Endocrine Abstracts

Dopamine agonist therapy is an effective long-term treatment in >90% of patients with hyperprolactinaemia, controlling both prolactin secretion and tumour growth. We describe the unusual late emergence of resistance to high-dose dopamine agonist treatment in two recent female patients. Both women presented with secondary amenorrhoea, were shown to have high prolactin levels and a pituitary microadenoma. Each had an excellent initial response to bromocriptine but years later developed a cabergoline-resistant macroadenoma.

Case 1: This 57 year old, first seen in 1985, responded well to dopamine agonist treatment over a fifteen year period. However from 2000 onwards, elevation of prolactin levels became unresponsive to carbergoline dose escalation and a macroadenoma developed. Transsphenoidal surgery was performed in 2003 with radiotherapy a year later. On continued carbergoline, prolactin levels are <40 mU/l.

Case 2: This 38 year old presented in 1993, tolerated carbergoline well at low doses and conceived in 1996. Persistent galactorrhoea one year post-partum prompted re-introduction of carbergoline. However despite dose escalation, prolactin levels continued to rise. CT pituitary confirmed the presence of an enlarging adenoma and the patient had transsphenoidal surgery in May 2005. Prolactin levels on continued carbergoline therapy (1.5 mg/week) are normal. Late onset of dopamine agonist resistance with progression of microadenoma to macroadenoma is most unusual and raises concerns regarding pituitary carcinoma. This diagnosis can only be made definitively in the presence of metastases. While histology cannot differentiate between benign and malignant pituitary tumours, immunohistochemical techniques may be useful, with carcinoma cells staining strongly for Ki67 and p53. Although tumour tissue from case 1 showed brisk Ki67 activity, this test in case 2 and p53 staining in both, was equivocal. In these cases neuropathological techniques provide only limited characterisation of the tumour and the need for careful ongoing clinical assessment in hyperprolactinaemia is emphasised.