CHALLENGES IN GYNECOLOGY
| CURRENT CONCEPTS IN GALACTORRHEA/HYPERPROLACTINEMIA —Roland Sakiyama, MD, Professor of
Family Medicine, David Geffen School of Medicine at the University of California, Los Angeles
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| Prolactin: normal levels <20 ng/mL for women; lower levels usually for men; secreted from anterior pituitary gland; suppressed
by prolactin inhibitory hormone (PIH); dopamine main component of PIH; elevated prolactin levels with altered
hypothalamic-pituitary axis (by surgery, trauma, or tumor); patient can have elevated prolactin and no galactorrhea or elevated
prolactin with galactorrhea; prolactin disorders—galactorrhea, oligomenorrhea, amenorrhea, and infertility;
prevalence of galactorrhea—0.1% to 30%; low incidence among nulligravid women and women with normal menstrual
periods; higher incidence among parous women and those with irregular menses
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 | Pituitary tumors: 20%; 34% if amenorrhea also present; amenorrhea with pituitary tumor known as Forbes-Albright syndrome;
prolactinoma most common functioning pituitary tumor (60% of functioning tumors and 33% of all pituitary
tumors); occurs in women and men; women usually present with microadenomas (defined as <1 cm) because symptoms
(eg, irregular periods, galactorrhea, infertility) more apparent than in men, who are generally diagnosed with
macroadenomas; tumor can secrete growth hormone and prolactin
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| Parapituitary lesions: causes—hypothalamic (eg, sarcoidosis, tuberculosis, tumors, trauma), pituitary stalk resection,
meningioma, craniopharyngioma, and empty sella syndrome
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| Oral contraceptives (OCs): of women with galactorrhea, 10% to 14% take OCs; prolactin elevated in about one third of
women taking OCs
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| Drug-induced galactorrhea: usually associated with—central nervous system (CNS) medications (phenothiazine, haloperidol
[Haldol], tricyclic antidepressants [TCAs], selective serotoin reuptake inhibitors [SSRIs], anxiolytics); blood
pressure medications (eg, reserpine, methyldopa [Aldomet]); gastrointestinal (GI) drugs (eg, metoclopramide [Reglan],
H2- receptor blockers); verapamil; recreational drugs (cannabis); herbs—anise, blessed thistle, fennel, fenugreek seed,
marshmallow, nettle, red clover, and red raspberry
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| Hypothyroidism and prolactin: elevated prolactin level can occur with primary hypothyroidism (high thyroid-stimulating
hormone [TSH] and high thyroid-releasing hormone [TRH]); 2% to 5% of women with hypothyroidism have galactorrhea
(usually resolves with treatment of hypothyroidism); 20% of hypothyroid patients have hyperprolactinemia
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| Neurogenic stimulation: association unclear; mechanical breast stimulation, herpes zoster in trunk area, or surgery may
cause galactorrhea; breast-feeding discontinued <1 yr can cause galactorrhea
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| Idiopathic galactorrhea: ≈50% of patients seen in primary care; normal or minimally elevated prolactin level; high percentage
of patients with idiopathic galactorrhea have regular menses and normal prolactin level; breakdown of causes
of galactorrhea—prolactinoma 20%, hypothyroidism 5%, drugs 10%, miscellaneous 20%, and idiopathic 45% to 50%
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| Clinical evaluation: history—neural or local stimulation; menstrual and obstetric history; medications (prescribed, over-
the-counter [OTC], and herbal), CNS symptoms (headaches, visual changes); symptoms of prolactinoma—galactorrhea
(most common symptom), infertility (about one third of patients), headache (50% to 75%), and visual defects; more symptoms
with macroadenoma and longer periods of amenorrhea; galactorrhea—usually milky discharge; can be clear; yellowish
discharge may be sign of infection; can occur spontaneously or with manipulation; 50% of women unaware of breast
discharge; 50% of patients have unilateral milky discharge; physical examination—“milk” breast from base to nipple;
fluid comes from multiple ducts; fat globules should be present on microscopy (if in doubt, use oil stain); differential
diagnosis—ductal carcinoma, ductal ectasia, Paget’s disease, breast carcinoma, acute mastitis, adenofibrosarcoma, and
papillary cystadenoma; laboratory evaluation—TSH and prolactin; measure prolactin in morning (level varies throughout
