Prolactinoma Unresponsive to Conventional Therapy


a 21 yr old man ,presented with headache for 6 monhs and RT eye decreased vision for 6 months .on ophthalmological evalutation found to have both eyes temporal pallor,bitemporal field defect more in the rt eye.MRI brain was done suggestive of a sellar and suprasellar mass measuring 4.2x3.4x2.5cm isointense to hypointense on T1WI and hyperintese on T2WI ,with heterogenous enhancement with contrast with subfrontal cyctic component on rt side and lt parasellar extension ,optic chaismatic compression present - suggestive of pituitary macroadenoma.hormonal profiles LH/FSH,FT4,TSH,TESTOSTERONE-NORMAL LEVELS.only PRL was >470ng/dl above the detectable levels.

Pt undewent endoscopic transphenoidal excision of tumour on 1/9/2006,the histopathological diagnosis was pituitary macroadenoma,immunochemistry was s/o prolactinoma.

The present problem is he ,after post operative scan after 1yrs and 2yrs was only minimal decrease in tumour size & the mass is surrounding the internal carotid in the rt side,mass is abutting the stalk. and the prolactin levels were in the range of (1350-700ng/dl) after maximum dose of t.cabergoline therapy 2mg thrice a week for almonst 6-8 months of therapy. P resently his testo is 2.5ng/ml(just below the normal),prl-752.he is only on cabergoline therapy.his HP axis,thyroid axis is normal.his present visual fields are stable. Question is to further manage this case?

2.if to plan for Radio Therapy he is 21 yrs -the chance of hypopit after RT?

3.if surgery ?difficult surgery because the mass is encasing the carotid?

thnaks. dr arun kannan

RE SPONSE-You really are dealing with a difficult case ! I would like to see his MRI´s, but in fact it seems to be a giant, invasive prolactinoma with neurological and visual complaints. Loss of libido was nor described in your report, but it seems to be likely due to the high prolactin and low testosterone levels presented by the patient. Endoscopic transsphenoidal approach improved headache and visual impairment but serum prolactin persisted high, paralleled by low testosterone levels. Treatment with high dose cabergoline did not improve his hormonal profile and, albeit not clear in your report, probably the tumor size was not reduced. This scenario points to a resistant macroprolactinoma.


to another dopamine agonist would be highly improbable, as cabergoline is currently considered the gold standard drug. Radiotherapy, besides the induction of hypopituitarism, brings the potential risk of neurologic, neuropsychiatric and visual impairment. Moreover, prolactin control, if occurs, usually takes a considerable time. I could suggest the following options:

1. A second surgery, either by extended endoscopic transsphenoidal approach or by transscranial route. Even considering that this particular case probably will not be cured even with sophisticated techniques performed by skilled surgeons, evidences from our group suggest that an extensive tumor debulking can improve the response to dopamine agonist drugs in partially resistant prolactinomas.

2. If sexual impairment is the main clinical complaint, testosterone replacement would be a reasonably approach. Nevertheless, androgen treatment often is less effective in the presence of hyperprolactinemia. Additionally, testosterone aromatization to estradiol may increase prolactin levels and tumor size, a complication that may be lessened by the concomitant use of an aromatase inhibitor.

3. Some reports point to temozolamide effectiveness in aggressive prolactinomas and in pituitary carcinomas. This drug is an alkilating agent used for the treatment of brain tumors as gliomas. Of course you need to evaluate in this particular case if the side-effects of temozolamide do not overcome its potential therapeutic effectiveness.

Best regards, Marcello D. Bronstein, MD

15 Year Old Girl with Hirsutism


Here I send my question about the girl with hirsutism once more, now with the units of the laboratory tests. . She is 15-years old.Her problem is hirsutism. She has a beard, hair on chest, back and lower abdomen and limbs. She has developed and grown up normally, menarche at age of 13. Last menstrual periods 7 months ago. With dydrogesterone 10 mg for 10 days, one day uternal bleedinq. No family history of hirsutism. Hirsutism started two years ago. Height 160 cm, weight, 58 kg. No signs of Cushing syndrome. Blood pressure normal. On abdominal ultrasound scan, uterus and ovaries normal. Here are her laboratory test results: Prolaktin 55.76 ng/ml ( 3.26-29.12 ng/ml) TSH 2,1 mU/l T4 1,37 pmol/l Testosterone 4.2 nmol/l (0.3-1.4 nmol/l) DHEAS 418 mikrog/dl (39-288 mikrog/dl) 17-Hydroksiprogesteron 0.3 ng/ml ( 0.3-1 ng/ml) There are Prolactin, testosteron and DHEAS elevated. 17-hydroksi progesterone was normal so it not CAH? Is this PCOS? What do you advice? Thank you for your help! Dr. Heli Efendi


The case you describe has features both typical for and atypical of PCOS. The following are consistent with PCOS: peripubertal onset, vaginal bleeding upon challenge with progestin, and elevation of testosterone level. The one feature that raises concern for another diagnosis (CAH has been excluded, Cushing’s seems unlikely) is the magnitude of the elevation of the testosterone level and the fact that she may have some evidence of virilization (does she have clitoromegaly or temporal balding? Any changes in muscle bulk?). This raises concern for the relatively rare conditions of hyperthecosis or ovarian neoplasm. The ultrasound findings are reassuring in this regard, but may not be definitive. The elevated prolactin level can be seen in PCOS and is thought to be due to a combination of increased GnRH pulse frequency and/or the effects of estrone to sensitize the lactotropes to the GnRH stimulus. In short, you may wish to consider more detailed imaging of the ovaries with CT or MRI. If these are negative, I would feel comfortable with the diagnosis of PCOS.

Treatment is most likely to involve an oral contraceptive with or without the addition of an antiandrogen. Here we would use Yasmin (an OCP that contains drosperinone). If cyproterone acetate (Diane) is available, this would be another good choice. I hope that this provides you with some useful suggestions. David Ehrmann, M.D.,The University of Chicago