The relationship of vitamin D status with the development and course of diabetes mellitus type 1

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that develops as a result of a genetic predisposition and environmental factors. Literature data indicate that the suboptimal status of vitamin D can be considered as a risk factor for the development of T1DM, especially at some stages of life. Adequate vitamin D supplementation in childhood may provide a protective effect and reduce the risk of developing T1DM at a later age. Pathogenesis of T1DM predisposes to abnormalities in the metabolism of vitamin D, including the development of vitamin D deficiency. Moreover, the immunomodulating effect of calcitriol (induction of immune tolerance and T-cell anergy, impaired B-cell activity and antibodies production) suggests the therapeutic potential of vitamin D in autoimmune diseases, including T1DM. A number of studies have demonstrated the positive clinical effects of various vitamin D preparations with respect to maintaining residual β-cell function, improving glycemia control in patients with T1DM. Determining the optimal doses of vitamin D for patients with T1DM may contribute to disease control and prevention of complications

National survey of doctors on hypo-and hypernatremia in the context of real clinical practice

BACKGROUND: The prevalence of dysnatremia varies widely (from 1 to 63%), and depends on comorbidities, the effects of more than 18 hormones and hormone-like substances, which confirms the importance of maintaining blood sodium levels in the tight physiologic range and makes it possible to consider its deviations as an endocrine pathology. Both hypo- and hypernatraemia are associated with a multiple increase in mortality, risk of fractures, and gross balance disturbances. At the same time, the clinical manifestations of dysnatremia are not specific, reflect an osmotically mediated decrease in brain function, which potentially may be missed in clinical practice. AIMS: to study the specifics of diagnosis, differential diagnosis and treatment of dysnatremia states by specialist doctors using a sociological survey method. MATERIALS AND METHODS: A cross-sectional sociological uncontrolled study was conducted by questioning doctors about hypo- and hypernatremia using the online questionnaire “Questionnaire on hypo-and hypernatremia in clinical practice” created on the Google forms platform. The invitation to fill in the questionnaire was sent to the email addresses included in the database of the Russian Association of Endocrinologists. A total of 353 completed questionnaires were received. RESULTS: The poll demonstrated a low frequency of determining blood sodium levels - less than 38% of specialists prescribe sodium in more than half of the cases, including the cases of diseases associated with dysnatremia, which correlates with less practical experience of doctors. The overwhelming majority of endocrinologists (82%) in their clinical practice encounters deviations of the sodium levels in patients, but only 6% recognize the possession of the competence of managing patients with dysnatremia. The discrepancy between the lower limit of normal range to 135-136 mmol/l was observed in 22% (62/278), the inconsistency of the upper normal limit to 145-146 mmol/l - in 47% (131/278) of laboratories, and in 33% (41/278) laboratories, which are used by doctors, there was a discrepancy along both limits of the reference interval. The presence of a hypertonic solution (3%) of sodium chloride in a hospital was noted only by 38% of respondents. Conclusions: There is an unphysiological variation in reference intervals for blood sodium concentration in 55% of laboratories, a low frequency of sodium levels evaluation in the blood (in more than half of clinical situations only 38.2% of doctors prescribe the estimation of blood sodium level) and the lack of educational competence in managing patients with syndromes of hypo- and hypernatremia in 94% of endocrinologists

Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review)

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of the adrenal cortex characterized by impairment of cortisol biosynthesis (with possible impairment of aldosterone biosynthesis) and excessive pituitary ACTH release, which promotes oversecretion of intact pathways products: 17-hydroxyprogesterone (17OHP), progesterone, and adrenal androgens – androstendione and testosterone. 21-hydroxylase deficiency, being the most common cause of congenital adrenal hyperplasia is a chronic disorder, that requires life-long glucocorticoid treatment, that aims both to replace cortisol and prevent ACTH-driven androgen excess. Nevertheless, reaching the optimal glucocorticoid dose is challenging because currently available glucocorticoid formulations cannot replicate the physiological circadian rhythm of cortisol secretion. The difficulties in striking the balance between uneffective normalizing of ACTH-level and excess glucocorticoid exposure leads to different abnormalities, that starts to develop at first months of life and progress, frequently gaining especial clinical meaning in adult age. In the present clinical case we introduce 35 years old male patient with salt-wasting form of 21-hydroxylase deficiency, which had either complications considered to progress due to insufficient glucocorticoid therapy, and some metabolic abnormalities, associated with supraphysiological doses of glucocorticoids

Hormonal regulation of menstrual function in patients of reproductive age with acromegaly

Background: The frequency of menstrual disorders in patients with acromegaly is 40–84% and are caused by three main reasons – the development of normal or hypogonadotropic hypogonadism due to hyperprolactinemia or a mass effect of the tumor and direct effects of GH and IGF-1 on the reproductive system. Nevertheless the exact mechanisms of reproductive dysfunction are not clear now. Hypothalamic structures play significant role in the regulation of hypothalamic-pituitary-ovary axis, so it’s important to study key neuropeptides and evaluate their effects to the pathogenesis of ovarian dysfunction during excessive secretion of growth hormone. Aim: The aim of the work is to study the hormonal regulation of menstrual function in patients of reproductive age with acromegaly in the active stage of the disease. Material and methods: The study included patients with a confirmed diagnosis of acromegaly and healthy women, comparable in age and BMI. Blood serum samples were taken in the morning (8–9 hours) on an empty stomach for 3–5 days of the menstrual cycle or on any day with amenorrhea and frozen at -70°C. The hormonal study was carried out by an enzyme immunoassay, in the case of a kisspeptin, with the preliminary extraction of serum samples. Results: The study included 31 patients with acromegaly and 15 healthy women. Between groups there was a statistically significant decrease in levels of LH (p = 0.001), FSH (p = 0.09), inhibin B (p = 0.003), and kisspeptin (p = 0.00005). The frequency of hyperprolactinemia in the cohort of patients was 51.6%. During the correlation analysis, a negative dependence of kisspeptin on the levels of GH and IGF-1 was detected (r = -0.54, p = 0.002 and r = -0.63, p = 0.0002). Conclusions: The severity of the central depression of regulation of menstrual function in patients with acromegaly may be due to the degree of disease activity

