SUN-930 A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine Tumour

Abstract

A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine TumourBackgroundAcromegaly due to ectopic GHRH secretion is a rare disorder and only accounts for less than 1% of all cases of acromegaly.CaseWe present the case of a 42-year old female with acromegaly from a bronchial neuroendocrine tumour (NET) secreting GHRH. The patient presented with gradual onset of dyspnea and wheezing. Subsequent imaging (chest X-ray, CT chest) revealed a large left-sided thoracic mass. Bronchoscopy was performed and a biopsy was taken from the mass. Initial histological examination reported small cell lung carcinoma (SCLC). Therefore, she underwent chemoradiotherapy. The patient was concurrently experiencing increased digital girth, weight gain, and enlarged tongue and was therefore referred to our endocrinology clinic for evaluation of acromegaly. Investigations revealed normal ACTH, markedly elevated IGF-1 (1031 μg/L, normal 63–215 μg/L), and non-suppressed GH levels following a 75g oral glucose tolerance test. The remainder of the pituitary panel, including TSH, prolactin, FSH, LH were all normal. An MRI sella showed a completely normal pituitary and pineal gland with no evidence of brain metastasis. She thus met clinical and biochemical criteria for acromegaly but a pituitary source could not be identified. Given her history, a paraneoplastic process or ectopic GHRH-producing tumour was suspected. Further workup showed a significantly elevated circulating GHRH levels of 73 pg/mL (normal 5 – 18 pg/mL). Subsequently, a second pathologist with expertise in NETs reviewed the same biopsy specimen. The specimen was found to be a GHRH-producing well differentiated pulmonary NET with a Ki67 index of 1.5%, and thus not a SCLC. Furthermore, a somatostatin receptor scintigraphy study was done which showed evidence of a somatostatin avid receptor rich lesion in the lung, corresponding to the known tumour. Thus, what initially appeared to be a SCLC was subsequently found to be a GHRH-secreting NET, illustrating the challenges of diagnosing these rare tumours. She was treated with intramuscular sandostatin 20mg q28days and then underwent a left pneumonectomy, resulting in biochemical resolution of her acromegaly (IGF-1 219 μg/L). Genetic testing for MEN1 was also completed as there is an association between ectopic GHRH NETs and MEN-1; however, genetic testing revealed no pathogenic variants and exon deletions or duplications suggestive of MEN-1.Learning pointsDiagnosis of acromegaly due to ectopic GHRH secretion requires high clinical suspicion by the treating clinicians (e.g., endocrinologist, oncologist) as well as review of histology by expert pathologists. Our case highlights that ectopic GHRH secretion is a rare but important cause of acromegaly, which should always be suspected when a clear pituitary cause is not identified.