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Endocrine Abstracts (2021) 73 S25.2 | DOI: 10.1530/endoabs.73.S25.2

ECE2021 Symposia Symposium 25: Parathyroid disorders (3 abstracts)

How to discriminate between PHPT and FHH

Ghada El-Hajj Fuleihan


American University of Beirut Medical Center, Beirut, Lebanon


Primary hyperparathyroidism (PHPT) is a common and for the most part an asymptomatic endocrine disorder, usually discovered by routine biochemical screening, in western populations; and increasingly now in other parts of the word. It is characterized by abnormal calcium-PTH dynamics, manifesting with mild hypercalcemia, with increased or inappropriately normal plasma parathyroid hormone (PTH) levels. PHPT is most commonly seen in older post-menopausal women. In countries where routine biochemical testing is lacking, patients present with symptoms of bony pain, fractures, and nephrolithiasis. Cardiovascular and neuropsychiatric abnormalities have been described, mortality is increased, and quality of life may be decreased. Parathyroidectomy is the treatment of choice in symptomatic patients, with improvement in bone density, and a decrease in stone risk. Reversibility of other above-mentioned associated conditions is less clear. PHPT may occur in the setting of heritable disorders in 10% of all cases, some syndromic (MENs) and other non-syndromic such as familial hypocalciuric hypercalcemia(FHH), presentations. The pathophysiology of non-hereditary PHPT is not totally clear. The calcium-sensing receptor (CaSR) is the major regulator of PTH release and plays a central role in keeping serum ionized calcium (Cai) within a very narrow physiologic range. Clonal somatic mutations and allelilc loss of the CaSR do not play a role in most cases of sporadic PHPT. Recent data suggest that certain SNPs of CASR gene may increase the risk of PHPT. Alterations in CaSR expression due to hypermethylation of the CaSR promoter or increased formation of heteromeric receptor complexes of the CaSR and GABAB1R may contribute to pathophysiology of PHPT. FHH: is an autosomal dominant benign condition characterized by loss of function mutations of CaSR, or distal to it. FHH is characterized by mild hypercalcemia, with inappropriately normal or slightly elevated serum PTH levels, and low urinary calcium excretion. A heterozygous germline inactivating mutation of the CASR on 3q21.1 accounts for 2/3 of cases (FHH1), while the remaining result from mutations downstream of the CaSR; in GNA11 located on 19p13.3 (FHH2), in AP2S1 on 19q13.2-q13.3 (FHH3), or from other unknown mutations. Presentation at a young age, before age 30 years, a family history of failed PTX, and the absence of end organ damage (low BMD, stones nephrolithiasis), are strong indicators of FHH. However, it has become increasingly clear that there may be overlap in the clinical presentation and biochemical phenotype of PHPT and FHH. DNA testing may be instrumental in differentiating the two entities.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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