The most common indications for measuring metanephrine and normetanephrine in plasma - a rational approach.

Aim To determine the most common indications for measuring metanephrine and normetanephrine in plasma by gender and age and to compare the concentrations of metanephrine and normetanephrine by indication, gender and age. Methods The study was conducted on 224 patients whose plasma metanephrine and normetanephrine concentrations were measured at the Clinical Institute for Laboratory Diagnostics at the University Hospital Centre Osijek for one year, until 1st January 2020. Results The most frequent indications for biochemical testing were adrenal incidentaloma, 138 (6.6 %), and symptoms of pheochromocytoma, 41 (18.3%). Metanephrine concentration was lower in females (p=0.009). No significant correlation was found between age and metanephrine concentration, while age and normetanephrine concentration were positively correlated (p=0.01). Of the 224 patients, only one patient was diagnosed with pheochromocytoma, whose indication for measurement of metanephrine and normetanephrine was adrenal incidentaloma. Conclusion Adrenal incidentalomas and symptoms suggestive of pheochromocytoma are very common in the general population, while the incidence of pheochromocytoma is extremely low. Clear guidelines for the referral of patients for biochemical testing are needed to avoid unnecessary costs and to identify the correct diagnosis promptly.

Pheochromocytoma in pregnancy - a rare but dangerous diagnosis.

Pheochromocytoma is a rare cause of hypertension in pregnancy. Unrecognized, it carries a great risk for both mother and the foetus. The main reason for missing the diagnosis is the misconception that any hypertension occurring in pregnancy is gestational hypertension or pre (eclampsia). As many as 90% of patients report one or more pheochromocytoma-related symptoms antenatally, but the diagnosis is made in 75% of patients, meaning that 3 out of 10 patients are diagnosed after childbirth or post-mortem. The symptoms are similar to other more common causes of hypertension in pregnancy, which presents a major diagnostic challenge. The diagnosis is based on determination of metanephrines in plasma or 24-hour urine. Magnetic resonance imaging (MRI) and ultrasound (US) are used to localize the tumour. If the diagnosis is made before the 24th week of pregnancy, laparoscopic removal of the tumour in the second trimester is recommended. If diagnosed later, the tumour could be removed during or after delivery. Preoperative preparation with alpha blockers is required to stabilize blood pressure. The decision on the mode of delivery depends on several factors, so an experienced multidisciplinary team is needed to minimize maternal and foetal mortality.

FROM ERECTILE DYSFUNCTION TO BRAIN SUBEPENDYMOMA: A CASE REPORT.

Endocrinopathies are relatively rare causes of erectile dysfunction. Cases of hyperprolactinemia and pituitary adenomas have been previously reported. We present a clinical case of a 27-year-old male with suspected infertility and recent symptoms of erectile dysfunction. Additional radiological and endocrinologic workup revealed underlying subependymoma, which was expanding in the sellar and suprasellar regions, causing pressure against the pituitary gland. The resulting endocrine disorder caused problems that were subjectively at first manifested mainly as erectile dysfunction. The case is an educative example pointing to the need of taking possible intracranial lesions in consideration when starting workup in a patient presenting with erectile dysfunction. It may be of broad clinical interest not only for endocrinologists but also for practitioners in various fields.

Predictors of short-term LAMA ineffectiveness in treatment naïve patients with moderate to severe COPD.

BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6­min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1), and as single components. RESULTS: Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001). CONCLUSION: Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.

From Postpartum Metastatic Cancer to Parathyroid Adenoma: A Case Report.

We present a 36 year old female patient with suspected postpartum advanced metastatic cancer and multiple osteolytic lesions due to which she was referred to the Internal medicine clinic for further diagnostic evaluation. After extensive investigation, it was discovered that the underlying condition was a parathyroid gland adenoma and the patient was treated surgically. Clinicians should note that parathyroid adenoma can mimic metastatic malignant disease, and should make appropriate diagnostic tests that will lead to the correct diagnosis.

Influence of short-term changes in sex hormones on serum concentrations of cellular adhesion molecules in young healthy women.

AIM: To determine if short-term changes in sex hormones (such as cyclic changes within the menstrual cycle) can influence the serum concentration of soluble cell adhesion molecules (CAMs). METHODS: Sixteen healthy young women with normal cycles participated in this study. Serum levels of sICAM-1, sVCAM-1 and E-selectin were determined in three different phases of the menstrual cycle: a) early follicular (EF) phase, b) ovulatory (O) phase and c) midluteal (ML) phase, by standardized ELISA-based kits. To confirm the exact assessment of menstrual cycle phases, serum levels of estrogen, progesterone, LH and FSH were measured. RESULTS: There were significant oscillations in serum female sex hormones concentration over the cycle duration, as expected the level of estrogen (E2) and progesterone (PROG) was the lowest in EF phase, the highest E2 appeared in O phase, and both E2 and PROG were present in high concentrations during ML phase. There was a significant positive correlation between E2 and serum soluble ICAM -1 concentrations (p=0,041, correlation coefficient 0,306). However, there was no significant change in other soluble CAMs concentration during the menstrual cycle. CONCLUSIONS: Results of our study suggest that short-term changes in female sex hormone levels could modulate expression of soluble ICAM-1, but not VCAM -1 or E-selectin in extent that would affect a young woman's health.

Impressive results of teriparatide treatment of postgastrectomy osteoporosis.

Patients who have undergone gastrectomy have a higher incidence of osteoporosis. We are presenting a patient with postgastrectomy osteoporosis who had been treated with multiple medications, including bisphosphonates, calcitriol and calcium, but with unsatisfactory results, low quality of life and a high risk of further fractures. However, after a treatment with teriparatide, a recombinant form of endogenous parathyroid hormone, the patient's bone mineral density increased considerably, with a substantial improvement of mobility and general condition. Since there do not seem to be specific any guidelines or recommendations for treating osteoporosis in postgastrectomy patients, our report may be very relevant for clinicians.

Insulin administration in the mild hyperglycaemia changes expression of proinflammatory adhesion molecules on human aortic endothelial cells.

An overexpression of cell adhesion molecules (CAMs) on the surface of endothelial cells is one of the first steps in a high glucose-mediated endothelial dysfunction in diabetic patients. The effect of insulin administration in the condition of elevated glucose concentration on the E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) expression on human aortic endothelial cells (HAEC) was investigated. Cells were cultured for 4 h in a medium supplemented with homocysteine (7 pM) and different concentration of glucose (5.5, 8.0, 12.0 and 16.5 mM respectively) with or without insulin (1 mlU/mL) addition. Expression of CAMs was analysed by flow-cytometry using monoclonal antibodies. Controls were CAMs expression in the medium with a corresponding glucose concentration. Obtained results show that short-term exposure of HAECs to moderate high glucose concentrations results in increased expression of E-selectin (2-fold), VCAM-1 (3-fold) and ICAM-1 (47%). At the same time, HAEC grown with 12 mM glucose expressed lesser E-selectin and, more ICAM-1 (for 64%) and VCAM-1 (41%) molecules. 16.5 mM glucose decreased expression of all investigated adhesion molecules. Addition of insulin was not changed expression of CAMs in a medium with 5.5 mM glucose. In conditions of elevated glucose concentration (12 mM), addition of insulin significantly dropped E-selectin (27%) and increased VCAM-1 (23%) expression. In conclusion, moderate elevated glucose concentration increased expression of cell adhesion molecules on HAEC. Insulin administration in the mild hyperglycaemia reduces an expression of the proinflammatory adhesion molecule E-selectin which could contribute in deceleration of macrovascular complications development in diabetic patients.