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Ovarian morphology in amenorrhea-galactorrhea syndromes
Ovarian morphology in amenorrhea-galactorrhea syndromes I.
NYIRJESY,
Bethesda,
COMMANDER
(MC)
USN*
Maryland
The ovaries of two patients tvith Ahumada-de1 Castillo syndrome were studied. The finding of ova, developing follicles, mnd abundant cortical stroma seems to contradict the concept of ovarian atrophy in amenorrhea-galactorrhea syndromes. The use of the term “uteroovarian atrophy” should be abandoned, as it may not always apply.
days until the age of 19, when amenorrhea and profuse galactorrhea had developed. The patient had had no previous operations or significant illnesses; her family history was noncontributory. She had consulted numerous physicians about her condition and her records indicate that her past work-up, including several endocrine studies, had been negative. Past treatment had consisted of the administration of cyclic estrogen and progesterone, which produced artificial menses without reducing the galactorrhea. The last such treatment had been administered over one year prior to admission. Physical examination revealed a well-developed, well-nourished woman with normal secondary sexual characteristics and no acne, seborrhea, or hirsutism. The breasts were of average size and appeared nulliparous. On slight pressure, copious amounts of milk were ejected from each nipple. Pelvic examination revealed a male type of pubic hair and normal external genitals. The vaginal mucosa appeared red, atrophic, and smooth. The cervix was nulliparous and clean; the corpus was anterior, small, with a cervicocorporeal ratio of 1: 1. Each ovary was palpable and had an estimated size of 5 by 3 by 3 cm. A skull x-ray revealed no sella turcica enlargement and the visual fields were normal. A vaginal smear showed no estrogen effect. No tissue was obtained on an attempted endometrial biopsy. The 24 hour urinary 17-ketosteroid excretion was 12 mg., the 17-hydroxysteroid excretion was 3.8 mg., the protein-bound iodine (PBI) was 5.3 hormone pg per cent, the follicle-stimulating (FSH) was less than 5 M.U. on two occasions. The glucose tolerance was normal. No withdrawal blerding occurred after the
FIRST G.~L.~CTORRHEA syndrome was described by Chiari, Braun, and Speeth, and later by Frommel, as “persistent postpartum lactation with uteroovarian atrophy.“’ Subsequently Krestin,” Ahumada and de1 Castillo,’ and Forbes and associates,s described patients with a similar clinical profile but without a prior pregnancy. Since these historical writings, much thought has been given to the pathophysio!ogy and management of amenorrhea-galactorrhea syndromes, but published information on ovarian morphology in such patients has remained scant.3+ ’ The purpose of this paper is to describe the ovarian morphology of two nulligravid patients with amenorrhea-galactorrhea syndrome, and to question the accuracy of the term “uteroovarian atrophy” in these syndromes. THE
Case
reports
1. S. W., a 30-year-old Negro gravida 0, had had her menarche at the age of 13; this had been followed by a regular menstrual cycle of 28 Case
From the Gynecology-Obstetrics Service, United States Naval Station Hospital, NAVSUPPACT Naples, Box 19, FPO New York 09521. The opinions expressed herein are strictly those of the author and do not represent the oficial views of the U. S. Nauy. ‘Present address: United States Naval Hospital, National Naval Medical Center, Bethesda, Maryland 20014. 458
Ovarian
morphology
in Ahumada-del
Castilio
syndrome
459
Fig. 1. Photomicrograph of a portion of the ovary of Patic=nt 1 showing a somewhat thickened tunica albug-inea, abundant cortical stroma. and a dc\rFlopin,c follicle. (Hematoxylin and rosin. ~60.1
Fig. 2. Pkotomicrograph of the same patient showing developing follicles and theta lutcinization. (Hematoxylin and eosin. x30.)
