Pasireotide therapy in a rare and unusual case of plurihormonal pituitary macroadenoma

Abstract

SummaryWe report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease.Learning points Plurihormonal pituitary adenomas are rare and unusual.Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.Pasireotide holds potential where conventional somatostatin analogues are not effective in acromegaly due to higher affinity for somatostatin receptor subtypes 1, 2, 3 and 5.Significant deterioration in glycaemic control remains a concern in the use of pasireotide.Currently, long-term safety and efficacy of pasireotide in patients with acromegaly and/or Cushing's disease are not fully clear.

How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

“…These unusual combinations have been scarcely documented, and most publications have been on isolated cases or double PitNETs. Moreover, the typification of these tumors has been based on the IHC study of pituitary-specific hormones [28][29][30][31][32]. Only Kageyama et al [33] have described the IHC co-expression of NEUROD1, Tpit, and Pit-1 in a silent PitNET with positivity for ACTH and PRL.…”

Cushing’s Disease of Unknown Etiology: A Clinical Case Report

“…Instead in this case a large (19 × 12 mm) lesion that seems to include all the pituitary with pituitary stalk widening, no clearly visible neurohypophysis bright spot and hypointense in both T1 and T2 is found with homogenous contrast uptake. This might suggest either corticotroph hyperplasia (although evidence for CRH oversecretion is lacking as noted), silent corticotroph macroadenomas (but there is clear analytical evidence for hypercortisolism) or mixed type corticotroph adenomas (but no evidence for other hormone secretion is found) [26][27][28]30]. Most interestingly is the pituitary stalk widening; this finding has been reported in relation to granulomatous or immune-mediated pituitary diseases in regard with hypopituitary states [15,16].…”

“…Despite a standardized clinical diagnostic and treatment approach [22][23][24], CD may be difficult to diagnose and to treat; and several uncommon variants are recognized like cyclic CD [25], intermediate lobe corticotroph adenomas [26], mixed corticotroph adenomas [27], silent corticotroph macroadenomas [28] and even the exceedingly rare corticotroph carcinoma [29]. Also apparent CD because of CRH hypersecretion, either a hypothalamic tumor or a peripheral neuroendocrine tumor [30], and the classic Nelson' syndrome [31] after bilateral adrenalectomy must be considered.…”

Successful Therapy Using Pasireotide Long-acting Release for Cushing's Disease Merged with Biochemical Acromegaly

“…It also suggests the superior efficacy of pasireotide-LAR compared to a first-generation somatostatin analog, octreotide LAR, for the treatment of patients with acromegaly. Rajendran et al reported the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin, and ACTH ( 10 ). In that case, the GH and IGF-1 levels improved significantly, but intermittent hypercortisolemia persisted.…”