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Acromegaly.

S Melmed
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Abstract

Subcellular mechanisms support the notion of an intrinsic pituitary defect in acromegaly, with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels that affect the cardiovascular and respiratory system, as well as neoplastic cell proliferative activity. Surgery, even with external-beam irradiation adjuvant therapy, is only successful in less than 60% of patients, and there are side effects. Normalization of GH levels may improve survival rates. Octreotide has revolutionized patient management, normalizing GH and IGF-1 levels in up to 60%, ameliorating soft-tissue abnormalities and reducing tumor size in up to 50%, and attenuating GH levels in more than 90% of patients. Issues concerning the role of octreotide, as well as clarifying precise outcome measures, still need to be resolved.

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AcromegalyAdenomaGrowth HormoneHumansOctreotidePituitary NeoplasmsJournal ArticleReview

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BibTeXRIS

S Melmed. 1996. Acromegaly.. https://doi.org/10.1016/s0026-0495(96)90081-5

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PubMed1998

Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly.

Acromegaly was diagnosed in 3 cats with insulin-resistant diabetes mellitus (DM) on the basis of history and physical examination findings, which ruled out other causes of insulin-resistant DM, and by documenting high plasma concentrations of growth hormone. Computed tomography revealed a mass in the area of the pituitary gland in each cat. Pituitary gland tumors were irradiated with cobalt 60, and none of the cats developed complications to radiotherapy. Each cat received a total dose of 48 Gy of cobalt 60 during 12 treatments. After completion of radiotherapy, insulin requirements were less for all cats, although in 1 cat, this improvement was transient. Diabetes mellitus resolved in 2 of 3 cats. After treatment, decreases in insulin requirements correlated with decreases in plasma growth hormone concentrations in 2 of 3 cats in which DM resolved. On the basis of these findings, irradiation of pituitary gland tumors appears to be a treatment option for cats with acromegaly.

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PubMed1998

Impaired activation of phosphoinositide 3-kinase by insulin in fibroblasts from patients with severe insulin resistance and pseudoacromegaly. A disorder characterized by selective postreceptor insulin resistance.

Some patients with severe insulin resistance develop pathological tissue growth reminiscent of acromegaly. Previous studies of such patients have suggested the presence of a selective postreceptor defect of insulin signaling, resulting in the impairment of metabolic but preservation of mitogenic signaling. As the activation of phosphoinositide 3-kinase (PI 3-kinase) is considered essential for insulin's metabolic signaling, we have examined insulin-stimulated PI 3-kinase activity in anti-insulin receptor substrate (IRS)-1 immunoprecipitates from cultured dermal fibroblasts obtained from pseudoacromegalic (PA) patients and controls. At a concentration of insulin (1 nM) similar to that seen in vivo in PA patients, the activation of IRS-1-associated PI 3-kinase was reduced markedly in fibroblasts from the PA patients (32+/-7% of the activity of normal controls, P < 0.01). Genetic and biochemical studies indicated that this impairment was not secondary to a defect in the structure, expression, or activation of the insulin receptor, IRS-1, or p85alpha. Insulin stimulation of mitogenesis in PA fibroblasts, as determined by thymidine incorporation, was indistinguishable from controls, as was mitogen-activated protein kinase phosphorylation, confirming the integrity of insulin's mitogenic signaling pathways in this condition. These findings support the existence of an intrinsic defect of postreceptor insulin signaling in the PA subtype of insulin resistance, which involves impairment of the activation of PI 3-kinase. The PA tissue growth seen in such patients is likely to result from severe in vivo hyperinsulinemia activating intact mitogenic signaling pathways emanating from the insulin receptor.

Acromegaly↗