[Overcoming therapy resistance in prolactinomas: from perspectives to real clinical practice].

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

[Predictors of postoperative remission of acromegaly. (Experience of the Burdenko Neurosurgical Center)]. / Prediktory posleoperatsionnoi remissii akromegalii. (Opyt FGAU «NMITs neirokhirurgii im. akad. N.N. Burdenko¼).

BACKGROUND: Treatment of acromegaly is still an unresolved problem. Overall postoperative remission rate ranges from 34 to 85%. These values are better for microadenomas (75-90%) and worse for macroadenomas (45-70%). Identification of predictors of acromegaly remission after surgical treatment is an urgent objective to improve the quality of medical care for these patients. OBJECTIVE: To analyze postoperative freedom from acromegaly and predictors of remission. MATERIAL AND METHODS: A retrospective single-center study included 227 patients with acromegaly who underwent resection of pituitary adenoma between August 2018 and August 2021. RESULTS: Remission (normalization of serum IGF-1) was achieved in 65 (55%) patients. Growth hormone and IGF-1 index decreased after surgery in all patients. Mean preoperative serum growth hormone was 12.45 [6.88, 29.85] ng/ml, early postoperative concentration - 1.54 [0.80, 3.38] ng/ml, in delayed period - 1.15 [0.57, 3.80] ng/ml. Mean IGF-1 index was 2.18 [1.69, 2.71], 1.47 [0.99, 1.90] and 0.99 [0.74, 1.43], respectively. CONCLUSION: Significant predictors of acromegaly remission after neurosurgical treatment were age, preoperative level of growth hormone, tumor size and location, growth hormone and IGF-1 index in early postoperative period and residual tumor after surgery. Multivariate analysis revealed a significant association of acromegaly remission with small tumor size, low postoperative level of growth hormone and no residual tumor within 3-6 month after surgery.

[Reset osmostat syndrome - when hyponatremia become «a normal¼: diagnostics, case report].

Reset osmostat syndrome (ROS) is characterized by a change of normal plasma osmolality threshold (decrease or increase), which leads to chronic dysnatremia (hypo- or hypernatremia). We have described a clinical case of ROS and chronic hyponatremia in a patient with chordoid glioma of the III ventricle. It is known that the patient had previously been diagnosed with hyponatremia (131-134 mmol/l). She has not hypothyroidism and hypocorticism. There is normal filtration function of the kidneys was (CKD-EPI 91.7 ml/mi/1,73m2). Urine osmolality and sodium level were studied to exclude of concentration kidney function disorder. During first three days after removal of the tumor of the third ventricle (chordoid glioma, WHO Grade II), the sodium level decreased to 119 mmol/l. Repeated infusions of 200-300 ml hypertonic 3% sodium chloride solution, gluco- and mineralocorticoid therapy was ineffective, increasing plasma sodium levels by 2-3 mmol/l with the return to the initial level during 6-8 hours. Hypopituitary disorders did not develop after surgery. With further observation, the sodium level remained within 126-129 mmol/l for 6 months after surgery. The water load test make exclude the classic syndrome of inappropriate secretion of antidiuretic hormone, and confirmed the diagnosis of RSO. Because of absence of clinical symptoms associated with hyponatremia, no medical correction was required, patient was recommended to clinical follow-up.

[Permanent central diabetes insipidus after traumatic brain injury. Case report and literature review]. / Razvitie postoyannogo tsentral'nogo nesakharnogo diabeta posle travmaticheskogo povrezhdeniya golovnogo mozga. Klinicheskii sluchai i obzor literatury.

The authors report permanent central diabetes insipidus (CDI) in a patient after severe traumatic brain injury (TBI) in traffic accident. A 16-year-old boy entered to a medical facility in coma (GCS score 6) with the following diagnosis: acute TBI, severe cerebral contusion, subarachnoid hemorrhage, depressed comminuted cranial vault fracture, basilar skull fracture, visceral contusion. CDI was diagnosed in 3 days after injury considering polyuria and hypernatremia (155 mmol/l). Desmopressin therapy was initiated through a feeding tube. Thirst appeared when a patient came out of the coma after 21 days despite ongoing desmopressin therapy. Considering persistent thirst and polyuria, we continued desmopressin therapy in a spray form. Under this therapy, polyuria reduced to 3-3.5 liters per a day. Symptoms of CDI persisted in long-term period (2 years after TBI) while function of adenohypophysis was intact. This case demonstrates a rare development of permanent diabetes insipidus after TBI. CDI manifested only as polyuria and hypernatremia in coma. Thirst joined after recovery of consciousness. Probable causes of CDI were damage to neurohypophysis and partially injury of pituitary stalk because of extended basilar skull fracture and/or irreversible secondary lesion of hypothalamus following diffuse axonal damage after TBI.

