Case 3 (jb David Deo Glenn Cap)

Villegas, Jose Bernabe Vinluan, Joseph Wong, Deo Adiel Yague, Glenn Yang, Caprice

GYNECOLOGY Section III-D6 Dr. Teresa Luna

Case #3 A 17 year old, single, nulligravid consulted because of absence of menses. She denies having cyclic crampy pains. On PE, the breasts are well developed with pale areola. There is moderate amount of axillary hair and pubic hair. Abdomen is flat, soft, no masses palpated. The hymen is intact. On proving into the vagina, the cotton tip applicator can be inserted up to 2 cm from the hymen. On rectal examination, there is no mass palpated. 1. What additional data should be asked in the history? a. It is important to ask the patient if she had began her menstrual periods. What age? This is to determine whether the case is a primary or secondary amenorrhea. b. If she had began her menses, ask further questions like when did her last period start, and, if possible, the one before that? How often does she have periods (as measured by the intervals between the first days of successive periods)? Are they regular or irregular? How long do they last? How heavy is the flow? c. It is also necessary to ask if the patient had recent sexual contact to check for the possibility of a pregnancy. d. Ask if there is any difficulty in urination to determine if there is obstruction by a mass located proximal to the urethra and introitus. e. Medications that decrease production of hormones that aid in ovulation might as well be asked. f. When primary amenorrhea is owing to pituitary-hypothalamic disorders, additional symptoms related to its underlying cause or to the loss of specific tropic hormones may occur. Ask for headaches, visual disturbances, polydipsia, polyuria, easy fatigability or episodic weakness and failure of the skin to tan. g. Ask for increases in body and facial hair to check for possible polycystic ovaries h. Some patients present with a history of voiding difficulties, urinary incontinence, or recurrent urinary tract infections (UTIs). Might as well ask for them for possible Mayer-Rokitansky Syndrome. 2. What is the term to describe her chief complaint? (Primary) amenorrhea What are the different causes of this condition? Etiologies of amenorrhea are categorized by where in the hormone cascade the lesion is.

Hypothalamic Causes of Amenorrhea All hypothalamic causes result in ↓ FSH / LH levels: - Kallman’s syndrome : Congenital lack of GnRH - Pituitary stalk compression : Tumors, granulomas, irradiation - ↓ GnRH release : Stress, anorexia, hyperprolactinemia, severe weight loss, extreme exercise Pituitary Causes of Amenorrhea All pituitary causes result in ↓ FSH / LH levels: - Sheehan’s syndrome : Pituitary infarction resulting from hypotension during delivery, usually resulting from hemorrhage - Tumors : Either compress stalk or are prolactin-secreting tumors - Hemosiderosis : Iron deposition in pituitary that impairs its function Ovarian Causes of Amenorrhea All ovarian causes result in ↑ FSH / LH levels: - Premature ovarian failure : Menopause before age 35 - Savage’s syndrome : Ovarian resistance to FSH / LH - Enzyme defects : Most commonly 17α- hydroxylase deficiency - Turner’s syndrome (XO karyotype) : Ovarian dysgenesis - Polycystic ovary disease (PCOD) : ↑ Estrogen levels cause ↑ LH levels, which cause abnormal follicular growth and androgen secretion. Uterine Causes of Amenorrhea - Imperforate hymen - Uterine causes have normal levels of FSH / LH - Congenital absence of uterus - Asherman’s syndrome : Uterine scarring and adhesions following dilatation and curettage 3. What is the diagnosis? Mullerian agenesis refers to a condition in a female where the mullerian ducts fail to develop and a uterus will not be present. Primary amenorrhea is a leading symptom. No uterus, no upper 1/3 of the vagina short vagina, but with ovaries. (Ovaries come from germinal epithelium) Lower 2/3 of vagina  comes from lower urogenital sinus Since ovaries are present, breasts will develop

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Signs and symptoms A woman with this condition is hormonally normal, that is she will enter puberty with development of secondary sexual characteristics including thelarche and adrenarche. Her chromosome constellation will be 46,XX. Ovulation usually occurs. Typically, the vagina is shortened and intercourse will be difficult and painful. Medical examination supported by gynecologic ultrasonography demonstrates a complete or partial absence of the cervix, uterus, and vagina. Since there is no uterus, women with MRKH cannot carry a pregnancy. However, it is possible for these women to have genetic offspring by in vitro fertilisation (IVF)and surrogacy. Uterine transplantation is currently not a treatment that can be offered as the technology is still in its infancy. Women with MRKH typically discover the condition when, during puberty years, the menstrual cycle does not start. Some women find out earlier through surgeries for other conditions, such as a hernia. Other, less common symptoms include kidney problems, hearing loss, and bone malformations. 4. What ancillary procedure should be requested? Initial evaluation after careful history and physical examination includes: Serum or urine human chorionic gonadotropin – to rule out the possibility of pregnancy. Serum prolactin assay – to consider the possibility of a pituitary problem; and, Evaluation of estrogen status – with administration of 100mg progesterone in oil IM, if estrogen levels are adequate and the outflow tract is intact, menstrual bleeding should occur within one week of ending progestin treatment. If there is no withdrawal of menses, then: Measurements of normal circulating levels of leutinizing hormone (LH) and follicle-stimulating hormone (FSH) should be done to indicate appropriate ovarian function. Anatomic defects are usually diagnosed by physical exam and failure to induce menses, though hysterosalpingography or direct visual examination by hysteroscopy maybe required. Hysterosalpingography is a radiographic procedure that uses contrast media to visualize the outlines of the endometrial cavity and fallopian tubes. Hysteroscopy, on the other hand, is a diagnostic procedure that uses a tubular optical or video device and light source to visualize the uterine cavity, aided by fluid distention. However, in this case, the latter two procedures ought not be performed because of a suspected gonadal dysgenesis, which maybe better diagnosed thru chromosomal analysis.

