Hyperprolactinemia

Neuroendocrine Regulation of Prolactin (PRL) Secretion

Dual hypothalamic regulation

Estrogen stimulates lactotrophs directly

Prolactin is secreted episodically with nocturnal surge

Manifestations of Hyperprolactinemia

Galactorrhea indicates elevated PRL in 10% of women and 99% of men

Amenorrhea: indicates elevated PRL in 15 % of women

Galactorrhea plus amenorrhea: indicates elevated PRL in 75% of women

Infertility: indicates elevated PRL in up to 33 % of women

Osteoporosis: increased with elevated PRL--due to estrogen lack. If have normal menses, do not get osteoporosis.

MECHANISMS OF REPRODUCTIVE DYSFUNCTION IN HYPERPROLACTINEMIA

Inhibition of pulsatile GnRH secretion

Interference with gonadotropin action in ovary

Interference with estrogen positive feedback

Inhibition of FSH-directed ovarian aromatase

Inhibition of progesterone synthesis by granulosa cells

Inhibition of 5-a-reductase enzyme in men, thereby decreasing the conversion of testosterone to DHT

DIFFERENTIAL DIAGNOSIS OF HYPERPROLACTINEMIA

Medications: neuroleptics, methyldopa, reserpine, metoclopramide, MAO inhibitors, tricyclic antidepressants, verapamil

Hypothalamic disease: tumors, sarcoidosis, non-secreting pituitary tumors, neuraxis irradiation, stalk section

Empty sella syndrome

Acromegaly

Prolactinomas

Idiopathic

DIAGNOSTIC EVALUATION

Basal PRL levels at least twice: dynamic testing nonspecific and worthless

PRL > 200 ng/mL = prolaetinoma or renal failure

PRL < 200 rig/mi. = prolaetinoma or any of the other causes

Routine H and P, SMA 20 and TSH excludes almost all above except hypothalamic and pituitary disease

TREATMENT

A.Idiopathic hyperprolactinemia: bromocriptine effective in 85 %

B.Microprolactinomas

Transsphenoidal surgery: initial cure rate 80-85 % with hte recurrence rate of

Radiotherapy: ineffective and

Bromocriptine: restore PRL to normal in 80-85%

Observation only; follow PRL. Repeat CT/MRI if PRL levels rise

Macroprohcfinomas

Surgery: cure rates < 50% and very much dependent on size with recurrence rates 20-50%

Bromocriptine: size reduction to <50% of original size in 50%, to 50% in 16% and to 10-337'o in 33%

First evidence of size reduction may occur after 6 weeks

Size reduction does not correlate with basal or nadir PRL or percentage reduction in PRL levels

In first 2-3 years, most will reexpand

After a few years, few reexpand

VIII.PREGNANCY AND PROLACTINOMAS

No teratogenicity or other untoward effects on fetus of bromocriptine in > 6,000 pregnancies

Risk of symptomatic microadenoma enlargement: 1.6%

Risk of symptomatic macroadenoma enlargement: 15.5 % if no previous surgery/irradiation but only 4.3 % if