The state of erection in a patient with craniopharyngioma, panhypopituitarism and diencephalic obesity

The article presents a clinical case from the practice of a patient with craniopharyngioma. The man of reproductive age with diencephalic obesity (BMI 35 kg/m2), recurrent craniopharyngioma, a long history of endocrine disorders (panhypopituitarism, including secondary hypogonadism, with the corresponding sexual function disorders and the lack of sexual activity), with visual disorders and psychiatric symptoms in the early postoperative period after shunting surgery and reducing the volume of the craniopharyngioma cyst, erection conditions arose against the background of episodes of disorders of consciousness within the framework of sleep dissociation. After the operation (installation of the Ommaya system), the patient had a state of «spontaneous» erection lasting up to 30 minutes against the background of dream-oneiric states of impaired consciousness with erotic experiences. These states were observed for 3 nights, the patient remembered the experiences and events that occurred to him «in a dream», and could tell about them to others on the next morning. The identity of the patient remained intact, he was active in the department, ordered in behavior; memory for current events and new information was intact. These disorders in the patient did not require specialized treatment, regressed independently on the 6th day of the postoperative period

The efficacy of high-dose cabergoline treatment of prolactinomas resistant to standard doses: a clinical observation

Hyperprolactinemia (HP) is one of the most common neuroendocrine disorders. In 60% of cases, pathological HP is caused by pituitary prolactin-secreting adenoma. Therapy with agonists of dopamine type 2 receptors (D2 receptor agonists) is a method of choice for the treatment of pathological HP which allows to achieve prolactin normalization and reduction of pituitary adenoma in most cases. However, 15-20% of patients are resistant to D2 receptor agonists, and the question of overcoming this resistance is highly relevant. Different approaches are considered to solve this problem, one - is to increase the dose of D2 receptor agonists up to the maximally tolerated. In this article, we present a clinical observation of a patient with a partial resistance to D2 receptor agonists who demonstrated a good response to treatment with high doses of cabergoline

Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report)

This review provides the main results of clinical trials and the literature on the experience of using pegvisomant, the first drug from the class of growth hormone receptor antagonists. The mechanism of action of the drug, its effectiveness with respect to disease control and its effect on complications, information on adverse events, and brief information on the experience of use during pregnancy are discussed in detail. In conclusion, a clinical observation of successful use of pegvisomant in resistant to standart treatment acromegaly is given. A discussion of the available literature data, the results of clinical studies and practical experience allows us to conclude that the drug is highly effective in terms of achieving biochemical remission of acromegaly, and also has a number of additional valuable properties: it is capable of improvement of patients’ glucose metabolism and quality of life and has a minimal amount of adverse events. Pegvisomant is currently registered in the Russian Federation only for use in monotherapy; the possibility of combination therapy with somatostatin analogues will additionally allow to reliably control the growth of the pituitary adenoma and significantly cut treatment costs by reducing the dose of pegvisomant. These features of the drug make it very relevant when discussing issues related to drug therapy of acromegaly, and suggest a good prospect for use in clinical practice

Difficulties in diagnosis of adenomas with mixed prolactin and growth hormone secretion: case presentation

Hyperpolactinemia is a persistent excess of prolactin in the blood serum. The symptom complex of hyperprolactinemia primarily consists of disturbances in function of the reproductive system. The secretion of prolactin is under complex neuroendocrine control, which involves factors of different nature: neurotransmitters, hormones of the peripheral endocrine glands. In most cases, prolactin is secreted by pituitary cells - lactotrophs, but in some cases, hypersecretion of prolactin is combined with an excess production of growth hormone, which is typical for tumors originating from the line of progenitor cells of lactotrophs and somatotrophs of the pituitary gland, mammosomatotrophs. In this case, the symptom complex of hyperprolactinemia is accompanied by clinical manifestations of acromegaly. In patients with acromegaly, the cause of hyperprolactinemia may be pituitary stalk compression or mixed secretion of prolactin and growth hormone. Differentiation of lactotropic and somatotropic pituitary cells is determined by transcription factor Pit-1. These cell lineages are closely connected,  and this may be one of the reasons for formation of tumors with mixed secretion. Reports of late presentation of acromegaly in patients previously diagnosed with prolactinomas have also been described in literature.Clinical manifestations of hyperprolactinemia can cause the patient to seek doctor’s attention before acromegalic changes in appearance develop. Careful attention is needed both to the primary diagnosis and to the clinical course of the disease in patients with hyperprolactinemia and pituitary adenoma: full assessment of hormonal status with mandatory evaluation of IGF-1 is crucial at initial examination, during further observation it may be advised to consider periodic evaluation of IGF-1 in addition to assessment of prolactin and the size of adenoma.  Pituitary adenomas with mixed secretion may have a poorer prognosis

Primary hyperparathyroidism in combination with metabolic syndrome and sleep apnea

This paper presents a case of primary hyperparathyroidism with a broad spectrum of metabolic disturbances and concomitant sleep apnea syndrome. As shown a timely surgical treatment helps to improve the mineral parameters and alleviate the risk of possible cardiovascular complications in future. The article is the RePrint from the original publication in Obesity and Metabolism (2014) 11(3); pp. 51-55. doi: 10.14341/omet2014351-5

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course