day)
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| Hyperprolactinemia and hypothyroidism: increased TSH and decreased T4 ; treat with L-thyroxine; usually prolactin normalizes
in 3 to 6 mo and galactorrhea resolves; consider idiopathic galactorrhea if patient has normal prolactin and normal
menses
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| Prolactin and prolactinomas: higher prolactin level, more likely patient has prolactinoma or other pituitary tumor;
93% to 100% chance of prolactinoma or other pituitary tumor with prolactin level >200 ng/mL; 100 to 200 ng/mL, 50%,
20 to 100 ng/mL, 0 to 33%; prolactin >50 ng/mL—magnetic resonance imaging (MRI) with gadolinium of hypothalamus
and pituitary recommended; prolactin 20 to 50 ng/mL—if patient has regular menses, observe; MRI indicated if
patient has irregular menses; if MRI shows pituitary tumor—obtain formal visual fields; review other pituitary hormones
(adrenocorticotropic hormone [ACTH] and cortisol, TSH and T4 , leuteinizing hormone [LH] and follicle stimulating
hormone [FSH]); review estrogen level or obtain menstrual history; insulin-like growth factor used in acromegaly
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| Hyperprolactinemia and osteoporosis: increased risk; dual-energy x-ray absorptiometry (DEXA) scan or bone resorption
marker (N-telopeptide) recommended to measure rate of bone resorption
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| Treatment: galactorrhea does not require treatment for its own sake; indications—pituitary tumors, infertility, amenorrhea,
oligomenorrhea, osteoporosis, and disabling galactorrhea; natural history of women with hyperprolactinemia usually
stable; only 5% of microadenomas progress to macroadenomas; surgery—transsphenoidal resection generally not
first choice for treatment; medical therapy—almost always first choice; radiation therapy—usually third choice when
prolactinoma resistant to medical treatment or large, inoperable tumor
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| Medical therapy: bromocriptine (Parlodel) and cabergoline (Dostinex)—act at D2 dopamine receptor (dopamine
inhibitory hormone from hypothalamus to pituitary gland); Dostinex more specific, with longer duration of action than
Parlodel; goals for therapy—restore normal gonadal function, decrease tumor size, normalize prolactin, resolve galactorrhea,
improve CNS symptoms (headaches), and improve visual fields; medications do not cure prolactinomas; majority
begin to grow again if medication discontinued; prolactin level normalizes in 10% to 20% of patients taking medication
for 1 or 2 yr; Parlodel—start with nighttime dose of 0.625 to 1.25 mg with small snack; gradually increase to normalize
prolactin; patients may require 2 to 3 doses daily; adverse effects include postural hypotension and nausea (reason for
giving at nighttime with snack); headache or nightmares most common adverse effects; Dostinex— study shows more
effective than Parlodel and fewer gastrointestinal side effects (same rate of headache with either drug); long half-life; begin
with 0.25 mg twice weekly; measure prolactin level after 4 wk and gradually increase dosage
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| Pregnancy and prolactinoma: Dostinex and Parlodel potentially teratogenic; 1% to 5% increase in size of microadenoma
with pregnancy and ≈23% increase in size of macroadenoma; macroadenoma increasing in size may cause visual
compromise, so continuing medication during surgery recommended; monitor prolactin level routinely in patient with
macroadenoma who does not want to continue medication; no teratogenic effects in most women choosing to continue
medication in pregnancy
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| DIAGNOSIS AND MANAGEMENT OF BREAST CANCER —Darlene Miltenburg, MD, Assistant Professor of Surgery,
Texas A and M, Scott and White Hospital and Clinic, Temple, TX
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| Epidemiology: most common cause of cancer death in women after lung cancer; 1 in 9 women develop breast cancer if
they live to 85 yr of age; incidence—increase may be related to use of hormone replacement therapy (HRT); postmenopausal
estrogen-only therapy not thought to be associated with development of breast cancer; survival— improvement
in survival in last 20 yr attributed to screening mammography, chemotherapy, hormonal therapy, and radiation therapy;
survival not attributed to surgery, but decreased morbidity associated with improved surgery; mortality rate—highest