administration of 10 mg. of medroxyprogestrrone acetate per day for 5 days. Culdoscopic examination revealed a small uterine fundus and ovaries covered by a smooth, glassy capsule. The ovaries were larger than the fundus and \VCI‘C grossly indistinguishable from thoq;P found in patients with Stein-Leventhal syndrome. I’rfYTiusc~ of thr~ findings, rvcn though the
diagnosis of Ahumada-Argonz-de1 Castillo syndrome was probable, a bilateral ovarian wrdge resection was pt,rformed. On laparotomy, inspcction revealed a small uterine fundus and two normal-sized ovarics which were gray and had a somewhat thickened, glassy-appearing capsule. On incision, multiple subcapsular cysts wer<’ norfad. The patient had an uneventful postoperative course. She was observed for 6 months but no spontaneous menses occurred. She was then given cyclic conjugated estrogen-norethynodrpl therapy, which resulted in midcycle decrease of thr galactorrhea, withdrawal bleeding. and some growth of the uterine fundus. Case 2. T. N., a 25-year-old Caucasian nulligravida, had her menarche at the age of 18, followed by only two spontaneous menses, the last one at the age of 21. She was first seen at this clinic in June, 1964: at which time she denied any symptom other than amenorrhea. Physical examination revealed a Jvcll-dewho had at.nr: and velopcd, slightly obese woman, seborrhea. The breasts were well developed; no milk could be expressed on slight pressu~c applied around the nipples. Pelvic examination revealed normal ~~xtc~rnal genitals and vagina. The cervix was small. as well as the corpus, with a ratio of 1 : 1. The ovaries were felt to be larger than the corpus. A vaginal smear showed “slight cstroaen rffect” and there was no withdrawal hlcxrding fllllowing 1hr. ;Idrninistr;~tion of pro~rst~ro~~<‘.
460
Nyirjesy
The sella turcica appeared radiologically normal and there were no visual field defects, The 24 hour urinary 17-ketosteroid excretion was 6.6 mg., the 17-hydroxysteroid excretion was 3.5 mg., the PBI was 6.5 pg per cent, the FSH was 5 to 50 M.U. The glucose tolerance was normal. No endometrium was obtainable on a dilatation and curettage; culdoscopic examination showed glassysurfaced, polycystic ovaries. A bilateral ovarian wedge resection was performed in December, 1964. The gross appearance of the internal genitals was essentially the same as described in Patient 1. The ovaries were larger than the uterine fundus and numerous subcapsular cysts were noted upon incision. The postoperative course was uncomplicated. No spontaneous menses occurred postoperatively, and the patient was given conjugated estrogen-norethynodrel therapy which she discontinued after 3 months. The patient returned to this clinic in January, 1966, with the complaint of abundant galactorrhea, present for 2 months. On close questioning, she admitted that her brassieres had often been wet for “many years,” but she failed to realize that this was not normal. Retrospectively, the patient was also classified as having AhumadaArgonz-de1 Castillo syndrome.
had a smooth, glassy, gray surface and a somewhat thickened capsule. Upon incision. numerous cortical cysts were noted in each ovary. Histologically, the tunica albuginea was somewhat thickened and sclerotic (Fig. 1). In addition, each ovary contained a number of involuting and/or apparently unruptured follicles, follicles in all stages of development (Figs. 2 and 3)) ova, and abundant stroma. Theta luteinization was apparent in each specimen (Figs. 2 and 3) ; corpora lutea were uniformly absent. Historically the state of the ovaries in amenorrhea-galactorrhea syndromes has received little attention. In 1882, Frommel stated that the ovaries in 25 of his 28 patients were “small and atrophic,‘” and since his writing it has become a habit to use the term “uteroovarian atrophy.” Ovaries of patients with amenorrhea-galactorrhea were visualized through culdoscopy and described as sclerotic by Forbes and associates,” and by Dowling and associates,”
Comment In both patients, the ovaries appeared grossly normal in size on laparotomy. They
Fig. 3. A Graafian follicle from Patient 1 with theta luteinization. (Hematoxylin and eosin. x40.)
Fig. 4. Photomicrograph of ovarian wedge from Patient 2 showing a cortical cyst. (Hematoxylin and
eosin.
xl 1.)
