Endocrine Abstracts

Introduction: Aryl hydrocarbon receptor interacting protein (AIP) mutated Acromegaly is a complex rare disease. AIP mutations are associated with an aggressive, inheritable form of acromegaly that responds poorly to SST2-specific somatostatin analogues (SSAs). Literature reports demonstrate that second generation SSA, Pasireotide LAR, is superior to first generation SSAs in treating acromegaly with AIP mutation. Treating acromegaly with AIP mutation could be quite challenging. We describe an unusual case of acromegaly that has shown a good biochemical and clinical response to first generation Sandostatin LAR and also shows an uncommon histological picture of dense granulations.

Case report: A 19 year old male was referred by his GP after he had been complaining of headaches for 4 years. On examination he looked acromegalic with frontal bossing, thick skin, prognathism and big hands. Initial investigations showed a high IGF-1 1276 mcg/l, an OGTT with a nadir Growth hormone (GH) 33 mcg/l, a high Prolactin of 6724 mlU/l, and a low Testosterone of 3 nmol/l with a low normal FSH 1.5 IU/l and LH 2.5 IU/l. A MRI of the pituitary showed a 16 mm pituitary macroadenoma. Transsphenoidal excision was performed at 8 weeks after presentation. Histology showed a densely granulated somatotroph cell PitNET/adenoma with Ki67 mildly elevated. Post-surgery follow up investigations showed a high IGF-1 512 mcg/l, an average GH of 1.3 mcg/l on a growth hormone day curve (GHDC). Clinical review three months after surgery confirmed improvement in symptoms and facial appearance. Further investigations confirmed on-going evidence of acromegaly with a high average GH of 2.25 mcg/l on GHDC and a high IGF-1 of 526 mcg/l. Genetic testing confirmed AIP mutation which is heterozygous for c.805_825dup. Familial counselling and investigation confirmed maternal and brother AIP gene mutations. Baseline MRI pituitary post-surgery did not confirm a definite residual tumour and a methionine PET scan is pending. An Octreotide test was performed and GH levels improved from 1.8 mcg/l to 0.65 mcg/l after a test dose of 100 mcg Octreotide subcutaneously. Consequently, he was started on Sandostatin LAR 30 mg every 4 weeks. Good biochemical response was noted and IGF-1 returned to within the age and sex specific target range. The patient’s average GH on a GHDC is 0.8 mcg/l after 3 months on treatment.

Discussion: Despite the fact that AIP-mutated Acromegaly shows a better response to second generation SSA than first generation SSAs our patient has responded well to a first generation SSA. Further follow up is necessary to confirm whether a long term effect is maintained.