CYP24A1 gene defect manifesting with gestational hypercalcemia / A CYP24A1-gén terhességi hypercalcaemiát okozó defektusa

Hypercalcemia is a rare condition in pregnancy. It is most commonly caused by primary hyperparathyroidism and parathyroid hormone-related peptid (PTHrP)-producing malignant tumours, less frequently by increased intestinal calcium absorption, vitamin D intoxication, milk-alkali syndrome, and granulomatous diseases or lymphomas, in which vitamin D 1 alpha-hydroxylase expression is increased. Rarely, gestational hypercalcaemia may be caused by a disorder of vitamin D catabolism caused by loss-of-function mutations in the CYP24A1 gene. We report the case of a 34-year-old Caucasian female patient. She was diagnosed with hypercalcaemia, normal intact parathyroid hormone (PTH) level and lower left parathyroid adenoma. Investigations for malignancy showed no evidence of abnormality. The lower-left parathyroid adenoma was removed followed by cessation of hypercalcaemia. Fifteen months later, she had a spontaneous miscarriage at a gestational age of 8 weeks, when serum calcium was at the upper limit of normal. 25 months following parathyroid surgery, as a 12-week pregnant, our patient manifested with symptomatic, PTH-independent hypercalcaemia. 25-hydroxy-vitamin-D and PTHrP were within reference ranges while 1,25(OH)2D level was clearly elevated. Compound heterozygosity within the CYP24A1 gene was confirmed. By conservative treatment, no other complications were observed during pregnancy, and she finally gave birth to a healthy girl with a term. We present the difficulties of diagnosing and treating hypercalcaemia observed during pregnancy. According to our knowledge, our patient represents the first case of CYP24A1 gene defect diagnosed in Hungary.

Clinical Impact of Preoperative Magnetic Resonance Imaging in the Evaluation of Myometrial Infiltration and Lymph-Node Metastases in Stage I Endometrial Cancer.

Purpose: In the developed world, endometrial cancer is one of the most common malignant gynecological cancer types. Due to the highly available diagnostic modalities and patient education, the early detection of the tumor leads to high overall survival. Methods: In this study we analyzed the reliability of preoperative MRI findings in the staging of early stage endometrial cancer, as well as the clinical characteristics of patients underwent radical hysterectomy and the histopathologic evaluation of their tumor, with the retrospective data of radical hysterectomies performed in our hospital between 2010 and 2019. Results: The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI regarding stage were 94.7, 63.3, 94.8, 83.8, and 83.8%, respectively. The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI for the detection of the myometrial invasion were 69.8, 80.0, 60.8, 64.3, and 77.5%, respectively. The accuracy, sensitivity, specificity, negative- and positive predictive value of MRI for the detection of lymph node metastases were 78.1, 28.6, 82, 11.1, and 93.6%, respectively. Conclusions: Based on our results, MRI is the method of choice in terms of evaluating overall staging, as well as myometrial invasion, as its specificity and negative predictive value are relatively high. However, systematic lymphadenectomy showed improved cancer-related survival and recurrence-free survival. Our studies showed that the diagnosis of lymph node metastases is difficult with MRI modality since hyperplastic and metastatic nodes cannot easily differentiate, leading to a high percentage of false-positive results. Therefore, other imaging modalities may be used for more accurate evaluation. New findings of our study were that the role of the radiologist's expertise in the evaluation of MR imaging plays an essential role in lowering false-negative and false-positive results. Therefore, findings evaluated by a radiologist with high-level expertise in gynecological imaging can complement the clinical findings and help substantially define the needed treatment.

Unusual clinical history of a male infant with Edwards syndrome.

Edwards syndrome (trisomy of chromosome 18) is generally characterized by the disorders of central nervous system, as well as the musculoskeletal and genitourinary systems. In majority of the cases with trisomy 18 the following malformations can be found: ventricular septal defect, horseshoe kidneys, oesophageal atresia, omphalocele, facial clefts, diaphragmatic hernias and genital hypoplasia. We report a male patient with Edwards syndrome. The boy had a partial agenesis of corpus callosum, oesophageal atresia with tracheo-oesophageal fistula, renal agenesis, ventricular septal defect, Dandy-Walker cyst and low-set malformed ears. The first three features are unique based on previous literature reports on trisomy 18. This report allows a further delineation of the trisomy 18 syndrome.

