An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma / Presentación inusual de hiperparatiroidismo primario: múltiples tumores pardos y coexistencia de carcinoma tiroideo

We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography (AU)

Presentamos el caso de un paciente con un cuadro clínico de hiperparatiroidismo primario, con muchas lesiones óseas destructivas sospechosas de metástasis óseas y carcinoma tiroideo multifocal concomitante con un ganglio linfático metastásico central. Se presentó con agravamiento progresivo de dolor y restricción de movimiento en la cadera derecha. La resonancia magnética reveló múltiples lesiones líticas que implicaban principalmente al trocánter menor derecho y a las ramas púbicas izquierdas inferior y posterior. Las pruebas bioquímicas fueron consistentes con un hiperparatiroidismo primario. La ecografía cervical y la gammagrafía paratiroidea revelaron un único adenoma paratiroideo y un nódulo tiroideo, cuya citología preoperatoria confirmó un carcinoma papilar de tiroides, que fue confirmado también por la muestra final obtenida quirúrgicamente. Los resultados bioquímicos, en relación con el hiperparatiroidismo, descendieron a niveles normales tras la cirugía, y los dolores fueron remitiendo gradualmente. La gammagrafía ósea postoperatoria de cuerpo entero reflejó un incremento de captación del radiotrazador en múltiples localizaciones, que resultaron ser metabólicamente inactivas en la tomografía por emisión de positrones con fluorodesoxiglucosa/tomografía computarizada (AU)

An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma.

We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography.

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism.

Cardiometabolic diseases are prevalent in hypogonadism. The pathophysiologic mechanism of increased cardiometabolic risk in hypogonadal patients is not clear. Recently, trace elements have been linked to the development of chronic disease especially cardiovascular disease. We investigated the trace element levels in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and also searched for the relationship with metabolic risk factors. A total of 89 patients with CHH (mean age 21.8 ± 2.0 years) and 80 healthy control subjects (mean age 21.3 ± 1.1 years) were enrolled. The demographic parameters, homeostatic model assessment of insulin resistance (HOMA-IR) levels and plasma zinc, copper, and selenium levels, were measured in patients and healthy controls. The patients had higher waist circumferences (p = 0.014), triglyceride (p = 0.04), insulin (p = 0.004), HOMA-IR levels (p = 0.001), and lower selenium (p = 0.049), zinc (p = 0.004), and copper (p = 0.012) levels when compared to the healthy controls. There was a significant relationship between zinc levels and HOMA-IR levels (p = 0.015). In the regression analysis, zinc levels were independently associated with the calculated HOMA-IR levels (p = 0.015). The results of the present study show that plasma selenium, zinc, and copper levels are decreased in patients with CHH. Also, plasma zinc levels are independently associated with insulin resistance in patients with hypogonadism. Long-term follow-up studies are warranted to investigate the effect of trace elements on the increased cardiometabolic risk in hypogonadism.

Osteoprotegerin, fibroblast growth factor 23, and vitamin D3 levels in male patients with hypogonadism.

Cardiometabolic disorders and osteoporosis are prevalent in patients with hypogonadism. Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF-23), are co-secreted from bones and vascular endothelium, regulating bone mineral metabolism and vascular functions. Vitamin D is another hormone with dual effects on bone and vascular metabolism. The aim of this study was to search for any difference between the serum levels of OPG, FGF-23, and vitamin D in patients with hypogonadism and the healthy controls. We also aimed to search for any relationship between these parameters and endothelial dysfunction or insulin resistance. Forty-nine male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age 20.71 ± 1.75 years) and 43 BMI matched healthy male subjects (mean age 21.37 ± 1.04 years) were enrolled. OPG, FGF-23, vitamin D, and asymmetric dimethylarginine (ADMA) levels were measured from the fasting serum samples. The insulin sensitivity was estimated by homeostatic model assessment-insulin resistance (HOMA-IR) formula. Triglycerides, insulin, HOMA-IR, and ADMA levels in the patient group were significantly higher than the values of the control group (p = 0.014, p = 0.002, p = 0.003, p < 0.001, respectively). The OPG, FGF-23, and vitamin D levels of the patients were not significantly different from the healthy controls. In addition, these markers were not correlated to ADMA or HOMA-IR levels. The results show that young and treatment naive subjects with CHH have endothelial dysfunction and insulin resistance when compared to their healthy counterparts. However, the OPG, FGF-23, and vitamin D levels were similar in the 2 groups. In addition, these parameters are not significantly related to the endothelial functions or insulin resistance in these subjects.

