The present study aims to comprehensively evaluate metabolic, bone, and cardiovascular
disturbances in Bulgarian patients with different endocrine diseases. The main emphasis will be
on Cushing’s syndrome as a disease pattern with multiple comorbidities (arterial hypertension,
cardiomyopathy, ischemic heart disease, prediabetes or overt type 2 diabetes mellitus,
secondary osteoporosis, increased thrombotic risk, etc.). Metabolic, bone and cardiovascular
abnormalities would also be studied in other specific endocrine diseases, such as primary
aldosteronism (PA), primary hyperparathyroidism (PHPT), papillary thyroid carcinoma (PTC),
and thyroid-associated ophthalmopathy (TAO). The data of the patients enrolled to the different
disease groups will be compared to and age- and sex-matched healthy individuals as a control
group. Currently, scientific data about the comorbidities in patients with rare adrenal, thyroid,
and parathyroid diseases are insufficient or contradictory. Therefore, the present study would
help to fill the gaps in the knowledge.
More specifically, the project aims to explore the changes in cell membrane lipids and
disturbances in sphingolipid metabolism in different endocrine diseases, considering the specific
influence of aldosterone (in PA), cortisol (in CS), thyroid hormones (in PTC), parathyroid
hormone (in PHPT) and immunological parameters (in TAO) on cell membrane lipid structure.
Patients with adrenal, thyroid and parathyroid diseases suffer from increased cardiovascular
morbidity because of early metabolic dysfunction. However, the specific damage patterns might
differ with the particular hormonal abnormalities, and the current project could help determine
the distinct alterations in patients with different hormonal environments. Another goal of the
study is to investigate the possible associations between cell membrane lipid changes and
cardiovascular disturbances in the selected disease groups. Traditional and novel markers and
methods for assessing cardiovascular function would be used, such as plasma lipid profile,
ECG, 24-hour Holter ambulatory blood pressure monitoring, conventional and strain
echocardiography, etc. Changes in lipid membrane parameters will be studied at baseline and
prospectively after disease treatment (surgical or medical) in patients with CS, PA, PHPT, PTC,
and TAO. Thus, the project will explore the influence of the normalization of hormonal and
immunological parameters on cardiovascular function and lipidome changes. Additionally, in
PTC patients, the effect of levothyroxine suppression therapy on sphingolipid metabolism and
strain EchoCG parameters will be investigated, in regard to the early prevention of
cardiovascular complications and the life-long continuation of the treatment.
Longitudinal assessment of bone metabolism in patients with Cushing’s syndrome, thyroid, and
parathyroid diseases will also be performed. Specifically, the changes in calcium-phosphorus homeostasis and bone mineral density will be studied during the active disease phase and after
treatment. Moreover, possible associations between bone metabolic markers,
echocardiographic parameters, and lipidome analysis will be investigated.