Extremely large epithelial ovarian cancer associated with pregnancy: A case report.

Ovarian malignancies are rare in pregnancy; however, the incidence of abnormal adnexal masses diagnosed during pregnancy is increasing. The most common masses are ovarian cysts, and only 3-6% of those are malignant. The majority of ovarian masses are diagnosed at an early stage by routine ultrasound examinations. Malignant germ cell tumors are the most common ovarian malignancies associated with pregnancy, while the incidence of epithelial ovarian cancer is only 1:12,000-1:50,000 of pregnancies. The diagnosis and management of ovarian cancer during pregnancy remain unclear due to the rare occurrence and scant data on this condition. We herein report the case of 23-year-old woman with an extremely large ovarian papillary mucinous cystadenocarcinoma diagnosed during pregnancy, identified on ultrasound and magnetic resonance imaging, and treated by surgical resection followed by adjuvant chemotherapy with carboplatin and paclitaxel.

Rare virilizing granulosa cell tumor in an adolescent.

Hormone-producing malignancies are rare in children or adolescent patients: Only 0.1% of all ovarian tumors and 4-5% of granulosa cell tumors occur in the sexually non-active ages. Granulosa cell tumors (GCTs) are sex cord-stromal tumors of the ovary, representing 7-8% of all ovarian neoplasms. A total of 95% of all GCTs are adult-type, and only 5% are diagnosed as juvenile-type GCT. A majority of children with juvenile-type GCT present with isosexual precocious pseudopuberty due to excessive estrogen production, although virilizing, testosterone-producing, juvenile-type GCTs are rare, occurring only in 2-3% of cases. The present case study reports on a case of a virilizing, juvenile-type GCT in a 14-year-old girl, along with a review of the literature.

Antiphospholipid antibodies in relation to sterility/infertility.

Of the systemic autoimmune diseases that lead to sterility/infertility, antiphospholipid syndrome (APS) has an outstanding importance; it may be associated with abortion and premature birth which are included in its diagnostic criteria, as well as preeclampsia, pregnancy-induced hypertension, foetal retardation, miscarriage, stillbirth and sterility. Between 2004 and 2009, on the Department of Immunology in the Zala County Hospital, 100 female patients with sterility (st)/infertility (if) (33/67), (mean age: 34.08 years) underwent, in addition to history taking and physical examination, an assessment by immune-serologic tests (ANA, anti-dsDNA, ENA-Profile, anti-TPO, a-sperm, aCL, aPS, aß2GP1, aANX, and aPT). Positive aCL on two occasions could be demonstrated in 27/100 cases (27%) (st/if: 7/20). Among them 4 cases of primary APS have been diagnosed respectively. In the remaining 17 patients the clinical picture did not fulfil criteria. In addition to the twofold positive aCL, unusual antiphospholipid antibodies including aß2GP1, aPS or both were present in 1/27, 2/27 and 1/27 patients, as well as aANX and aPT in 3/26 and 1/27 patients respectively. One-time positive aCL occurred in 16/100 women (16%) (st/if: 5/11); among them aPT and aß2GP1 could be detected in 1/16 patient each. Based on the clinical picture, we raised the possibility of primary APS in 2/16 patients. Among the aCL-negative women, we found the unusual antibodies of APS in 8/57 patients (14%) including positivity of aß2GP1, aPS, aPT and aANX in 4/57, 4/57, 2/57 and 3/57 patients respectively; taking the clinical criteria of APS into consideration, primary APS could be stated in 2/57 patients of them. The 32 pregnancies developed in the follow-up period upon administration of acetylsalicylic acid (ASA) and maintenance dose low molecular weight heparin (LMWH), together with prednisolone in patients with secondary APS, resulted in 23 deliveries and 5 miscarriages; 4 pregnancies are currently in progress. The results of our investigations highlight the significance of demonstrating latent autoimmune diseases in female patients with sterility/infertility, as barrenness can be terminated by the appropriate treatment of these conditions.