophic thyroiditis." Gordin and Lamberg5 described this condition as "symptomless autoimmune thyroiditis." Bastenie asks why the patronym of the rarest form of autoimmune process (Hashimoto’s goitre) should be used to designate all aspects of autoimmune thyroiditis. The research committee on Hashimoto’s disease of the Ministry of Health and Welfare, Japan, have included spontaneous adult myxoedema with serum anti-thyroid antibodies in the diagnostic criteria of Hashimoto’s disease.** "Hashimoto’s disease" or "Hashimoto’s thyroiditis" (not "Hashimoto’s goitre") are widely used synonymously with autoimmune thyroiditis, just as "Graves’ disease" is often used to cover non-exophthalmic and non-goitrous hyperthyroid patients. Central Laboratory for Clinical Investigation, Osaka University Hospital, Osaka 553, Japan.
NOBUYUKI AMINO KIYOSHI MIYAI
ANTIBODIES TO HERPES SIMPLEX VIRUS TYPE 2 IN HUSBANDS OF PATIENTS WITH CERVICAL CARCINOMA
2)
SIR,-Antibodies against herpes simplex virus type 2 (H.s.v. are more common in patients with cervical carcinoma than
in controls.’ To see if these antibodies were also more common in sexual partners we measured titres against the early antigen of H.S.V. 2 in sera of patients with cervical carcinoma and in their husbands. In sera of 100 patients with cervical carcinoma, 50 female controls, 36 husbands of patients with cervical carcinoma, and in 36 male controls antibody titres against the early antigen of H.S.V. 1 and H.s.v. 2 were measured by immunofluorescence. The identification of antibodies was done according to Rawls’
!l/l index.8 Bastenie, P. A. Lancet, 1978, i, 1369. Yoshida, H., Amino, N., Yagawa, K., Uemura, K., Satoh, M., Miyai, K., Kumahara, Y.J. clin. Endocr. Metab. 1978, 46, 859. 3. Bastenie, P.A. Archs int. Méd. exp. 1937, 12, 1 4. Ammo, N. in Kojosen (edited by K. Shizume, T. Yamada, and K. Miyai); 1. 2.
p. 149. Tokyo, 1978. Concentrations of progesterone in saliva from normal females. . perimenopausal woman; 0 woman with primary amenhorrcea. area: mean + S.D. of results from seven normal females.
Shaded
5. Gordm, A., Lamberg, B. A. Lancet, 1975, ii, 1234. 6. Torizuka, K., Konishi, J., Mori, T. Naika, 1976, 38, 379. 7. Melnick, J. L., Rawls, W. E Ann. N.Y Acad. Sci. 1970, 174, 933. 8. Rawls, W. E., Iwamoto, K., Adam, E., Melnick, J. L.J. Immun. 1970, 104, 599.
SIR,-Salivary cortisol concentrations can be used to assess adrenal function.’ Further investigations have shown the value of a salivary 17-OH-progesterone assay in monitoring therapy in patients with congenital adrenal hyperplasia.2 Our studies have now been extended to include the determination of salivary progesterone for assessing ovarian function. Previous experience showed that salivary steroid concentrations rarely exceeded 3% of the usual plasma concentration. A sensitive, specific radioimmunoassay was therefore developed for measuring progesterone in saliva, based on that for plasmaprogesterone.3 The sensitivity of the saliva assay, defined as the least amount of steroid distinguishable from zero at the 95% confidence limit, was 7 pg/tube.4 This sensitivity allowed determination of progesterone concentrations in small volumes of saliva (400.1) collected during the luteal phase of the menstrual cycle. The intra-assay and interassay coefficients of variation of high, medium, and low quality control saliva samples were <10.6% and 7.2%, respectively. Seven normal women, aged 20-40 years provided daily samples of saliva (2 ml) for one complete menstrual cycle. A 25-year-old patient with primary amenorrhoea and a 46-yearold perimenopausal woman were studied daily for 46 and 28 days, respectively. In normal women, the length of the menstrual cycle varied from 21 to 34 days. It was not possible to establish by independent means the timing of ovulation in these women. To overcome this difficulty, the length of the menstrual cycle in each subject was adjusted to 28 days and the progesterone concentration (mean ± S.D.) in successive 3-day periods was calculated. During the follicular phase, progesterone concentrations in saliva were usually too low for accurate determination and rarely exceeded 40 pg/ml. After ovulation, progesterone levels increased rapidly, reaching peak values of 100-200 pg/ml (figure). Progesterone concentrations declined rapidly during the late luteal phase and rarely exceeded 40 pg/ml at the onset of menses. The pattern observed for salivary progesterone concentrations throughout the menstrual cycle closely reflected those well documented for plasma progesterone.5 The patient with primary amenorrhoea had consistently low salivary progesterone concentrations, whereas the perimenopausal woman had widely fluctuating progesterone levels which exceeded 80 1. 2. 3.