among black women, followed by white women, Hispanic, American Indian, Native Alaskan, Asian American, and
women from Pacific Islands
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| Clinical considerations: screening mammography— meta-analysis of 7 randomized controlled trials shows it saves
lives; start at 40 yr of age; no specific age for discontinuance of screening; should be individualized for each patient, taking
into consideration patient’s comorbid diseases; breast self-examination (BSE)—data show no benefit in saving lives, but
results in unnecessary biopsies; recommended women have awareness of normal breasts and changes; clinical breast
examination—should be part of woman’s periodic health assessment between 20 and 30 yr of age every 3 yr; yearly
mammography and breast examination recommended for women ≥40 yr of age; prevention—patient should be counseled
to avoid weight gain, engage in regular physical activity, and avoid or minimize alcohol consumption; alternative to estrogen
and progesterone for postmenopausal symptoms should be considered
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| Clinical presentations: nipple discharge—85% of women produce fluid; considered normal; 5% to 10% of cases of
spontaneous nipple discharge cancer; patient with persistent spontaneous discharge (with blood or yellow fluid) from only
one duct should undergo mammography (ductography and galactography not helpful) and be referred to surgeon; discharge
from multiple ducts considered normal; breast infection—treat early with antibiotics for 10 days and schedule reexamination;
if breast-feeding, instruct to continue or express milk and nurse on noninfected side (if discontinued, milk
stagnates in breast and infection continues); if infection does not resolve after 10 days, suspect breast abscess or cancer;
woman should undergo breast ultrasonography (US) if not lactating and be referred to surgeon for excisional biopsy
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| Palpable breast mass: patient <25 yr of age—mammography not recommended, breast too dense; breast US indicates
whether mass cystic or solid; if cyst resolves with aspiration, patient should be reexamined in 1 to 2 mo; if unresolved,
cyst should be excised; patient with solid mass should undergo excisional biopsy; fibroadenomas do not need to
be removed unless large; one third of fibroadenomas resolve, one third stay same, and one third grow larger; patient >25
yr of age—bilateral mammography and breast US recommended; remove mass if mammography and breast US negative;
US-guided core biopsy recommended if mass seen on breast US; stereotactic biopsy if mass seen on mammography;
needle-directed diagnostic modalities keep management options open and minimize number of patients with benign lesions
undergoing open surgical biopsy; progression from benign to malignant disease—believed to be continuum;
normal hyperplasia of breast can progress to atypical hyperplasia, ductal carcinoma in situ (DCIS), then invasive breast
cancer
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| Lobular carcinoma in situ (LCIS): not cancer; marker for increased risk for breast cancer; risk for both breasts and
all sites; risk increased 5 times with no family history, 20 times with family history
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| Ductal carcinoma in situ: usually presents as megacalcifications on screening mammography; microcalcifications not
palpable; important to recognize and adequately treat to prevent invasive breast cancer; diagnosis—usually made by stereotactic
breast biopsy (usually 6 cores); patient with thin breast or lesion close to surface requires placement of wire before
excision; treatment—lumpectomy with negative margins, followed by radiation therapy; 1 mm considered negative margin,
speaker obtains 2 mm; with positive margin and radiation therapy, patient at risk for local recurrence; simple mastectomy
(removal of breast tissue and nipple-areola complex) recommended for mass too large for good cosmetic result;
axillary lymph node dissection not necessary (cancer in duct, chance of metastases low); medical therapy—no chemotherapy;
tamoxifen daily for 5 yr reduces risk for recurrence; clinical breast examination every 6 mo for 5 yr, then annually; annual
mammography
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| Invasive breast cancer: in United States, ≈60% diagnosed in early stage (tumor <5 cm and ≤3 positive lymph nodes);
