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.

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.

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.

The role of vaspin as a predictor of coronary angiography result in SCAD (stable coronary artery disease) patients.

BACKGROUND: The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive. METHODS: The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed. The patients were divided into subgroups according to their pre-test probability (PTP) and according to the result of coronary angiography. Fasting vaspin concentrations were compared between subgroups of SCAD patients and between target group and controls. The effect of age and smoking on the result of coronary angiography was compared to the effect of vaspin using the binomial regression. RESULTS: We did not find significant difference in vaspin level between target group and controls. Unless the pre-test probability was taken into account, we did not find vaspin difference in the target group, when dividing patients on the basis of presence/absence of significant coronary stenosis. In the subgroup of SCAD patients with PTP between 15% - 65%, those with significant coronary stenoses had higher mean vaspin concentration (0,579 ± 0,898 ng/ml) than patients without significant stenoses. (0,379 ± 0,732 ng/ml) (t = -2595; p = 0,012; d = 0,658; 1-ß = 0,850). Age, smoking status and vaspin significantly contributed to the HSCS prediction in binomial regression model in patients with low PTP (OR: 1.1, 4.9, 8.7, respectively). CONCLUSION: According to our results, vaspin cannot be used as an independent marker for the presence of CAD in general population. However, our results indicate that measuring vaspin in SCAD patients might be clinically useful in patients with PTP below 66%.

["Snags" connected with establishing the vitamin D]. / Úskalia stanovenia vitamínu D.

OBJECTIVE: The aim of proposed paper was to compare a three total 25-hydroxy-vitamin D immunoassays to that of HPLC with UV detection. MATERIAL AND METHODS: Serum 25-(OH) D levels were measured from blood samples of 109 patients with different immunoassays (ABBOTT, ROCHE, SIEMENS) and method of HPLC which was chosen as the reference. In the first step immunoassays were compared to HPLC. In the second step immunoassays were compared to each other. Further purpose of methods comparison the Passing-Bablok regression and Bland-Altman analysis were used. The limits of maximum acceptable differences were set at 21.5 %, according to Vitamin D Standardization-Certification Program (VDSCP). In the last step, the concordance in the interpretation of measured results was evaluated. RESULTS: None of the examined 25-(OH) D immunoassays was comparable to HPLC and to each other. Bland-Altman analysis revealed, in comparison to HPLC, that ROCHE showed positive bias +28.0 %, ABBOTT +0.2 % and SIEMENS -23.4 %. Although average bias of ABBOTT immunoassay is insignificant, particular results do deviate significantly (-89.4 % to 89.0 %). The concordance in the interpretation of measured results, in comparison to HPLC, was highest with ABBOTT (65.21 %), then with ROCHE (59.63 %) and lowest with SIEMENS (47.79 %). CONCLUSION: The results of the proposed papers suggest low levels of 25-(OH) D immunoassays standardization and an alternative to use assay-specific decision limits.

[Parathyroid cancer]. / Karcinóm pristítneho telieska.

Parathyroid cancer is a rare endocrine malignancy, representing less than 1 % of all cases of primary hyperparathyroidism. The exact etiology of the disease remains unknown. Known risk factors include neck irradiation, end stage renal failure, genetic factors, particularly the the HPRT2/CDCT73 gene mutation. The clinical picture is often indolent, yet progressive with a trend of local invasion and metastasis formation in advanced disease. The clinical picture includes symptoms of severe and resistant hypercalcemia, requiring intensive therapy often with the need of dialysis. Radical surgery is the mainstay of the parathyroid cancer treatment. Chemotherapy and radiotherapy are generally ineffective. An early and correct diagnosis of parathyroid carcinoma significantly influences both morbidity and mortality.Key words: diagnosis - hyperparathyroidism - parathyroid cancer - treatment.

[Bone quality in patients with acromegaly]. / Kvalita kosti u akromegalikov.

The impact of acromegaly on bone and the risk of fractures has not been sufficiently investigated. GH hypersecretion stimulates bone turnover, leading to an increase in bone turnover markers. Normal or even increased bone mineral density (BMD) in comparison to healthy controls have been reported, but there are some works where decreased BMD was observed among acromegaly patients with hypogonadism, particularly at lumbar spine. Less pronounced effect of GH overproduction was observed at the femoral neck, as explained by the positive effect of hypersecretion on the cortical bone (due to periosseal ossification). Several studies have documented morphometric vertebral fractures (VF) in 1/3 of acromegaly patients. The major risk factors leading to the development of VF include hypogonadism, diabetes mellitus and previous VF. Because the risk of fractures does not correlate with BMD most of the studies are currently focused on bone quality, bone strength and microstructure.Key words: bone microstructure - growth hormone - IGF1 - vertebral fractures.

[Diabetic Kidney Disease 3rd stage - laboratory markers of mineral bone disorder]. / Diabetické ochorenie obliciek 3. stádia - laboratórne markery minerálovej a kostnej poruchy.