Ovarian
morphology
who found that they were normal in size, smooth, and glassy of surface. Cohen3 explored the abdomen of a patiellt with Chiari-Frommel syndrome because of a cystic, left adnexal mass. A biopsy of the right ovary showed a thickened tunica albuginea, small peripheral follicle cysts, and many ova in the stroma. The left ovary was replaced by a cystic mass lined by a single la) er of columnar epithelial cells. .4nderson, Erickson, and Luse2 described the ovaries of a patient with Chiari-Fromme1 syndrome associated with craniopharyngioma. The patient died; on autopsy, the ovaries were considered to be “atrophic,” although they contained “a few small primary follicles but only a single Graafian follicle.” Corpora lutea were absent. It would be unreasonable to draw final conclusions on the state of the ovaries in amenorrhea-galactorrhea syndromes from such a small series of patients, but it does at this time, that there are ova, wear, developing follicles, and abundant cortical
in Ahumada-del
Castillo
syndrome
46.1
stroma in the ovaries of patients with both Chiari-Frommel and Ahumada-de1 Castillo syndromes. These findings do suggest that there is no ovarian atrophy in the strict sense of the term and, consequently, that the W~Icept of “uteroovarian atrophy” may he moth historical than factual. It is further believed that the ovalian histology in these patients suggests anovlllation. Several noted features, such as the thickened capsule, atretic follicles, cortical cystic follicles (Fig. 4)) absence of corpora lutea, and marked luteinization also indic,atr some similarity with ovaries habitually four~cl in Stein-Leventhal syndromes. From the clinical standpoint, it shoulti be noted that wedge resection of the ovaries did not induce ovulation in these patients. The author thanks N. A. Janovski, Gonnnander (MC) USN, and the staff of the Armed Forces Institute of Pathology, particularly I)r. H. B. Taylor, for their assistance in the study of the histologic specimens.
REFERENCES
1. Ahumada, J. C., and de1 Castillo, E. B.: Bol. Sot. obst. y ginec. Buenos Aires 11: 64, 1932. 2. Anderson, M. S., Erickson, D. S., and Luse, S. A.: Nrurology
12: 583,
3. Cohen, A.: Australian 4.
Ann. Med. 8: 77, 1959. J. B., Freinkel, Int. Med. 107:
265,
1954.
6. Krestin, D.: Lancet 1: 928, 1932.
1962.
Dowling, J. T., Richards, and Inghar, S. H.: Arch. 1961.
5. Forbes, A. P., Henneman, P. H., Griswold, G. C., and Albright, F.: J. Clin. Endocrinol. 14:
N., 151,
7.
Sharp, 1935.
E. A.:
AM.
J. OBST.
& GYREC.
30:
4.11,
NYIRJESY,
Bethesda,
COMMANDER
(MC)
USN*
Maryland
The ovaries of two patients tvith Ahumada-de1 Castillo syndrome were studied. The finding of ova, developing follicles, mnd abundant cortical stroma seems to contradict the concept of ovarian atrophy in amenorrhea-galactorrhea syndromes. The use of the term “uteroovarian atrophy” should be abandoned, as it may not always apply.
days until the age of 19, when amenorrhea and profuse galactorrhea had developed. The patient had had no previous operations or significant illnesses; her family history was noncontributory. She had consulted numerous physicians about her condition and her records indicate that her past work-up, including several endocrine studies, had been negative. Past treatment had consisted of the administration of cyclic estrogen and progesterone, which produced artificial menses without reducing the galactorrhea. The last such treatment had been administered over one year prior to admission. Physical examination revealed a well-developed, well-nourished woman with normal secondary sexual characteristics and no acne, seborrhea, or hirsutism. The breasts were of average size and appeared nulliparous. On slight pressure, copious amounts of milk were ejected from each nipple. Pelvic examination revealed a male type of pubic hair and normal external genitals. The vaginal mucosa appeared red, atrophic, and smooth. The cervix was nulliparous and clean; the corpus was anterior, small, with a cervicocorporeal ratio of 1: 1. Each ovary was palpable and had an estimated size of 5 by 3 by 3 cm. A skull x-ray revealed no sella turcica enlargement and the visual fields were normal. A vaginal smear showed no estrogen effect. No tissue was obtained on an attempted endometrial biopsy. The 24 hour urinary 17-ketosteroid excretion was 12 mg., the 17-hydroxysteroid excretion was 3.8 mg., the protein-bound iodine (PBI) was 5.3 hormone pg per cent, the follicle-stimulating (FSH) was less than 5 M.U. on two occasions. The glucose tolerance was normal. No withdrawal blerding occurred after the