HDL cholesterol subfractions and the effect of testosterone replacement in hypogonadism.

Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.

Women with polycystic ovary syndrome have increased plasma chitotriosidase activity: a pathophysiological link between inflammation and impaired insulin sensitivity?

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated macrophages, has been shown to be involved in chronic inflammatory responses. In the present study, serum chitotriosidase activity and its relationship with insulin resistance were determined in patients with PCOS.34 patients with PCOS and 44 age and body mass index (BMI) matched healthy controls were enrolled in the study. ChT activity was measured by the fluorescence method. High sensitivity C reactive protein (hs-CRP) and adiponectin levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma ChT activity, hs-CRP level and HOMA-IR score were significantly higher (p=0.024, p=0.002, p=0.001, respectively) while plasma adiponectin concentration was significantly lower (p=0.018) in women with PCOS compared to healthy controls. Blood ChT activity correlated positively with age, waist-to-hip ratio (WHR), BMI, hs-CRP, HOMA-IR and negatively with blood adiponectin level. After adjustment for age and BMI, ChT activity, total testosterone level and WHR remained as the independent predictors of HOMA-IR score in logistic regression analysis.ChT activity is increased in patients with PCOS in concordance with insulin resistance. These findings may reflect the pronounced risk for metabolic syndrome and atherosclerotic diseases in this particular patient group.

Metabolic syndrome and the effect of testosterone treatment in young men with congenital hypogonadotropic hypogonadism.

OBJECTIVE: The relationship between metabolic syndrome (MS) and hypogonadism has always been investigated in study groups confounded with aging, obesity or chronic metabolic disorders. So far, there has been no data about the presence of MS in young hypogonadal patients. Also, there is controversial data about the metabolic effects of testosterone replacement therapy. We investigated the frequency of MS in treatment-naïve, young men with congenital hypogonadal hypogonadism (CHH). We also searched for the effect of testosterone replacement on the metabolic profiles of this specific patient group. DESIGN: Retrospective analysis. METHODS: A total of 332 patients (age 21.68 ± 2.09 years) were enrolled. The control group included 395 age- and body mass index (BMI)-matched healthy young men (age 21.39 ± 1.49 years). Standard regimen of testosterone esters (250 mg/3 weeks) was given to 208 patients. RESULTS: MS was more prevalent in CHH (P<0.001) according to healthy controls. The patients had higher arterial blood pressure, waist circumference (WC), triglyceride (P<0.001 for all), fasting glucose (P=0.02), fasting insulin (P=0.004), homeostatic model assessment of insulin resistance (HOMA-IR) (P=0.002) and lower high density lipoprotein (HDL) cholesterol (P<0.001) levels. After 5.63±2.6 months of testosterone treatment, the BMI, WC (P<0.001 for both), systolic blood pressure (P=0.002) and triglyceride level (P=0.04) were increased and the total and HDL cholesterol levels were decreased (P=0.02 and P<0.001 respectively). CONCLUSIONS: This study shows increased prevalence of MS and unfavorable effects of testosterone replacement in young patients with CHH. Long-term follow-up studies are warranted to investigate the cardiovascular safety of testosterone treatment in this specific population.

Cutaneous silent period changes in Type 2 diabetes mellitus patients with small fiber neuropathy.

OBJECTIVE: Small myelinated (A-delta) and unmyelinated (C) somatic sensory fibers are initially affected and may be the earliest exhibited sign of neuropathy in glucose dysmetabolism. Cutaneous silent period (CSP) is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers. The aim of this study was to evaluate CSP changes in Type 2 diabetic patients with small fiber neuropathy. METHODS: Forty-three patients and 41 healthy volunteers were included. CSP latency and duration, as well as CSP latency difference of the upper and lower extremities, were examined. RESULTS: Nerve conduction studies were within normal limits in both groups. Lower extremity CSP latency was longer (122.1+/-15.5 vs. 96.4+/-6.4 ms; p<0.001), CSP duration was shorter (29.5+/-8.9 vs. 43.1+/-5.0 ms; p<0.001), and latency difference was longer (48.1+/-12.6 vs. 22.7+/-3.7; p<0.001) in patients than controls. The difference was more significant in patients with neuropathic pain. No significant difference existed in upper extremity on CSP evaluation. CONCLUSION: The CSP evaluation together with nerve conduction study, has been demonstrated to be beneficial and performance of latency difference in addition to CSP latency and duration may be a valuable parameter in electrophysiological assessment of diabetic patients with small fiber neuropathy. SIGNIFICANCE: An additional CSP evaluation may be considered in cases which nerve conduction studies do not provide sufficient information.

