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Abstract

The primary treatment of acromegaly remains transsphenoidal adenomectomy, yet the tissue overgrowth of acromegaly often progresses following surgery, and responds to radiotherapy only after significant delay. Persistently elevated serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations can be normalized in about half of post-surgery acromegalics using the pharmacologic alternatives presently available, the dopamine agonists (DA) and somatostatin (SST) analogs. Cabergoline, the most efficacious DA, normalizes IGF-I in approximately 37% of patients, whereas the long-acting SST analogs, Octreotide LAR and Lanreotide SR, do so in 66%. Significant tumor shrinkage may be attained with SST analogs in particular, and when necessary, the primary medical treatment of acromegaly may be successfully addressed with this class of drugs. Greatly enhanced efficacy is expected from the GH receptor antagonist pegvisomant, which is nearing market availability and will enable the normalization of serum IGF-I in virtually all patients treated. We review here the pharmacologic treatments of excessive GH secretion.

GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly

“…Medical therapy Table 1 summarizes the advantages and drawbacks of each of these treatment regimens. In most patients a combination of these therapies is used for efficient management of disease symptoms [13]. Despite multiple therapeutic approaches, uncontrolled disease occurs in a significant portion of patients and thus novel therapeutic agents are needed to treat this disorder.…”

“…Surgery via the transsphenoidal route permits visualization of the tumor, avoids contact with the optic chiasm and nerves, potentially allows complete resection producing rapid decline in serum GH and IGF-1 levels, restoration of anterior pituitary functions and immediate amelioration of the symptoms of the disease. Postoperative complications are rare and include CSF leak, meningitis, hematoma, sinusitis and new hypopituitarism [2,4,8,13,14]. As with any type of pituitary tumor, the surgical outcome depends on two factors: the size of the tumor and the expertise of the surgeon.…”

“…The overall success rate of dopamine agonist in suppressing GH secretion (<5µg/l) is about low, whereas IGF-1 levels are only normalized in 10% of the patients. The clinical efficacy of dopamine agonists has been extensively reviewed elsewhere (for excellent reviews see [8,13,14,22]). Since, dopamine is a powerful physiological inhibitor of prolactin [23], dopamine agonists are more efficacious for tumors, which secrete both GH and prolactin ( Table 1).…”

“…The present manuscript describes the GH-inhibitory activity of promising new somatostatin agonists with improved endocrine selectivity and pharmacological profile [13,16,40,41]. Additionally, a short description of the clinical efficacy of currently available somatostatin agonists namely, octreotide and lanreotide in patients has been included.…”

“…The GH-inhibitory activity of cyclic somatostatin analogs, possessing high affinity to sst2, like octreotide, lanreotide and RC-160 has been extensively examined in vitro as well as in animal models [33,39]. Octreotide, RC-160 and lanreotide show potent abrogation of GH release in rat pituitary adenoma cell lines like GH3 and GH4C1 [13,35,106,107]. Hofland et al (1994) have compared the GH-inhibitory profiles of octreotide, RC-160 and lanreotide in human GHsecreting pituitary tumor cells as well as normal rat anterior pituitary cell in vitro.…”