Milica Medic-Stojanoska

Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress

Recent studies have demonstrated that hypopituitarism, in particular GH deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or yr following head trauma. We present the results of endocrine, neurological, neuropsychological and psychiatric evaluation in a group of 67 patients who suffered TBI at least one yr ago. Our study shows that decreased endocrine function is either restricted to one or more anterior pituitary hormones and is present in 34% of patients with any pituitary hormone deficit, while multiple pituitary hormone deficiencies are found in 10% of patients. GH/ IGF-I axis was evaluated by GHRH+GHRP-6 test and IGF-I measurement. Severe GHD is the most frequent deficiency present in 15% of TBI patients. Gonadotrophin deficiency was present in 9% of patients with TBI, while thyrotroph and corticotroph function seemed more refractory to impairment. Patients with moderate-to-severe trauma are not necessarily more likely to have hypopituitarism than those with mild injury. Neuropsychological testing revealed a significant positive correlation of peak GH levels after GHRH+GHJRP-6 test with verbal learning and verbal short term memory (RAVLT total score p=0.06, immediate free recall p=0.02 and delayed free recall p=0.04). Verbal and visual memory was significantly lower in elderly patients and in males. Visoconstructional abilities (RCF copy) were significantly lower in the elderly (p<0.01) and undereducated (p=0.02). Visual memory (free recall of complex figure after 30 min) significantly correlated with lower IGF-I levels (p=0.01). Gonadotrophins and testosterone correlated significantly with visoconstructional abilities. Simple and complex conceptual tracking (TMT A and B) was significantly more impaired in older TBI patients (p<0.01) and with longer time from trauma (TMT B only, p=0.03). The psychiatric evaluation by using two different scales showed depression, phobic anxiety and psychoticism to be more prominent in the TBI group. Paranoid ideation and somatization negatively correlated with the peak GH responses to GHRH+GHRP-6 test (p=0.04 and p=0.03, respectively). Depression scale showed that nearly half of patients suffered from mild to moderate depression. The benefits of hormone replacement therapy on cognitive functioning and mental distress in TBI patients are eagerly awaited.

Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults.

Objective:  The objective of the study was to asses the possible influence of hypothalamo–pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency.

Neuroendocrine dysfunction in patients recovering from subarachnoid hemorrhage.

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a recently identified risk factor for hypopituitarism, particularly growth hormone (GH) and corticotrophins deficiencies. The aim of our study was to identify possible predictor(s) for neuroendocrine dysfunction in SAH survivors. DESIGN: Pituitary function was evaluated in 93 patients (30 males, 63 females), aged 48.0±1.1 years (mean±SE), and with a Glasgow Outcome Scale score of 4.6±0.6 (mean±SE) more than one year following SAH. In the acute phase, SAH was complicated by vasospasm (VS) in 18 and by hydrocephalus (HDC) in 9 patients. Baseline serum values of Insulin Growth Factor 1 (IGF-I), cortisol, Thyroxine (T4), Thyroid Stimulating Hormone (TSH), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), testosterone (in males), estradiol (in females) and prolactin were determined. RESULTS: According to the results of baseline hormonal evaluation, 47 patients (50.5%) had no hormonal abnormalities. Seven patients (7.5%) had multiple pituitary hormone deficiencies: Four patients (4.3%) had two (GH and cortisol), one patient had three (gonadal, adrenal and GH) and two patients had deficiency of all pituitary axes. Thirty-nine patients (42%) had one abnormal axis (13 adrenal, 2 thyroid, 4 gonadal and 20 GH). None of the subjects was treated with desmopressin or exhibited symptomatic polyuria. The VS and HDC during the acute phase of SAH were related to abnormal pituitary status (VS with low IGF-I levels and HDC with low cortisol levels). CONCLUSION: Through a screening procedure, neuroendocrine dysfunction was identified in a substantial number of asymptomatic patients with previous SAH. Cerebral VS and HDC at the time of SAH emerged as risk factors possibly predicting development of pituitary dysfunction. Low basal levels of IGF 1 and cortisol may help in selecting patients requiring further evaluation of pituitary function.

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood—call for attention

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.

Estimation of in vivo and in vitro exposure to bisphenol A as food contaminant

The goal of this cross-sectional study was to examine the occurrence of bisphenol A (BPA) in the morning spot urine taken from 145 female volunteers of various ages. Total urine BPA concentration was detected in 38.6% samples in the 0.92-70.96 μg/g Cr range. The majority of BPA + women belonged to the 25 + body mass index (BMI) group (54.5% were overweight and 43.4% were obese women). Occurrence of BPA in the urine samples was higher at 40 + ages. The maximum BPA concentration of 70.96 μg/g Cr was detected in the urine sample of an obese woman. It is known that BPA is highly toxic in vitro. In this study BPA impaired significantly the growth of all investigated cell lines, i.e. the EC50 values were reached at very low concentrations, in the range from 3.24 to 34.85 μg/mL. The obtained in vivo results suggest that a higher exposure to BPA could contribute to weight problems in women and the absence of the BPA in vitro selective toxicity studies indicates to its general toxic mode of action and raises awareness of the health risks associated with its ubiquitous presence in the environment.

Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia

Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment.

May Patients with Alcohol Liver Disease Benefit from Herbal Medicines

Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD.

Multiple Causes of Hyponatremia: A Case Report

Objective: To present a case with 4 different potential causes of hyponatremia. Clinical Presentation and Intervention: The patient presented with the following symptoms: nausea, vomiting, diarrhea, and dark urine after drinking large amounts of fluids that included alcohol and caffeine. Laboratory, microbiological, and morphological examinations revealed the existence of severe hyponatremia and acute poststreptococcal glomerulonephritis. The patient developed acute symptomatic seizures and coma. Gradual normalization of the sodium level led to a recovery of consciousness. Conclusion: Treatment with hypertonic sodium, fluid restriction, and antibiotics led to a complete recovery. In the case of multiple causes of hyponatremia, it is necessary to treat all causes.

Influence of some traditional risk factors for osteoporosis on bone metabolism during substitution therapy of primary hypothyroidism

INTRODUCTION The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. MATERIAL AND METHODS In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type l-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. RESULTS AND DISCUSSION A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p = 0.000024), CL (p = 0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p = 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p = 0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. CONCLUSION It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long-term prospective studies in patients on replacement l-thyroxine therapy.