Joseph A. Gaines

Diffuse luteinization of the ovaries associated with the masculinization syndrome

Abstract The syndrome of masculinization in the female, attributed to pituitary basophilism or adrenal cortical lesions, usually includes regressive changes in the ovaries. At times, however, as evidenced by the two cases described in this report, there may be bilateral ovarian enlargement, due to excessive perifollicular proliferation and luteinization of the theca cells and diffusely scattered luteinized cells within the ovarian parenchyma. The ovrian effects are suggestive of increased gonadotropic stimulation and are probably secondary. It does not appear that they are responsible for the production of the masculinization syndrome. In the clinical investigation of virilism the presence of an ovarian enlargement has been and should be regarded as suspicious evidence of a possible arrhenoblastoma or adrenal rest neoplasm of the ovary. In view of this report, a third possibility exists, namely, enlargement of the ovary due to diffuse luteinization. It may be possible to decide, at operation, by incision of the ovaries, whether or not tumor is present. If, in young patients, tumor can unequivocally be ruled out by this device, one or both ovaries may be left in situ.

Theca cell tumors

Abstract The anatomic and histologic characteristics of theca cell tumors are described, together with their distinctive clinical and hormonal features. Descriptions are given of six cases illustrating variations from the more benign fibroma type to the highly cellular and malignant type. A correlation is made between the presence of hormonal changes and the presence of intracellular, doubly refractile fat containing cholesterol and cholesterol esters. It is suggested that some of the ovarian neoplasms previously diagnosed as fibromas or fibrosarcomas may on further investigation prove to be of theca cell origin.

Uterine arteriovenous fistula.

Abstract An arteriovenous fistula within the uterus is a rare occurrence. Only three previous cases have been reported. A review of their distinctive features is presented. The etiology of this unusual uterine vascular abnormality is undetermined. The symptomatology and physical findings are sufficiently characteristic to suggest the diagnosis of this condition preoperatively. The usual presenting symptom is postmenopausal bleeding, sometimes of severe degree. The uterus is symmetrically enlarged and soft, simulating an intrauterine gravidity. A definite pulsation and thrill are palpable in the vaginal fornices. An audible murmur with systolic accentuation may be heard through the vagina. Systemic circulatory disturbances are minimal. The pathologic findings of uterine arteriovenous fistulas are discussed. At operation, numerous dilated, tortuous vessels fill the broad ligaments. The enlarged, distended, and vascular uterus may pulsate visibly. Surgical

Experimental biologically active ovarian tumors in mice

Abstract X-ray irradiation of mice at puberty results in the production of two types of ovarian tumors: tubular adenomas derived from the surface epithelium and parenchymal lutein tumors. The parenchymal lutein tumors alone exhibit hormonal activity expressed in proliferative changes in the endometrium and vaginal mucosa. Histologically, these tumors are composed of granulosa and theca cells with varying degrees of luteinization. They are entirely comparable to the granulosa cell tumor and its excessively luteinized variant, the Lecene tumor, and the theca cell tumor of the human ovary. The luteinized ovarian tumors in mice are derived from the undifferentiated parenchyma. While the theca interna cells participate in the early proliferation and luteinization, the mature granulosa cells play no role in the genesis of these neoplasms. The histogenesis of the analogous human tumors may well be identical.

Chromosomal sex detection in the human newborn and fetus from examination of the umbilical cord, placental tissue, and fetal membranes.

