Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study.

CONTEXT: Pheochromocytoma and sympathetic paraganglioma (PPGL) are rare catecholamine-secreting tumors but recent studies suggest increasing incidence. Traditionally, PPGL are described to present with paroxysmal symptoms and hypertension, but existing data on clinical presentation of PPGL come from referral centers. OBJECTIVE: We aimed to describe time trends in clinical presentation and incidence of PPGL in a population-based study. METHODS: We conducted a nationwide retrospective cohort study of a previously validated cohort of 567 patients diagnosed with PPGL in Denmark 1977-2015. We collected clinical data from medical records of a geographic subcohort of 192 patients. We calculated age-standardized incidence rates (SIRs) and prevalence for the nationwide cohort and descriptive statistics on presentation for the subset with clinical data. RESULTS: SIRs increased from 1.4 (95% CI 0.2-2.5) per million person-years in 1977 to 6.6 (95% CI 4.4-8.7) per million person-years in 2015, corresponding to a 4.8-fold increase. The increase was mainly due to incidentally found tumors that were less than 4 cm and diagnosed in patients older than 50 years with no or limited paroxysmal symptoms of catecholamine excess. On December 31, 2015, prevalence of PPGL was 64.4 (CI 95% 57.7-71.2) per million inhabitants. Of 192 patients with clinical data, 171 (89.1%) had unilateral pheochromocytoma, while unilateral paraganglioma (n = 13, 6.8%) and multifocal PPGL (n = 8, 4.2%) were rare. CONCLUSION: Incidence of PPGL has increased 4.8-fold from 1977 to 2015 due to a "new" group of older patients presenting with smaller incidentally found PPGL tumors and few or no paroxysmal symptoms.

Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS: In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (1:1:1) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distal forearm after 1 year. Additionally, effects on bone-metabolic biochemistry were explored. Patients and investigators were masked. All enrolled patients were included in efficacy analyses. The trial was done in an outpatient setting and is registered at ClinicalTrials.gov, NCT03027557, and has been completed. FINDINGS: Between March 14, 2017, and March 16, 2018 we recruited 285 participants. 16 patients were randomly allocated to the denosumab group, 15 to the combination group, and 15 to the placebo group. Dropout was limited to one patient in the combination group. Compared with placebo, BMD improved in groups receiving denosumab: lumbar spine (combination group 5·4% [95% CI 2·7-8·1], denosumab group 6·9% [95% CI 4·2-9·6]; p<0·0001), total hip (combination group 5·0% [3·0-6·9], denosumab group 4·1% [2·5-5·8]; p<0·0001), and femoral neck (combination group 4·5% [1·9-7·9]; p=0·0008, denosumab group 3·8% [1·4-6·3]; p=0·0022]). Changes in BMD at the third distal forearm were borderline significant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION: Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. FUNDING: Aalborg University Hospital and Aalborg University, Denmark.

Associations between trabecular bone score and biochemistry in surgically vs conservatively treated outpatients with primary hyperparathyroidism: A retrospective cohort study.

PURPOSE: Trabecular Bone Score (TBS) is a software-based method for indirect assessment of trabecular bone structure of the spine, based on analysis of pixels in dual energy x-ray absorptiometry (DXA) images. Few studies describe the use of TBS in patients with primary hyperparathyroidism (PHPT). This study aimed at further describing this relationship, investigating possible correlations between biochemistry, body mass index (BMI), fracture incidence and TBS. METHODS: Cross-sectional study of 195 patients with verified PHPT, surgically (27) or conservatively (168) treated at the Department of Endocrinology, Aalborg University Hospital. TBS was acquired by reanalyzing DXA-images of the included subjects from the outpatient clinic. Biochemical variables were obtained from clinical routine blood samples taken in relation to the DXA-scans. History of fractures and medical history was obtained from radiology reports and medical charts. RESULTS: Patients with active PHPT had a TBS-score signifying a partly degraded bone structure, whereas surgically treated patients had a normal bone structure as judged by TBS, though the difference in TBS-score was not statistically significant. Use of antiresorptive treatment was negatively associated with BMD but not TBS. No correlations between the biochemical variables and TBS were found. A negative correlation between TBS and BMI in patients with PHPT was present. Patients experiencing a fragility fracture had a significantly lowered TBS, BMD and T-Score. CONCLUSION: Biochemistry does not seem to predict bone status in terms of TBS in patients with PHPT. TBS is negatively correlated to BMI, which is also seen in patients not suffering from PHPT. The lack of a predictive value for antiresorptive treatment for TBS may raise concern. TBS appears to have a predictive value when assessing risk of fracture in patients with PHPT. MINI ABSTRACT: This cross-sectional study investigates possible correlations between biochemical variables, body mass index (BMI) and trabecular bone score (TBS) in 195 patients with primary hyperparathyroidism. It finds no correlation between biochemical variables and TBS, but finds a negative correlation between TBS and BMI and a clear association between fracture incidence and low TBS-score.

