Vitamin D Metabolism in Patients With Endocrine Disorders

Prospective Non-randomised Controlled Study of Vitamin D Metabolism in Patients With Endocrine Disorders (Acromegaly, Cushing's Disease, Primary Hyperparathyroidism, Diabetes Mellitus Type 1) Treated With Cholecalciferol Bolus Dose

This prospective controlled interventional study aims to reveal the diversity of vitamin D metabolism in patients with certain endocrine disorders (Cushing's disease, acromegaly, primary hyperparathyroidism, diabetes mellitus type 1) compared to healthy adults. All patients will receive a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3 and D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters will be performed before the intake and on Days 1, 3 and 7 after the administration.

Inclusion Criteria:

• confirmed diagnosis (arms "Cushing's Disease", "Acromegaly", "Diabetes Mellitus Type 1", "Primary Hyperparathyroidism")
• active phase of the disease (arms "Cushing's Disease", "Acromegaly")
• no history of surgical and specific pharmacological treatment (arm "Primary Hyperparathyroidism")
• HbA1c <8.0% (arm "Diabetes Mellitus Type 1")
• absence of the specified endocrine disorders (arm "Control group")

Exclusion Criteria:

• factors associated with vitamin D level

  • intake of the following drugs during the 3 months preceding the study: vitamin D medications; glucocorticosteroids; antiretroviral drugs; antifungal drugs; cholestyramine, orlistat; antiepileptic drugs; antidepressants (fluoxetine); diuretics (spironolactone); antimicrobial agents (macrolides, tetracyclines, isoniazid, rifampin, primaquine); chemotherapy (cyclophosphamide, tamoxifen, paclitaxel, ifosfamide, irinotecan, etoposide, vinblastine); immunosuppressants (cyclosporin A, tacrolimus, sirolimus); H2 receptor antagonists.
  • BMI >35 kg/m2
  • pregnancy
  • granulomatous disease (sarcoidosis, tuberculosis, histoplasmosis, berylliosis, coccidiomycosis)
  • disease with malabsorption syndrome (Crohn's disease, ulcerative colitis, celiac disease, post-bariatric surgery condition, decompensation of chronic pancreatitis)
  • reduced renal function (eGFR <60 ml/min/1.73m2)
  • laboratory signs of liver failure (hypoalbuminemia, hypoprothrombinemia)

• hypercalcemia or risk factors for hypercalcemia

  • serum total calcium >3.0 mmol/L
  • myeloma
  • immobilization
  • thiazide diuretics intake

• allergy to vitamin D drugs

• total 25(ОН)D >60 ng/ml (determined by chemiluminescent immunoanalysis)