7/31/2019 Nej m Cpc 1004359

1/9

case records of themassachusetts general hospital

T h e n e w e n g l a n d j o u r n a l o f medicine

n engl j med 363;2 nejm.org july 8, 2010178

Founded by Richard C. CabotNancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor

Jo-Anne O. Shepard, m.d.,Associate Editor Alice M. Cort, m.d.,Associate EditorSally H. Ebeling,Assistant Editor Christine C. Peters, Assistant Editor

From the Neuroendocrine Unit (A.L.U.)and the Departments of Radiology (P.W.S.)and Pathology (M.S.), Massachusetts Gen-eral Hospital; and the Departments ofMedicine (A.L.U.), Radiology (P.W.S.), andPathology (M.S.), Harvard Medical School both in Boston; and the Pituitary Cen-ter, Vanderbilt University Medical Center,Nashville (A.L.U.).

N Engl J Med 2010;363:178-86.Copyright 2010 Massachusetts Medical Society.

Presentation of Case

Dr. Elizabeth Guancial (Medicine): A 32-year-old woman was evaluated because of oli-gomenorrhea and diff iculty becoming pregnant.

Menarche had occurred at 12 years of age and menses were regular until thepatient began taking oral contraceptives at 20 years of age. At 25 years of age, shediscontinued oral contraceptives and irregular menstrual cycles developed, rang-ing from 31 to 51 days, with menstrual flow of 7 days duration. Between the agesof 28 and 32 years, she had unprotected coitus with her husband but did not con-ceive. At 32 years of age, her primary care provider referred her to a gynecologistbecause of infertility. The patient reported that testing with over-the-counter ovula-tion-predictor kits did not show evidence of ovulation. Pelvic examination revealedno abnormalities. Clomiphene citrate was administered (100 mg on days 5 through9 of the menstrual cycle). Laboratory-test results are shown in Table 1. A hystero-salpingogram was normal.

Two months later, the patient was seen in the reproductive endocrine clinic ofanother hospital. She reported frequent acne and facial hair that she removed manu-ally. She had no pain with menstruation and no intermenstrual bleeding. Papani-colaou smears had been normal, and there was no history of sexually transmitteddiseases, use of intrauterine devices, or exposure to diethylstilbestrol. Her onlymedications were prenatal vitamins and folate, and results of hemoglobin electro-phoresis and cystic fibrosis screening tests had reportedly been normal. Clomi-phene citrate (150 mg) was administered (on days 5 through 9 of the cycle). Ultra-

sonography of the pelvis revealed that the endometrium was 8.8 mm thick andhomogeneously echogenic; fluid and echogenic material that was thought to beblood was present in the cavity, and 5 to 10 simple cysts were present in the rightovary. Laboratory-test results are shown in Table 1.

One month later, the serum level of human chorionic gonadotropin was elevated;ultrasonography revealed a single intrauterine fetus. Routine laboratory-test resultswere normal. The pregnancy was complicated by gestational diabetes mellitus,which was diet-controlled. After a 40-week gestation, the patient delivered a healthyinfant by means of spontaneous vaginal delivery. She breast-fed her child for 12months and had one spontaneous episode of menstrual f low during that time. Glu-

Case 20-2010: A 32-Year-Old Womanwith Oligomenorrhea and Infertility

Andrea L. Utz, M.D., Ph.D., Pamela W. Schaefer, M.D., and Matija Snuderl, M.D.

The New England Journal of Medicine

Downloaded from nejm.org on July 14, 2012. For personal use only. No other uses without permission.

Copyright 2010 Massachusetts Medical Society. All rights reserved.

7/31/2019 Nej m Cpc 1004359

2/9

case records of the massachusetts general hospital

n engl j med 363;2 nejm.org july 8, 2010 179

cose intolerance persisted, but she declined treat-ment. She had frequent headaches, attributed tosinusitis.

When the patient was 34 years of age, com-puted tomography (CT) of the sinuses, performedbecause of persistent frontal headaches and na-sal discharge, revealed a lesion in the sella. Mag-

netic resonance imaging (MRI) performed 11 dayslater revealed a lesion (2.8 cm by 2.4 cm by 2.4 cmand isointense to gray matter on T

