Evidence of a Functional Estrogen Receptor in Parathyroid Adenomas

Haglund, Felix; Ma, Ran; Huss, Mikael; Sulaiman, Luqman; Lu, Ming; Nilsson, Inga-Lena; Höög, Anders; Juhlin, C. Christofer; Hartman, Johan

doi:10.1210/jc.2012-2484

Cited by 33 publications

(31 citation statements)

References 216 publications

(210 reference statements)

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“…inhibitory feedback by the vitamin D receptor (VDR) and fibroblast growth factor 23 (FGF23)/Klotho-axes (14, 15, 16). Additional effects mediated by estrogens and progesterone have been described previously (17, 18). …”

Section: Introductionsupporting

confidence: 59%

“…The rationale behind these discrepancies may be due to differences in the study populations, including the degree of vitamin D insufficiency. Specifically, the impact of vitamin D insufficiency may be limited in primary hyperparathyroidism diagnosed at an early stage (18, 19, 20, 21, 32, 40, 41). Indeed, our semi-quantitative immunohistochemistry may be too crude to accurately quantify the tumor PTH levels for weaker statistical relationships.…”

Section: Discussionmentioning

confidence: 99%

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Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones

Haglund

Juhlin

Kiss

et al. 2016

European Journal of Endocrinology

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ObjectivePrimary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium–PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23.DesignA total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR.ResultsLow tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium-sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25-hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH.ConclusionsNo areas with apparently higher PTH expression were identified, perhaps suggesting that hyper functioning parathyroid tumor subclones should be rare. Circulating 25-hydroxyvitamin D levels may influence tumor PTH expression in vivo. If PTH immunoreactivity reflects the tumor calcium–PTH set point, our data imply that the main determinant of disease severity should be tumor weight.

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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones

Haglund

Juhlin

Kiss

et al. 2016

European Journal of Endocrinology

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“…Clinically, sporadic primary HPT can present at any age, with an increased incidence in postmenopausal women 4 7 30 42 52 53. A wide spectrum of clinical manifestations can be encountered, depending on the duration and degree of PTH oversecretion and resultant hypercalcaemia (tables 1 and 2).…”

Section: Clinical and Biochemical Featuresmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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“…Interestingly, further analysis of ERβ variants revealed that ERβ1 nuclear staining in the tumors was weaker compared to in the normal parathyroid rim (p = 0.026), and this difference was more evident in atypical adenomas (p = 0.045) and larger tumors (p = 0.029) [47]. The results from this study were repeated in a larger number of parathyroid tumors (n = 172) and 10 normal parathyroid glands [48].…”

Section: Expression Of Female Sex Steroids In Sporadic Parathyroid Tumentioning

confidence: 60%

“…By contrast, Wong et al [46] demonstrated ERα and ERβ expression in 100% of tissue samples from patients with primary and secondary hyperparathyroidism, although in some cases of secondary hyperparathyroidism the expression was weak. The expression of ERα and two other variants of ERβ, namely ERβ1 and ERβ2, were also studied by Haglund et al [47] in 37 sporadic parathyroid adenomas at both the mRNA and protein levels. In this study, parathyroid adenomas expressed low levels of the ERα gene, but relatively high levels of the ERβ gene.…”

Section: Expression Of Female Sex Steroids In Sporadic Parathyroid Tumentioning

confidence: 99%

Gender Predilection in Sporadic Parathyroid Adenomas

Yavropoulou

Anastasilakis

Panagiotakou

et al. 2020

IJMS

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Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas.

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Evidence of a Functional Estrogen Receptor in Parathyroid Adenomas

Abstract: Parathyroid tumors express ERβ1 and ERβ2. Transcriptional changes after ERβ1 activation and correlation to clinical features point to a role of estrogen signaling in parathyroid function and disease.

Cited by 33 publications

References 216 publications

Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones

Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones

Clinicopathological correlates of hyperparathyroidism

Gender Predilection in Sporadic Parathyroid Adenomas

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