Management of acromegaly: Is there a role for primary medical therapy?

Abstract

Acromegaly is a chronic, debilitating disease caused by chronic growth hormone (GH) hypersecretion which results in chronic medical comorbidities, poor quality of life and high mortality rates. Successful treatment can improve clinical signs and symptoms and normalize mortality rates. Over 95% of acromegaly is caused by a somatotroph adenoma of the pituitary, and the first-line treatment is generally transsphenoidal surgery, which can be curative in 50-60% of patients. Nonetheless, high rates of persistent acromegaly following surgery and the limited efficacy of radiation therapy necessitate chronic medical treatment for many patients. Somatostatin analogues have become the preferred first-line medical therapy for many practitioners, as they achieve better biochemical and direct tumor control than the dopamine agonists, and long-acting preparations make once monthly administration possible. Cabergoline, a dopamine agonist, offers a lower-cost option and may be effective in patients with a pituitary tumor that co-secretes GH and prolactin. Pegvisomant is a GH receptor antagonist that produces exceptional biochemical response rates but lacks any direct effects on the tumor, which may limit its effectiveness as life-long monotherapy. Combinations of these three drug classes have not been rigorously studied, and preliminary trials do not suggest improved clinical outcomes. While medical treatment options for acromegaly have significantly improved over the last 30 years, limitations remain, and a multi-specialty team approach is necessary for the effective long-term management of patients with acromegaly.

Outcomes after a purely endoscopic transsphenoidal resection of growth hormone–secreting pituitary adenomas

“…A significant proportion of patients with large macroadenomas extending outside the sella will experience persistently elevated GH levels postoperatively, often requiring subsequent medical therapy and/or radiosurgery to gain satisfactory biochemical control. 5,18 Some authors have argued primary medical therapy may be used for patients with GH-secreting macroadenomas with extrasellar extension, which makes complete surgical resection unfeasible. 5,18 However, other authors have asserted that initial operative debulking of these macroadenomas may increase the proportion of patients that subsequently attain hormonal control with adjunctive therapy, particularly if more than 75% of the initial tumor volume is resected.…”

“…5,18 Some authors have argued primary medical therapy may be used for patients with GH-secreting macroadenomas with extrasellar extension, which makes complete surgical resection unfeasible. 5,18 However, other authors have asserted that initial operative debulking of these macroadenomas may increase the proportion of patients that subsequently attain hormonal control with adjunctive therapy, particularly if more than 75% of the initial tumor volume is resected. 17,35,48,54 To demonstrate safety and efficacy an attempt was made to carefully evaluate and report the biochemical results of endoscopic resection of GH-secreting adenomas in the current series.…”

Surgical Results of Growth Hormone-Secreting Pituitary Adenoma

“…An endocrinological "cure" for acromegaly, as defined by the stringent criteria of biochemical remission 10,21) , was achieved in 64% of patients, similar to that reported in the most recent series 16,[19][20][21]25) . TSS remains an effective treatment for acromegaly, whereas medical treatment and/or radiotherapy should be reserved for patients with persistent GH/IGF-I hypersecretion after surgery 4) . However, for patients with cavernous sinus invasion of Knosp grade III and IV 15) , invasive GH-secreting pituitary adenoma may be unresectable due to the involvement with structures of the cavernous sinus; the GH level can't be normalized, the surgical cure rate is low while the incidence of complications is high and the GH level must still be observed after the operation.…”

“…In a recent study, it was found that there may be a role for pre-operative medical management if tumor shrinkage can be achieved prior to surgery. Surgical outcomes may also be improved by lowering preoperative GH and IGF-I levels 4,5) . For residual tumor within the cavernous sinus area after medical or surgical treatment, gamma knife radiosurgery is a viable option.…”

Bromocriptine, a Dopamine Agonist, Increases Growth Hormone Secretion in a Patient with Acromegaly

“…Medical treatment, however, is commonly done for the patients who do not wish the surgery or who have not been cured by the surgery (Melmed et al 2009). Medical treatment is also carried out before the surgery in order to shrink the tumor size (Bush and Vance 2008). Dopamine agonists, also known as stimulators of GH secretion in healthy subjects (Eddy et al 1971), act as suppressors of GH secretion in patients with acromegaly and have been used for the medical therapy of acromegaly as well as prolactinoma (Thorner et al 1975).…”