[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

AIM: To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. SUBJECTS AND METHODS: Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. RESULTS: Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. CONCLUSION: The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

[Multiple endocrine neoplasia type 1 variants and phenocopies].

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MENI tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MENI gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

[A clinical example of conservative management of a female patient with manifestation of primary hyperparathyroidism].

The problems of the timely diagnosis and treatment of primary hyperparathyroidism (PHPT) have recently attracted more and more attention because this disease now ranks third in incidence rates among endocrine diseases. Older women form a group at risk for this disease. Surgical removal of the source of parathyroid hormone hypersecretion is the only radical treatment option for this disease, which is performed in the majority of patients with PHPT. Occasionally, surgical treatment is contraindicated or unadvisable. In these cases, the possibilities of long-term medical treatment become relevant. For this, there are several groups of drugs available, such as bisphosphonates to maintain bone tissue, calcium-sensing receptor agonists (calcium mimetics) that are effective in reducing blood calcium levels. The patients frequently require combined therapy to control the major manifestations of the disease. There are limited data on the long-term medical management of patients with manifest PHPT in the literature.

[The saliva cortisol level test using the automatic immunochemical analyzer Cobas e601 (Roche) to diagnose endogenous hypercorticalism in patients with obesity].

The saliva cortisol level test applies to diagnose endogenous hypercorticalism. However the methods of die format immunoassay traditionally used do not make it possible to get the study results on-the-fly. Also, reference interval and optimal takeoffs differ under implementing various techniques of cortisol tests. The purpose of actual study is to investigate the possibilities of electrochemiluminescent technique of testing free cortisol in saliva. The device Cobas e601 was applied to diagnose endogenous hypercorticalism in patients with obesity. The saliva samples were collected at 11 PM from 98 healthy volunteers and 123 patients with obesity (in 45 cases endogenous hypercorticalism was diagnosed). In total, 205 persons donated saliva at 11 PM two days running to evaluate the technique reproducibility. The samples of 197 individuals were frozen to implement the immune-enzyme assay. The minor test with dexamethasone was applied to patients with suspected endogenous hypercorticalism. The diagnosis of endogenous hypercorticalism was finally confirmed after the results of histological analysis of post-operative material or autopsy. Among healthy volunteers, the reference interval on indicators consisted 0.5-9.4 nMol/l. The correlation coefficient under free cortisol measuring at the same time two days running was -0.785. The optimal takeoff to diagnose endogenous hypercorticalism in patients with obesity consisted 9.4 nMol/l, sensitivity--84.4% (95% confidence band 71.2-92.2%), specificity--92.3% (95% confidence band 84.2-96.4%), predictive value of positive result--11.0 (95% confidence band 5.0-23.9), predictive value of negative result--0.17 (95% confidence band 0.08-0.33) and likelihood ratio for positive result--65.1 (95% confidence band 20.4-207.6). The two-fold cortisol test in saliva using immune-enzyme assay and minor test with dexamethasone with their diagnostic capabilities corresponded to one-fold saliva free cortisol test using electrochemiluminescent technique. The one-fold free cortisol test in saliva collected in 11 PM using the analyzer Cobas e601 for electrochemiluminescent immunoanalysis is a convenient and informative endogenous hypercorticalism screening technique in patients with obesity.

[Sexual and reproductive function in males with somatotropinoma].

The examination of 72 males with somatotropinoma has found that 65% of such patients have hypogonadism which is essential in pathogenesis of sexual dysfunction and spermatogenetic disorders. However, hypogonadism in males with somatotropinoma does not provoke sexual dysfunction in most the cases. High production of somatotropic hormone and insulin-like growth factor 1 in somatotropinoma leads to prostatic hyperplasia which is not accompanied with a rise of a PSA level and symptoms of infravesical obstruction.

[Prognostic value of of the expression Ki-67, CD31, and VEGF in somatotropinomas].

