Male Repro Tract Pathology Flashcards
GDPP
Gonadotropin-dependent premature puberty
Due to early maturation of the hypothalamic pituitary gonadal axis
More than 80% idiopathic
Almost all idiopathic cases are in girls
Causes of GDPP
Idiopathic
CNS lesions – hamartomas
Other CNS tumors – astrocytoma, ependymoma, pinealoma, optic and hypothalamic glioma
CNS irradiation, hydrocephalus, cysts, trauma, inflammatory disease, congenital midline defects
Previous excess steroid exposure
Primary hypothyroidism – regresses with thyroxine therapy
What is a genetic cause of GDPP premature male puberty?
Gain of function mutations in Kisspeptin 1 gene and KISS-1R
Loss of function mutations in MKRN3
GIPP
Gonadotropin-independent premature puberty
Due to excess secretion of sex hormones derived from gonads or adrenal glands, exogenous sources of steroids, or ectopic production of gonadotropin from a germ cell tumor
May be genre appropriate or inappropriate
Isosexual GIPP
Leydig cell tumors
Human chorionic gonadotropin (hCG) secreting germ cell tumors
Dysgerminomas to embryonal cell carcinoma and choriocarcinoma
What can cause familial male limited premature puberty?
Activating mutation in LH receptor gene
Rare
What are some adrenal pathologies that may lead to premature puberty?
Androgen secreting tumors
Enzymatic defects and adrenal steroid biosynthesis – 11 beta hydroxylase deficiency, 3B-HSD deficiency, hexose 6 phosphate DH deficiency, PAPSS2 deficiency
Estrogen secreting tumors
Androgen and estrogen secreting tumors
What are some other causes of premature male puberty?
Exogenous estrogen
Pituitary gonadotropin secreting tumors
McCune Albright syndrome - rare, triad of peripheral premature puberty, cafe au lait skin pigmentation and fibrous dysplasia of bone
What causes incomplete premature puberty?
Due to increased adrenal androgen production
Isolated male hormone mediated sexual characteristics (pubic/axillary hair, acne, and apocrine odor)
What labs should you do to evaluate premature male puberty?
Basal LH levels, if elevated –> GDPP
If not elevated stimulated with GnRH agonist –> elevated LH and FSH means GDPP, lack of significant increase means GIPP
What should you do if you have determined GDPP with initial labs?
Get a pituitary MRI
Measure estradiol, testosterone, TSH, free T4
GH if prior cranial irradiation
What should you do if you have determined GIPP with initial labs?
Get testosterone, estradiol, LH, FSH, cortisol and DHEA, DHEAS, 17-hydroxyprogesterone, hCG
If hCG elevated and tumor in mediastinum a karyotype for Klinefelter syndrome recommended for mediastinal germanium
Testicular ultrasound
Treatment for GDPP
Direct therapy toward underlying pathology for identifiable CNS lesions
Exception – benign hypothalamic hamartoma
Majority require treatment with GnRH agonist – Leuprolide
*Primary goal is to achieve normal adult height –> DO NOT treat to address perceived psychosocial consequences
How should GDPP be followed?
Measure LH and sex steroid levels prior to 2nd or 3rd monthly doses or after change in dose
Measure bone age every 6-12 months
Success can be measured by performing a diagnostic GnRH agonist stimulation test
Continue treatment until 12 years of age or however long desired
Normal puberty returns on average 17 months after stopping therapy
Treatment fro GIPP
Requires addressing the underlying cause
Tumors require surgery
Radiation and chemo may be necessary depending on the site and histological type
Identify and remove exogenous steroid sources
Glucocorticoids for congenital adrenal hyperplasia
Anti-androgens with aromatase inhibitor if needed for McCune Albright syndrome
Familial male limited premature puberty treated with spironolactone (anti-androgen) and testolactone (aromatase inhibitor)
Ketoconazole - androgen inhibitor
