Dopaminergic treatment of patients with acromegaly: still kicking after all these years

Abstract

I n this issue of the Archives of Endocrinology and Metabolism, the article "Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature", by Kizilgul and cols. (1), shares an excellent opportunity to review the history and to reappraise the role of dopaminergic treatment in acromegaly.It all started 50 years ago, when Liuzzi and cols.(2) reported in The Journal of Clinical Endocrinology and Metabolism an inhibitory effect of L-Dopa in patients with acromegaly. That observation was particularly intriguing because L-Dopa, a dopamine precursor, was known to stimulate GH secretion in healthy subjects (3).Here is a quote from the discussion in that seminal paper: On the basis of clinical and experimental knowledge we are unable to explain these results.... we believe that the paradoxical fall of plasma GH we observed in some patients affected by acromegaly is of interest and needs more extensive studies. It suggests a new therapeutic approach to the treatment of acromegaly.Indeed, in the following years, that same group of investigators showed that a new ergot derivative, 2-Br-alpha-ergocryptine (bromocriptine), a dopamine agonist, was also able to reduce growth hormone secretion in patients with acromegaly (4). Soon after, bromocriptine proved to be even more effective in reducing prolactin secretion in various physiological and pathological conditions and became the first choice treatment for prolactinomas (5). The effect of bromocriptine on growth hormone secretion and tumor growth in acromegaly was later shown to be mediated by dopaminergic receptors (particularly type 2), which are usually expressed in growth hormone and other pituitary adenomas (6). Notwithstanding its modest efficacy and several side effects, bromocriptine remained, for a whole decade, as the only pharmacological treatment available for acromegaly.In the mid-eighties, treatment of acromegaly changed dramatically with the development of octreotide, a somatostatin analogue much more effective than bromocriptine in controlling growth hormone secretion and tumor growth in patients with acromegaly (7). Thereafter, octreotide and, also, lanreotide (another first generation somatostatin analog), became the first line of pharmacological treatment for that disease. Nevertheless, almost half of patients do not attain disease control under treatment with those somatostatin analogs even with higher than usual doses (8).At about the same time, cabergoline, another ergot-derivative with a more potent dopaminergic activity and less side effects than bromocriptine, showed a remarkable superiority in relation to bromocriptine in the treatment of prolactinomas (9). Later, in the late 90's, two preliminary reports of treatment of acromegaly with cabergoline, alone or in combination with somatostatin analogues, showed promising outcomes

The first spectrofluorimetric protocol for sensitive quantitative analysis of bromocriptine in its pure and pharmaceutical forms: evaluation of the greenness of the method

“…The ergot derivative, bromocriptine (Fig. 1), known as 2-bromoalpha-ergocryptine, which acts as a dopamine D 2 receptor agonist, 1 is a treatment used in many cases of hormonal imbalance and plays an important role in hyperprolactinemia, 2,3 infertility, 4 acromegaly, 5 Parkinson's disease, 6 and diabetes. 7 Despite its therapeutic importance, there are only a few analytical techniques available for quantitative analysis of bromocriptine mesylate, such as HPLC, [8][9][10][11][12][13] voltammetry, 14 and spectrophotometric methods.…”