DeCure for Prolactin-Producing Pituitary Gland Adenoma

In a 1993 study, Pit-1, a transcription factor that activates prolactin and GH gene expression, was found in a range of human pituitary adenomas. Pit-1 mRNA, immunoreactivity and DNA-binding activity were all detectable. Gel mobility shift assays using adenoma protein extracts with two Pit-1-binding sites from the human prolactin gene promoter showed several DNA sequence-specific protein-DNA complexes; some were accounted for by Oct-1-binding activity. Pit-1 activity was anticipated in prolactin- and GH-secreting adenomas but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target genes. Different adenomas generated slightly differing patterns of DNA-binding activity, though Pit-1 mRNA and protein size appeared normal in all tumours examined.

A 2006 study examined 60 patients with gross pituitary adenomas and moderate hyperprolactinaemia. Morphological analysis of intraoperative samples included histological and immunohistochemical studies with antibodies to adenohypophysis hormones. Among gross pituitary adenomas presenting with moderate hyperprolactinaemia, the probable frequency of prolactin-secreting tumours was 25%. Among tumours regarded as prolactinomas in the preoperative period, the probable frequency of hormonally inactive pituitary adenomas was 16%.

A 2020 retrospective analysis of 75 patients undergoing transsphenoidal surgery for functioning and non-functioning pituitary adenomas (prolactinomas excluded) found that 21.3% (n=16) had at least one pituitary axis requiring replacement at three years postoperatively. Mean age was 55 ± 16 years, 55% were female, and 81% were Caucasian. Mean adenoma size was not different between normal pituitary function and hypopituitary groups (24.0 ± 11.9 mm versus 25.3 ± 10 mm, p=0.7). Factors associated with long-term hypopituitarism were older age (mean 64 ± 4 versus 53 ± 2 years, p=0.02), preoperative secondary adrenal insufficiency (AM cortisol 6.4 ± 3.7 versus 12.0 ± 6.5 µg/dL, p=0.03), preoperative secondary hypothyroidism (0.8 ± 0.2 versus 12.0 ± 6.5 ng/dL, p<0.01), low immediate postoperative cortisol (5.3 ± 3.1 versus 26.1 ± 18.3 µg/dL, p<0.01), and persistence of adrenal insufficiency (10.7% versus 2.7%, p<0.01) and secondary hypothyroidism (13.3% versus 5.3%, p<0.01) at three months. Change in prolactin concentration from preoperative to postoperative day 1-7 was not significantly different between groups (p=0.09) due to higher variability in the hypopituitary group (median 0.2 ng/mL, IQR -0.5 to 0.8 ng/mL) compared to the normal pituitary function group (median 0.7 ng/mL, IQR 0.5-0.8 ng/mL). Adenoma size, optic chiasm and cavernous sinus involvement were not associated with long-term hypopituitarism. In patients who developed postoperative hypopituitarism, there was a higher frequency of adenoma persistence or recurrence (20% versus 47%). There was a high rate of patients lost to follow up (56%). The authors concluded that prolactin concentrations were not a good surrogate marker to predict long-term hypopituitarism.

What is still missing is prospective data with complete follow-up to confirm the predictive value of clinical and biochemical factors, and a clear understanding of the molecular mechanisms linking Pit-1 expression to adenoma behaviour in non-secreting tumours. No trial has yet tested whether stratifying patients by preoperative pituitary function or postoperative cortisol response can reduce the rate of long-term hypopituitarism.