[Adipsic diabetes insipidus after transsphenoidal surgery for suprasellar intraventricular].

Presented case demonstrates a rare diencephalic pathology - adipsic diabetes insipidus (ADI) with severe hypernatremia in a 58-year-old woman after ttranssphenoidal removal of stalk intraventricular craniopharyngioma. ADI was diagnosed because of hypernatremia (150-155 mmol/L), polyuria (up to 4 liters per day) and absence of thirst. Normalization of water-electrolyte balance occurred on the background of desmopressin therapy and sufficient hydration in postoperative period. After release from the hospital, the patient independently stopped desmopressin therapy and did not consume an adequate amount of fluid of the background of polyuria. This led to severe hypernatremia (155-160 mmol/L) and rough mental disorders.Patients with ADI need closely monitoring of medical condition and water-electrolyte parameters, appointment of fixed doses of desmopressin and adequate hydration.

[Radiosurgical hypophysectomy in cancer pain treatment. Literature review and clinical case]. / Radiokhirurgicheskaya gipofizektomiya v lechenii farmakorezistentnoi onkologicheskoi boli. Obzor literatury i opisanie klinicheskogo sluchaya.

Cancer pain is one of the main problem in modern medicine. According European Society for Medical Oncology data, cancer pain prevalence is 64% among patient with terminal stage of disease and in 46% standard pain therapy was ineffective. Radiosurgical hypophysectomy is one of the important and perspective method in cancer pain treatment. This method could be offered patient with chronic disease. According literature review, endocrinology complications were very rare and occurred 10 months after therapy. Value of analgesic effect was 70-90%. In some trials, procedure was effective not only nociceptive, but also in neuropathic pain. More trials require for determination of indications and mechanism of action. The case of successful relief of resistant pain in patient with pancreatic cancer by means of radiosurgical hypophysectomy is described.

[Pituitary microadenomas - current diagnostic and treatment methods]. / Mikroadenomy gipofiza: sovremennoe sostoyanie metodov diagnostiki i lecheniya.

According to previously accepted criteria, pituitary microadenoma is characterized by a diameter of less than 10 mm. Improvement and widespread use of MRI are accompanied by increased incidence of diagnosis of these neoplasms. Pituitary microadenomas is an extremely heterogeneous group of tumors with different biological behavior, endocrine secretion and clinical symptoms despite the common MR characteristics. Treatment is mainly determined by endocrine secretion. Endocrine-active microadenoma requires medication (in case of microprolactinoma) and surgical treatment (in case of microsomatotropinoma and ACTH-releasing tumor). Follow-up is advisable for endocrine-inactive microadenoma (microincidentaloma). Modern data on the incidence, clinical and endocrine features, diagnosis and treatment of various pituitary microadenomas are discussed in the article.

[Transsphenoid extirpation of pituitary adenomas in patients with McCune-Albright syndrome (two cases from practice and literature review)]. / Transsfenoidal'noe udalenie adenom gipofiza u patsientov s sindromom MakK'iuna-Olbraita (dva sluchaia iz praktiki i obzor literatury).

INTRODUCTION: McCune-Albright Syndrome is a rare genetic disease characterized by the formation of fibrous osteodysplasia foci of various localization, including the bones of skull base. Having a gross lesion of the main bone body and the simultaneous formation of the pituitary adenoma, its transnasal removal becomes very difficult. MATERIAL AND METHODS: Two clinical observations are presented where at patients with the classic manifestation of McCune-Albright syndrome we were able to successfully remove somatotropinomas with endoextrasellar growth. In both cases the presence of visual disorder was the indication for surgery. RESULTS: Despite pronounced deviations in the anatomy of the skull base bones in both cases we managed to access the Turkish saddle. Removal of the pituitary tumor did not differ from standard surgery. Improved vision after surgery was observed in two patients. Tumors were removed subtotally and clinical and biochemical remission of acromegaly was not achieved. In both cases, the tumors had morphological signs of atypia. Patients continued to receive therapy with somatostatin analogues and radiation. CONCLUSION: The possibility of performing transnasal surgery in this category of patients using specific instruments and intraoperative navigation is shown.

[Manifestation of Graves' disease, resulting from radiosurgical treatment of acromegaly, in a patient with panhypopituitarism].

