[Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors].

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

[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.

Prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region.

AIM: Assessment of prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region. MATERIALS AND METHODS: Cardiorespiratory monitoring was executed to 55 patients with acromegaly (18 men and 37 women): 27 patients with de novo disease, 28 patients on treatment of acromegaly (including 18 patietns with uncontrolled and 10 - with controlled acromegaly). All subgroups did not differ on sex, BMI and age. Also 24-hour monitoring of arterial blood pressure was carried out in 39 patients (12 men and 27 women, 14 patients with de novo acromegaly, 15 and 10 patients with uncontrolled and controlled acromegaly, respectively). RESULTS: The high prevalence of sleep breathing disorders (SBD) was revealed in patients with acromegaly from Moscow Region. SBD was found in 92.6%, 83.5% and 70.0% patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. The majority of patients had severe/moderate SBD in all subgroups (78.8%, 72.2% and 60.0%, respectively). In patients with newly diagnosed and uncontrolled acromegaly index of apnea-hypopnea (31 and 38.5 respectively), number of apnoe episodes (76 and 72) and saturation level (93% and 93.5%) did not differ significantly while these parameters were better in patients with a controlled acromegaly (apnea-hypopnea index 20, apnea episodes 45.5 and saturation level 95%). The peak of desaturation was subphysiological in 91.7%, 86.7% and 77.8% of patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. Severity of SBD did not depend on GH and IGF-1 levels as well as acromegaly duration. Such all-population risk factors of SBD as BMI and age were valuable for patients with acromegaly, however gender did not matter. SBD were associated with lack of physiological decrease of systolic and diastolic night BP. CONCLUSION: Acromegaly per se is a strong risk factor of sleep breathing disorders. The high prevalence of sleep breathing disorders in patients with acromegaly even after achievement of control over a disease emphasized need of specialized treatment of these violations.

[Clinical and functional characteristics of giant pituitary adenomas in the population of patients in the Moscow region]. / Klinicheskie i funktsional'nye kharakteristiki gigantskikh adenom gipofiza v populiatsii patsientov Moskovskoi oblasti.

Benign pituitary tumors are the most common sellar neoplasms. Lesions larger than 39 mm in the maximum dimension are called giant. They are rare, and, therefore, there are few data on the clinical and morphological features of giant pituitary tumors with different hormonal activity. AIM: The aim of this study was to identify the clinical and functional features of giant pituitary tumors with different hormonal activity. MATERIAL AND METHODS: We analyzed data of clinical, laboratory, and instrumental examinations of 351 patients diagnosed with pituitary macroadenomas at the Moscow Regional Research Clinical Institute in the period between 2008 and 2017: there were 144 hormonally inactive pituitary adenomas and 207 hormonally active pituitary adenomas (65 prolactinomas and 142 somatotropinomas). RESULTS AND DISCUSSION: Among 351 patients with pituitary macroadenomas, there were 32 (9.1%) giant adenoma cases: 18 (12.5%) 144 patients with hormonally inactive pituitary adenomas and 14 (6.8%) 207 patients with hormonally active pituitary adenomas 6 (3.9%) 65 prolactinomas and 6 (2.9%) 142 somatotropinomas. The volume of giant adenomas was somewhat larger among somatotropinomas 48 926 [35 067; 97 650] mm3 and prolactinomas 36 872 [15 281; 75 102] mm3 compared to that of hormonally inactive pituitary adenomas 26 933 [21 910; 42 895] mm3. Tumors had predominant suprasellar and posterosellar growth (31 (97.8%) and 29 (90.6%) cases, respectively). The most common first patient complaints were visual impairments (59.4%) and headache and/or dizziness (43.8%). Correspondingly, due to these complaints, 16 (50%) patients first consulted an ophthalmologist. Hypopituitarism detected before any treatment was present in 16 (50%) patients. CONCLUSION: In most cases, visual impairments and headaches/dizziness were the first manifestations of giant pituitary adenomas; therefore, ophthalmologists and neurologists should always refer patients with these complaints to MRI. Patients with identified giant pituitary tumors should be referred to an endocrinologist for exclusion of hypopituitarism and, if necessary, timely prescription of hormonal therapy.

[Central female hypogonadism as a model of premature aging].

Central (hypogonadotropic) hypogonadism in women could also be a cause of persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate symptoms of premature aging in women of young age with central hypogonadism. 88 young women (25 [21; 30] y.o.) with central hypogonadism (with isolated hypogonadotropic hypogonadism n=42, and associated with the other types of pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50 healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women with central hypogonadism frequency of psychoemotional, neurovegetative and urogenital disorders, peripheral sex steroid concentrations, lipid and mineral homeostasis parameters differed significantly from the healthy young women of similar age and were comparable with postmenopausal women of middle/older age. Thus, according to clinical, hormonal and biochemical abnormalities biological age of female patients with central hypogonadism advanced significantly chronological young age and corresponded to middle/older age. The central female hypogonadism is a model of premature aging.