Pituitary adenomas are benign, but 30-50% of patients do not achieve remission after treatment. The purpose of the study was to analyze the prognostic value of immunoexpression of the proliferation marker Ki-67 and the angiogenetic factors CD31 and VEGF in somatotropinomas. Ki-67, CD31, and VEGF were immunohistochemically studied in the samples of 52 somatotropin-removed samples; medical records were used to analyze the outcome of treatment in the early and late postoperative periods. Ki-67 immunoexpression proved to be significantly higher in the patients who had not achieve remission both in the early (p = 0.042) and late (p = 0.012) postoperative period than in those who had achieved remission and in patients who were resistant to postoperative treatment with somatostatin analogues (p = 0.040) than in those who were sensitive to therapy. The immunoexpression of CD31 and VEGF was not associated with the outcome of treatment. Thus, high Ki-67 levels may be regarded as a poor postoperative prognostic factor in acromegaly.

[Maldiagnosis of giant-cell tumor of the bone in a patient with hyperparathyroid osteodystrophy].

The paper describes a case of maldiagnosis of giant-cell tumor in a patient with parathyroid osteodystrophy, in this connection elbow joint resection and replacement were made. Parathyroid adenoma with the symptoms of primary hyperparathyroidism was diagnosed only two years after surgery. Progression of diseases was accompanied by severe bone changes and the development of urolithiasis complicated by chronic renal failure. Thus, the interpretation of bone tissue changes without considering clinical and laboratory data led to the unwarranted surgical intervention and the late diagnosis of primary hyperparathyroidism. Differential diagnosis of a giant-cell tumor should be made, by obligatorily considering clinical and laboratory data, including the parameters of calcium metabolism.

[Recurring secondary hyperparathyroidism: case report].

The authors report a rare case of persistently recurring secondary hyperparathyroidism concomitant with chronic renal insufficiency. The patient underwent multiple surgical interventions (parathyroidectomy, implantation of parathyroid autograft into a forearm muscle, removal of hyperplastic autograft tissue). Results of clinical, laboratory, instrumental, and morphological studies are presented. Possible causes of relapses and problems of morphological diagnosis are discussed.

[Efficacy and safety of bivalos therapy for postmenopausal osteoporosis. Results of Russian multicenter trial].

AIM: To study effects of one-year therapy with bivalos on mineral bone density (MBD) of the spine in patients with postmenopausal osteoporosis (PMO), effects of bivalos (strontium ranelate) on MBD of the neck of the femur and femur, the levels of bone metabolism markers, quality of life, tolerance of long-term therapy. MATERIAL AND METHODS: The study was made of 60 females aged 54-75 years with PMO. MBD was measured with x-ray absorptiometry in the vertebra and proximal femur. Bone markers in blood serum were detected by enzyme immunoassay. RESULTS: After a year of taking bivalos MBD in lumbar vertebra increased by 4.68 +/- 4.94%, in the neck of the femur--by 2.0 +/- 4.29%, in the proximal femur--by 3.10 +/- 3.34%. A significant 19.5% rise in bone alkaline phosphatase and a 16.5% fall in the level of CT were noted showing a stimulating effect of bivalos on bone formation and an inhibiting effect--on bone tissue resorption. Bivalos treatment raised quality of life of the patients: better motility, regress of depression, improved self-appraisal, decreased number of patients with pain in the spine, attenuated pain. The drug was well tolerated, unwanted effects arose in 15% patients, discontinuation of the drug because of toxicity occurred in 5%. Serious side effects were not observed. CONCLUSION: Strontium ranelate is effective in PMO and is well tolerated.

[Vitrum osteomag in prevention of osteoporosis in postmenopausal women: results of the comparative open multicenter trial]. / Vitrum osteomag v profilaktike osteoporoza u zhenshchin v postmenopauze: rezul'taty sravnitel'nogo otkrytogo mnogotsentrovogo issledovaniia.