1-weighted

and T2-weighted images) that extended into the

suprasellar region and abutted the optic chiasm,with mild compression and possible invasion ofthe right cavernous sinus. With the administrationof contrast material, mild patchy enhancementwas evident. The skull was diffusely thickened,and the frontal sinuses were prominent. Resultsof laboratory tests are shown in Table 1. The pa-tient was referred to the neuroendocrinology clinic

of this hospital.The patient reported decreased libido after

stopping oral contraceptives, intermittent hotflashes accompanied by palpitations, and amen-orrhea for almost 1 year. She had occasionalfloaters in her vision but no loss of peripheralvision. She had chronic pain and stiffness in theknees, shoulders, and hands, as well as occasionalnumbness and tingling in the hands, which hadbeen occurring for approximately 13 years. Duringthe same period, increasing numbers of coarsedark hairs grew on her face; darkening of theskin of the back of her neck, axilla, and groinoccurred; her weight had increased 18.1 kg; andsnoring, fatigue, and occasional daytime somno-lence, suggestive of obstructive sleep apnea, de-veloped. Her shoe size had increased from size7 (European size 38) medium to size 8 (Europeansize 39) double-wide, her ring size had also in-creased, and she thought that her nose had be-come larger. She did not have abdominal pain,nausea, vomiting, diarrhea, dizziness, chest pain,respiratory symptoms, peripheral edema, or ex-

cessive thirst or hunger or polyuria. Approximately2 years earlier, during her pregnancy, a sharpheadache, associated with visual changes, haddeveloped during an airplane flight to anothercity. CT scans of the brain at a local hospital re-portedly showed evidence of left frontal sinus-itis. After receiving the report of the abnormalCT shortly before the present evaluation, she con-tacted the other facility and was told that the re-port of the earlier CT had described expansionof the sella turcica.

For the previous 2 years, the patient had hadintermittent episodes of acute sinusitis, treatedwith antibiotics and nasal spray, and seasonalenvironmental allergies; plantar warts had beenexcised, and wisdom teeth had been extracted inthe past. She lived with her husband and baby,worked in academics, drank alcohol rarely, and did

not smoke or use illicit drugs. She was of whiteand Asian ancestry. Her mother had high choles-terol and osteoporosis; her father was obese, withperipheral edema and prostatic hypertrophy; anda maternal aunt had diabetes mellitus type 2.Medications included vitamins, calcium, n3 fishoil, topical tretinoin, benzoyl peroxide, and lorata-dine as needed. She had no known allergies tomedications.

The vital signs were normal. The weight was74.8 kg, the height 162.6 cm, and the body-massindex (the weight in kilograms divided by the

square of the height in meters) 29.2. The face andnose were broad, the brow was prominent, andthe teeth and jaw revealed a slight underbite; therewas no macroglossia. There was facial acne, mul-tiple skin tags, and acanthosis nigricans. Thehands were large, and the fingers were thick. Theremainder of the examination was normal.

A diagnostic test was performed.

Differential Diagnosis

Dr. Andrea L. Utz: This woman presented at 32 yearsof age with the very common condition of inter-mittent oligomenorrhea. The differential diagno-sis for secondary oligomenorrhea and amenorrheais broad and includes physiological causes, suchas pregnancy, lactation, and menopause; anatomi-cal causes, such as Ashermans syndrome (acquiredintrauterine adhesions); and multiple causes of ano-vulation. This patient had evidence of anovulation.

Anovulation

Anovulation may be caused by either ovarian im-

pairment or dysregulation of the cyclicity of go-nadotropin secretion. Ovarian dysfunction is mostcommonly due to autoimmune destruction of theovary, chemotherapeutic agents, pelvic irradiation,or genetic abnormalities (e.g., Turners syndromeor premutations for the fragile X syndrome). Sup-pression or disruption of the rhythm of gonado-tropin release can be caused by lesions of the hy-pothalamus, lesions of the infundibulum or thepituitary or both, malnutrition or excessive energyexpenditure, other hormonal dysfunction (e.g., hy-

The New England Journal of Medicine

Downloaded from nejm.org on July 14, 2012. For personal use only. No other uses without permission.

Copyright 2010 Massachusetts Medical Society. All rights reserved.

7/31/2019 Nej m Cpc 1004359

3/9

T h e n e w e n g l a n d j o u r n a l o f medicine

n engl j med 363;2 nejm.org july 8, 2010180

Table1.ResultsofLaboratoryTests.*

Variable

ReferenceRange,Adults

3

2YrofAge,GynecologistsOffice

2MoLater(32YrofAge),

ReproductiveEndocrineClinic

1WkbeforeNeuroendocrine

Evaluation(34YrofAge),

OtherHospital

3rdDayof

Menstrual

Cycle

10thDayofCycle

(after100mg

Clomiphene

onDays59)

30thDayofCycle

3rdDayof

Menstrual

Cycle

10thDayofCycle

(after150mg

Clomiphene

onDays59)

30th

DayofMenstrualCycle

Thyrotropin(IU/ml)

0.35.5

0.9

1.4

Estradiol(pg/ml)

Follicularphase,0212;midcycle,

0480;lutealphase,0247