[Development of sarcoidosis after successful treatment of Cushing's disease].

Cushing's disease is a rare severe neuroendocrine disorder caused by chronic overproduction of adrenocorticotropic hormone by a pituitary tumor. Supraphysiological concentrations of cortisol in endogenous hypercortisolism have an immunosuppressive and anti-inflammatory effect similar to therapy with systemic glucocorticosteroids. This may reduce the activity of the patient's concomitant autoimmune inflammatory diseases. On the other hand, a decrease in cortisol levels during treatment for Cushing's disease may be associated with a reactivation of the immune system that pose a risk of onset or recurrence of an autoimmune disorder. We present our own clinical case demonstrating the development of sarcoidosis after surgical treatment of Cushing's disease.

[Acromegaly screening in patients with hyperprolactinemia and pituitary adenoma].

BACKGROUND: Hyperprolactinemia accompanies growth hormone hypersecretion in approximately 25-39% of cases. There is a recommendation to determine the level of prolactin in clinical guidelines for diagnosis and treatment of acromegaly. However, there is no understanding of the necessity to investigate the IGF-1 level in patients with hyperprolactinemia and a pituitary adenoma. AIM: Determining the proportion of patients with hyperprolactinemia and pituitary adenoma, who were examined for IGF-1 levels, and identifying the proportion of patients with acromegaly among this cohort. MATERIALS AND METHODS: Between December 2019 and December 2022 a single-center observational single-stage single-sample uncontrolled study was conducted. At the first stage of the study, the proportion of patients with pituitary adenoma and hyperprolactinemia with studied IGF-1 levels was determined, according to medical records. At the second stage of the study, patients without known indicators of IGF-1 were determined. The concentration of growth hormone was studied during the oral glucose load in the case of increased IGF-1 levels. RESULTS: At the first stage, 105 patients were included in the study. The level of IGF-1 was determined in 41/105 (39%) cases. There were 22/41 (53.7%) cases in the subgroup with pituitary incidentalomas and 19/64 (29.7%) cases in the subgroup with hyperprolactinemia among them. At the second stage, the IGF-1 level was additionally determined in 53 patients with hyperprolactinemia and pituitary adenoma (total 94 patients). The level of IGF-1 was elevated in 11/94 patients, further acromegaly was confirmed in 3/94 patients (3.2%). CONCLUSION: In real clinical practice the level of IGF-1 is studied only in 39% of cases in patients with pituitary adenoma and hyperprolactinemia. The disease was detected in 3 cases (3.2%) out of 94 people with hyperprolactinemia and pituitary adenoma without clinical manifestations of acromegaly. We consider the study of IGF-1 levels justified as a screening for acromegaly in patients with hyperprolactinemia and pituitary adenoma.

[Neurofibromatosis type 1 associated with pheochromocytoma: a case report with a brief review of the literature].

We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient's follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.

[Panhypopituitarism as the first manifestation of sarcoidosis: case report].

Sarcoidosis is a systemic inflammatory disease of unknown etiology characterized by the formation of noncaseating granulomas in various organs and tissues and the activation of T-cells at the site of granulomatous inflammation with the release of various chemokines and cytokines [1]. The incidence on average ranges from 10 to 20 per 100,000 population [2]. Most often in patients with sarcoidosis, lesions of the lungs and intrathoracic lymph nodes are detected. Significantly less often (in about 5-20% of patients) damage to the nervous system is noted [6,7,9]. In 9-18% of patients with neurosarcoidosis, involvement of the pituitary gland, pituitary infundibulum and hypothalamus is found, which is manifested by a variety of clinical symptoms [8,10]. We observed a patient with sarcoidosis whose disease debuted with clinical symptoms of hypogonadism, followed by the development of signs of secondary hypothyroidism, adrenal insufficiency, and diabetes insipidus, which was initially regarded as panhypopituitarism against the background of a hypothalamic lesion of unknown origin. Later, additional examination revealed signs of intrathoracic lymphadenopathy and focal changes in the lung parenchyma on CT, as well as skin lesions. Despite the biochemical compensation of hypopituitarism, the clinical efficacy of hormonal therapy with cabergoline, testosterone, hydrocortisone and levothyroxine sodium was insufficient, and the patient's condition improved after the addition of immunosuppressive and anti-inflammatory therapy with methotrexate and methylprednisolone.