Case File

Case # 14
• A 30-year-old parous woman notes a watery breast
discharge of 6 months’ duration. Her menses have
been somewhat irregular. She denies a family history
of breast cancer. The patient had been treated
previously with radioactive iodine for Graves disease.
Currently, she is not taking any medications. On
examination, she appears alert and in good health. The
blood pressure (BP) is 120/80 mm Hg, and heart rate
(HR) is 80 beats per minute (bpm). The breasts are
symmetric and without masses. No skin retraction is
noted. A white discharge can be expressed from both
breasts. No adenopathy is appreciated. The pregnancy
test is negative.
Our Approach to patient
• ➤ What is the most likely diagnosis?
• ➤ What is your next step?
• ➤ What is the likely mechanism for this
disorder?
Summary:
• A 30-year-old parous woman with
irregular menses notes a watery
breast discharge of 6 months’
duration. She had been treated
previously with radioactive iodine for
Graves disease. The pregnancy test
is negative.
➤ Most likely diagnosis:.
➤ Next step:
➤ Likely mechanism:
➤ Most likely diagnosis:.
Galactorrhea due to
hypothyroidism
➤ Next step:
Check serum prolactin
and TSH levels.
➤ Likely mechanism: Hypothyroidism is associated with an
elevated thyroid releasing hormone
(TRH) level, which acts as a prolactin-
releasing hormone.
The hyperprolactinemia then induces
the galactorrhea.
Hyperprolactinemia
• Levels of circulating prolactin above normal
(>20 to 25 ng/mL) that can cause
galactorrhea or amenorrhea or both.
• The optimal time to obtain a blood sample
for assay to diagnose is during the
midmorning hours.
• Reference range
• Female - gravid/nonlactatin : 2-29 ng/ml
– Gravid : 10-29 ng/ml
– Male : 2-18 ng/ml


Prolactin
• Polypeptide hormone
• Contains 198 amino acids
• MW of 22,000 daltons.
• Different molecular sizes:
– Monomeric(small): 22,000 daltons
– Polymeric(big): 50,000 daltons
– Larger polymeric(big-big): > 100,000 daltons

FORMS
1. Larger forms - contain added sugar moieties
(glycosylation) which decreases biologic
activity.
2. Small form(80%) - biologically active
3. Polymeric forms - have reduced biologic
activity and reduced binding to mammary
tissue membranes.



8
• Synthesized and stored in the pituitary gland
in chromophobe cells (lactotrophs), which are
located mainly in the lateral areas of the gland

• Encoded by its gene (10 kb) on chromosome 6

Prolactin
9
• At the molecular level, it is stimulated and
suppressed by multiple factors.

– Thyroid-releasing hormone(TRH) - Principal
stimulating factor
– Dopamine - Major inhibiting factor
– Estrogen - Enhances the effects of TRH and
inhibits the effects of dopamine
– Galanin - May also mediate a potential direct effect
Prolactin 10
• In addition, PRL is synthesized in decidualized
stroma of endometrial tissue.

• From these tissues PRL is secreted into the
circulation and, in the event of pregnancy, into
the amniotic fluid.

• The control of decidual PRL is different from
that of the pituitary and does not respond to
dopamine.
Prolactin 11
• Normally present in measurable amounts in
serum

• Mean levels of about 8 ng/mL in adult women

• Circulates in an unbound form

• 20-minute half-life

• Cleared by the liver and kidneys


Prolactin 12
• Main function is to stimulate the growth of
mammary tissue as well as to produce and
secrete milk into the alveoli(mammogenic and
lactogenic).

• Specific receptors for PRL are present in the
plasma membrane of mammary cells as well
as many other tissues
Prolactin
13

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