Pheochromocytoma in Denmark during 1977-2016: validating diagnosis codes and creating a national cohort using patterns of health registrations.

BACKGROUND: Pheochromocytoma and catecholamine-secreting paraganglioma (PPGL) are rare but potentially life-threatening tumors. We aimed to validate diagnosis codes for PPGL in the Danish National Patient Registry, the Danish National Pathology Registry, and the Danish Registry of Causes of Death and to create a national cohort of incident PPGL patients by linking these three registries. PATIENTS AND METHODS: We obtained data from the three abovementioned registries for all individuals registered with pheochromocytoma or catecholamine hypersecretion in Denmark during 1977-2016 (average population 5.30 million). We then reviewed health records for all individuals living in the North Denmark Region and Central Denmark Region (average population 1.75 million) to validate the diagnosis of PPGL. We tested a number of algorithms for accurately identifying true cases of PPGL to maximize positive predictive values (PPVs) and completeness. The best algorithm was subsequently validated in an external sample. RESULTS: We identified 2626 individuals with a PPGL diagnosis code in Denmark, including 787 (30.0%) in the North Denmark Region and Central Denmark Region. In this subsample, we retrieved the health records of 771/787 (98.0%) individuals and confirmed 198 incident PPGL patients (25.3%). The PPV of PPGL diagnosis codes was 21.7% in the Danish National Patient Registry, 50.0% in the Danish Registry of Causes of Death, and 79.5% in the Danish National Pathology Registry. By combining patterns of registrations in the three registries, we could increase the PPV to 93.1% (95% confidence interval [CI]: 88.5-96.3) and completeness to 88.9% (95% CI: 83.7-92.9), thus creating a national PPGL cohort of 588 patients. PPV for the optimal algorithm was 95.3% (95% CI: 88.5-98.7) in the external validation sample. CONCLUSION: Diagnosis codes for pheochromocytoma had low PPV in several individual health registries. However, with a combination of registries we were able to identify a near-complete national cohort of PPGL patients in Denmark, as a valuable source for epidemiological research.

Induction of puberty with human chorionic gonadotropin (hCG) followed by reversal of hypogonadotropic hypogonadism in Kallmann syndrome.

INTRODUCTION: Kallmann syndrome (KS) is a rare, congenital disorder combining hypogonadotropic hypogonadism (HH) due to GnRH-deficiency with anosmia. Traditionally thought to require lifelong therapy it turns out to be a reversible condition in some patients. CASE REPORT: We present a case of a 22-year old man with absent puberty due to KS, in whom genetic testing revealed heterozygosity for a mutation in the PROK2 gene. Pubertal development and virilisation was achieved by using human chorionic gonadotropin (hCG) injections followed by testosterone replacement. During the follow-up we observed reversal of hypogonadism allowing discontinuation of testosterone treatment. Normalisation of testicular volume as well as gonadotropin and inhibin B levels through a 2-year postreversal period was seen. CONCLUSIONS: Treatment with hCG is effective in inducing pubertal development and may have advantage over testosterone replacement due to a potential of gonadal maturation. A regular assessment of testicular volume and biochemical surveillance including measuring of serum inhibin B and gonadotropins are necessary for a timely detection of reversal of GnRH deficiency.

Corrigendum: Contemporary Medical Management of Primary Hyperparathyroidism: A Systematic Review.

[This corrects the article on p. 79 in vol. 8, PMID: 28473803.].

Contemporary Medical Management of Primary Hyperparathyroidism: A Systematic Review.