FIRST G.~L.~CTORRHEA syndrome was described by Chiari, Braun, and Speeth, and later by Frommel, as “persistent postpartum lactation with uteroovarian atrophy.“’ Subsequently Krestin,” Ahumada and de1 Castillo,’ and Forbes and associates,s described patients with a similar clinical profile but without a prior pregnancy. Since these historical writings, much thought has been given to the pathophysio!ogy and management of amenorrhea-galactorrhea syndromes, but published information on ovarian morphology in such patients has remained scant.3+ ’ The purpose of this paper is to describe the ovarian morphology of two nulligravid patients with amenorrhea-galactorrhea syndrome, and to question the accuracy of the term “uteroovarian atrophy” in these syndromes. THE
Case
reports
1. S. W., a 30-year-old Negro gravida 0, had had her menarche at the age of 13; this had been followed by a regular menstrual cycle of 28 Case
From the Gynecology-Obstetrics Service, United States Naval Station Hospital, NAVSUPPACT Naples, Box 19, FPO New York 09521. The opinions expressed herein are strictly those of the author and do not represent the oficial views of the U. S. Nauy. ‘Present address: United States Naval Hospital, National Naval Medical Center, Bethesda, Maryland 20014. 458
Ovarian
morphology
in Ahumada-del
Castilio
syndrome
459
Fig. 1. Photomicrograph of a portion of the ovary of Patic=nt 1 showing a somewhat thickened tunica albug-inea, abundant cortical stroma. and a dc\rFlopin,c follicle. (Hematoxylin and rosin. ~60.1
Fig. 2. Pkotomicrograph of the same patient showing developing follicles and theta lutcinization. (Hematoxylin and eosin. x30.)
administration of 10 mg. of medroxyprogestrrone acetate per day for 5 days. Culdoscopic examination revealed a small uterine fundus and ovaries covered by a smooth, glassy capsule. The ovaries were larger than the fundus and \VCI‘C grossly indistinguishable from thoq;P found in patients with Stein-Leventhal syndrome. I’rfYTiusc~ of thr~ findings, rvcn though the
diagnosis of Ahumada-Argonz-de1 Castillo syndrome was probable, a bilateral ovarian wrdge resection was pt,rformed. On laparotomy, inspcction revealed a small uterine fundus and two normal-sized ovarics which were gray and had a somewhat thickened, glassy-appearing capsule. On incision, multiple subcapsular cysts wer<’ norfad. The patient had an uneventful postoperative course. She was observed for 6 months but no spontaneous menses occurred. She was then given cyclic conjugated estrogen-norethynodrpl therapy, which resulted in midcycle decrease of thr galactorrhea, withdrawal bleeding. and some growth of the uterine fundus. Case 2. T. N., a 25-year-old Caucasian nulligravida, had her menarche at the age of 18, followed by only two spontaneous menses, the last one at the age of 21. She was first seen at this clinic in June, 1964: at which time she denied any symptom other than amenorrhea. Physical examination revealed a Jvcll-dewho had at.nr: and velopcd, slightly obese woman, seborrhea. The breasts were well developed; no milk could be expressed on slight pressu~c applied around the nipples. Pelvic examination revealed normal ~~xtc~rnal genitals and vagina. The cervix was small. as well as the corpus, with a ratio of 1 : 1. The ovaries were felt to be larger than the corpus. A vaginal smear showed “slight cstroaen rffect” and there was no withdrawal hlcxrding fllllowing 1hr. ;Idrninistr;~tion of pro~rst~ro~~<‘.
460
Nyirjesy
The sella turcica appeared radiologically normal and there were no visual field defects, The 24 hour urinary 17-ketosteroid excretion was 6.6 mg., the 17-hydroxysteroid excretion was 3.5 mg., the PBI was 6.5 pg per cent, the FSH was 5 to 50 M.U. The glucose tolerance was normal. No endometrium was obtainable on a dilatation and curettage; culdoscopic examination showed glassysurfaced, polycystic ovaries. A bilateral ovarian wedge resection was performed in December, 1964. The gross appearance of the internal genitals was essentially the same as described in Patient 1. The ovaries were larger than the uterine fundus and numerous subcapsular cysts were noted upon incision. The postoperative course was uncomplicated. No spontaneous menses occurred postoperatively, and the patient was given conjugated estrogen-norethynodrel therapy which she discontinued after 3 months. The patient returned to this clinic in January, 1966, with the complaint of abundant galactorrhea, present for 2 months. On close questioning, she admitted that her brassieres had often been wet for “many years,” but she failed to realize that this was not normal. Retrospectively, the patient was also classified as having AhumadaArgonz-de1 Castillo syndrome.