Walker, R. F., Fahmy, D. R., Llewelyn, D. E. H. J. Endocr. 1978, 77, 26P. Walker, R. F., Fahmy, D. R. ibid. (in the press). DeVilla, G. O., Roberts, K. Wiest, W. G., Mikhail, G., Fhckinger, G.J. clin. Endocr. Metab. 1972, 35. 4. Kaiser, H., Specker, H. Z. Anal. Chem. 1956, 46, 149. 5. Ross, G. T., Cargille, C. M., Lipsett, M. B., Rayford, P. L., Marshalle, J. R., Strott, C. A., Rodbard, D. Recent Prog. Hormone Res. 1970, 26,
on four occasions during the 28-day study. This illusthe need for serial sampling if ovarian function is to be assessed accurately. Daily venepunctures are obviously impractical in routine clinical practice. Daily samples of saliva, however, can be collected with ease at home, stored deepfrozen in a domestic refrigerator, and then brought to the laboratory at weekly or monthly intervals for determination of progesterone concentrations. The availability of a salivary progesterone radioimmunoassay will greatly facilitate the investigation of women with disorders of ovarian function. RICHARD F. WALKER IEUAN A. HUGHES Tenovus Institute for DIANA RIAD-FAHMY Cancer Research, Cardiff CF4 4XX GRAHAM F. READ
pg/ml trates
AUTOIMMUNE THYROIDITIS AND HASHIMOTO’S DISEASE
SiR,—Bastenie* described the variants of autoimmune thyroiditis. We confirmed2 his earlier observation3 of a high incidence of "asymptomatic atrophic thyroiditis" at necropsy; all the patients were clinically euthyroid and only 5 of 13 patients showed atrophic thyroiditis less than 15 g. This form of autoimmune thyroiditis was found in 4-2% of adult males and in 8.5% of adult females of general population in Japan.4 Serum-thyrotropin in this condition was usually norrnal.4 Therefore we prefer to use the term "subclinical autoimmune thyroiditis" instead of "asymptomatic atrophic thyroiditis." Gordin and Lamberg5 described this condition as "symptomless autoimmune thyroiditis." Bastenie asks why the patronym of the rarest form of autoimmune process (Hashimoto’s goitre) should be used to designate all aspects of autoimmune thyroiditis. The research committee on Hashimoto’s disease of the Ministry of Health and Welfare, Japan, have included spontaneous adult myxoedema with serum anti-thyroid antibodies in the diagnostic criteria of Hashimoto’s disease.** "Hashimoto’s disease" or "Hashimoto’s thyroiditis" (not "Hashimoto’s goitre") are widely used synonymously with autoimmune thyroiditis, just as "Graves’ disease" is often used to cover non-exophthalmic and non-goitrous hyperthyroid patients. Central Laboratory for Clinical Investigation, Osaka University Hospital, Osaka 553, Japan.
NOBUYUKI AMINO KIYOSHI MIYAI
ANTIBODIES TO HERPES SIMPLEX VIRUS TYPE 2 IN HUSBANDS OF PATIENTS WITH CERVICAL CARCINOMA
2)
SIR,-Antibodies against herpes simplex virus type 2 (H.s.v. are more common in patients with cervical carcinoma than
in controls.’ To see if these antibodies were also more common in sexual partners we measured titres against the early antigen of H.S.V. 2 in sera of patients with cervical carcinoma and in their husbands. In sera of 100 patients with cervical carcinoma, 50 female controls, 36 husbands of patients with cervical carcinoma, and in 36 male controls antibody titres against the early antigen of H.S.V. 1 and H.s.v. 2 were measured by immunofluorescence. The identification of antibodies was done according to Rawls’
!l/l index.8 Bastenie, P. A. Lancet, 1978, i, 1369. Yoshida, H., Amino, N., Yagawa, K., Uemura, K., Satoh, M., Miyai, K., Kumahara, Y.J. clin. Endocr. Metab. 1978, 46, 859. 3. Bastenie, P.A. Archs int. Méd. exp. 1937, 12, 1 4. Ammo, N. in Kojosen (edited by K. Shizume, T. Yamada, and K. Miyai); 1. 2.
p. 149. Tokyo, 1978. Concentrations of progesterone in saliva from normal females. . perimenopausal woman; 0 woman with primary amenhorrcea. area: mean + S.D. of results from seven normal females.
Shaded
5. Gordm, A., Lamberg, B. A. Lancet, 1975, ii, 1234. 6. Torizuka, K., Konishi, J., Mori, T. Naika, 1976, 38, 379. 7. Melnick, J. L., Rawls, W. E Ann. N.Y Acad. Sci. 1970, 174, 933. 8. Rawls, W. E., Iwamoto, K., Adam, E., Melnick, J. L.J. Immun. 1970, 104, 599.