SAT-809 - Expression of Growth Hormone Receptor and Insulin-Like Growth Factor 1 Receptor in Parathyroid Tumors of Patients with A Combination of Acromegaly and Primary Hyperparathyroidism

Aims: Multiple endocrine neoplasia type 1 (MEN1) cases without MEN1 mutations are designated as MEN1 phenocopies, the majority of which are patients with pituitary adenomas (PA) and primary hyperparathyroidism (PHPT), and somatotroph tumors prevail among PA. We hypothesized that in some patients with acromegaly (MEN1 phenocopies) PHPT may develop due to increased expression of growth hormone receptor (GHR) and/or insulin-like growth factor 1 receptor (IGF-1R) on parathyroid glands. Expression of GHR and IGF-1R in parathyroid tumors of patients with acromegaly was evaluated in MEN1 phenocopies (group 1), genetically confirmed MEN1 (group 2) and sporadic PHPT (group 3) as control.

Methods: Patients from groups 1 and 2, and some patients from group 3 underwent genetic testing for MEN1 mutations. All patients underwent surgical removal of parathyroid tumors in 2014-2024. 43 formalin-fixed paraffin embedded samples from 37 patients were immunohistochemically (IHC) stained (Leica, Bond) for GHR ([10C11] (ab288372), Abcam) and IGF-1R (GTX79046, GeneTex).

Results: Group 1 included 16 patients (3 men, 13 women). 4 patients had multiple lesions (1 – 3 adenomas, 1 – 2 adenomas, 1 – adenoma and atypical adenoma, 1 – adenoma and oncocytic adenoma), 12 patients had solitary lesions (10 – adenomas, 1 – hyperplasia, 1 – atypical adenoma). IHC staining was performed on 19 samples. GHR expression was negative in 6 (32%). In 13 (68%) it was focal: weak in 9 (69%), moderate in 4 (31%). IGF-1R expression was negative in 3 samples (16%). In 16 (84%) it was focal: weak in 8 (50%), moderate in 5 (31%), strong in 3 (19%). Group 2 included 6 patients (2 men, 4 women) (in all PA had mixed GH and prolactin secretion). 3 patients had multiple lesions (1 – 4 adenomas, 1 – 2 adenomas, 1 – 3 hyperplasia), 3 patients had solitary adenomas. IHC staining was performed on 9 samples. GHR expression was positive in all samples: weak in 5 (55.5%), moderate in 4 (44.5%). IGF-1R expression was negative in 1 (11%). In 8 (89%) it was focal: weak in 3 (37.5%), moderate in 3 (37.5%), strong in 2 (25%). Group 3 included 15 patients (4 men, 11 women). 14 patients had solitary adenomas, 1 – atypical adenoma. GHR expression was focal in all samples: weak in 12 (80%), moderate in 3 (20%). IGF-1R expression was negative in 3 samples (20%). In 12 (80%) samples it was positive (11 (73%) – focal, 1 (7%) – diffuse): weak in 8 (66.7%), moderate in 3 (25%), strong in 1 (8.3%). Intensity of GHR and IGF-1R expression does not differ among the 3 groups (p>0.05). The presence of GHR expression is higher in sporadic PHPT compared to MEN1 phenocopies (p=0.02), but not in genetically confirmed MEN1.

Conclusions: There is no difference in intensity of GHR and IGF-1R expression in parathyroid tumors of patients with acromegaly between MEN1 phenocopies and genetically confirmed MEN1 as well as sporadic PHPT. GHR expression is slightly increased in sporadic PHPT in comparison with MEN1 phenocopies.

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