The Significance of Histologically "Large Normal" Parathyroid Glands in Primary Hyperparathyroidism

We investigated outcomes in a cohort of patients with a biochemical diagnosis of primary hyperparathyroidism (pHPT) undergoing surgery for asymptomatic disease or target organ damage, where a focussed or four-gland operation was undertaken and the histopathology only reported a "large normal" parathyroid gland (LNP).

Patients subjected to a parathyroidectomy for pHPT between 2012 and 2018 with a pathology of LNP were included. Patients with fat depletion or additional histological features of adenoma or hyperplasia in any of the resected glands were excluded. A control group was formed from 50 consecutive patients with the histological finding of adenoma or hyperplasia during the same study period. The primary outcome was biochemical normalisation of pHPT at 1-2 weeks and after 6 months post-operatively.

Forty-eight LNP patients (2% of all parathyroidectomies) were included in the study group with 50 matched controls. LNP patients had a lower biochemical cure rate (81% vs. 98% P < 0.05) and a higher risk of recurrence (10% vs. 0%, P = 0.06). LNP patients had a milder form of pHPT (Ca²⁺ 2.63 vs. 2.68 P < 0.05) with a smaller PTH and Ca²⁺ drop post-operatively. For LNP patients with failure, a definite additional cause of pHPT was found in only two patients.

This study highlights a controversial area in pHPT and reports LNP as a cause of pHPT. The biochemical analysis of this LNP group supports a benefit in resection in the setting of pHPT, although the risk of failure (persistence/recurrence) is higher than those with adenoma or hyperplasia. Stricter post-operative follow-up of LNP patients should be considered.