2 types, ie, invasive ductal (85%-90%) and invasive lobular (10%-15%); same treatment for both types; treatment
options—breast-conservation surgery (lumpectomy with negative margins, sentinel lymph node biopsy, or axillary
lymph node dissection followed by radiation therapy), simple mastectomy and sentinel node biopsy, or modified radical
mastectomy (simple mastectomy with removal of axillary lymph nodes); chemotherapy if tumor >1 cm or if tumor <1 cm
with positive lymph nodes; endocrine therapy if tumor hormone receptor-positive (tamoxifen for premenopausal women,
anastrozole [Arimidex] for postmenopausal)
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| Stage 3 breast cancer: tumor >5 cm or <5 cm with 3 positive lymph nodes, inflammatory breast cancer, or locally advanced
breast cancer; inflammatory breast cancer—erythema covering >50% of breast, occurring in last 3 mo; diagnosis
made clinically; skin biopsy obtained; erythema caused by invasion of lymphatics of dermis; mastitis differential
diagnosis; early diagnosis critical because of poor prognosis; neoadjuvant chemotherapy used initially to shrink tumor to
facilitate surgical removal; surgery is modified radical mastectomy (simple mastectomy with axillary lymph node dissection);
sentinel lymph node mapping generally not done; postoperative chemotherapy followed by irradiation of chest
wall; hormonal therapy after radiation therapy if tumor hormone receptor-positive
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Educational Objectives
| The goal of this program is to educate the listener about the diagnosis and treatment of galactorrhea/hyperprolactinemia and
breast cancer. After hearing and assimilating this program, the clinician will be better able to:
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| 1. State the causes of galactorrhea.
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| 2. Recognize the importance of galactorrhea as a sign of prolactinoma.
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| 3. Discuss the evaluation and management of galactorrhea.
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| 4. Determine when mammography screening should begin and be discontinued.
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| 5. Summarize the diagnosis and management options for a patient with a palpable breast mass, ductal carcinoma in
situ, or stage 3 breast cancer.
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Discussed on This Program
Anastrozole [Arimidex]
Bromocriptine mesylate [Parlodel, Parlodel Snap Tabs]
Cabergoline [Dostinex]
Haloperidol [Haldol, Haldol Decanoate 50, Haldol Decanoate 100]
Levothyroxine sodium (T4 ; L-thyroxine) [Levothroid, Levoxyl, Synthroid, Thyro-Tabs, Unithroid]
Metoclopramide [Maxolon, Metoclopramide Intensol, Octamide PFS, Reclamide, Reglan]
Promensil (isoflavone plant estrogens derived from red clover)
Reserpine [Rau-Sed, Sandril, Serpasil, Serpiloid]
Stinging nettle (Urtica dioica)
Tamoxifen citrate [Nolvadex]
Veralipride
Verapamil HCl [Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM]
Suggested Reading
Campos-Outcalt D: Clarifying the US Preventive Services Task Force’s 2005 recommendations. J Fam Pract
55(5):425, 2006; Lakhani SR et al: The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal
carcinoma in situ (DCIS)? Eur J Cancer [Epub ahead of print], 2006; Pena KS et al: Evaluation and treatment of galactorrhea.
Am Fam Physician 63(9):1763, 2001; Sahoo S et al: Defining negative margins in DCIS patients treated with
breast conservation therapy: The University of Chicago experience. Breast J 11(4):242, 2005; Wallace AE et al:
Women’s primary care providers and breast cancer screening: who’s following the guidelines. Am J Obstet Gynecol
194(3):744, 2006; Whitman-Elia GF et al: Galactorrhea may be clue to serious problems. Patients deserve a thorough
workup. Postgrad Med 107(7):165, 2000; Yazigi RA et al: Prolactin disorders. Fertil Steril 67(2):215, 1997.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Sakiyama was recorded at Office Gynecology/Women’s Health for Primary Care sponsored by the Office of Continuing
Medical Education at the David Geffen School of Medicine at the University of California, Los Angeles and
the UCLA Department of Family Medicine, held July 27-30, 2006, in Anaheim, CA. Dr. Miltenburg was recorded at
The Female Patient sponsored by Scott and White Hospital and Clinic, held June 19-23, 2006, in South Padre Island,
TX. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this
program.
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