Age, body composition parameters and glycaemic control contribute to trabecular bone score deterioration in acromegaly more than disease activity.

Introduction: Impairment of bone structure in patients with acromegaly (AP) varies independently of bone mineral density (BMD). Body composition parameters, which are altered in patients with acromegaly, are important determinants of bone strength. Purpose: The aim of this study was to examine BMD and lumbar trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and to assess its relationship with disease activity, age, glucose metabolism, and body composition parameters. Methods: This cross-sectional prospective study involved 115 patients with acromegaly (70 F, 45 M) and 78 healthy controls (CON) (53 F, 25 M) matched for age, gender, and BMI. Bone mineral density, TBS and body composition parameters were measured using DXA. Results: AP presented with lower TBS compared to CON (1.2 ± 0.1 v 1.31 ± 0.1, P< 0.001). No significant correlation was observed between IGF-1/GH levels and TBS. Age, glycated haemoglobin, BMI, waist circumference, fat mass, and lean mass negatively correlated with TBS in both sexes. Multiple linear regression analysis of all these parameters revealed age and waist circumference as independent significant predictors of TBS in AP. We did not find difference in BMD (lumbar and femoral sites) between AP and CON nor between active and controlled AP. We observed negative correlation between age and BMD of the femoral neck and total hip (P < 0.001). Testosterone levels in males, BMI, waist circumference, fat mass, and lean mass positively correlated with BMD in AP, with stronger correlation between lean mass and BMD compared to fat mass. Conclusion: Patients with acromegaly have lower TBS than controls, confirming impaired bone microarchitecture in acromegaly regardless of BMD. Age, body composition parameters and glucose metabolism contribute to TBS deterioration in AP more than disease activity itself.

Filling the gap between the heart and the body in acromegaly: a case-control study.

OBJECTIVE: Cardiovascul diseases are the most common comorbidities in acromegaly. Potential parameters in pathology of cardiovascular comorbidities are changes in levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) as well as body composition parameters. PURPOSE: The aim of this study was to examine morphological and functional parameters of the cardiovascular system by echocardiography and to assess its relationship with disease activity and body composition parameters. METHODS: We prospectively enroled 129 acromegalic patients (82 females, 47 males) and 80 healthy controls (53 females, 27 males) matched for age, gender, and BMI. All patients underwent two-dimensional echocardiography. Body composition parameters were assessed by dual-energy X-ray absorptiometry. RESULTS: Acromegaly patients presented with higher left ventricle mass (LVM) compared to controls (LVMI: 123 ± 45 g/m2 vs 83 ± 16 g/m2, P < 0.001). Prevalence of left ventricle hypertrophy in acromegaly patients was 67% (78% concentric, 22% eccentric). IGF -1 levels, BMI, and lean mass positively correlated with LVM in all acromegaly patients (P < 0.001). Fat mass positively correlated with LVM in females (R = 0.306, P = 0.005), but this correlation was not found in males. We did not find any difference in size of the left and right ventricle between acromegaly patients and controls. Acromegaly patients presented with left atrium enlargement, diastolic dysfunction and low incidence of systolic dysfunction. Valvopathy was found in 43% of patients with predominant (31%) prevalence of mitral regurgitation. CONCLUSION: Our study demonstrates higher prevalence of cardiovascular comorbidities in acromegaly patients and the impact of IGF-1 levels and body composition parameters in pathology in some of these comorbidities.

Supplementation with myo-inositol and Selenium improves the clinical conditions and biochemical features of women with or at risk for subclinical hypothyroidism.

