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Nontruncated amino‐terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation
Author(s) -
Caron Philippe,
Simonds William F.,
Maiza JeanChristophe,
Rubin Mishaela,
Cantor Tom,
Rousseau Louise,
Bilezikian John P.,
Souberbielle JeanClaude,
D’Amour Pierre
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04021.x
Subject(s) - hypercalcaemia , parathyroid hormone , medicine , endocrinology , parathyroid carcinoma , calcium , primary hyperparathyroidism , chemistry
Summary Objective Some patients with parathyroid carcinoma present with an over‐production of nontruncated amino‐terminal (NT‐N) parathyroid hormone (PTH), a post‐transcriptionally modified form of PTH(1‐84). This is usually picked up on an elevated whole (W) PTH (third‐generation)/total (T) (second‐generation) PTH assay ratio (N > 0·8). Patients and design Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W‐PTH, T‐PTH and circulating PTH molecular forms separated by high‐pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. Results The first patient had total calcium of 3·8 and 3·22 mmol/l before the fourth and fifth surgeries, and third/second‐generation PTH ratios of 2·95 and 3·6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3·6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over‐expression of NT‐N PTH to 82·2% (N < 10%) relative to hPTH(1‐84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W‐PTH/T‐PTH ratio was 0·89 when serum calcium was 3·3 mmol/l. NT‐N PTH was also over‐expressed at 51·9%. An inactivating mutation of the HRPT2 gene was also identified. Conclusions This may suggest that a progressive rise in third/second‐generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT‐N PTH overproduction and HRPT2 gene inactivation is also suggested.