Introduction: Acromegaly is usually caused by a pituitary adenoma; ectopic or eutopic secretion of GHRH is a rare condition, responsible for <1% of the cases. Ectopic secretion of GH itself is even rarer.
Case report: A 34-year-old woman was referred to the Endocrine Clinic with a multinodular goiter. However, on physical examination there were some physical signs of acromegaly: coarsening of facial features, protusion of the lower jaw and thick, oily skin. In her past medical history there was a right lung lower lobectomy with a histologic diagnosis of a typical carcinoid. Laboratory investigation showed a seric concentration of IGF1 of 826 ng/ml (136449), and a fine-needle aspiration of a thyroid nodule revelead a cytologic diagnosis suspicious of papillary carcinoma. A random GH level was 7.7 ng/dl, and after a 75 g oral glucose load the GH was 9.4 ng/dl. The pituitary MRI, however, did not show a tumor, but its dimensions were increased, which raised the possibility of ectopic acromegaly. Since our patient had an history of a pulmonary carcinoid, it was asked a chest and abdominal CT, which showed eight nodules in the liver, highly suspicious of metastatic involvement by the primary neuroendocrine tumor. She had a discrete elevation of chromogranin A and no elevation of 5-hydroxyindoleacetic acid. A Ga68 PET DOTANOC revealed an increased captation in the hepatic lesions, and a biopsy was performed, confirming the neuroendocrine origin of the metastasis; immunohistochemical staining was positive for GH and negative for GHRH (Cohen antibody, 1:2000, automated method). The patient was initiated on monthly intramuscular octreotide (20 mg), and was submitted to radioembolization of the hepatic lesions, with a notable reduction in the size of the metastasis. A total thyroidectomy confirmed the diagnosis of papillary thyroid carcinoma, but with no indication for radioiodine ablation. Posteriorly it was asked a plasmatic determination of GHRH, which was negative (<60 ng/dl). At the moment the IGF1 levels are in the normal range and the GH level is <1 ng/dl, and the size of the hepatic metastasis is stable.
Clinical lessions: The diagnosis of ectopic secretion causing acromegaly may be suspected in any case of clinically suspected and biochemically proven acromegaly with no pituitary adenoma. However, this case has many peculiarities: in spite of the hyperplasia of the pituitary (which is suspicious of GHRH hypersecretion), the immunohistochemical staining was negative for this hormone and positive for GH; it is important to note that the biopsy sample was very small and the expression of GHRH is usually focal. So, to clarify this situation it was asked a determination of plasmatic GHRH, which is the gold-standard for the diagnosis: it was negative (even when the patient is under somatostatin analogues this value is positive in cases of ectopic secretion of GHRH). Therefore, it remans the doubt: is this clinical picture caused by ectopic secretion of GH? Or it may be caused by ectopic secretion of a truncated form of GHRH not detectable by radioimmunoassay but with biological activity?
17 - 19 Feb 2016
European Society of Endocrinology