AIM: To investigate efficacy, tolerance and safety of the drug vitrum osteomag one tablet of which contains 600 mg calcium (1500 mg calcium carbonate), 200 IU of cholecalcepherol, 40 mg of magnesium, zinc (7.5 mg), copper (1 mg), manganese (1.8 mg) and boron (250 mcg) in women with osteopenia for prevention of osteoporosis. MATERIAL AND METHODS: A multicenter comparative open trial of vitrum osteomag influence on mineral bone density (MBD), change of pain syndrome in bones, index of calcium-phosphorous metabolism covered 334 postmenopausal women with osteopenia. MBD was measured in low-back spine and proximal part of the hip with DEXA method. All the patients were divided into 3 groups: 125 women taking 2 tablets of vitrum osteomag daily for 12 months (group 1); 111 women taking 1500 mg calcium carbonate (group 2); 96 women--control group (only observation). RESULTS: Vitrum osteomag relieved pain in the back and joints, had a positive effect on bone density (+1.5%) and proximal parts of the hip (0.6-0.93%) exceeding the effect of calcium carbonate only which preserves the initial MBD in low back spine but does not prevent bone loss in the hip. MBD dynamics in patients given vitrum osteomag differs essentially from one in the control group (from -1.9 to -2.91%) which demonstrates a reliable preventive anti-osteoporotic effect of this medication. The drug increases the level of general and ionized calcium in blood but does not cause hypercalcemia lowering the level of parathormone in blood. The rate of side effects in group 1 was 14.4% and did not differ much from that in group 2 (16.2%). CONCLUSION: The results of the study allow to recommend vitrum osteomag for prophylaxis of a rapid loss of bone tissue mineral density.

[Osteoporosis: diagnosis of disorders of bone tissue and calcium-phosphorus metabolism (lecture)]. / Osteoporoz: diagnostika narushenii metabolizma kostnoi tkani i kal'tsii-fosfornogo obmena (lektsiia).

Tentative diagnoses of lymphadenitis or Hodgkin's disease were not confirmed in a 12-year-old child by cytological investigations. Along with lymphoid cells, individual leukocytes, histiocytes, macrophages, and glandular cancer cells, the cytological preparation of the cervical lymph node biopsy specimen contained uncommon multinuclear cells looking like interfollicular thyroid islets. This indicated cancer metastasis and the site of primary involvement: the thyroid. The diagnosis was confirmed by the histological and radionuclide methods.

[Steroidogenesis in patients with various adrenal and gonadal dysfunctions]. / Steroidogenez u bol'nykh s razlichnymi disfunktsiiami nadpochechnikovykh i polovykh zhelez.

The paper deals with the results of investigations of steroidogenesis in patients with ACTH-dependent Icenko-Cushing's disease (CD), congenital adrenal hyperplasia (CAH), and stromal hyperthecosis (SH). Along with the traditional methods of evaluating the activity of steroid-producing glands (diurnal variations of steroid hormones and their precursors in the peripheral blood, their mean daily concentrations), the authors used a simultaneous selective catheterization technique for adrenal and ovarian veins. No pronounced circadian rhythms were revealed in most of the steroids measured in patients with CD. A sharp rise in the mean daily serum 17-hydroxypregnenolone concentrations coupled with the steady-state 17-hydroxyprogesterone level is considered to reflect the activation of steroid biosynthesis via the delta 5-pathway. CD patients were demonstrated to exhibit great differences in the daily pattern of aldosterone secretion depending on the development of essential hypertension. CAH patients had high 17-hydroxypregnenolone and 17-hydroxyprogesterone levels. Like 17-hydroxyprogesterone, 17-hydroxypregnenolone may be used as a diagnostic marker of CAH. Hyperandrogenism in this disorder was largely due to enhanced adrenal production of testosterone and delta 5 androgens DHA and DHA-S. Unlike CAH, SH was not associated with excessive secretion of either DHA or DHA-S, but the ovaries of these patients released greater amounts of testosterone, which led to hyperandrogenism.

[Osteopenic syndrome in liquidators of the aftereffects of the accident at the Chernobyl power plant]. / Osteopenicheskii sindrom u uchastnikov likvidatsii posledstvii avarii na Chernobyl'skoi atomnoi élektrostantsii.

Bone system was examined in 112 liquidators; in 71 of these osseous tissue density was studied by osseous densitometer using bienergetic x-ray absorptiometry and in 45 x-ray examinations, analyses of biochemical and hormonal parameters were carried out. Spinal painful syndrome was detected in 61 to 82% of the examinees. For analysis of densitometric and x-ray parameters the liquidators were divided into 2 groups: group 1 included those who worked at the power plant in 1986 (55%) and group 2 were those who worked there in 1987-1989. Radiation doses in group 1 reliably surpassed those in group 2 (p < 0.001). Bone mineral density in the lumbar vertebrae was significantly lower in group 1 as against group 2 and lower in both groups vs. controls. More than 5% osseous mineral loss was revealed in 73% of group 1 liquidators and in 43% of group 2 ones. Analysis of spinal roentgenograms in 45 liquidators showed a high incidence of negligible and moderately expressed osteoporosis without compression fractures of vertebral bodies: osteopenia signs were found in 87% of group 1 examinees complaining of pain in the spine and in 73% of group 2 examinees; signs of osteochondrosis and spondylosis were detected in 40% of group 1 and in 47% of group 2 subjects. Hence, a higher incidence of osteopenia in liquidators, more manifest condition and its higher detection rate in subjects exposed to higher radiation doses indicate a certain contribution of radiation factor to the development of the osteopenia syndrome in liquidators.