Five years ago Barr and his associates (Moore et al., 1953) announced a new and relatively simple histological method utilizing a skin biopsy for the diagnosis of sex. This is based upon the fact that intermitotic nuclei of females contain a characteristic mass of chromatin, the sex chromatin which is rarely, if ever, present in males. Since these particular chromocenters presumably represent fused heterochromatic portions of the XX sex-chromosomal complex of females, nuclei possessing the sex-chromatin body are found only in specimens from chromosomal females (Barr, 1957; Reitalu, 1957). Rapidly confirmed by numerous investigators (Hunter et al., 1954; Marberger and Kelson, 1954; Emery and McMillan, 19.54; Sohval et al., 1955), these observations have been applied to a variety of anatomical preparations and clinical conditons. As a result there have been two salient developments: first, cytological methods for the detect-ion of chromosomal sex have been described employing buccal scrapings (Moore and Barr, 1955; Marberger el al., 1955), smears from the vagina and urogenital sinus (Carpentier et al., 1956), leukocytes from the peripheral blood (Davidson and Smith, 1954), and cells of the amniotic fluid obtained prenatally (Scrr et al., 1955; James, 1956). In the last instance, the cells are of €eta1 origin, derived principally from the mucosae of the alimentary and genitourinary tracts rather than from the skin or amnion (Rosa and Fanard, 1951; Lennox, 1956; Makowski el al., 1956). I n addition, a nuclear sex difference has been observed histologically by nilarberger and Nelson (1955) in mesenchymal cells of thc amnion of human fetal membranes, by Roitman (1955) in the nuclei of smooth muscle cells of the umbilical vessels, by Glcnister (1956) and by I’ark (1957) in early human trophoblastic nuclei, and by Bohle and Hienz (1056) in the connective tissue and endothelial cells of human term placental villi. Second, t h e determination of chromosomal sex in certain patients with congenital errors of sex development has contributed significantly to our understanding of the pathogenesis and to the management of these conditions. The purpose of this communication is to report the results of a systematic investigation of the nuclear sex chromatin in the umbilical cord, placental tissue, and fetal membranes of the human newborn and of fetuses of various ages. The demonstration of concordant nuclear sex differences i n these structures represents an additional technique for chromosomal sex detection. Some advantage accrues from the fact that availability or manipulation of the newborn or fetus itself is not required.

Sarcoidosis of the uterus

Abstract 1. 1. A case of generalized sarcoidosis with asymptomatic uterine involvement is reported. Characteristic epithelioid granulomas were found in the endometrium and myometrium of a uterus removed by vaginal hysterectomy. 2. 2. Although sarcoidosis is a systemic affection with multiorgan involvement, localization in the uterus is extremely rare. A survey of the literature discloses reports of only five previous instances of uterine sarcoidosis. 3. 3. Though in three cases curettage was performed for abnormal bleeding, it seems unlikely that the sarcoid uterine granulomas were responsible for the symptoms. 4. 4. The finding of tuberclelike granulomas in the endometrium or myometrium should alert one to the possibility of sarcoidosis. The diagnostic criteria of this disease are described. Differentiation must be made from tuberculous and foreign body reactions.

Inhibitory Action of Testosterone Propionate on the Human Ovary

Summary and Conclusions Two women with regular menstrual cycles were injected with testosterone propionate (925 and 1,225 mg), in order to determine whether ovtilation could be inhibited. In one patient, the ovaries, examined on the 34th day of the cycle, showed no evidence of a recent corpus luteum or mature graafian follicle. In the second patient, examination of the ovaries, on the 17th day of the cycle, did not reveal any evidence of ovulation. In the latter case, while ovulation might have occurred after the 17th day, it was deemed unlikely in an individual with a regular 26 to 28 day cycle. It appears from this study that testosterone propionate, if administered in adequate amounts to the cyclical human female, can inhibit full follicle maturation, ovulation and corpus luteum formation, associated with regressive changes in the endometrium and vaginal mucosa. The question arises as to whether the testosterone propionate acts directly upon the follicular apparatus or indirectly through inhibition of the gonadotropic activity of the pituitary. In view of the fact that testosterone has been shown to suppress the gonadotropic activity of the hypophysis in post-menopausal women14 15 and rats,16-18 it is logical to conclude that the inhibitory effect of testosterone propionate upon the human ovary is mediated through the pituitary.

Massive puberty hypertrophy of the breasts

Abstract A case of puberty hypertrophy of the breasts in a girl of fourteen years is described, including endocrinologic studies. The pathologic anatomy indicates a marked hyperplasia of the glandular and connective tissue elements with preservation of the unripe lobular structure ordinarily encountered at puberty. The hormonal factors responsible for mammary growth are discussed and a correlation made with normal physiologic development of the breast. The weight of evidence indicates that the estrogenic hormone and possibly also the corpus luteum hormone is directly responsible for growth of the breast and is concerned in the etiology of puberty hypertrophy.