Purpose: The present study aims to evaluate the effect of myo-Inositol plus Selenium supplementation in patients affected by subclinical hypothyroidism. Methods: One hundred and forty-eight patients were included in the study from 8 different centers of Slovakia, and treated for 6 months with a daily dose of 600 mg myo-Ins plus 83 mcg Se. The patients included at the enrollment were women of reproductive age (18-50), who exhibit values of TSH in the range 2.5-5 mU/l and positivity to antibodies TPO-Ab/TG-Ab, or otherwise values of TSH in the range 5-10 mU/l both with and without positivity to antibodies TPO-Ab/TG-Ab. Results: Patients affected by subclinical hypothyroidism exhibited a significant improvement of their condition when treated for 6 months with a combination of myo-Inositol and Selenium. The TSH values significantly ameliorated along with the index of autoimmunity and the thyroid status. In a sub-class of patients, the auto-antibody titer decreased after myo-inositol + Selenium administration. The treatment also induces a regularization of the menstrual cycle and a reduction of the cholesterol in the patients enrolled for the study. Furthermore, a significant improvement is observed in the perception of the symptoms associated with subclinical hypothyroidism over the treatment period. Conclusion: A dietary supplementation with of myo-Inositol and Selenium in the treatment of patients affected by subclinical hypothyroidism exhibits a beneficial role in the recovery of TSH values, in the improvement of the symptoms associated to this condition and in the maintenance of the thyroid functions.The trial was approved by the Ethical Committee from National Institute of Endocrinology and Diabetology of Lubochna, Slovakia, date 18.12.2018, registration number: 3124/2018.

Pegvisomant in the treatment of acromegaly.

Despite improvements in surgical techniques, current radiotherapy options and development of long-acting somatostatin analogues, biochemical control of acromegaly is not achieved in some patients. The failure to achieve optimal serum growth hormone (RH) and insulin-like growth factor-1 (IGF-1) levels means increased morbidity and mortality of acromegaly patients. The RH receptor antagonist pegvisomant (PEG) is a genetically engineered RH analog that prevents of RH receptor dimerization, i.e. a process that is crucial for the action of RH at the cellular level. The effect of the treatment is suppression of IGF-1 production. In pilot studies, normalization of IGF-1 levels was achieved in up to 90 % of patients receiving PEG. However, PEG efficacy in clinical settings is slightly lower (65 to 97 %) than reported in the key studies. A rare side effect of treatment is elevations of liver transaminases. In addition, pituitary tumor growth progression has been reported in several cases. In this review article, we present long-term data on pegvisomant treatment and discuss its associated risks and benefits.

Changes in Cross-Sectional Area of the Median Nerve and Body Composition Parameters after Treatment of Acromegaly: 1 year Follow-Up.

Objective: Median neuropathy is a common manifestation of acromegaly, although its pathology is uncertain. Changes in levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) and body composition are potential parameters in pathology of median neuropathy in acromegaly. We aimed to assess changes in the cross-sectional area (CSA) of the median nerve and body composition in newly diagnosed acromegalic patients 1 year after treatment and to determine their mutual relationships. Design: This prospective study included 30 patients with newly diagnosed acromegaly and 30 healthy controls matched for age, gender, and body mass index. Physical and laboratory examinations, dual-energy X-ray absorptiometry (DXA), and ultrasound evaluations were performed at baseline and 1 year after initial treatment. Results: The CSA of the median nerve was increased in acromegalic patients compared with controls (13.1 mm2 [12.2-14.9] vs 7.5 mm2 [6.4-8.4], P < 0.001). One year after treatment of acromegaly, GH and IGF-I levels decreased significantly. The median nerve CSA was significantly reduced after treatment (11.6 mm2 [10.2-13.1], P < 0.001). Reduction of IGF-I levels correlated with a decrease in lean mass and increase in fat mass. The median nerve CSA positively correlated with IGF-I levels (R = 0.492, P=0.006) and lean mass (R = 0.419, P=0.021) in acromegalic patients before treatment. Conclusion: This study demonstrates a reduction in the median nerve CSA 1 year after treatment of acromegaly. These changes are closely associated with a reduction in IGF- I levels and in lean body mass. The enlargement of the median nerve in acromegaly can be reversed with adequate treatment.

An atypical cause leading to a diagnosis of acromegaly.

