Acromegaly

Abstract

In the majority of cases, acromegaly is due to GH hypersecretion by a somatotroph pituitary tumor. The etiology of acromegaly is not known, and may be related to GHRH hypersecretion, intrinsic pituitary defect, or a combination thereof. Recent physiologic data and molecular biology techniques provide insights into the pathophysiology of this condition. Treatment options include surgery, radiation, and judicious administration of pharmacologic compounds inhibiting GH secretion and tumor growth.

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

“…Growth hormone (GH) has long been recognized as being essential for somatic growth, differentiation, metabolism and thymic development (Clark 1997, Barkan 1992. The GH receptor (GHR) is a member of the cytokine/ haematopoietin family of receptors (Kelly et al 1993).…”

Assessment of long-term remission of acromegaly following surgery

“…Thus, whereas some authors advocate additional exploratory surgery under certain conditions, 20,46 others do not. 6,24,52 Radiation therapy significantly lowers postoperative GH levels in a large number of patients with refractory disease (a 50-79% response is commonly cited 8,15,[28][29][30][31]34,36,43,53 ), but it can take as long as 10 years to have a significant effect, during which time the patient continually experiences the deleterious effects of GH excess. Medical therapy with the dopamine agonist bromocriptine or the somatostatin analog octreotide lowers GH levels in many patients, but these medications are often poorly tolerated and rarely result in a cure of the disease process.…”

“…The production of IGF-I, a peptide whose plasma concentration is largely attributable to hepatic release, but which is found in many tissues, is the major determinant of acromegalic activity. 3,6,7,16,19,22,27,41 Although GH stimulates the production and release of IGF-I, controversy exists as to the log-linear correlation of GH and IGF-I levels. Nevertheless, it seems that the major end-tissue effects of cellular proliferation are directly mediated by IGF-I.…”

“…Other tests, such as the OGTT and the TRH stimulation test have been performed and usually suppress GH in patients who have been cured. 3,5,6,19,22,38,41,51,54 Recent consensus has suggested that an OGTT in which the nadir GH level is less than 1 ng/ml following oral glucose loading, together with a normal sex-and age-matched IGF-I level should be used to define chemical control following either medical or surgical treatment. 23 Unfortunately, administration of an OGTT during the early postoperative period may be impractical and, for reasons previously stated, IGF-I measurement may be unreliable.…”

Cellular alterations in pituitary tumors

“…While it is well estabfished that ectopie overproduction of hypothalamic releasing hormones by neuroendocrine tumors may cause hyperplasia of target pituitary cells, possibly evolving in tumoral transformation (74)(75)(76), the assess¬ ment of releasing hormone concentrations in portal blood from patients with pituitary tumors is indirect and largely speculative. In this regard, it has been proposed that an increased GHRH secretion by the CNS may be responsible for the accelerated GH pulse frequency and nocturnal GH rise that occur frequently in patients with acromegaly (77). While the existence of alterations in the central neurotransmission may only be hypothe¬ sized, cellular alterations that are observed frequently in pituitary tumors may result in amplication of stimula¬ tory neurohormone action and reduction of inhibitory signals, both events having possible implications in tumor formation and/or progression.…”