Endocrine Abstracts

Background: Pituitary neuroendocrine tumours (PitNETs) that cause acromegaly are often collectively categorised as ‘growth hormone (GH) secreting adenomas’. The 2022 WHO classification however identifies 7 histological variants that can secrete GH: densely granulated somatotroph (DGST), sparsely granulated somatotroph (SGST), mammosomatotroph (MST), mixed somatotroph and lactotroph (MSLT), mature plurihormonal PIT1 (MPPT), immature PIT1 (IPT) and acidophil stem cell (ASCT) tumours. Although differences in clinical behaviour have been outlined in studies comparing select tumour subgroups, there is currently insufficient evidence to include tumour histotype in therapeutic or prognostic algorithms for acromegaly. We analysed all tumour variants of acromegaly to assess differences in clinical characteristics.

Methods: We conducted a retrospective assessment of all PitNETs resected from 2011 to 2018 at Westmead Hospital. Tumour specimens underwent assessment for expression of transcription factors, co factors, anterior pituitary hormones, cytokeratin and somatostatin receptor (SSTR) 2 and 5 using immunohistochemistry. All PitNETs were then assigned a morphological subtype according to the 2022 WHO classification. Variants that can cause acromegaly were selected. Multilineage PIT1 and SF1 tumours (MPST) were identified as an eighth distinct subtype that causes acromegaly and included in our analysis. Correlation was sought with clinical data from medical records.

Results: Of the 47 tumours, 40 (85.1%) had clinical or biochemical acromegaly at presentation. Tumour size differed by histological type; SGSTs (mean diameter 23.4 ±5.9mm) larger than DGSTs (13 ±7.1mm, P=0.03) or MSTs (11.8 ±7.6mm, P=0.002). The number of therapeutic interventions after initial surgery was not different between SGST and MST groups (1.11±0.93 vs 1.00 ±0.82, P=0.40), but was lower for the MPST group (0.29 ±0.49, P=0.03 vs SGST). At 3 months after surgery, normalisation of IGF-1 was achieved in a higher proportion of MPST than SGST (66.7% vs 14.3%, P=0.05). 17 PitNETs (42.5%) required treatment with somatostatin receptor ligands (SRL), 29.4% were SGST and 29.4% were MST. Over a mean follow up duration of 75 months, tumour regrowth or recurrence was observed in 25% of SGST and 40% of IPT, but was not seen with any other variants. Proportion of ‘high-risk’ variants (SGST and IPT) needing radiotherapy was higher than other groups combined (42.9% vs 9.1%, P=0.01).

Conclusion: Our data suggests that there are differences in clinical behaviour and outcome among histological variants that cause acromegaly. Tumour histotype potentially has a role in directing individualised management plans for acromegaly and may be useful for prognostication.