Not required for Clinical Vignette.

Multiple idiopathic external cervical root resorption in patient treated continuously with denosumab: a case report.

BACKGROUND: External root resorption is an irreversible loss of dental hard tissue as a result of odontoclastic action. Multiple external cervical root resorptions in permanent teeth are rare. The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts. CASE PRESENTATION: This case report demonstrates aggressive and generalized idiopathic external cervical root resorption that started and advanced during ongoing antiresorptive therapy with the human monoclonal RANKL-blocking antibody denosumab without discontinuation of therapy in a 74-year-old female patient treated for postmenopausal osteoporosis. The extent of resorptive defects was too large and progressively led to fractures of the teeth. The number of teeth involved and the extend of destruction excluded conservative treatment. The affected teeth had to be extracted for functional prosthetic reconstruction. CONCLUSIONS: This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.

Vertebral Fractures Occur Despite Control of Acromegaly and Are Predicted by Cortical Volumetric Bone Mineral Density.

CONTEXT: Recent studies suggest that cortical bone could also play a role in vertebral fracture (VF) development in acromegaly. OBJECTIVE: Evaluate the occurrence of VFs and their relationship to dual energy x-ray absorptiometry-derived bone parameters. METHODS: A single-center 2-year prospective study of acromegaly patients was conducted. Each subject had L1-4 spine, femoral neck and total hip (TH) areal BMD measured using DXA, and trabecular bone score (TBS) measurement performed. 3D Shaper™ was used to assess proximal femur trabecular and cortical volumetric (v)BMD, cortical surface (s)BMD, and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using a semiquantitative approach. Study outcomes were assessed at 2 time points: baseline and month 24. RESULTS: 70 acromegaly patients (34 M/36F; average 55.1 years) were studied, including 26 with active disease. In 13 patients, 9 with controlled disease, VF was observed. A decrease in TBS, sBMD, neck trabecular vBMD, TH, and neck cortical vBMD in VF compared with non-VF subjects was observed (P < .05). Multivariate analysis of fracture prediction showed TH cortical vBMD as the best fracture prediction parameter with area under the curve of 0.774. TBS was negatively associated with fasting plasma glucose and glycated hemoglobin (HBA1c) at each time point during the follow-up. CONCLUSION: From the total number of 13 VF subjects, 9 were in the controlled disease group. The most sensitive and specific predictor of incident VF was TH cortical vBMD, suggesting that cortical bone is involved in fracture development.

Two rare endocrinological diagnoses in one patient.

Not required for Clinical Vignette.

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

Introduction: Patients with primary adrenal insufficiency receive long - term glucocorticoid replacement therapy, which may cause osteoporosis.

AIM OF THE STUDY: The aim of the study was to assess the effect of glucocorticoid replacement therapy in patients with Addison´s disease on bone mineral density (BMD), parameters of calcium - phosphate (Ca-P) metabolism as well as on bone turneover markers. PATIENTS AND METHODS: The study group consisted of 46 patients with Addison´s disease (12men, 17 pre- and 17 postmenopausal women, the control group consisted of 44 healthy individuals (8 men, 16 prepre- and 16 postmenopausal women). Ca-P metabolism parameters, bone turnover markers and adrenal hormones were examined in all groups. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine (BMD lumb) and forearm (BMDfore). RESULTS: We did not confirm an increased prevalence of osteoporosis and osteopenia in patients with Addison´s disease. BMD values did not correlate with hydrocortisone (HCT) doses, HCT doses calculated on body weight and body surface area as well as with duration of substitution treatment. Patients with daily HCT doses > 25 mg had significantly lower BMD in lumbar spine compared with patients with daily HCT doses 25 mg. In study group we observed decreased levels of adrenal androgens, in women also estradiol. Decreased level of serum calcium and increased level of osteocalcin, bone alkaline phosphatase, 25- hydroxyvitamin D were present in women with Addison´s disease. RANKL/OPG ratio was higher in patients with Addison´s disease compared with controls. CONCLUSION: Glucocorticoid replacement therapy is not a significant risk factor for development of osteoporosis in patients with Addison disease, because this therapy only physiologically replaces endogenous cortisol deficiency. An increased RANKL / OPG ratio may indicate a relative lack of OPG. It is possible that female patients, despite adequate substitution, have an increased bone turnover and a relatively higher risk of decrease in BMD. Potential risks are higher doses of glucocorticoid replacement therapy (HCT > 25 mg daily) and a typical steroid constellation (decreased adrenocortical androgens DHEA and DHEAS and in women also estradiol).