INTRODUCTION: Primary hyperparathyroidism is increasingly an asymptomatic disease at diagnosis, but the recognized guidelines for management are based on evidence obtained from studies on patients with symptomatic disease, and surgery is not always indicated. Other patients are unable to undergo surgery, and thus a medical treatment is warranted. This systematic review provides an overview of the existing literature on contemporary pharmaceutical options available for the medical management of primary hyperparathyroidism. METHODS: Databases of medical literature were searched for articles including terms for primary hyperparathyroidism and each of the included drugs. Data on s-calcium, s-parathyroid hormone, bone turnover markers, bone mineral density (BMD) and hard endpoints were extracted and tabulated, and level of evidence was determined. Changes in s-calcium were estimated and a meta-regression analysis was performed. RESULTS: The 1,999 articles were screened for eligibility and 54 were included in the review. Weighted mean changes calculated for each drug in s-total calcium (mean change from baseline ± SEM) were pamidronate (0.31 ± 0.034 mmol/l); alendronate (0.07 ± 0.05 mmol/l); clodronate (0.20 ± 0.040 mmol/l); mixed bisphosphonates (0.16 ± 0.049 mmol/l); and cinacalcet (0.37 ± 0.013 mmol/l). The meta-analysis revealed a significant decrease of effect on s-calcium with time for the bisphosphonates (Coef. -0.049 ± 0.023, p = 0.035), while cinacalcet proved to maintain its effect on s-calcium over time. Bisphosphonates improved BMD while cinacalcet had no effect. DISCUSSION: The included studies demonstrate advantages and drawbacks of the available pharmaceutical options that can prove helpful in the clinical setting. The great variation in how primary hyperparathyroidism is manifested requires that management should rely on an individual evaluation when counseling patients. Combining resorptive agents with calcimimetics could prove rewarding, but more studies are warranted.

Quality of life assessment in patients with Graves' disease and progressive infiltrative ophthalmopathy during combined treatment with methylprednisolone and orbital radiotherapy.

INTRODUCTION: The aim of the study was to assess quality of life (QoL) in patients with infiltrative form of Graves' ophthalmopathy (GO) during the combined pulse treatment with methylprednisolone and orbital radiotherapy, and also to search for the relation between the results of ophthalmopathy treatment and changes in QoL. MATERIAL AND METHODS: The study involved 29 patients aged 25-74 (the mean age: 52 +/- 6 years) with infiltrative form of GO. They were classified for ophthalmopathy treatment on the basis of the following factors: the obtained euthyreosis, progressive character of eye changes, the level of eye changes determined on the basis of NO SPECS classification (at least class 3c), ophthalmopathy index (OI) according to Donaldson >or= 4. GO was diagnosed as active if CAS (clinical activity score) >or= 4. During the treatment, the patients received 6 cycles of methylprednisolone sodium succinate in doses of 1,0 g/24 h given as one-hour-long intravenous infusions for three successive days in a week. Between the 2nd and 4th cycle of Solu-Medrol, orbital radiotherapy with 10 MeV X-rays was performed. The control group was made up of healthy volunteers selected with regard to sex, age, educational background and nicotine addiction so as they corresponded with the study group. It involved 53 individuals aged 21-75 (the mean age: 52,4 +/- 14 years). QoL was assessed by means of the MOS SF-36 questionnaire. RESULTS: Patients with GO evaluated their QoL lower than healthy individuals, which referred to physical functioning, physical and emotional role functioning, general health, vitality, social functioning, mental health and bodily pain. No correlation was found between quality of life and such factors as age, sex, or duration time of Graves disease and ophthalmopathy. Analogically, no relation was observed between the activity and stage of clinical development of eye changes and QoL. The use of the combined GO therapy contributed to a considerable decrease in the development of eye changes and the disease activity. After treatment, the patients' QoL improved which referred to physical role functioning, bodily pain, and vitality. Other QoL parameters did not statistically significantly differ. CONCLUSIONS: GO causes a considerable worsening of QoL. The stage of clinical development and activity of GO find no reflection in QoL. Effectiveness of treatment for GO cannot be evaluated on the basis of changes in QoL.

[Preproghrelin gene, ghrelin receptor and metabolic syndrome]. / Gen preproghreliny i receptor ghreliny a zespól metaboliczny.

Obesity is a multi-gene syndrome, expression of which is modulated not only by environmental factors but above all by a number of modified genes interacting with each other. Among candidate genes related to obesity phenotype is ghrelin gene. Ghrelin plays a significant role in feeding regulation and is the strongest stimulator of growth hormone secretion. Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor). Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals. Among identificated mutations, two Arg51 Gln and Leu72Met are most often described and change amino-acid sequence of ghrelin (Arg51Gln) and preproghrelin (Leu72Met). Although no direct relationship between Arg51Gln mutation and obesity phenotype was found, it had been shown that carriers of Arg51Gln mutation had significantly decreased plasma ghrelin levels. Furthermore 51Gln allele carriers had higher prevalence of type 2 diabetes mellitus and hypertension than non-carriers. Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity. No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity. The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects. On the other hand, some mutations in preproghrelin gene could be protective against metabolic syndrome.

