Current diagnosis of acromegaly

Abstract

Acromegaly is a rare and chronic condition that is characterized by sustained unregulated hypersecretion of growth hormone (GH). More than 99% of the cases of acromegaly are due to a pathologic proliferation of pituitary somatotrophs presenting in the form of a pituitary adenoma. The excessive amounts of GH and its target hormone, insulin like growth factor-1 (IGF-1) cause metabolic changes and tissue enlargement that, collectively, lead to significant morbidity and a two to threefold increase in mortality. Thus, early diagnosis has proved to be crucial to improve survival and quality of life in this condition. The development of radioimmunoassay (RIA) in the 1960s provided clinicians with a biochemical tool to diagnose acromegaly. Many limitations were inherent to this methodology which necessitated the development of more sensitive tools, such as immunoradiometric (IRMA) or immunoluminometric (ILMA) assays for GH and IGF-1 measurements. These newer assays have not come without imperfections. The reference ranges to describe normalcy of the somatotropic axis and the biochemical criteria of "cure" of acromegaly are areas of great debate. Nevertheless, the current international consensus agrees that the diagnosis of acromegaly should be based on both clinical presentation and biochemical data.

GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

“…Clinically, the most commonly presented symptoms are coarsened facial features, enlarged hands and feet, hypertension, and macrognathia [55]. Acromegaly and its effects on brain function are reviewed by Werner [56].…”

An unusual cause of acromegaly

“…It develops insidiously and progresses slowly, and typically remains undiagnosed for about 10 years. 1 More than 95% of cases are caused by autonomous secretion of GH from anterior pituitary tumours and result in clonal expansion of somatotrophs. Less than 1% are due to ectopic GHRH production, with bronchial carcinoids being the most common cause (70%) followed by pancreatic islet cell carcinoids.…”

Laboratory investigation of acromegaly: Is basal or random GH > 0.4 µg/L in the presence of normal serum IGF-1 an important result?

“…The samples were collected in the morning after an approximately 10-h fast and the subject rested for 20 min before and during the OGTT. Patients with nadir GH > 0.4 µg/L (5,7,8,11,(14)(15)(16)(17)19,22,23,(25)(26)(27)(28)(29)(30)(31)(32) were submitted to MRI of the pituitary using gadolinium as contrast agent.…”

“…In the case of clinical suspicion of acromegaly, investigation is traditionally started by the measurement of IGF-1 combined with basal GH (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The disease is ruled out if IGF-1 is normal and basal GH is less than 0.4 µg/L.…”

“…Thus, diagnosis cannot be ruled out in patients with normal IGF-1 but basal GH > 0.4 µg/L. In this situation, investigation is based on GH suppression test after oral glucose overload (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). This strategy is justified by the analytical and normative limitations related to this hormone, conditions that interfere in IGF-1 measurements (reducing it), and cases of acromegaly with normal IGF-1 (5,8,12,17,18,20,23,24).…”