Familial isolated hyperparathyroidism (FIHP)

Pratibha Machenahalli, Kevin Shotliff, James Smellie.

Chelsea and Westminster Hospital.


Abstract: 49 year graphic designer referred due to vitamin D deficiency and elevated PTH. He denied symptoms of hypo/hypercalcemia. On a vitamin D supplement his ca©-2.7 mU/L (2.15-2.60), vitamin D 58mmol/L (70-150), phosphate-0.82 (0.8-1.4), PTH-10, normal renal and liver functions. Thyroid autoantibodies were strongly positive with normal TFT’s.

This gentleman had background of type 2 diabetes mellitus, hypertension, pernicious anaemia, obstructive sleep apnoea. He had an interesting family history with a sister and niece having a goitre needing surgery and two brothers with hyperparathyroidism had parathyroidectomy. The niece with a goitre had two parathyroid resection (pathology results are unknown).

Due to his strong family history, as FHH has been excluded localisation studies were carried out. USS of neck revealed normal thyroid gland.  MIBI parathyroid scan showed Left upper and right lower parathyroid adenomas. Post-operatively, corrected calcium normalised. DEXA scan of the left forearm had T score -2.9, left distal radius -3.3. Due to the above reasons, he underwent global parathyroidectomy. Histology- parathyroid hyperplasia. In view of the strong family history of hyperparathyroidism, genetic tests were carried out. Our patient has been found to have a G to A nucleotide substitution in exon 3 of MEN1 (C.494G>A), which is predicted to result in replacement of the amino acid cysteine with tyrosine at residue 165, confirming diagnosis of familial isolated hyperparathyroidism. He is awaiting results of  further screening of MEN1.

Discussion: FIHP is an autosomal dominant condition that can present as an allelic variant of MEN1 or hyperparathyroidism jaw tumour syndrome. FIHP can also present without any association with other tumour and has been described as a separate entity.  It is associated with germ line mutation of CDC73. The vast majority of individuals with FIHP and a germline CDC73 mutation have at least one family member with a histopathologic diagnosis of parathyroid carcinoma and/or had a parathyroid adenoma with atypical or cystic features. Missense mutations are more likely to be associated with the FIHP phenotype whereas mutations that cause gross disruption of the protein product are more likely to be associated with the HPT-JT phenotype.

Parathyroid surgery is indicated if the patient has end organ damage due to hypercalacemia. Genetic screening of the family member and screening investigations for MEN1 should be considered.  Long term follow up is needed to identify other endocrine related conditions particularly of pituitary and pancreas.