[Magnetic resonance imaging and soluble forms of adhesion molecules: sICAM and sVCAM in assessing the activity of thyroid orbitopathy]. / Magnetyczny rezonans jadrowy oraz stezenia rozpuszczalnych form molekul adhezyjnych: sICAM-1 i sVCAM-1 w ocenie aktywnosci orbitopatii tarczycowej.

The aim of this study is to compare two different diagnostic methods (magnetic resonance imaging (MRI) and soluble forms of adhesion molecules: ICAM-1 and VCAM-1 measurement) in assessment of the activity of thyroid orbitopathy (TO) in patients with Graves' disease. 21 patients with infiltrative TO were treated with modified method by Bartalena et al. MRI scans and the measurement of soluble forms of ICAM-1 and VCAM-1 were performed before treatment, after methylprednisolone pulses along with radiotherapy of the retroorbital spaces and after the end of prednisone treatment. MRI scans did not reveal active stage of the disease in 4/21 patients with infiltrative TO, despite elevated levels of sICAM-1 and sVCAM-1. Patients both with active stage of the disease and with the results of MRJ scans revealing fibrotic changes in muscles responded well to therapy parallel with a significant decrease in levels of sICAM-1 and sVCAM-1. Levels of sVCAM-1 increased slightly under prednisone treatment despite improvement of clinical picture of TO, a significant decrease in sICAM-1 levels and in the number of muscles with active inflammatory process on MRI scans. In conclusion, serum levels of ICAM-1 seem to be more sensitive marker than MRI in assessment of the activity of TO. Concentrations of sVCAM-1 do not correspond with the clinical picture of the disease and the results of MRJ during treatment of TO.

[Late diagnosis of a severe attack of acute intermittent porphyria (AIP)--diagnostic dilemmas]. / Pózne rozpoznanie ciezkiego napadu ostrej przerywanej porfirii (AIP)--dylematy diagnostyczne.

The article presents diagnostic problems concerning the case of 54-year old woman with a delayed diagnosis of a severe attack of acute intermittent porphyria (AIP), which on admission manifested mainly as flaccid quadriplegia. The signs of neurological deficit were accompanied by changes in electrocardiographic recording that suggested acute myocardial ischaemia without apparent chest pain. Based upon a detailed history and identification of potential factors that might have triggered the attack the suspicion of acute hepatic porphyria was raised. The suspicion was confirmed by biochemical testing in the Institute of Hematology and Transfusiology in Warsaw. The treatment with glucose was administered, drugs contraindicated in porphyria were excluded, and early rehabilitation programme was instituted, which led to a marked improvement of general status and resolution of quadriplegia after 16 weeks. Parallel to the improvement of neurological status and a decrease in urinary excretion of heme precursors the normalisation of ECG changes was observed. The authors point out that differential diagnosis of abdominal pain with concomitant hyponatraemia should include an attack of acute porphyria since early administration of proper management prevents the development of life-threatening neurological signs accompanying the severe attack. The diagnosis of an attack of acute porphyria in the phase of predominant neurological signs, in the absence of abdominal pain, may be difficult and always warrants, apart from anamnestic data, the confirmation with appropriate biochemical testing.

[Assessment of soluble E selectin levels in patients with Graves' disease and thyroid orbitopathy]. / Analiza stezen rozpuszczalnej postaci E selektyny-1 (sELAM-1) u pacjentów z orbitopatia tarczycowa w przebiegu choroby Graves-Basedowa.

The aim of this study is to evaluate serum concentrations of sELAM-1 in patients with Graves' orbitopathy (GO). We studied levels of soluble form of E selectin -1 in patients with euthyroid progressive GO (group I) and euthyroid stable GO (group II), hyperthyroid Graves' disease (GD) without GO (group III) and in healthy controls (group IV). sELAM-1 levels were measured by ELISA method. The highest serum levels of sELAM-1 were found in group III. Mean sELAM-1 concentrations in patients with progressive and stable GO were slightly lower than those in group III patients. The sELAM-1 serum concentrations in group I and II were comparable, nearly the same despite the different clinical picture of the disease in both groups. Mean serum concentrations of sELAM-1 decreased significantly during treatment of progressive GO, parallel to the improvement of the eye changes. In conclusion, sELAM-1 concentrations do not reflect the degree of GO activity. A significant decrease in sELAM-1 concentrations are associated with the efficient outcome of treatment. Increased sELAM-1 levels seem to result form both GO and GD.

[Plasma leptin levels in relation to body composition and body fat distribution in patients with Cushing's syndrome]. / Stezenie leptyny w osoczu w odniesieniu do skladu tkanek ciala i rozmieszczenia tkanki tluszczowej u pacjentów z zespolem Cushinga.

