Libuse Tauchmanovà

High prevalence of endocrine dysfunction in long‐term survivors after allogeneic bone marrow transplantation for hematologic diseases

The progressively increasing number of long‐term survivors after allogeneic bone marrow transplantation (allo‐BMT) led researchers to focus on the early and late complications of this procedure. Endocrine dysfunction occurred mostly in patients who had undergone total body irradiation (TBI) as part of pretransplantation treatment. The extent to which chemotherapy and immune system derangement affect endocrine function in allo‐BMT recipients is still unclear.

Avascular necrosis in long-term survivors after allogeneic or autologous stem cell transplantation: A single center experience and a review

The most debilitating skeletal complication of stem cell transplantation (SCT) is avascular necrosis (AVN).

Andrenocortical Carcinomas: Twelve-year Prospective Experience

Adrenocortical carcinoma (AC) is a rare tumor with poor prognosis. Twenty-two patients (14 F, 8 M; age 22 to 59 years; median, 43 years) with AC were evaluated prospectively in a single center: tumor stage was I–II in 12 cases and III–IV in 10. The overall survival in our cohort was 41.6 ± 42 months; 16 subjects are still alive. Curative surgery was followed by longer survival than debulking or no surgery (p < 0.0001). The first relapse was highly predictive for further recurrences. Recurrent ACs were progressively more aggressive, and they occurred with variable but ever shorter intervals. At diagnosis, 14 patients (63.5%) presented with features of clear adrenocortical hyperactivity. Despite the absence of clinical signs of hormonal excess, all other patients presented some abnormalities of steroid secretion. The most common clinical finding was a recent diagnosis of moderate-to-severe hypertension (68%), poorly controlled by pharmacological treatment, often associated with multiple cardiovascular risk factors. High mitotic rate and undifferentiated polymorph cellular pattern were associated with worse prognosis. Response to treatments other than surgery (mitotane chemotherapy) was better in patients treated early after the first surgery. In conclusion, curative surgery was the most effective treatment. Monitoring arterial pressure, endocrine parameters, and metabolic parameters can be helpful for the early detection of AC recurrences.

Is plasminogen activator inhibitor-1 a cardiovascular risk factor in young women with polycystic ovary syndrome?

This study aimed to evaluate plasminogen activator inhibitor-1 (PAI-1) activity in PCOS. Thirty women with PCOS - 15 normal-weight and 15 obese - and 30 healthy women matched as a group for age and body mass index (BMI) were recruited. The homeostasis model assessment (HOMA) score was significantly elevated in obese compared with normal-weight women, in both PCOS women and controls. HOMA score was significantly higher in both PCOS groups relative to controls. After further adjustment for BMI, PAI-1 activity (IU/ml +/- SD) was significantly higher in the PCOS groups compared with controls. A significant positive correlation was found between HOMA score and BMI in PCOS and control groups. Serum PAI-1 activity was significantly related to BMI and HOMA score. When considering two BMI subgroups, there was no significant difference in the relationship between serum PAI-1 activity and HOMA score in both the control and PCOS groups. No other significant relationship was found between serum PAI-1 activity and any other hormonal or metabolic parameter. In conclusion, women with PCOS have significantly elevated PAI-1 activity independent of obesity, and it is speculated that elevated PAI-1 activity may be a factor in the increased cardiovascular morbidity seen in PCOS.

