Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- hyperkalcemie krev vrozené diagnóza diagnostické zobrazování MeSH
- lidé MeSH
- následné studie MeSH
- PET/CT metody MeSH
- primární hyperparatyreóza krev diagnóza diagnostické zobrazování MeSH
- prognóza MeSH
- receptory "calcium-sensing" krev MeSH
- vápník krev MeSH
- vitamin D krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- receptory "calcium-sensing" MeSH
- vápník MeSH
- vitamin D MeSH
BACKGROUND: Oncological diseases have, in most cases, a multifactorial etiology, composed of a combination of external and internal environmental factors. Hereditary tumorous syndromes are mostly autosomal dominant diseases with incomplete but very high penetrance. OBSERVATION: The patient, an 18-year-old virgin female, consulted a gynecologist in June 2018 because of metrorrhagia. Magnetic resonance imaging revealed a cervical tumor with the dimensions 80 × 90 × 80 mm. Histological analysis confirmed the presence of a very rare hypercalcemic type of small-cell carcinoma of the cervix. Further investigation of the germinal exom of the patient showed pathological variations in genes PALB2 and BRCA2, presented with recommendation of detailed examination by medical genetics. CONCLUSION: Clinical experience with this type of tumor is very limited, but it still comes with some useful outcome. Small cell carcinomas of the gynecologic tract are very rare, aggressive diseases, with very poor prognosis, affecting mainly young women. Their origin is most often the ovaries, based on most clinical data, but these tumor also localize to the endometrium, cervix, vagina and vulva. It is an extremely rare type of cancer, for which clinical data is scant due to the extremely low number of reported cases. In this patient, the carcinoma had an unusual genetical mutation burden, which she inherited from her parents. In the light of these findings, we recommend that patients suspected of having a small-cell of the gynecologic tract provide a detailed family history, and that genetic testing be considered in similar cases. This work was supported by MH CR grant 16-33209A and research program of Charles University Progress Q40/06. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 10. 6. 2019 Accepted: 9. 9. 2019.
- Klíčová slova
- PALB2, BRCA2 mutation, hereditary neoplastic syndromes, rare cervical cancer, small-cell carcinoma, hypercalcemic type, whole exome sequencing,
- MeSH
- hyperkalcemie diagnostické zobrazování genetika patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malobuněčný karcinom diagnostické zobrazování genetika patologie MeSH
- mladiství MeSH
- mutace MeSH
- nádory děložního čípku diagnostické zobrazování genetika patologie MeSH
- protein BRCA2 genetika MeSH
- protein FANCN genetika MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- BRCA2 protein, human MeSH Prohlížeč
- PALB2 protein, human MeSH Prohlížeč
- protein BRCA2 MeSH
- protein FANCN MeSH
PURPOSE: Identification of pathologic parathyroid glands in primary hyperparathyroidism, traditionally based on neck ultrasound (US) and/or 99mTc-Sestamibi scintigraphy, can be challenging. PET/CT with 18F-Fluorocholine (18F-FCH) might improve the detection of pathologic parathyroid glands. We aimed at comparing the diagnostic performance of 18F-FCH-PET/CT with that of dual-phase dual-isotope parathyroid scintigraphy and neck US. METHODS: Thirty-four consecutive patients with primary hyperparathyroidism were prospectively enrolled, 7 had normocalcemic hyperparathyroidism, and 27 had classic hypercalcemic hyperparathyroidism. All patients underwent high-resolution neck US, dual-phase dual-isotope 99mTc-Pertechnetate/99mTc-Sestamibi scintigraphy, and 18F-FCH-PET/CT. RESULTS: In the whole patients' group, the detection rates of the abnormal parathyroid gland were 68% for neck US, 71% for 18F-FCH-PET/CT, and only 15% for 99mTc-Sestamibi scintigraphy. The corresponding figures in normocalcemic and hypercalcemic hyperparathyroidism were 57 and 70% for neck US, 70 and 71% for 18F-FCH-PET/CT, and 0 and 18% for 99mTc-Sestamibi scintigraphy, respectively. In the 17 patients in whom the abnormal parathyroid gland was identified, either at surgery or at fine needle aspiration cytology/biochemistry, the correct detection rate was 82% for neck US, 89% for 18F-FCH-PET/CT, and only 17% for 99mTc-Sestamibi scintigraphy. CONCLUSIONS: 18F-FCH-PET/CT can be considered a first-line imaging technique for the identification of pathologic parathyroid glands in patients with normocalcemic and hypercalcemic hyperparathyroidism, even when the parathyroid volume is small.
- Klíčová slova
- Normocalcemic hyperparathyroidism, PETC/CT with 18F-Choline, Primary hyperparathyroidism,
- MeSH
- cholin analogy a deriváty MeSH
- dospělí MeSH
- hyperkalcemie diagnostické zobrazování patologie chirurgie MeSH
- hyperparatyreóza diagnostické zobrazování patologie chirurgie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory příštítného tělíska diagnostické zobrazování patologie chirurgie MeSH
- následné studie MeSH
- PET/CT metody MeSH
- prognóza MeSH
- radiofarmaka MeSH
- radioisotopová scintigrafie metody MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ultrasonografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholin MeSH
- fluorocholine MeSH Prohlížeč
- radiofarmaka MeSH