BACKGROUND: Diabetes mellitus is the most common cause of end stage kidney disease in the developed countries. Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops with deteriorating of the renal functions. Diabetic patients on hemodialysis are characterized by low bone turnover, higher prevalence of severe and progressive vascular calcification with increased cardiovascular morbidity and mortality. The main factor which causes vascular calcification in patients with diabetic kidney disease (DKD) is poor glycemic control. The recent trial findings describe an inverse correlation between intact parathyroid hormone (iPTH) serum levels and glycemic control in a group of diabetic patients on hemodialysis. AIM: The objective of the proposed project is to access the difference of the laboratory markers MBD in the group of patients with 3rd stage DKD depending on glycemic control. We focused on the relationship between the glycemic compensation of diabetes (HbA1c) and iPTH serum level. PATIENTS AND METHOD: Ninety one patients with 3rd stage DKD were investigated. There were 46 women (50.5 %) and 45 men (49.5 %), average age of patients was 71.2 ± 7.0 years, with creatinine level 128 ± 30 µmol/l and estimated glomerular filtration (eGF, MDRD) 0.82 ± 0.16 ml/s. There were 60 patients with better glycemic control of diabetes (HbA1c < 7 %) vs 29 patients with poorly controlled diabetes (HbA1c > 7 %). MBD markers were compared in both groups. Patients were further stratified into subgroups based on the serum level of iPTH (iPTH < 35 pg/ml vs iPTH > 35 pg/ml) and MBD markers compared. Statistical analysis was performed using and Mann-Whitney test. RESULTS: We have found the statistical significance in the serum phosphate and proteinuria levels in between groups with HbA1c < 7 % vs patients with HbA1c > 7 %. Diabetics with better glycemic control had significant reduction in serum phosphate level (1.14 ± 0.20 vs 1.23 ± 0.18 mmol/l, p = 0.038) and in 24 hrs proteinuria level (0.56 ± 1.35 vs 1.30 ± 1.61 g/day, p = 0.007). In the group of presumed low bone turnover (iPTH < 35 pg/ml) we have found the trend towards increased serum calcium level (2.49 ± 0.12 vs 2.43 ± 0.10 mmol/l, p = 0.063) and increased HbA1c value (7.5 ± 1.8 vs 6.4 ± 1.6 %, p = 0.023). CONCLUSION: Our results suggest the closer relationship between glycemic control of diabetes and mineral-bone disorder in earlier stages of DKD. KEY WORDS: diabetes mellitus type 2 (DM2T) - chronic kidney disease (CKD) - mineral and bone disorder (MBD).

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.

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.

Prevalence of Positivity for Diabetes-Associated Autoantibodies in Individuals with Type 2 Diabetes and Their Further Characterisation: Cross-sectional Study from Slovakia.

BACKGROUND: Individuals initially diagnosed with type 2 diabetes (T2D) might exhibit positivity for diabetes-associated autoantibodies (DAA +). We investigated the prevalence of DAA positivity in a group of individuals with T2D who were referred to a tertiary diabetes centre within a pre-specified period of time. We aimed to identify characteristics linked with DAA positivity by comparing DAA + individuals with their DAA-negative counterparts. METHODS: This was a cross-sectional study into which all T2D patients referred to the National Institute of Endocrinology and Diabetology, Lubochna, Slovakia, between 1 January and 30 June 2016 were included. Data on > 70 participants' characteristics, including antibodies against glutamic acid decarboxylase (anti-GAD65), insulinoma-associated antigen IA-2 (IA-2A) and insulin (IAA), were collected. RESULTS: Six hundred and ninety-two individuals (387, 55.6% female) with a median (range) age of 62 (24-83) years, HbA1c of 8.9 (5.0-15.7)% [74 (31-148 mmol/mol)] and diabetes duration of 13.0 (0-42) years were analysed. One hundred and forty-five (145/692, 21.0%) tested positive for at least one DAA; 136/692 (19.7%) were positive for anti-GAD65, 21/692 (3.0%) were positive for IA-2A and 9/692 (1.3%) were positive for IAA. Only 84.9% of the DAA + individuals aged > 30 years at the time of diabetes diagnosis met the current diagnostic criteria for latent autoimmune diabetes of adults (LADA). DAA + differed from DAA - individuals in multiple characteristics, including the incidence of hypoglycaemia. CONCLUSION: Several pathological processes linked with distinct types of diabetes can develop in parallel, including insulin resistance and autoimmune insulitis. In this single-centre cross-sectional study from Slovakia, we report a higher than previously published prevalence of DAA positivity in a group of individuals with a formal diagnosis of T2D.

An atypical cause leading to a diagnosis of acromegaly.

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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.

Two rare endocrinological diagnoses in one patient.

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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.

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.