TREATMENT OF FUNCTIONING ADENOMAS

1. Prolactinomas
Prolactin-secreting adenomas (prolactinomas) account for approximately 30% of pituitary adenomas and 50 to 60% of functional pituitary tumours.
Although prolactinomas are found to be distributed equally between men and women, women are four times more likely to become symptomatic than men. Women commonly present with galactorrhea, amenorrhea, and infertility. Women generally present earlier in the course of the disease and with smaller tumours (mostly microprolactinomas) at the time of diagnosis. In contrast, men commonly present with larger tumours (mostly macroprolactinomas), which cause local mass effect, and symptoms of visual loss, cranial nerve dysfunction, and/or hypopituitarism.

Physiological and medication-induced hyperprolactinemia is associated with levels of prolactin in the range of 25 to 100 ng/ml; masses in the sellar and suprasellar region, such as craniopharyngiomas, non functioning macroadenomas, hypothalamic tumours, granulomatous lesions, and lymphocytic hypophysitis, can compress the pituitary stalk and interrupt the dopaminergic inhibition of lactotrophs (“stalk-section effect”) resulting in elevated prolactin levels in the range of 50 to 125 ng/ml. The stalk effect rarely causes the serum prolactin level higher than 100 ng/ml, whereas prolactinomas typically generate much higher levels.

Goals of treatment of prolactinomas
1. Suppress excessive hormone secretion and its clinical consequences
2. Restore fertility
3. Remove tumour mass (for microprolactinomas, removal of the tumour mass is of secondary importance because the tumour is not likely to produce symptoms by mass effect)
4. Preserve residual pituitary function
5. Prevent disease recurrence or progression

A. Medical therapy
Dopamine agonists are the mainstay of treatment.

1) Bromocriptine
To start bromocriptine at a dose of 0.625 mg at bedtime with a snack. After one week, a morning dose of 1.25 mg to be added to the regimen. At weekly intervals, the dose is to be increased by 1.25 mg, for a total dose of 5.0 mg.
To repeat serum prolactin after one month
Usually, 5-7.5 mg is required to regain menses and normal prolactin level for microprolactinomas and 7.5-10 mg to control tumour size and prolactin level for macroprolactinomas.
Intravaginal bromocriptine may be given for patients not tolerating adverse GI effects, in doses of 2.5-5 mg but may cause vaginal irritation.
Women should be advised to use a mechanical form of contraception until two regular menstrual periods have occurred, and bromocriptine should be stopped when one menstrual cycle has been missed.
Bromocriptine to continue for 2 years.
Bromocriptine has a high degree of potency and its use has resulted in the normalization of prolactin levels in 70%- 90% of cases and a significant reduction of tumour mass in approximately 85% of cases. However, sustained normoprolactinemia after bromocriptine withdrawal is achieved in 20%-30% of patients only.

2) Cabergoline
This is the first line of therapy today if pregnancy is not required. It has less side effects than bromocriptine and was previously used when patient did not tolerate side effects or was not responding to bromocriptine.

Cabergoline should be started at a dose of 0.25 mg twice weekly and increased monthly gradually to the required dose (upto 7 mg has been used) for 2 years and then tapered and withdrawn. This drug is not recommended to be used during pregnancy.

Cabergoline is effective in 70% of patients resistant to bromocriptine.

Both dopamine agonists decrease the serum prolactin levels within days and result in a decrease in the size of the tumour and restoration of anterior pituitary function.

Response to be assessed by
1. Fasting serum prolactin level
2. MRI at 6 weeks and 6 months

B. Indications for surgery for prolactinomas

1. Drug intolerance
2. Tumours resistant to medical therapy
3. Persistent tumour mass effects in spite of medical treatment
4. Patients not willing for long term medical therapy
5. Patients on antipsychotic medications
6. First line treatment for microprolactinomas with prolactin < 200 ng/ml

C. Radiation Therapy
Radiation therapy is reserved for symptomatic patients resistant to medical treatment and to be considered after maximal safe resection. Dose recommended is 45 Gy/25#/5 weeks, preferably with 3D CRT.