Evaluation of breast enlargement in young males and factors associated with gynecomastia and pseudogynecomastia.

INTRODUCTION: Gynecomastia is defined as a palpable enlargement of the mammary gland in males that is distinguishable from lipomastia. The aim of this study was to assess the prevalence and characteristics of different causes of breast enlargement in young males referred to our tertiary center, and evaluation of the factors associated with gynaecomastia. MATERIALS AND METHODS: One hundred thirty-five male recruits aged 20-30 years were enrolled in the study. A control group comprising 32 age-matched healthy individuals aged 20-25 years was also studied. RESULTS: Idiopathic gynecomastia (IG) was diagnosed in 31 of 135 patients (23%) and Klinefelter' syndrome (KS) was diagnosed in 70 cases (52%). Patients with KS had significantly higher body mass index (BMI) and waist and hip circumference waist/hip ratio than the control group. FSH, LH and SHBG were significantly higher and DHEAS, free testosterone (fT) and total testosterone (tT) were lower in patients with KS than the control group. Anthropometric measurements revealed significant increase in body weight and BMI in patients with IG compared with healthy controls. FSH and LH levels were significantly higher in the patients with IG. Patients with pseudogynecomastia alone were not obese and hypogonadism was observed in 35.1% of patients. CONCLUSION: We concluded that gynaecomastia in young adult males is mostly because of KS or idiopathic in origin. IG seems to be the result of androgen resistance and in part increased aromatization because of increased adiposity. Symptoms or findings for hypogonadism must be evaluated carefully in patients with pseudogynecomastia. We also suggest that the presence of both gynecomastia and azoospermia necessitate further karyotypic analyses for KS.

Ovotesticular disorder of sex development with a prostatic gland and review of literature.

Ovotesticular disorder of sex development (OTDSD) is a rare condition and defined as the presence of ovarian and testicular tissue in the same individual. Most of patients with OTDSD have female internal genital organs. In this report, we present a case in which, we demonstrated prostate tissue using endoscopic and radiologic methods in a 46-XX, sex determining region of the Y chromosome negative male phenotypic patient, with no female internal genitalia. Existence of prostate in an XX male without SRY is rarely seen and reveals a complete male phenotype. This finding is critical to figure out what happens in embryonal period.

Insulin-like growth factor-1 is essential to the increased mortality caused by excess growth hormone: a case of thyroid cancer and non-Hodgkin's lymphoma in a patient with pituitary acromegaly.

The effects of growth hormone are mediated in part by stimulating the production of insulin-like growth factor-1. Insulin-like growth factor-1 has significant effects on cell proliferation and differentiation, it is a potent mitogen, and it is a powerful inhibitor of programmed cell death (apoptosis). Insulin-like growth factor-1 also has a well-established role in the transformation of normal cells to malignant cells. Case reports on a possible association between elevated growth hormone and cancer risk in a variety of patient groups have been published. Here, we describe clinical and laboratory findings for a patient with acromegaly who first developed thyroid cancer, and then, in the follow up period, probably due to poorly controlled insulin-like growth factor-1 levels, developed a large cell non-Hodgkin's lymphoma. A search revealed that a case with these peculiarities had not previously been reported.

Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque.

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Serum sIL-2r, IL-6, IL-10 and TNF-alpha level in familial Mediterranean fever patients.

In this study we investigated cytokine levels in patients with familial Mediterranean fever (FMF). Twenty patients and 20 healthy controls were included. Ten patients had acute attacks of FMF, whereas the other 10 were in the silent period. Patients with the acute exacerbation of FMF had higher soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), tumour necrosis factor-alpha, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen levels than those in the silent period ( P<0.001) and controls ( P<0.001). In patients with acute attacks of FMF, interleukin-10 (IL-10) levels were not significantly different from those in the other patients or the controls ( P>0.05). In FMF patients IL-6, TNF-alpha, sIL-2r, ESR, CRP and fibrinogen levels increased with the acute-phase reaction, especially in the attack period. On the other hand, anti-inflammatory cytokine IL-10 levels did not increase as much as did the inflammatory cytokines. The balance between the cytokines may help us to understand the pathophysiology of FMF and to develop therapies. We conclude that the levels of the acute-phase reactants and the cytokines could be useful for diagnosis of acute exacerbations, follow-up and treatment. However, the cost of cytokine measurement analyses seems disadvantageous at present.