It is known that body composition, especially body fat content, determines plasma leptin (LEP) levels. Clinical observation confirms that glucocorticoids (GS) have a considerable impact on body composition and body fat distribution which leads to visceral fat accumulation and a decrease in muscle mass in limbs. On the other hand, in experimental models GS stimulate ob mRNA expression in adipose tissue and LEP secretion into bloodstream. The aim of the study was to evaluate changes in body composition and fat and fat-free mass distribution in the conditions of endogenous hypercortisolism as well as to determine whether changes in body composition parameters may influence plasma LEP levels in patients with Cushing's syndrome (CUS). The study group was composed of 14 patients (12 F, 2 M) with ACTH-dependent and ACTH-independent CUS (BMI 29,5 +/- 1,0 kg/m2, aged 41,6 +/- 2,9 yrs.). The control group (KON) included 14 overweight/obese subjects (12 F, 2 M; WHR>0.8) matched for age, height, weight, and BMI with CUS group. Basal plasma LEP levels were measured by RIA kit. Total fat mass (BFM), fat-free mass (FFM), their regional depots (arms, legs, trunk) as well as bone mineral content (BMC) were determined by DEXA method (Lunar Co., USA). Values of BFM and %BF were comparable in both groups whereas the amount of FFM was lower in CUS group than in controls. Patients with CUS had less BF in limbs than controls whereas the difference in the amount of trunk BF in favour of CUS reached a borderline significance. Moreover, subjects with CUS exhibited decreased amount of FFM both in arms and legs when compared to controls, which may be explained by limb muscle and connective tissue wasting observed clinically. However, the amount of trunk FFM did not differ between both groups. Eventually, subjects with CUS had lower BMC values than controls. Absolute plasma LEP levels were 2-fold higher in CUS group than those in KON group (34,03 +/- 4,45 vs. 17,04 +/- 1,88, ng/ml; p=0.006), however, in both groups they were highly correlated with BFM and %BF. Multiple linear regression analysis revealed that in CUS group 64% of the variation of plasma LEP levels is explained by trunk BF and in KON group 92% of the variation of LEP levels is dependent of arms BF (+, 18%) and legs BF (+, 69%) and arms FFM (-, 5%). In conclusion, endogenous hypercortisolismus leads to the augmentation of truncal (visceral) fat accumulation as well as to a marked decrease in fat-free mass in limbs and in bone mineral content. In Cushing's syndrome, irrespectively of its cause (pituitary gland, adrenal glands), plasma LEP levels are elevated in relation to body fat content. Truncal (visceral) fat may have a relatively stronger influence on plasma LEP in Cushing's syndrome than in subjects with normal cortisolaemia, however, changes in body composition and tissue distribution do not fully account for the presence of markedly elevated LEP levels in this syndrome.

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol]. / Ocena stezen leptyny w osoczu i jej zaleznosci z innymi czynnikami hormonalnymi wplywajacymi na zawartosc tkanki tluszczowej u osób z róznymi stezeniami endogennego kortyzolu.

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

[Usefulness of soluble ICAM-1 measurements for the evaluation of the disease activity and efficiency of therapy in patients with infiltrative Graves' ophthalmopathy]. / Przydatnosc oznaczen rozpuszczalnej formy czasteczki adhezyjnej ICAM-1 do oceny aktywnosci choroby i efektów leczenia obrzekowo-naciekowej postaci oftalmopatii tarczycowej w przebiegu choroby Gravesa i basedowa.

The authors studied serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) in patients with progressive Graves' ophthalmopathy (GO), stable GO, hyperthyroid Graves' disease (GD) without GO and in healthy controls. The highest serum concentrations of sICAM-1 were observed in patients with progressive GO. In patients with stable GO and GD mean serum levels of sICAM-1 were elevated to a lesser degree. Mean serum concentrations of sICAM-1 decreased significantly during treatment of patients with the progressive GO parallel to the improvement of the eye changes. In patients with hyperthyroid GD serum levels of sICAM-1 decreased significantly after they had become euthyroid. Mean sICAM-1 level in the euthyroid GD was markedly decreased in comparison to the group of patients with progressive GO and slightly elevated when compared to stable GO. In conclusion, serum levels of sICAM-1 seems to be a good parameter of disease activity in progressive infiltrative GO. The decrease in sICAM-1 concentrations in patients with the progressive GO closely corresponds to the improvement of the clinical picture of the progressive GO.