Heart failure as a manifestation of acromegaly.

Acromegaly is a rare disease with incidence of 3-4 patients per 1 000000 per year, which is mainly caused by benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF-1) levels accompanying this disease is associated with rheumatologic, cardiovascular, pulmonary and metabolic complications. Cardiovascular complications of acromegaly include a cardiomyopathy, arterial hypertension, arrhytmias, valvulopathy as well as endothelial dysfunction. Cardiovascular diseases are the leading cause of mortality in patients with acromegaly. An early diagnosis of acromegaly significantly influences both morbidity and mortality of patients suffering from this disease. We describe a 39-year-old patient with undiagnosed acromegaly presented with acute heart failure caused by acromegalic cardiomyopathy.

Cushings syndrome and acromegaly based on picoadenoma of the pituitary gland.

Cushings syndrome (CS) is a relatively rare disease characterized by autonomous hypersecretion of cortisol. The incidence of CS is estimated to be equal to 2-3 cases per million inhabitants per year. The incidence of acromegaly is 3-4 patients per 1 000 000 per year. The disease is caused by hypersecretion of growth hormone which is mainly caused by benign tumour of the pituitary gland. In our case report we present a 41- year old woman suffering from both Cushings syndrome and acromegaly. The patient was examined in National Institute of Endocrinology and Diabetology Ľubochňa for a centripetal type of obesity and hirsutism. Laboratory tests revealed high plasma cortisol levels without circulating variation, hypercortisoluria and elevated plasmatic levels of ACTH. A 2 mg dexamethasone blockade was performed without adequate cortisol suppression in serum and urine up to 8 mg blockade resulted in suppression of 24 hour urine free cortisol. A magnetic resonance imaging (MR) scan revealed suspect pikoadenoma of the pituitary gland (size 2mm). Subsequently trans-sphenoidal resection was performed. Histopathological and immunohistochemical examinations did not reveal the ACTH-producing pituitary adenoma. After surgery hypercortisolism persisted with newly revealed hypersomatotropism. Treatment with Ketoconazole at dose 200mg 1/ 2-0-1 and somatostatin analogues (Lanreotide) at dose 120mg every 42 days were initiated. Control magnetic resonance imaging of the sella demonstrated small tumour of pituary gland of size 3×5mm. Later 3 years after first surgery another trans-sphenoidal resection of residue was performed. Histological and immunohistochemical examinations did not confirm adenoma with ACTH and RH secretion. After second surgery, IGF-1 plasma levels were not normalized with persistence of hypercortisolism. The treatment with Lanreotide at the initial dose as well as Ketoconazole was reinitiated (with increased dose of Ketoconazole to 1-1-1 tbl per 200mg).

The combination of acromegaly and Klinefelter syndrome in one patient.

