ESA-SRB-AOTA 2019

Growing concerns: an unusual case of acromegaly (#648)

Linda Wu 1 , Benjamin Harris 2 3 , Lyndal Tacon 1 3
  1. Department of Endocrinology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  3. Northern Clinical School, University of Sydney, Sydney, NSW, Australia

 

 A 41 year old lady presented with menstrual irregularities, increasing shoe size and snoring. Examination revealed prognathism, macroglossia, thickened skin and acral enlargement. Blood pressure and visual fields were normal. Investigations confirmed elevated growth hormone (GH) 55.8 mIU/L (0-15) that failed to suppress after 75g glucose load (74.7 mIU/L). IGF-1 was elevated, 69 nmol/L (11-35). The remainder of the pituitary profile, serum calcium and parathyroid hormone, were normal. MRI revealed diffuse enlargement of the pituitary with a possible 2-3 mm microadenoma. Background history included a 10 year history of slowly enlarging left lower lobe pulmonary nodule. FDG-PET/CT scan revealed the lesion to be minimally FDG avid; it demonstrated internal calcifications and distal bronchiectasis, consistent with a carcinoid tumour.  The patient underwent resection of the lesion. Post-operatively, GH and IGF-1 returned to within the reference range. The patient reported normalisation of menses, cessation of snoring, and 7 kg weight reduction. Histology confirmed grade 1 neuroendocrine tumour (NET). Immunostaining for GH was negative, and immunohistochemistry for growth hormone releasing hormone (GHRH) is awaited. MEN1 gene analysis is underway.

Discussion

Acromegaly due to ectopic secretion of GHRH accounts for less than 1% of cases 1. Literature is limited to case reports2 and two case series 3,4. The clinical phenotype varies in severity, and IGF-1 values range from 1.1 to 4.2 times the upper limit of normal. When available, GHRH is always elevated and is a helpful distinguishing tool3. Pituitary imaging reveals diffuse enlargement in the majority of cases, with the minority being normal or having a pituitary adenoma2,3. Bronchial and pancreatic NETs are most often causative and, when performed, GHRH immunostaining is positive2,3.

Conclusion

Acromegaly secondary to ectopic GHRH secretion from a NET is rare, but should be considered in cases where pituitary imaging is not strongly suggestive.

  1. Thorner MO, Frohman LA, Leong DA, et al. Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients. J Clin Endocrinol Metab. 1984;59(5):846-849.
  2. Ghazi AA, Amirbaigloo A, Dezfooli AA, et al. Ectopic acromegaly due to growth hormone releasing hormone. Endocrine. 2013;43(2):293-302
  3. Garby L, Caron P, Claustrat F, et al. Clinical characteristics and outcome of acromegaly induced by ectopic secretion of growth hormone-releasing hormone (GHRH): a French nationwide series of 21 cases. J Clin Endocrinol Metab. 2012;97(6):2093-2104.
  4. Biermasz NR, Smit JW, Pereira AM, Frolich M, Romijn JA, Roelfsema F. Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients. Pituitary. 2007;10(3):237-249.