Preoperative Diagnosis Of Acromegaly by Growth Hormone-Releasing Factor Radioimmunoassay

Abstract

Acromegaly was diagnosed in a 37-year-old woman with classical physical and biochemical findings; an enlarged sella on computed tomography suggested the presence of a pituitary macroadenoma. Radiologic evidence of a lung mass prompted radioimmunoassay of plasma growth hormone-releasing factor (7,500 pg/ml; normal less than 100 pg/ml). After resection of a bronchial carcinoid, which stained positive for growth hormone-releasing factor, circulating growth hormone-releasing factor levels normalized. Subsequently, her clinical, biochemical, and radiologic evidence for acromegaly resolved. This case represents the first reported use of the human pancreatic growth hormone-releasing factor 1-40 radioimmunoassay to preoperatively diagnose this rare etiology of acromegaly.

Pathophysiology and clinical aspects of the ectopic GH‐releasing hormone syndrome

“…Interestingly recovery of normal pituitary morphology was slowly progressive in one patient (Barth et al, 1991) the first CT scan 3 months after surgery showed a decrease in the vertical height of the pituitary lesion, whereas a repeated CT scan at 10 months was entirely normal. Logically, surgery was ineffective in patients with metastatic spread of the GHRHsecreting tumour (von Werder et al, , 1987Lefebvre et al, 1995;Genka et al, 1995), even though a slight reduction in GHRH and GH level occurred in our two cases.…”

“…Resolution of acromegaly was evident in the first weeks after operation, even though the paradoxical GH response to TRH persisted initially and disappeared only after some months (Spero & White, 1985;Boizel et al, 1987), suggesting that basal GH hypersecretion needs to be continuously stimulated by elevated GHRH level, whereas disappearance of the abnormal GH responsiveness to dynamic testing requires a longer period of time, probably because involution of the hyperplastic somatotrophs is not immediate. Reversibility of somatotroph hyperplasia is further demonstrated by normalization of the neuroradiological picture in six patients who had a demonstrable pituitary lesion before surgery and complete resection of the GHRH-secreting tumour Spero & White, 1985;Carroll et al, 1987;Ramsay et al, 1987;Hawkins et al, 1985;Barth et al, 1991).…”

“…In fact, 11 of 14 tumours (78%) were located in the right lung. Since then, seven additional cases of ectopic acromegaly due to a lung carcinoid have been reported (Gilsanz Peral et al, 1987: Moller et al, 1989Popovic et al, 1990;Barth et al, 1991;Glikson et al, 1991;Ezzat et al, 1994;Lefebvre et al, 1995); in five cases the tumour was located in the right lung. The reason for this apparently uneven distribution of the lung carcinoids remains elusive.…”

“…The cornerstone in the hormonal evaluation of patients with suspected ectopic GHRH syndrome is the measurement of the peptide in the peripheral plasma (Barth et al, 1991). To date, all the reported cases in whom such a measurement was available demonstrated clearly elevated plasma GHRH levels, usually 100-1000 times the value detected in normal subjects (Losa et al, 1993).…”

O Laboratório no Diagnóstico e Seguimento da Acromegalia

“…Nos raros casos de acromegalia causada por tumores hipotalâmicos secretores de GHRH, como hamartoma ou gangliocitoma, os níveis de GHRH não estão aumentados no sangue periférico, pois o GHRH hipotalâmico não entra na circulação sistêmica. Portanto, a dosagem de GHRH deve ficar restrita aos casos de acromegalia confirmados clinica e laboratorialmente, com exame de imagem não evidenciando tumor hipofisário, onde se suspeite da presença de um tumor ectópico produtor de GHRH (6)(7)(8)(43)(44)(45).…”