High prevalence of low vitamin D levels in endocrine disorders

BACKGROUND: Vitamin D deficiency and insufficiency are widespread medical abnormalities, but their frequency in endocrine diseases has generally not been studied.AIM: To provide a comparative assessment of vitamin D levels in patients with diabetes mellitus type 2, primary hyperparathyroidism (PHPT), central hypercortisolism (Cushing’s disease; CD) and acromegaly.MATERIALS AND METHODS: Total 25(OH)D was determined using the immunochemiluminescent method (the laboratory participates in the DEQAS program). All patients had GFR > 60 ml/min, no history of use of vitamin D supplementation within previous month.RESULTS: The study included 365 patients who, after applying the inclusion/exclusion criteria, were divided into 5 main research groups: 33 patients with diabetes mellitus type 2, 23 patients with PHPT, 68 patients with CD, 22 patients with acromegaly, and 141 apparently healthy patients. Significantly low levels of vitamin D were found in patients with diabetes mellitus type 2 (14.8 ng/ml), acromegaly (14.9 ng/ml), CD (14.6 ng/ml), and PHPT (15.9 ng/ml) compared with a group of otherwise healthy patients (18.8 ng/ml).CONCLUSION: The results of the study demonstrate a high prevalence of vitamin D deficiency not only in groups of patients with chronic diseases, but also among practically healthy patients. Further studies are needed to address the causes of high vitamin D deficiency in the described endocrine diseases

Correction of endocrine complications of oncoimmunotherapy

Over the years, immunotherapy with immune checkpoint inhibitors (ICI) has become an effective treatment for malignant neoplasms. However, checkpoints play a crucial role in immunological tolerance and prevention of autoimmune diseases. Interfering with this mechanism can cause immune-related adverse events (IRAEs) that affect multiple organs in the body. Endocrinopathies are among the most common IRAES associated with ICI therapy. Given the unique nature of adverse events caused by the use of ICI drugs, a multidisciplinary team approach is required to effectively manage patients, minimize complications associated with drug toxicity, and fully realize the therapeutic potential of this treatment method. Taking into account the difficulty of detecting nonspecific symptoms, the importance of follow-up and timely intervention in case of toxicity detection, regular clinical and laboratory monitoring is necessary, as well as informing patients and doctors about the variants of endocrine adverse events and their treatment. While non-endocrine IRAES often require discontinuation of immunotherapy and are usually resolved by immunosuppressive therapy with high doses of glucocorticoids, endocrine IRAES usually do not need discontinuation of ICI treatment and rarely require immunosuppressive therapy, but seldomly regress and therefore demand a long-term treatment

Absorption and metabolism of vitamin D in health and in gastrointestinal tract diseases

Over the past decades, we have witnessed many remarkable advances in understanding the impact of vitamin D on human health. There is an exponential growth of new data covering both the fundamental biology of vitamin D and the clinical implications of deficiency and the effects of vitamin D supplementation. This literature review has been prepared to combine and interpret the current scientific evidence on the mechanisms of vitamin D absorption, with a focus on vitamin D absorption through the apical membrane of enterocytes in various pathologies of the gastrointestinal tract. Reviewed studies have identified some distinctive aspects of vitamin D bioavailability that should be considered in the treatment or prevention of vitamin D deficiency in patients with malabsorption syndromes, especially in the active phase of the disease. Moreover, recent in vivo experiments and in vitro studies have demonstrated that vitamin D absorption is not a simple diffusion process as previously thought, but rather a mechanism that also involves multiple membrane transporters. Maintaining or improving vitamin D intake through diet or increased sun exposure is problematic, so oral supplementation may be an effective and safe approach to improving vitamin D status. Vitamin D3 is the recommended form for both prevention and treatment of vitamin D deficiency, which is associated with more stable pharmacokinetics. Vitamin D absorption is improved when vitamin D is taken with a small amount of fat-containing food and medium chain triglycerides. In malabsorption syndromes, it is optimal to increase the general population doses of vitamin D by 2–3 times both for prevention and for the treatment of deficiency and insufficiency. While vitamin D deficiency is more common among people with gastrointestinal disease, data have not been able to establish whether the relationship is causal or the result of intestinal inflammation and malabsorption syndrome. However, owing to the understanding of the mechanisms of action of vitamin D, there is evidence that its deficiency can be directly related to the severity of the disease, and partly to the etiology or pathogenesis of the disease itself

The role of the apelin/APJ system in water homeostasis regulation

Water balance in the body is achieved by balancing renal and non-renal water losses with corresponding water intake. It is under the control of both the central nervous system, which integrates many parameters of water and electrolyte balance in the body, including inducing important adaptive behavioral responses, and three hormonal systems: vasopressinergic, renin-angiotensin-aldosterone and apelinergic. A lot of research is devoted to the regulation of water-electrolyte metabolism. However, this process is still quite difficult to understand, especially since more and more of its regulators are being discovered over time. One of them is the hormone apelin, an endogenous ligand for the APJ receptor. As is known, the receptor is highly expressed in many organs, such as the brain, heart, liver and kidneys, lungs, and has multidirectional effects.This literature review discusses the main characteristics and features of the regulation of these systems in relation to water-electrolyte metabolism, as well as issues of intersystem interaction and modulation of the effects of apelin

