The Link Between Bone Osteocalcin and Energy Metabolism in a Group of Postmenopausal Women.

There is a dual relationship between bone and tissues involved in energy metabolism (fat tissue and beta-pancreatic cells). Thus, bone remodeling is an energy consuming process, but osteocalcin, the main on-collagenic protein, synthesized by osteoblas during bone formation exerts a number of biological effects on beta-pancreatic and adipose cells. With this data, we wanted to see if the presence of a chronic metabolic disorder such as type 2 diabetes mellitus (T2DM) influence this complex dual relationship. For this, we conducted a cross-sectional study to evaluate the relation between osteocalcin and energetic metabolism in a group of 146 postmenopausal womens with and without T2DM at CI Parhon National Institute of Endocrinology, Bucharest. Clinical, metabolic and hormonal parameters were evaluated. For statistical analysis we used Student t-test and the Spearman correlation (statistical significance: p <0.05). Results: 63 patients with T2DM (63.88±8.56 years) and 83 women in the control group (60.21±8.77 years) were included. Diabetic women showed a lower level of serum total osteocalcin (p<0.05) HDL-cholesterol (p=0.02), and 25-hydroxyvitamin D (25(OH)D). The body mass index (BMI), glycemic metabolism parameters and triglyceride levels (p<0.05) were higher in this group. We found correlations between osteocalcin and metabolic elements: negative with BMI (r=-0.329, p<0.05), glycated hemoglobin (HbA1c) (r=-0.398, p<0.05), and serum triglycerides (r=-0.329, p<0.05) respectively positive with HDL-cholesterol (r=0.279, p=0.001) for the entire group of patients. Conclusions: Our study indicated the presence of significant correlations between serum osteocalcin and glycemic and lipid metabolism parameters, independent of the presence of diabetes.

MENOPAUSAL ANDROGEN EXCESS - ASSOCIATED CARDIO-METABOLIC RISK: CLUES FOR OVARIAN LEYDIG CELL TUMOUR (CASE REPORT AND MINI-REVIEW OF LITERATURE).

BACKGROUND: Ovarian Leydig cell tumour is a very rare steroid hormones producing mass, causing clinical and biochemical hyperandrogenism. Even if the level of evidence is based on case studies, many authors (but not all) agree that raised androgens increase the cardio-metabolic risk thus early diagnosis and treatment are necessary On the other hand, the endocrine features pointing an ovarian tumour source of testosterone do not indicate the specific histological finding which needs a post-operative conformation. CASE PRESENTATION: We report a case of a 60-year-old woman with a 4-year history of progressive virilisation in association with hypertension, high number of red blood cells, impaired glucose tolerance and dyslipidemia. Total testosterone was 20 times above normal with suppressed gonadotropins, inadequate for menopause. Trans-vaginal ultrasound and pelvic and abdominal computerized axial tomography imaging revealed a right ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumour. After surgery, androgen levels returned to normal and the doses of anti-hypertensive drugs were reduced. CONCLUSIONS: The hyperandrogenic state with elevated plasma testosterone and progressive signs of virilization raises suspicion of an ovarian androgen-secreting tumor. For a postmenopausal patient with hyperandrogenism the diagnosis of Leydig cell tumour should be considered. However, the exact diagnosis is provided by post-operative histological exam. Prolonged exposure to hyperandrogenism may generate cardiovascular abnormalities and metabolic syndrome which after tumor excision and removal of the source of androgen hormones are expected to significantly improve.

Adrenalectomy for Cushing's syndrome: do's and don'ts.

Aim. To present specific aspects of adrenalectomy for Cushing's syndrome (CS) by introducing well established aspects ("do's") and less known aspects ("don'ts"). Material and Method. This is a narrative review. Results. The "do's" for laparoscopic adrenalectomy (LA) are the following: it represents the "gold standard" for secretor and non-secretor adrenal tumors and the first line therapy for CS with an improvement of cardio-metabolic co-morbidities; the success rate depending on the adequate patients' selection and the surgeon's skills. The "don'ts" are large (>6-8 centimeters), locally invasive, malignant tumors requiring open adrenalectomy (OA). Robotic adrenalectomy is a new alternative for LA, with similar safety and conversion rate and lower pain drugs use. The "don'ts" are the following: lack of randomized controlled studies including oncologic outcome, different availability at surgical centers. Related to the sub-types of CS, the "do's" are the following: adrenal adenomas which are cured by LA, while adrenocortical carcinoma (ACC) requires adrenalectomy as first line therapy and adjuvant mitotane therapy; synchronous bilateral adrenalectomy (SBA) is useful for Cushing's disease (only cases refractory to pituitary targeted therapy), for ectopic Cushing's syndrome (cases with unknown or inoperable primary site), and for bilateral cortisol producing adenomas. The less established aspects are the following: criteria of skilled surgeon to approach ACC; the timing of surgery in subclinical CS; the need for adrenal vein catheterization (which is not available in many centers) to avoid unnecessary SBA. Conclusion. Adrenalectomy for CS is a dynamic domain; LA overstepped the former OA area. The future will improve the knowledge related to RA while the cutting edge is represented by a specific frame of intervention in SCS, children and pregnant women. Abbreviations: ACC = adrenocortical carcinoma, ACTH = Adrenocorticotropic Hormone, CD = Cushing's disease, CS = Cushing's syndrome, ECS = Ectopic Cushing's syndrome, LA = laparoscopic adrenalectomy, OA = open adrenalectomy, PA = partial adrenalectomy, RA = robotic adrenalectomy, SCS = subclinical Cushing' syndrome.

