Endocrine Abstracts

Case history: A 26 year old lady presented in 1999 with a 3 year history of worsening headache, increased sweating, excessive tiredness and progressive enlargement of hands and feet. She was otherwise well and had no family history of pituitary tumors, hypercalcaemia or renal stones. On examination she had typical facial features of acromegaly and acral enlargement. Her blood pressure was normal and visual fields were full.

Investigations: Oral Glucose Tolerance Test (OGTT) confirmed Acromegaly (nadir GH: 772 mU/L). Biochemistry suggested excessive disease burden (IGF-1 −1710 μg/l, mean GH >600 mU/l). Other hormone testing showed, secondary hypogonadism (LH<0.5, FSH <0.37, Oestradiol <50 pmol/l), elevated prolactin of 796 mU/l and hypothyroidism (TSH 10.8 IU/l, free T4 of 6 pmol/l). MRI scan showed a 4×2×3 cm pituitary macroadenoma with suprasellar extension and right sided cavernous sinus invasion.

Treatment: She underwent Transsphenoidal Pituitary Surgery (TSS) of the pituitary tumor. Histology revealed moderate amounts of sparsely granular eosinophilic cytoplasm. Immunohistochemistry was positive for growth Hormone and negative for other pituitary hormones.

Postoperatively, Acromegaly remained uncontrolled with an IGF -1 of 1474 μg/l and mean GH 228 mU/l. An MRI of the pituitary revealed residual tumor in the cavernous sinus and close to the optic chiasm. The patient underwent external beam fractionated radiation five months after surgery. Over the following years she was treated with Octreotide LAR up to 30 mg every 2 weeks and Lanreotide autogel up to 120 mg every 2 weeks. Lanreotide was also combined with Cabergoline 1 mg twice per week. The lowest IGF-1 level achieved was still >600 μg/l.

In 2004, she was treated with Pegvisomant which resulted in some control of the disease, IGF-1 levels dropped from above 1000 to 340 μg/l. Pegvisomant had to be stopped as the patient developed abnormal liver function tests. In 2010, the patient had Stereotactic radiosurgery targeting tumor within the cavernous sinuses as a form of debulking. She was also part of a trial with antisense therapy to the GH receptor.

Over 15 years none of the treatments were able to control the disease burden and the patient remained highly symptomatic with headaches, fatigue, and osteoarthritis.

In October 2015, the patient was treated with Pasireotide 40 mg four weekly. Within a month of starting treatment the IGF-1 levels dropped and remained within the normal range for age (103–310 μg/l). Pasireotide is well tolerated, the patients symptoms have greatly improved she is now back to work and riding her bike. The patient has not developed glucose intolerance. In view of the good response to Pasireotide, somatostatin receptor (SSR) subtyping was done. This revealed positivity for SST5 and SST2a subtypes.

Conclusion: This case demonstrates that there are patients with severe acromegaly resistant to first generation SRLs’ that can be well controlled on Pasireotide.