Acromegaly is a rare disorder usually caused by a benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF1) levels accompanying this disease is associated with complications such as cardiomyopathy, diabetes mellitus, sleep apnoea and arthropathy. Incidence of acromegaly is 3-4 patients per million per year. Klinefelter syndrome (KS) is the most common sex chromosome disorder occuring in about 1/500 live male births. Common physical features include particularly small testes, among other symptoms are tall stature, reduced muscle tone, delayed pubertal development, lack of secondary male sex characteristics and gynecomastia. We present a 32-year-old man suffering from both acromegaly and 47, XXY Klinefelter syndrome. The patient with typical acromegalic features. Laboratory tests revealed high level of GH which was not suppressed after glucose administration, high level of IGF1, low testosterone concentration with high concentation of luteinizing hormone and follicle stimulating hormone. A magnetic resonance imaging scan revealed a 25 × 18 × 18 mm macroadenoma involving the pituitary gland. A diagnosis of acromegaly was established. After this examination trans-sphenoidal resection was performed. Histopathologic and immunohistochemical findings revealed growth hormoneproducing pituitary adenoma. The presence of infertility with clinical features such as small testes, lack of secondary male sex characteristics and laboratory findings revealed hypergonadotropic hypogonadism that could not be explained by the diagnosis of acromegaly. A chromosomal karyotyping revealed a 47, XXY, confirming the diagnosis of KS. Testosterone replacement therapy wasn´t begun because of patient disagreement Postoperatively elevated plasma concentration of GH and IGF1 levels persist. Treatment by somatostatin analogues (lanreotid) was initiated at dose 120 mg every 28 days. Control magnetic resonance imaging of the sella demonstrated a residue of pituary adenoma size 14 × 14 × 7 mm. The patient is currently undergoing endoscopic revision of the residue. acromegaly - growth hormone - IGF1 - Klinefelter syndrome - testosterone.

Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study.

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach. Results One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07-6.78), 2.84 (1.24-6.51) and 2.38 (1.11-5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model. Conclusions Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.

High Serum Fractalkine is Associated with Lower Trabecular Bone Score in Premenopausal Women with Graves' Disease.

Chemokine CX3CL1 (fractalkine) may be an important factor linking thyroid status and bone remodeling, through tetrac, a derivative of thyroxine. This study explores the relationship between serum fractalkine levels and parameters of thyroid status and bone in premenopausal women with Graves' disease (GD) in comparison to healthy controls. This cross-sectional study included three premenopausal female groups: active GD; cured GD, and healthy age-, gender-, and BMI-matched controls. Measurement of serum fractalkine levels (Quantikine® ELISA), total amino-terminal peptide of procollagen type 1 (P1NP), CTx, thyroid hormones, BMD and trabecular bone score (TBS) were performed in all study subjects. Sixty women (21, 16, and 23 in active GD, cured GD, and healthy control groups, respectively) were included. Serum fractalkine levels were higher (p<0.05) in active and cured GD subjects compared to healthy controls (mean 0.7±0.14; 0.93±0.15, and 0.48±0.13 ng/ml, respectively). Lumbar spine BMD was lowest in the cured GD group in comparison to active GD and control group subjects (0.926±0.03; 1.016±0.03; 1.051±0.03 g/cm2; p<0.05, respectively). TBS was lower (p<0.05) in both GD groups than controls being lowest in those with active GD (1.395±0.02; 1.402±0.02, 1.469±0.02, respectively). Serum fractalkine concentration was positively correlated with fT4, and negatively correlated with TBS values. GD in pre-menopausal females is associated with increased serum fractalkine concentration and decreased TBS. Fractalkine may be a currently unappreciated link between hyperthyroidism and bone; further research into this possibility is needed.

[Rare combination of Turner syndrome and congenital adrenal hyperplasia with 21-hydroxylase deficiency: case report]. / Raritná kombinácia Turnerovho syndrómu a kongenitálnej adrenálnej hyperplázie s deficitom 21-hydroxylázy: kazuistika.