Parathyroidectomy: is vitamin D a player for a good outcome?

Background: The field of parathyroidectomy (PTx) is complex and brings together many specialists. Even if the surgical approaches changed from classical to minimally invasive PTx, a good outcome is correlated with an adequate localization before and during PTx, while blood assays, such as parathormone (PTH) or 25-hydroxyvitamin D, become useful additional markers. Aim. Specific aspects related to parathyroidectomy and vitamins D (VD) were introduced. Material and Method. The article represents a PubMed-based narrative review. Results. The growing evidence regarding the high prevalence of hypovitaminosis D and early detection of primary hyperparathyroidism (HPT) requires a particular attention to the association of these two disorders, which may be incidental, but some common pathogenic links are displayed. Low VD stimulates PTH production as a secondary or even tertiary type of HPT diagnosis. VD deficiency is associated with larger parathyroid adenomas and higher levels of PTH before and after surgery for primary HPT. Asymptomatically and normocalcemic forms of primary HPT, which are not immediately referred to PTx, require a normalization of the VD levels. VD supplements are safe under some serum calcium cutoffs and offer a better outcome after PTx. However, primary HPT is cured by surgery and, if the indication is well established, this should not be delayed too long to replace VD. Up to half of PTx cases may experience increased PTH levels after surgery, but most of these are transitory if rapid VD correction is done and only a few remaining cases will eventually develop persistent / recurrent primary HPT. Conclusion. A close following of 25-hydroxivitamin D represents one of the keys for a good outcome in the field of parathyroid surgery. Abbreviations: HPT = hyperparathyroidism, MEN = Multiple Endocrine Neoplasia Syndrome, PTx = parathyroidectomy, PTH = parathormone, VD = Vitamin D.

Prevalent osteoporotic fractures in 622 obese and non- obese menopausal women.

Hypothesis. The osteoporotic fractures represent a worldwide economical issue. In order to prevent them, we need to understand the risk factors constellation. Although obesity was traditionally considered as protective against osteoporosis, recent data exposed an increased risk of falling and thus a high risk of some fractures. Objective. We aimed to analyze the body mass index (BMI) in relationship with the bone mineral density (BMD) and the prevalent fractures. Methods and Results. Between 2008 and 2014, a cross-sectional observational study included Romanian menopausal Caucasian women without a previous diagnosis of bone maladies, or specific anti-osteoporotic therapy. Prevalent fragility fractures were both self-declared and incidental vertebral. All the subjects had lumbar BMD (GE Lunar Prodigy DXA machine). Out of 622 females (mean age of 58.65 years, mean BMI of 30.30 kg/ m2), 39.22% were obese (BMI ≥ 30kg/ m2). The fracture prevalence was 1.35% versus 1.67% in obese versus non-obese patients. The correlation coefficient between lumbar BMD and BMI was r=0.165, p<0.005. BMI in the fracture group was 31.68 kg/ m2 vs. 30.04 kg/ m2 in the non-fracture group (p=0.08). 15.91% of the entire cohort had prevalent fractures. Obesity prevalence among females with fractures was 30.3% versus 40.73% in the non-fracture group. The most frequent sites were distal forearm (42.42%) and vertebral (21.21%). Discussions & Conclusions. Although the vertebral fractures might be underdiagnosed in our study and despite the fact that we enrolled a relatively young menopausal population, BMI positively correlated with BMD, regardless of the fractures' prevalence. In early menopause, the most frequent fracture is distal forearm. BMI is higher in patients with prevalent fractures vs. non-fractures (borderline significance). Obesity might not protect from any type of fracture but future evidence is necessary since one third of osteoporotic fractures are met in women with a BMI ≥ 30kg/ m2.

Glycemic profile in patients with acromegaly treated with somatostatin analogue.