Cushing's syndrome: aftermath of the cure

Cushings syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism

OBJECTIVE Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Nevertheless, limited data are available on bone status in patients with endogenous cortisol excess. This study is aimed at investigating the role of sex steroids and severity of hypercortisolism on bone mineral density (BMD) and prevalence of vertebral fractures in female patients. DESIGN Cross-sectional, case-control study. PATIENTS Seventy-one consecutive women were enrolled: 36 with overt hypercortisolism (26 with ACTH-secreting pituitary adenoma and 10 with cortisol-secreting adrenal tumor) and 35 with subclinical hypercortisolism due to adrenal incidentalomas. They were compared with 71 matched controls. METHODS At diagnosis, we measured serum cortisol, FSH, LH, estradiol, testosterone, androstenedione and DHEAS, and urinary cortisol excretion. BMD was determined by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. Vertebral fractures were investigated by a semiquantitative scoring method. RESULTS Between women with overt and subclinical hypercortisolism BMD values and prevalence of any vertebral (69 vs 57%, P = 0.56), clinical (28 vs 11.4%, P = 0.22), and multiple vertebral fractures (36 vs 31%, P = 0.92) did not differ. Among patients with subclinical hypercortisolism, amenorrhoic women had a lower BMD (P = 0.035) and more frequent vertebral fractures (80 vs 40%; P = 0.043) when compared with the eumenorrhoic ones. Among women with overt hypercortisolism, there was no difference in lumbar BMD (P = 0.37) and prevalence of fractures (81 vs 60%; P = 0.26) between those amenorrhoic and eumenorrhoic. By logistic regression analysis, lumbar spine BMD values and cortisol-to-DHEAS ratio were the best predictors of vertebral fractures (P < 0.01). CONCLUSIONS Vertebral fractures are very common in women with endogenous cortisol excess, regardless of its severity. The deleterious effects of hypercortisolism on the spine may be partly counterbalanced by DHEAS increase at any degree of cortisol excess, and by preserved menstrual cycles in women with subclinical but not in those with overt hypercortisolism.

Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

Objective: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor &kgr;&bgr; ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. Design: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17&bgr;-estradiol at a dose of 50 &mgr;g/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. Results: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. Conclusions: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.

Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients

Background  In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated.

Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing's syndrome

Introduction: Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women. Currently, it is unclear if patients with subclinical Cushing’s syndrome (SCS) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given. Objective: This pilot randomized study was aimed at evaluating the effects of 12-month im administration of clodronate (100 mg every week) on vertebral and femoral bone mineral density (BMD), bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas. Methods: Forty-six women (age, 43.1 ±7.7 yr) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were randomized to receive clodronate plus supplement of Calcium (500 mg daily) and Vitamin D3 (800 mg daily) (group 1, no.=23) or supplements only (group 2, no.=23). Both groups were similar in terms of age, body mass index, cortisol levels, BMD values, and bone turnover markers. All of the women were re-evaluated after 12 months. Results: After 12 months of treatment, in group 1, a significant increase in lumbar BMD occurred (p=0.04), while bone turnover markers decreased by about one third (p<0.05). In group 2, bone turnover markers did not change and BMD values slightly decreased (p=ns). The differences in bone turnover markers and in lumbar BMD between the two groups were significant (p<0.05, all). No new vertebral fracture occurred in group 1, while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures. An improvement in subjective back pain, assessed by visual analogue scale pain score was observed in group 1 (from 4.3±2.7 to 2.9±2.0; p<0.05) but not in group 2 (from 4.4±3.1 to 4.2±3.4; p=ns). No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study. Conclusions: Intramuscular administration of clodronate effectively increased lumbar BMD values, preserved bone mass at the femoral neck, stabilized vertebral fracture index, and decreased subjective back pain in pre-menopausal women with SCS. Since the untreated group continued to lose bone, antiresorptive treatment should be considered in patients with SCS, according to the prevision of surgical treatment, prevalent fractures, BMD values, age, concomitant morbidities, and desire for pregnancy.

Idiopathic chronic urticaria and thyroid autoimmunity: Experience of a single center

Urticaria is one of the most frequent dermatosis, being its prevalence in general population estimated about 20%. This prospective case-control study was aimed at determining the prevalence of thyroid autoimmune disorders in a cohort of patients with chronic urticaria (CU), all living within an area with mild-to-moderate iodine deficiency. Fifty four consecutive patients affected by CU were recruited and compared to 108 healthy controls. Assessment of the thyroid function included measurement of serum concentrations of TSH, FT3, FT4, anti-thyreoglobulin (anti-TG) and anti-peroxidase (anti-TPO) antibodies. Ultrasound scan of the thyroid gland was performed in all subjects using a 7.5 MHz linear transducer. All subjects were followed up for 6 months. The prevalence of thyroid antibodies was significantly higher in our cohort of patients with CU than in controls (22% vs. 6.5 %). Hashimoto’s thyroiditis was also more frequent in patients than controls (18.5% vs. 1.8%). These frequencies do not differ from those previously reported by some other authors and confirm the association between CU and thyroid autoimmunity also in the area of iodine deficiency. However, presence of antibodies or thyroiditis does not seem to influence clinical course of CU. These results suggest that screening for thyroid function may be useful in all the patients with CU.