Chromosomal analysis is essential to exclude karyotypic abnormalities. Basically, chromosome analysis can be done on any tissue you can grow. The most common are peripheral blood and bone marrow. The blood is mixed with an anticoagulant (heparin), is incubated at body temperature, and the WBCs are grown on tissue culture until a sufficient number for chromosome analysis is reached (3-4 days). Of the many indications for cytogenetic analysis includes confirmation of a suspected classical chromosomal syndrome, primary amenorrhea/secondary amenorrhea of unknown etiology, pubertal failure in either sex and ambiguous genitalia. In general, signs of a genetic disorder will fall under three categories: growth abnormalities, abnormal/subnormal intelligence or physical characteristics. Based from these, amenorrhea and the finding that the applicator tip can be inserted up to 2cm from the hymen give good reason for performing chromosomal analysis on our patient. Have in mind that the previous procedures were based on the algorithm of managing a patient presenting with amenorrhea, with the students being open to the possibility that the patient has a chromosomal problem. Furthermore, to help establish congenital abnormalities, an ultrasound maybe used. It makes use of high frequency sound waves to create images. Also, it easily depicts upper level of the vagina and its length (to identify any obstruction) even up to the fallopian tubes. Other optional imaging studies that maybe used are magnetic resonance imaging (to clarify inconclusive sonography results, assess subperitoneal structures, visualize cervix), laparoscopy (indirect assessment of uterine cavitation), pyelography (if there is a need to assess renal structure) and radiography (if you suspect a concomitant vertebral anomaly). 5. What is the recommended management? Management issues in syndromes of androgen insensitivity include decisions on sex assignment, timing of gonadectomy in relation to tumour risk, and genetic and psychological counselling. (1) Although controversial, most endocrinologists agree that gonadectomy may be performed after puberty with minimal risk of testicular neoplasm. (2) In patients with complete androgen insensitivity, the testes should be removed after pubertal development is complete to prevent malignant degeneration. In patients with testes, 52% develop a neoplasia, most often a gonadoblastoma. In patients who develop virilization and have an XY karyotype, the testes should be removed immediately to preserve the female phenotype and to promote female gender identity. Bilateral laparoscopic gonadectomy is the preferred procedure for the removal of the intraabdominal testes. Such patients are treated as normal but infertile, hypogonadal women; hence should be informed regarding the issue of infertility. Considering that the patient has Mayer-Rokitansky-Kuster-Hauster Syndrome, in which there is hypoplasia or absent uterus, cervix, and vagina, the appropriate

management of the anomaly includes the creation of a neovagina, and various surgical or non-surgical techniques have been described. Among them the Creatsas modification of Williams vaginoplasty is an operative technique (3). If the vagina is absent or short, progressive dilation is usually successful in making it functional. If dilation fails or if patient is unable to perform dilation, the McIndoe split thickness graft technique may be performed. The initial use of vaginal dilators is required to maintain a functional vagina.

REFERENCES: (1) Best Pract Res Clin Endocrinol Metab. 2006 Dec;20(4):577-98. Androgen resistance. Hughes IA, Deeb A. Department of Paediatrics, University of Cambridge, Box 116, Level 8, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. [email protected] (2) Am Surg. 2005 Mar;71(3):241-3. Complete androgen insensitivity syndrome: the role of the endocrine surgeon. Alvarez NR, Lee TM, Solorzano CC. (3) Eur J Obstet Gynecol Reprod Biol. 2007 Apr;131(2):248-52. Epub 2007 Mar 12. Expert opinion: vaginal aplasia: creation of a neovagina following the Creatsas vaginoplasty. Creatsas G, Deligeoroglou E. (4) Berek, J.S. Novak’s Gynecology 14th Edition. Lippincott Williams and Wilkins. Copyright 2007. (5) Bickley, L.S. Bates’ Guide to Physical Examination and History Taking 9 th Edition. Lippincott Williams and Wilkins. Copyright 2007. (6) Friedman, H. H. Problem-Oriented Medical Diagnosis 7th Edition, Lippincott Williams and Wilkins. Copyright 2001.