[Comparative characteristics of steroidogenesis and its biorhythm in the hyperfunctioning adrenal cortex]. / Sravnitelnaia kharakteristika steroidogeneza i ego bioritma v kore nadpochechnikov v usloviiakh ikh giperfunktsii.

The paper summarizes the results od several studies of the daily rhythms of steroid hormones in patients with ACTH-dependent Itsenko-Cushing's disease (CD) and congenital adrenal hyperplasia (late-onset forms) (CAH). Normal daily rhythms of adrenal C21- and C19-steroids and ACTH were observed in 23.5% of CD patients. CAH patients had the marked daily rhythms of adrenal androgens and testosterone which were typical of those of cortisole. The ratios of steroid hormones to its precursors provide evidence for enhanced activities of 17-, 11 beta- and 18-hydroxylases in CD patients and normal enzymatic activities in CAH patients, whereas 21-hydroxylase being an exception.

[Digital bone densitometry]. / Digital'naia osteodensitometriia.

Normal values of bone mineral composition were defined, based on examinations of 600 male and female volunteers of various age groups by digital roentgenodensitometry. The mineral compactness was found reduced in the patients with endocrine diseases, in subjects who participated in liquidation of the Chernobyl power plant accident aftereffects, and in those suffering from skeletal pains. The authors emphasize the value of digital roentgenodensitometry as a method for monitoring the efficacy of treatment of patients with endocrine diseases and chronic renal insufficiency.

[Bone tissue in patients with hyperprolactinemic hypogonadism]. / Sostoianie kostnoi tkani u bol'nykh s giperprolaktinemicheskim gipogonadizmom.

Sixteen women with hyperprolactinemia were examined for Ca metabolism, osseous metabolism, mineral saturation of bone tissue in the thoracic portion of the spine and radius. Lowered mineral saturation of the thoracic vertebrae was detected in 69% of the examinees, that of the distal segment of the radius in 44%. Reduction of the mineral saturation of the spine was in negative correlation with the blood prolactin level and length of amenorrhea. No changes in the bone resorption biochemistry or Ca metabolism were detected. A marked reduction of blood osteocalcin level that reflects osteoblast function was detected, its blood concentration being in negative correlation with prolactin level. No relationships between mineral saturation of bone tissue, prolactin, and osteocalcin, on the one hand, and blood estradiol level, on the other, were observed. These data suggest that osteopathy in hyperprolactinemic hypogonadism is due to reduced bone formation and not to reduced estradiol production.

[Osteocalcin--a marker of bone metabolism and calcium regulating hormones in steroid osteoporosis]. / Osteokal'tsin--marker kostnogo metabolizma i kal'tsiireguliruiushchie gormony pri steroidnom osteoporoze.

Altogether 15 patients with Itsenko-Cushing disease with moderate osteoporosis and 10 healthy persons were investigated. Calcium metabolism, calcium regulating hormones and osteocalcin were studied. Endogenous hypercorticoidism was characterized by a higher secretion of parathyroid hormone against a background of hypercalcemia. Positive correlation of these indices was revealed. In patients with Itsenko-Cushing disease the blood level of vitamin D was decreased as compared to that in the controls. A significant decrease in the blood level of osteocalcin was observed in patients with endogenous hypercorticoidism, there being close negative correlation between the level of osteocalcin and cortisol, and between osteocalcin and 17-hydroxycorticosteroid excretion with urine. A conclusion has been made that the excess of glucocorticosteroids suppresses osteoblast function, slows, down osteogenesis, disturbs the secretion of calcium regulating hormones and calcium metabolism enhancing resorption; this combined action of glucocorticoids causes rapid development of osteoporosis in endogenous hypercorticoidism.