had a smooth, glassy, gray surface and a somewhat thickened capsule. Upon incision. numerous cortical cysts were noted in each ovary. Histologically, the tunica albuginea was somewhat thickened and sclerotic (Fig. 1). In addition, each ovary contained a number of involuting and/or apparently unruptured follicles, follicles in all stages of development (Figs. 2 and 3)) ova, and abundant stroma. Theta luteinization was apparent in each specimen (Figs. 2 and 3) ; corpora lutea were uniformly absent. Historically the state of the ovaries in amenorrhea-galactorrhea syndromes has received little attention. In 1882, Frommel stated that the ovaries in 25 of his 28 patients were “small and atrophic,‘” and since his writing it has become a habit to use the term “uteroovarian atrophy.” Ovaries of patients with amenorrhea-galactorrhea were visualized through culdoscopy and described as sclerotic by Forbes and associates,” and by Dowling and associates,”
Comment In both patients, the ovaries appeared grossly normal in size on laparotomy. They
Fig. 3. A Graafian follicle from Patient 1 with theta luteinization. (Hematoxylin and eosin. x40.)
Fig. 4. Photomicrograph of ovarian wedge from Patient 2 showing a cortical cyst. (Hematoxylin and
eosin.
xl 1.)
Ovarian
morphology
who found that they were normal in size, smooth, and glassy of surface. Cohen3 explored the abdomen of a patiellt with Chiari-Frommel syndrome because of a cystic, left adnexal mass. A biopsy of the right ovary showed a thickened tunica albuginea, small peripheral follicle cysts, and many ova in the stroma. The left ovary was replaced by a cystic mass lined by a single la) er of columnar epithelial cells. .4nderson, Erickson, and Luse2 described the ovaries of a patient with Chiari-Fromme1 syndrome associated with craniopharyngioma. The patient died; on autopsy, the ovaries were considered to be “atrophic,” although they contained “a few small primary follicles but only a single Graafian follicle.” Corpora lutea were absent. It would be unreasonable to draw final conclusions on the state of the ovaries in amenorrhea-galactorrhea syndromes from such a small series of patients, but it does at this time, that there are ova, wear, developing follicles, and abundant cortical
in Ahumada-del
Castillo
syndrome
46.1
stroma in the ovaries of patients with both Chiari-Frommel and Ahumada-de1 Castillo syndromes. These findings do suggest that there is no ovarian atrophy in the strict sense of the term and, consequently, that the W~Icept of “uteroovarian atrophy” may he moth historical than factual. It is further believed that the ovalian histology in these patients suggests anovlllation. Several noted features, such as the thickened capsule, atretic follicles, cortical cystic follicles (Fig. 4)) absence of corpora lutea, and marked luteinization also indic,atr some similarity with ovaries habitually four~cl in Stein-Leventhal syndromes. From the clinical standpoint, it shoulti be noted that wedge resection of the ovaries did not induce ovulation in these patients. The author thanks N. A. Janovski, Gonnnander (MC) USN, and the staff of the Armed Forces Institute of Pathology, particularly I)r. H. B. Taylor, for their assistance in the study of the histologic specimens.
REFERENCES
1. Ahumada, J. C., and de1 Castillo, E. B.: Bol. Sot. obst. y ginec. Buenos Aires 11: 64, 1932. 2. Anderson, M. S., Erickson, D. S., and Luse, S. A.: Nrurology
12: 583,
3. Cohen, A.: Australian 4.
Ann. Med. 8: 77, 1959. J. B., Freinkel, Int. Med. 107:
265,
1954.
6. Krestin, D.: Lancet 1: 928, 1932.
1962.
Dowling, J. T., Richards, and Inghar, S. H.: Arch. 1961.
5. Forbes, A. P., Henneman, P. H., Griswold, G. C., and Albright, F.: J. Clin. Endocrinol. 14:
N., 151,
7.
Sharp, 1935.
E. A.:
AM.
J. OBST.
& GYREC.
30:
4.11,