Hyperprolactinemia/Hypogonadism
What is the general differential diagnosis of hyperprolactinemia?
- Pregnancy - Prolactinoma - Dopamine antagonism - Pituitary stalk disorder - Severe hypothyroid - Renal insufficiency/failure - Sarcoidosis
What tests do you want to perform when evaluating for hyperprolactinemia?
- TSH to eliminate hypothyroidism as a cause. - TRH in hypothyroidism will promote prolactin release - Pregnancy testing in premenopausal women in any setting of amenorrhea - Renal and liver function as prolactin is a peptide hormone - Pituitary MRI to evaluate for a pituitary/stalk lesion
During the menstrual cycle, what happens after the LH surge?
1) The follicle erupts through the ovarian surface 2) The remaining cells of the follicle terminally differentiate to form a corpus luteum
What is the typical length of therapy for hyperprolactinemia?
12-24 months
If a patient has a pituitary macroadenoma and only mildly elevated prolactin levels, when follow-up study should be performed?
A diluted serum prolactin study should be performed, as an extremely high prolactin level can be underestimated by the immunometric assays.
What is bromocriptine?
A dopamine agonist
Prolactin secretion in pregnancy promotes what?
Breast development in preparation for milk productions and then stimulates lactation postpartum
How does hyperprolactinemia lead to hypogonadism?
By alteration in hypothalamic control of gonadotropin secretion (decreases the "pulse" of gonadotropin release).
What is the role of LH in females?
Control of ovulation and follicular luteinization
What are the treatment determinants of hypogonadism?
Depends upon gender and desire for fertility
What are the steps in diagnosing hypogonadism in females?
Determine levels of: - LH - FSH - Estradiol - Prolactin - Thyroid function
What are the steps in diagnosing hypogonadism in males?
Determine levels of: - LH - FSH - Testosterone - Prolactin - Thyroid function
What is the medical treatment of choice in symptomatic hyperprolactinemia?
Dopamine agonist - bromocriptine mesylate - cabergoline (expensive, can't be used in pregnancy)
What hormone controls prolactin levels?
Dopamine provides negative control
What drugs can cause hyperprolactinemia?
Dopamine-receptor antagonists, dopamine-depleting agents, antipsychotics, metoclopramide, and others
What are the surgical indications for a prolactinoma?
Drug intolerance, tumors resistant to medical therapy, persistent visual-field defect despite medical trial, and large cystic/hemorrhagic tumor.
How do you treat a female with hypogonadism that is NOT interested in fertility?
Estrogen-progestin replacement
What is the clinical manifestation of hypogonadism in PRE-pubescent males?
Eunuchoidism: Sparse body hair, poor development of skeletal muscles, delay in epiphyseal closure (long arms and legs)
What is significant about the hormone levels hypogonadotropic hypogonadism?
FSH and LH are low for the levels of the sex hormones
What is the clinical manifestation of hypogonadism in PRE-pubescent females?
Failure to progress through puberty and/or primary amenorrhea
How do you treat a male with hypogonadism that IS interested in fertility?
Gonadotropins or gonadotropin-releasing hormones
Why is there no milk production pre-partum if prolactin levels are high?
High estrogen levels prevent lactation. In the post-partum period, estrogen levels drop, prolactin remains high, and milk production ensues.
How is thyroid function related to prolactin release?
In profound hypothyroidism, TRH release is increased which will increase prolactin levels
What is the predominant signal in prolactin secretion?
Inhibitory
How can prolactin excess effect GnRH?
It can impair the GnRH pulse generator function and hypogonadotropic hypogonadism
What is the role of FSH in females?
It controls follicular granulosa cell growth (i.e. follicle cell stimulation) and estradiol production
What cell types produce prolactin?
Lactotrophs
What type of prolactin adenoma do post-menopausal women typically present with?
Macroadenomas
How do you treat a female with hypogonadism that IS interested in fertility?
Ovulation induction with gonadotropin therapy or pulsatile GnRH
What population tends to have prolactin microadenomas more often?
Pre-menopausal women
Prolactinomas may increase in what setting?
Pregnancy
Contraindication for testosterone replacement?
Prostate tumor
How is prolactin cleared?
Renally
What are the treatment goals in hyperprolactinemia?
Resolving symptoms or reducing tumor size
What is the clinical manifestation of hypogonadism in POST-pubescent females?
Secondary amenorrhea
What is the clinical manifestation of hypogonadism in POST-pubescent males?
Severe fatigue and decreased sexual function are primary, but also have gynecomastia, decreased bone density and anemia
What feedback-inhibits FSH?
Sex steroids and the Sertoli cell product "inhibin"
What feedback-inhibits LH?
Sex-steroid mediation
In what states does prolactin secretion increase?
Sleep, stress, pregnancy and nipple/chest wall stimulation/trauma
What is the primary action of prolactin?
Stimulate breast epithelial cell proliferation and induce milk production
What is the effect of Gonadotropin-releasing hormone (GnRH) release?
Stimulates release of FSH and LH
What is the effect of LH in males?
Stimulates testosterone production fron Leydig cells in the testes
What is the effect of FSH in males?
Testicular growth and enhances the production of androgen-binding protein
How do you treat a male with hypogonadism that is NOT interested in fertility?
Testosterone replacement
What are the clinical manifestations of elevated prolactin?
galactorrhea, amenorrhea and infertility
What is secondary amenorrhea?
When a pre-menopausal woman has menses and then suddenly stops menstruating
How to prolactinomas differ in men compared to women?
They are often larger tumors and have mass effect, as well as impotence, decreased libido. Less often galactorrhea or gynecomastia.
What hormone serves as a stimulatory factor for prolactin release?
Thyrotropin releasing hormone
How is the diagnosis of prolactinemia typically made?
With the aid of laboratory studies