Treatment results of acromegaly as analyzed by different criteria

Abstract

Results of treatment of acromegaly are often incomparable due to the different criteria which have been used for defining cure or control of disease. At the present time it is widely accepted, that the main criteria of cure must be normalization of IGF-1 and a GH in the OGTT < 2 ng/ml. In this retrospective study we investigated the endocrinological results of 56 patients, who were surgically treated because of a GH-producing pituitary adenoma, by different criteria. Twelve of our patients had had additional medical treatment after surgery, two received radiotherapy. At a mean follow-up of 34 months after surgery 66% of patients had a basal GH < 5 ng/ml, 64% had a GH in the OGTT < 2 ng/ml and 73% had normalization of IGF-1. The combined criteria of OGTT < 2 ng/ml and IGF-1 normalization have been fulfilled in 59% of patients. None of these latter patients developed a clinical recurrence during the follow-up period. An optimal result (endocrinological cure, no permanent surgical complications and intact pituitary function) was achieved in 43% of patients. Although surgery was responsible for 19 new pituitary axis deficiencies (7 corticotropic axis, 8 thyrotropic axis and gonadotropic axis), 22 partial deficiencies improved to normalization after surgery (respectively 6, 3, and 13). Pre-operatively 55% of patients had no pituitary deficiency, after surgery this was 61%, leaving a net positive result of 6% less pituitary deficiencies. The authors conclude that normalization of IGF-1 combined with an OGTT < 2 ng/ml are adequate criteria for the definition of cure of acromegaly. However, the authors propose to include post-treatment hypopituitarism as an additional criterion by which treatment of acromegaly should be evaluated.

Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature.

“…An important finding of the present study was the absence of tumour recurrence after a mean follow-up of 8 years. Our results compare favourably with previous series reporting recurrence rates ranging from 0 up to 10% of successfully operated patients (Ross & Wilson 1988, Buschfelder et al 1991, Valdemarsson et al 1991, Falbusch et al 1992, Tindall et al 1993, Van Lindert et al 1997, Abosch et al 1998, Freda et al 1998, Shimon et al 2001. Analysis of these series clearly indicates that such variations mainly depend on the criteria used to define surgical cure and on the duration of follow-up (see Table 6).…”

“…Based on epidemiologic evidence that mortality rates among treated acromegalic patients are higher than those of the normal population until GH and IGF-I levels are normalised (Bates et al 1993, Rajasoorya et al 1994, Swearingen et al 1998, Beauregard et al 2003, more stringent criteria to define the biochemical remission of acromegaly have been proposed in recent years. Using a mean GH < 2 ng/ml during OGTT and normal IGF-I levels, biochemical remission of acromegaly has been reported in 55-70% of patients (Falbusch et al 1992, Van Lindert et al 1997, Freda et al 1998, Shimon et al 2001. More recently, a GH < 1 ng/ml during an OGTT and normal IGF-I levels have been considered to be the leading criteria for the cure of acromegaly (Giustina et al 2000, Melmed et al 2002.…”

“…Indeed, the concept of biochemical remission of the disease has changed noticeably over the past two decades, so that basal GH < 2.5 ng/ml or GH < 1 ng/ml during the oral glucose tolerance test (OGTT), and the normalisation of age-related insulin-like growth factor-I (IGF-I) are now widely accepted as modern criteria to define the biochemical remission of the disease (Giustina et al 2000, Melmed et al 2002. According to such stringent criteria, normalisation of GH hypersecretion after surgery is achieved in about 40-60% of patients in the few recently published series (Laws et al 2000, Kreutzer et al 2001, in contrast with older series reporting a surgical success, as defined by plasma GH levels < 5 ng/ml, in more than 75% of patients (Ross & Wilson 1988, Tindall et al 1993, but similar to series considering a glucose-suppressed GH < 2 ng/ml (Falbusch et al 1992, Sheaves et al 1996, Van Lindert et al 1997, Freda et al 1998, Shimon et al 2001.…”

“…Transsphenoidal surgery (TSS) remains the first choice treatment for acromegaly (Melmed et al 2002). It is effective and safe (Ross & Wilson 1988, Tindall et al 1993, Davis et al 1993, Van Lindert et al 1997, Abosch et al 1998, Freda et al 1998, Ahmed et al 1999, Laws et al 2000, Shimon et al 2001, even in elderly patients (Minniti et al 2001a), and it is able to reverse metabolic and cardiovascular complications related to the disease (Colao et al 2001, Minniti et al 2001b, Jaffrain-Rea et al 2002. However, complete removal is not always possible and evolutive acromegaly may continue.…”

“…Medical therapy with somatostatin analogues (Lamberts et al 1992, Freda 2002 or radiotherapy (Barrande et al 2000, Powell et al 2000 are usually administered as post-operative adjuvant treatments for acromegaly. Surgical cure rates range from 40 to 80% in most surgical series, depending on the criteria used to define the biochemical remission of the disease (Ross & Wilson 1988, Losa et al 1989, Tindall et al 1993, Van Lindert et al 1997, Abosch et al 1998, Freda et al 1998, Ahmed et al 1999, Laws et al 2000, Kreutzer et al 2001, Shimon et al 2001. Indeed, the concept of biochemical remission of the disease has changed noticeably over the past two decades, so that basal GH < 2.5 ng/ml or GH < 1 ng/ml during the oral glucose tolerance test (OGTT), and the normalisation of age-related insulin-like growth factor-I (IGF-I) are now widely accepted as modern criteria to define the biochemical remission of the disease (Giustina et al 2000, Melmed et al 2002.…”