Cases of thyrotoxicosis associated with a previous case of secondary hypothyroidism are extremely rare. This article presents a rare clinical case of Graves' disease manifestation in a patient with secondary hypothyroidism after radiosurgical treatment of acromegaly. A 38-year old woman presented with acromegaly and endo-supra-laterosellar pituitary adenoma. After non-radical removal of the pituitary adenoma, radiosurgical treatment of the of the residual tissue of the pituitary tumor in the cavernous sinus area was performed. After 14 months of radiation therapy, the acromegaly was in remission; after 24 months of radiation therapy, panhypopituitarism developed (secondary hypothyroidism, adrenal insufficiency, hypogonadism, and growth hormone deficiency). Furthermore, 1.5 years after the panhypopituitarism was diagnosed, the manifestation of Graves' disease was also noted, requiring thyrostatic and radioactive iodine treatments. Diagnostic criteria for secondary hypothyroidism are low levels of the thyroid hormones free T4 and free T3, with a reduced, normal or slightly elevated level of thyroid stimulating hormone (TSH). The criterion for the development of thyrotoxicosis in the context of the secondary hypothyroidism was the persistent increase in the level of free T4 despite adequate drug therapy with levothyroxine. In the case report, the patient's diagnosis of Graves' disease was confirmed by the presence of a high level of antibodies to the TSH receptor.

[Sex hormone receptors in pituitary prolactinomas].

An attempt was made to interpret the mechanism responsible for the occurrence of pituitary tumors - prolactinoma in persons of different sex. The presence or absence of androgenic receptors in the tumors was studied. Analysis of the concentration of nuclear receptors, estrogen ones in particular, showed their higher concentration in prolactin-positive pituitary adenomas than in inactive pituitary adenomas. Androgen receptors were detected in the gonadotropic and lactotropic cells of the Intact pituitary. Analysis of the concentration of nuclear testosterone receptors in different morphological types of pituitary adenomas revealed no differences in the luteinizing hormone/follicle-stimulating hormone-positive and prolactin-positive tumors.

[Comparative study of prolactin-secreting and hormonally inactive pituitary adenomas in patients with moderate hyperprolactinemia].

The present paper deals with the differential prolactin diagnosis of pituitary adenomas with moderate prolactin hyperproduction and hormonally inactive pituitary adenomas. Sixty patients with gross pituitary adenomas were examined. Morphological analysis of in-traoperative samples included histological, immunohistochemical studies with antibodies to hormones of the adenohypophysis. There was a probable frequency of prolactin-secreting tumors among gross pituitary adenomas proceeding with moderate hyperprolactinemia (25%) and that of hormonally inactive pituitary adenomas among the tumors regarded as prolactinomas (16%) in the preoperative period.

[Drug treatment for acromegaly: results of long-term use of Sandostatin LAR].

То evaluate the effectiveness and safety of drug treatment for acromegaly, the authors conducted an open-labeled prospective study of the impact of treatment with long-acting octreotide Sandostatm LAR) on the content of growth hormone (GH) and IRF-1 and on the size of a pituitary tumor. The study covered 40 patients (28 females and 12 males) aged 21 to 65 years (median 45 years) who had active acromegaly; 4 (10%) patients were diagnosed as having pituitary microadenoma; 36 (90%) had pituitary macroadenoma. Twenty-four patients received no therapy; 16 patients had tumors after their ineffective removal. All the patients took Sandostatin LAR, 20 mg intramuscularly, once every 28 days. The mean duration of treatment was 8.25 months (range: 3 to 12 months). Clinical and hormonal parameters were estimated 3, 6, and 12 months of treatment. A treatment-induced decrease in GH and/or insulin-like growth factor 1 (ILGF-1) by at least 30% of their baseline values considered effective. The state of a tumor was evaluated by brain magnetic resonance imaging in 26 patients. Three month following Sandostatin LAR treatment, the median concentration of GH significantly decreased from 33.5 to 5.55 ng/ ml (p < 0.001) and later on it remained nearly at this level (5.1 ng/ml and 5.35 ng/ml after 6 and 12 months, respectively). The concentrations of ILGF -1 similarly changed: its median was 779 ng/ml at baseline, 390 (p < 0.001), 390, and 330 ng/ml after 3, 6, and 12 months, respectively. Following 12 months of treatment, there were reductions in GH levels in 52.2% of the patients (including a < 2.5-ng/ml reduction in 33.3% of the patients) in the concentration of ILGF-1 by more than 50% of the baseline values in 49.9% (including a complete ILGF-1 concentration normalization in 33.3%). Twelve months after treatment, there was a reduction in the size of a tumor in 38.4% of the patients (by an average of41.25±7.22% of the baseline volume) and its growth stabilization in 59.1%. The findings suggest that treatment with Sandostatin LAR in a dose of 20 mg Is an effective and safe treatment, leads to a significant reduction in the values of GH and IL GF-1 just 3 months after treatment, and controls hormonal secretion and tumor growth in most patients with acromegaly.