Combination of Turner syndrome (TS) and classic congenital adrenal hyperplasia (CAH) is rare. Globally, the incidence of CAH, autosomal recessive disorder caused by enzyme defect of steroidogenic pathway, is very low (1 : 10 000-16 000). 90 % of CAH cases are caused by 21-hydroxylase gene mutation (CYP21A2). Globally, the incidencie of Turner syndrome reaches 1 : 2 500. Phenotypically, females with TS may render wide spectrum of clinical features. Dominant symptoms are lowered terminal height and gonadal dysgenesia, ultimately leading to absence of puberty and infertility. Virilisation may be evident among TS women with chromosome Y 45, X/46, XY. We present a 57 year old woman suffering from both TS 45, X/46, XX and 21-hydroxylase deficiency. Based on the intersex, she was misdiagnosed as a male after the birth. Dominant signs were intrauterine growth retardation and Prader 5 virilisation of the external genitalia. Testes were not palpable. Laparoscopy at the age of 6 showed uterus and ovaries. After this examination, clitoroplasty and vaginoplasty was performed. Karyotyping revealed a 45, X/46, XX pattern. The presence of virilising features at the time of puberty however could not be explained with the diagnosis of Turner syndrome. Laboratory tests revealed elevated level of 17-hydroxyprogesterone, dehydroepiandrosterone with low cortisol concentration and elevated ACTH. With the genomic analysis CYP21A2 gene, namely IN2G (IVS 2-13 A/C>G), large deletion/conversion was detected. Glucocorticoid treatment was initiated. Due to increased plasma renin concentration, fludrocortisone therapy was also initiated. Within this therapy, patient´s state improved significantly.Key words: congenital adrenal hyperplasia - CYP21A2 - Turner syndrome - 21-hydroxylase deficiency.

[Virilization as demonstration of hypertestosteronism by ovarian tumor: case report]. / Virilizácia ako prejav hypertestosteronizmu pri ovariálnom tumore: kazuistika.

Hypertestosteronism as part of hyperandrogenic states in women is generally defined as abundance of male hormones (in this case abundance of testosterone). Spectrum of clinical symptoms include menstrual disorders, amenorrhoea, different range of hirsutism and virilization. Statistically, most androgen secreting tumors are ovarian aetiology (testosterone secreting tumors located in suprarenal gland are very rare). This rare tumor may produce excess amounts of testosterone, as well as its precursor androstenedione. The highest incidence is between 20-40 years and in postmenopausal period. The treatment is essentially surgical; with gradual adjustment of the hormones.Key words: androgen secreting ovarian tumors - hyperandrogenic states - testosterone - virilisation.

Intraoperative calcitonin stimulation testing in the surgical treatment of C-cell disease.

OBJECTIVE: The prognosis of medullary thyroid carcinoma (MTC), derived from parafollicular C-cells, depends on the completeness of the initial surgical excision. The C-cells produce calcitonin, a peptide hormone used as a biochemical and immunohistochemical tumor marker. The aim of the study was to evaluate an individualized approach to patients with C-cell disease, i.e. MTC and C-cell hyperplasia (CCH), using the intraoperative calcitonin testing-assisted surgical strategy as a predictor of the final outcome. STUDY DESIGN: A unicentre cross-sectional study. METHODS: From June 2009 to May 2015, thirty one patients with MTC/CCH were surgically treated primarily (n=24) or reoperated for persistence of the disease (n=7). Depending on the result of intraoperative calcitonin stimulation testing (iCST), patients underwent total thyroidectomy with or without lymph node dissection. All patients were tested repeatedly in the postoperative period (range 1 to 48 months). RESULTS: The iCST was true negative in all CCH, and ten out of eleven N0 MTC primarily operated patients, and true positive in one N0 patient and six of the seven reoperated patients. The test was false negative in two patients preoperatively evaluated as N+, one primarily operated and one reoperated, respectively. CONCLUSION: The results encourage the use of an individualised approach on patients with MTC/CCH, e.g. to be less radical surgically in cases of negative iCST, and to be more radical in those patients with persistent increase of serum calcitonin. The absence of post-stimulation calcitonin elevation in iCST seems to be a good prognosis indicator in patients with an early-stage C-cell disease, but longer follow-up is needed.

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood]. / Problematika sekundárnej osteoporózy pri deficite rastového hormónu v dospelosti.

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.