Resistance to drug treatment of acromegaly and ways to overcome it

Acromegaly is a severe disabling neuroendocrine disease caused by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The problem of resistance to drug therapy in patients with acromegaly is quite common in clinical practice and requires a personalized approach, considering various predictors of sensitivity to the choice of the treatment method. To date, first-generation somatostatin analogues are first-line drugs in the medical treatment of acromegaly, but up to 50% of patients do not achieve biochemical remission of the disease. The prognosis of sensitivity to somatostatin analogues is of great importance and the selection of patients in whom this therapy will be not successful provides invaluable assistance in choosing the optimal treatment approach. This review summarizes potential predictors of sensitivity and resistance to existing drug treatment of acromegaly, discusses possible ways to overcome the resulting resistance to therapy, suggests options for a personalized approach to choosing a treatment strategy in the absence of disease control against the background of monotherapy with somatostatin analogues, including «off-label» combinations. Timely addition of growth hormone receptor antagonist (pegvisomant) avoids repeated neurosurgical intervention, radiation therapy or prescribing excessively high doses of somatostatin analogues. Optimal use of mono- or combination therapy contributes to the achievement of biochemical remission in most resistant patients

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 course of gout in a patient with Cushing’s disease after successful surgical treatment

Endogenous  hypercortisolism  is a severe endocrine  disease characterized by prolonged  exposure to excessive amounts of glucocorticoid hormones, accompanied by a wide range of symptoms and complications, including immunosuppression. Timely surgical treatment in most cases allows to save the patient’s life, significantly improve its quality. However, restoration of the normal concentration of glucocorticoid  hormones can become a trigger factor in the development or exacerbation of autoimmune and auto-inflammatory diseases. We present a clinical case of atypical gout in a patient with hypercortisolism and a progressive increase in symptoms of the disease after successful surgical treatment for Cushing’s disease and achieving stable remission. The issues of diagnosis and treatment of this group of autoinflammatory diseases are highlighted, the leading clinical and radiological  symptoms are considered, the differential diagnosis  of microcrystalline (metabolic) arthritis is presented. Despite the widespread, the diagnosis and treatment of this group of diseases still cause difficulties for specialists. A competent choice of drug therapy allows to fully control diseases considered in the article, including when they are combined, and thereby improve the quality of life of the patient

Efficacy of long-term octreotide therapy of acromegaly as the first-line medical treatment

Acromegaly is a severe neuroendocrine disease characterized by hypersecretion of growth hormone (GH) caused in 95% of cases by pituitary adenoma, which leads to the development of pathology of various organs and systems. The severity of the condition is due not only to the direct effect of somatotropic hormone on the body and the effect of the adenoma on the surrounding structures, but also to the age of the patient and complications associated with the disease. Improvement in treatment methods allows for a personalized approach to patient management, taking into account various aspects of the clinical case. It is important for a specialist to take into account comorbidity in acromegaly, both in terms of pathological disorders and the impact on the patient’s psycho-emotional state. We present a clinical case of successful treatment with somatostatin analogues (ASS) in a patient who is afraid of surgery and has cardiovascular complications of acromegaly. Since the onset of acromegaly, confirmed by an elevated level of insulin-like growth factor-1 (IGF-1) and an endosellar pituitary macroadenoma measuring 11x9.5x8 mm, ASS therapy was initiated in the patient. The choice in favor of conservative treatment was due to a burdened cardiovascular history and the patient’s fear of surgery. Within three years from the start of drug therapy, there was a significant improvement in overall well-being, a tendency to reduce the size of the pituitary adenoma, and biochemical remission was achieved. The clinical case described by us confirms the possibility of successful primary treatment of ASS in a patient with acromegaly, taking into account all individual characteristics

The effect of a structured non-pharmacological treatment of type 2 diabetes on glycated hemoglobin and body weight: a randomized controlled trial

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p<0.001, while for the control group the level of HbA1c remained the same at 6.5% (p=0.703). Patients in both groups significantly reduced body weight, however, the decrease in the intervention group was more significant: by 6.7% of the initial level, while in the control group, only 1.1%. LDL, triglycerides, cholesterol level, HOMA-IR 2, and diastolic blood pressure did not decline significantly in the control group. All biochemical characteristics except triglycerides and LDL decreased significantly in the intervention group.CONCLUSION: The use of a structured program of non-pharmacological treatment of type 2 diabetes mellitus among compensated (HbA1c ≤7%) middle-aged patients who took metformin significantly reduced body weight and glycated hemoglobin in 24 weeks

Experiense of treatment with a growth hormone receptor antagonist in patients with hereditary form of acromegaly: clinical cases

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly