[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

[Olfactory function and olfactory bulbs in patients with Kallmann syndrome].

BACKGROUND: The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don't have such complaints but olfactory dysfunction is diagnosed via olfactometry. Nowadays there is the lack of information about correlation between olfactometry results and subjective complaints. Correlation between olfactory bulbs size and olfactory dysfunction has been little studied. AIM: To explore olfactory bulb size and olfactory function in patients with congenital isolated hypogonadotropic hypogonadism. To correlate olfactory bulb sizes and smell test scores. MATERIALS AND METHODS: Single-centre comparative study. 34 patients were included. The main group consisted of 19 patients with hypogonadotropic (15 -with Kallmann syndrome, 4 - with normosmic hypogonadism). Olfactory bulbs MRI were provided to all the patients, olfactory test (Sniffin' Sticks Test) and molecular-genetic studies were provided in all patients with hypogonadism. Control group consisted of 15 patients who were provided with orbits MRI. Olfactory bulbs were evaluated additionally in them. RESULTS: Normal size of olfactory bulbs were only in 1 patient with hypogonadism. Olfactory bulbs height and width were significantly smaller in patients with hypogonadism in comparison with control group (p<0.01). Height median of right bulb was 1.0 mm [0.2; 1.8] in patients from the main group vs. 3.0 [2.5; 3.2] in controls, width median of right bulb was 1.0 mm [0.2; 1.9] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Height median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 3.0 [2.7; 3.2] in controls, width median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Correlation has been established between left bulb height (r=0.59) and width (r=0.67) and olfactometry results (p<0.05). 4 patients had no anosmia complaints but had olfactory dysfunction according to Sniffin' Sticks Tests. CONCLUSION: Olfactometry was able to diagnose olfactory dysfunction in 78.5% (i.e. in 15 out of 19 patients with congenital isolated hypogonadotropic hypogonadism. However, anosmia complaints had only 11 out of 19 patients. It is the first results of olfactory bulb sizes in patients with hypogonadotropic hypogonadism in Russia. Uni - or bilateral hypoor aplasia were diagnosed in 94.7% patients with hypogonadism regardless of olfactory dysfunction. Bilateral olfactory bulbs hypoplasia were the most common MRI-finding (36.8%). Unilateral hypoor aplasia was diagnosed in 31.6% patients.

[Hypophysitis and reversible hypopituitarism developed after COVID-19 infection - a clinical case report].

AIM: To present a clinical case of reversible hypopituitarism due to hypophysitis developed after COVID-19 infection. MATERIALS AND METHODS: A patient with residual clinical manifestations of hypopituitarism underwent clinical evaluation at the time of symptoms of hypopituitarism and in follow-up. Morning serum cortisol (171-536 nmol/l) was measured by electrochemiluminescence immunoassay. Morning ACTH (7.2-63.3 pg/ml), prolactin (66-436 mU/l), TSH (0.25-3.5 mIU/L), fT4 (9-19 pmol/l) and fT3 (2.6-5.7 pmol/l) were measured by chemiluminescence immunoassay. Data were analyzed throughout the course of the disease. RESULTS: A 35-year-old female developed clinical symptoms of hypopituitarism two months after recovery from a confirmed COVID-19 infection. Laboratory investigation confirmed hypocorticism, hypothyroidism, hypogonadism and the patient was prescribed appropriate hormonal therapy in January 2021. Four months later the symptoms were alleviated (April 2021) and there were signs of recovery shown by imaging and hormonal: morning serum cortisol 227 nmol/l, morning ACTH 33.96 pg/ml, prolactin 68.3 mU/l, TSH 2.626 mIU/L, fT4 10.75 pmol/l, fT3 3.96 pmol/l. Thyroid hormone was discontinued, but hypogonadism and hypocorticism persisted with estradiol - 51.48 pmol/l, 24h urine cortisol level - 41.8 nmol/day. MRI results showed that the signs of hypophysitis were alleviated in comparison with MRI from January 2021. Full recovery of pituitary axis was reported in October 2021, with recovery of normal menstrual cycle. Furthermore, hormonal profile was likewise normal. CONCLUSION: This report provides evidence of delayed damage to the pituitary gland after infection with the COVID-19, with recovery of its function and structure. To date, the mechanisms of such an impact are not entirely clear; further collection of data on such cases and analysis is required.

Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

BACKGROUND: Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. AIM: Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. MATERIALS AND METHODS: We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. RESULTS: The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients [41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71% [45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р<0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.>< 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

[Clinical and radiological diagnosis of hypophysitis: a review of literature and own data].

This article presents a literature review of the various forms of hypophysitis, its varieties, as well as the problem of radiation diagnosis and treatment of this pathology. Hypophysitis is a poorly understood and multifactorial disease which the difficulty of diagnosing is not only to a variety of nonspecific clinical manifestations and hormonal research data, but also the ambiguous results of MRI studies, the lack of clear MR patterns. The article reflects the main histological types of hypophysitis, the peculiarities of diagnosis in connection with general clinical symptoms, outlines the features of each type of hypophysitis with their own clinical observations. This review is devoted to modern ideas about the clinical course of hypophysitis, presented a set of characteristic diagnostic signs of the disease according to MRI and the treatment algorithms recommended today are also highlighted. The article summarizes data from foreign literature and our own clinical observations in order to develop an optimal protocol for MRI studies in patients with suspected hypophysitis, to develop recommendations for radiologists and endocrinologists for the correct results interpretation. The uniqueness of this review is the lack of data on the clinic, diagnosis and treatment of hypophysitis in the Russian literature today.

[Cross-sectional controlled study of the morphometric parameters of the epiphysis in patients with hyperpolactinemia by magnetic resonance imaging].

A cross-sectional study of the cerebral epiphysis, by using brain magnetic resonance imaging was studied in 146 patients with hyper-prolactinemia and 141 persons without diseases of the endocrine or central nervous system. The purpose of the study was to compare the volume and structure of the pineal gland in hyperprolactinemic patients with the similar values in apparently healthy individuals. There was a significant increase in the volume of the epiphysis and a rise of the proportion of cysts and cystic changes in the structure of the epiphysis in patients with idiopathic hyperprolactinemia as compared with healthy individuals. The increased volume of the epiphysis and the change in its structure may be pathogeneticalfy associated with idiopathic hyperprolactinemia. To clarify this as-sumption, it is necessary to perform a larger study and to include hormonal tests characterizing epiphyseal function into the study protocol and to reveal a relationship between the changes in the sizes and structure of the epiphysis and the level of secretion of major hormones.