X-linked hypophosphataemic rickets: Report of a novel PHEX mutation and cinacalcet as adjuvant therapy in the mineral metabolism control.

X-linked hypophosphataemic rickets (XLH) is a rare disease caused by a mutation in the phosphate-regulating neutral endopeptidase (PHEX) gene, located on the X chromosome. This gene encodes the phosphate-regulating endopeptidase, and its inactivation leads to increased levels of circulating phosphatonins responsible for renal phosphate loss. The treatment for XLH is still carried out with long-term administration of phosphate and calcitriol, which can be complicated by hyperparathyroidism, nephrocalcinosis, renal failure, and hypertension. We describe the case of a four-decade follow-up patient with XLH. When she was diagnosed, at 19 years, due to bone pain and deformities, she was put on therapy with phosphorus and cholecalciferol. Despite the clinical improvement, serum phosphorus remained difficult to control. At the age of 44 years, she developed tertiary hyperparathyroidism and was submitted to parathyroidectomy. Five years later, parathyroid hyperfunction recurred. This time, cinacalcet was started, 30 mg alternating with 60 mg/day. Currently, she is 59-years old and remains with controlled mineral metabolism. The genetic study of this patient revealed a nonsense heterozygous mutation (c.501G>A) in PHEX gene that was not previously described. In this case, the off-label use of cinacalcet resulted in the normalisation of serum parathormone and phosphorus levels, eliminated recurrent secondary hyperparathyroidism, which aggravates the bone fragility inherent to XLH, and prevented a new parathyroidectomy. This report also adds important information to the genetic basis of XLH with the identification of a new nonsense mutation of the PHEX gene.

Is Gonadal Therapy a Promoter of Breast Cancer? Incidence of Breast Cancer in a Cohort of Survivors of Oncological Diseases Treated with Gonadal Steroids.

There is a great controversy about hormonal replacement therapy in women among the members of the scientific community. Cancer survivors have sometimes had their ovary function totally or partially destroyed, thus affecting their development and quality of life. In this study, we were looking for adverse effects caused, eventually, by estroprogestative therapy in a cohort of supplemented survivors. The occurrence of breast cancer was our main concern. Ours is a retrospective study based on the clinical records of 174 survivors of several cancer diseases. Their median ages within each of the following time frames were: diagnosis - 22 years old; start of endocrine treatment - 26 years old, and duration of treatment - 12 years old. Evaluation was composed of breast cancer assessment, osteopenia and osteoporosis incidence, and vascular events. We have found a very low incidence of breast cancer as well as of vascular events. After treatment, a high percentage of our sample displayed bone mass improvement.

Endocrine Health Problems Detected in 764 Patients Evaluated in a Late Effects Clinic.

BACKGROUND: Many pediatric cancer survivors have endocrine conditions. After treatment with alkylating agents, steroids, methotrexate, and radiation, several endocrine dysfunctions may appear. Surveillance for late effects is recommended by guidelines worldwide. OBJECTIVE: The objective of this study was to describe the endocrine outcomes of 764 patients followed during a 20 years' period in our out-patient clinic. DESIGN: We retrospectively reviewed the medical records. PATIENTS: The study included 764 patients whose oncological or hematological dangerous diseases appeared before they were 18 years old. Larger groups were constituted by leukemias, central nervous tumors, and lymphomas. OUTCOME MEASURES: The frequency and types of endocrine conditions were analyzed. RESULTS: 1,091 endocrine conditions were observed in all groups. The most common types of endocrine conditions were problems with growth and the thyroid. We found puberty abnormalities and bone problems in third and fourth places of frequency. ACTH insufficiency was found in seventh place. CONCLUSION: Endocrine dysfunctions are very common in survivor populations. Endocrinologists should be aware of international guidelines and make an effort to optimize screening and treatment of endocrine effects of cancer therapy. The crucial period is the puberty with growth spurt failure and accelerated maturity both of which can bring future social and professional difficulties.

Adipsia in a Diabetes Insipidus Patient.

Central diabetes insipidus is a very common disorder after brain surgery or/trauma or even in the presence of brain inflammatory diseases. Polyuria and polydipsia are the clinical markers, but sometimes clinical situations are presenting with no thirst. These are not frequent but are life-treating conditions. Diagnosis is not easy, and for this reason some cases are treated late. We describe here a very infrequent oncological case of dangerous adipsic diabetes insipidus in a young girl who survived.

Sperm Count Improvement in a Cancer-Surviving Patient.

OBJECTIVE: To describe the case of a cancer-surviving patient who was treated with an aromatase inhibitor for fertility reasons with successful results. CLINICAL CASE: A 30-year-old patient from our institute who had been submitted to bone marrow transplantation in the past as part of treatment for Hodgkin's disease had revealed oligospermia several times. His sperm count mean value was 33,500 cells/ml. He was treated with an aromatase inhibitor (letrozole, 2 mg/day) for 8 months. After this period, his sperm count had increased significantly to 1,000,000 cells/ml. CONCLUSION: A large number of cancer survivors express a wish for having babies. After their cure, a lot of them have a low count of spermatozoids, and we think that our results show an easy way of helping them.

Latency Period until the Development of Thyroid Cancer in Young Patients Submitted to Radiotherapy: Report of 10 Cases.

BACKGROUND: Radiotherapy increases the risk of thyroid cancer (TC); patients submitted to this treatment should undergo a long-term follow-up. Our aim is to describe the features and outcomes of young patients who developed TC after radiotherapy. METHODS: At our center, patients undergoing radiotherapy directly or indirectly involving the thyroid are regularly followed up in order to detect early dysfunction or nodules. Herein, we report the cases of 10 patients who were submitted to radiotherapy and developed TC. CLINICAL FINDINGS: Seven patients were irradiated in the neck and 3 in nearby regions. The mean age at the last radiotherapy session was 10 ± 5.5 years. The average time until the appearance of the first thyroid nodule was 14 ± 4.7 years. The mean size increment of the nodules was 2.4 ± 1.6 mm/year. On the first cytology, only 2 results were suspicious of papillary thyroid cancer (PTC). All patients presented a histology of PTC. Eight were in stage I and 2 in stage II. The median follow-up from primary diagnosis to TC and beyond was 20 and 3 years, respectively. CONCLUSIONS: In these patients, cytologies may be difficult to interpret due to persistent benign results. The threshold for surgical indication may be anticipated, considering the increased risk of TC. We report the evolution of these nodules over time, from the end of primary oncological treatment.