HYPOTHESIS: The growth hormone (GH) excess displayed in acromegaly induces insulin resistance up to diabetes mellitus (DM). The somatostatin analogues (as octreotide LAR) are useful in controlling the GH levels but disturbances of glucose metabolism might be seen. OBJECTIVE: This study evaluates the acromegalic glycemic profile under octreotide. METHODS & RESULTS: Out of the total number of patients (N=34) diagnosed with active acromegaly, only some were followed (N=25; male/ female ratio: 6/ 19; mean age: 51.8 years) by testing GH, IGF1 (Insulin Growth Factor 1), basal glucose and oral glucose tolerance test (OCGTT) at baseline, 6 and 12 months under Octreotide (first 6 months with 20 mg/ 28 days + 6 months with 30 mg/ 28 days). Pre-treatment values were 17.6% of patients had DM, 14.7% - impaired glucose tolerance, 26.5% - impaired fasting glucose, and 41.2% - normal assays. From the statistical point of view, the DM patients were significantly older and had higher GH levels than the acromegalic without glycaemia disturbances. They did not achieve significant changes in basal blood glucose and glycated hemoglobin after 6 months, neither after 12 months. After 6 months, there were no significant changes in basal glycaemia in patients with normal baseline glycaemia but 2-hours OGTT glucose values were significantly lower than initially (82.35 mg/ dl vs. 93 mg/ dl, p=0.005) consistent with reduced levels of GH and IGF1. After 12 months, both basal and 2-hours glucose levels in OGTT were similar to baseline despite the significant lower GH (3.3 vs. 6.61 ng/ mL, p=0.003) and IGF1 (332 vs. 713 ng/ mL, p=0.001). CONCLUSIONS: Octreotide therapy induces an improvement in glycemic profile in patients with active acromegaly without diabetes mellitus consistent with decreased levels of GH and IGF1. In patients with diabetes, partial control of glucose metabolism is due to inadequate suppression of GH and IGF1 after one year of treatment.

Serotonin and the bone assessment.

INTRODUCTION: Lately, the in vitro and in vivo studies on serotonin metabolism have been pointing its influence in bone health. Also, there are no particular recommendations in performing the serum serotonin assessment in order to evaluate the skeletal status. AIM: We aimed to correlate the bone turnover markers and lumbar bone mineral density (BMD) with serotonin. MATERIAL AND METHODS: There is a cross-sectional study in Caucasian postmenopausal women. They were not diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment (including antiresorptives). The following bone formation markers were performed: serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid chromatography), as well as central DXA (GE Prodigy) were assessed. RESULTS: 191 women of 57.1 years mean age were grouped according to DXA (WHO criteria). The linear regression analysis between serum serotonin and CL were not statistically significant (SS), between serotonin and OC was SS in the newly diagnosed osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP SS was found in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for age and BMI. The partial correlation between serotonin and BMD was not SS. DISCUSSION: The study raises the question of serotonin as a bone metabolism marker seeing that the results were not consistent. The main limit of our study was that we did not analyze the possible use of antidepressants to these women. Overall, this was a pilot study in clinical practice where few reports have been published, but still necessary, because the use of serum serotonin in current skeletal evaluation is still unclear.

Adrenal and pituitary incidentalomas in a case of Cushing's syndrome.

Cushing's syndrome is a pathological condition where surgery may be lifesaving. The proper diagnosis depends upon the hormonal pattern of the patient, various dynamic tests and imagistic investigations. We report a case of a patient with Cushing's syndrome, with bilateral adrenal tumors and a pituitary microadenoma. She presented increased levels of basal cortisol, unsuppressed during a low and a high dose Dexamethasone test. She underwent right laparoscopic adrenalectomy and developed acute adrenal insufficiency. Two years after the intervention, she still requires adrenal substitution therapy. Acute adrenal crisis is a serious complication of adrenal surgery, with high mortality if unrecognized.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

The serotonin and the bone assessment.

INTRODUCTION: Lately, the in vitro and in vivo studies on serotonin metabolism pointed their influence in bone health. In addition, there are no particular recommendations in performing the serum serotonin assessment in order to evaluate the skeletal status. Aim. We aimed to correlate the bone turnover markers and lumbar bone mineral density (BMD) with serotonin. MATERIAL AND METHODS: There is a cross-sectional study in Caucasian postmenopausal women. They were not diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment (including antiresorptives). We performed the bone formation markers: serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid chromatography), as well as central DXA (GE Prodigy) were assessed. RESULTS: 191 women of 57.1 years mean age were grouped according to DXA (WHO criteria). The linear regression analysis between serum serotonin and CL was not statistically significant (SS), between serotonin and OC was SS in the newly diagnosed osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP we found SS in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for age and BMI. The partial correlation between serotonin and BMD was not SS. DISCUSSION: The study raises the question of serotonin as a bone metabolism marker seeing that the results were not consistent. The main limit of our study is that we did not analyze the possible use of antidepressants by these women. Overall, this is a pilot study in clinical practice in which few reports have been published yet, but still necessary because the use of serum serotonin in current skeletal evaluation is still unclear.

Hypokalemic periodic paralysis as first sign of thyrotoxicosis.

BACKGROUND: periodic paralysis related to hypokalemia is seldom reported in thyrotoxicosis, and it usually occurs in Asian males. PATIENTS AND METHODS: Two Romanian (Caucasian) young patients presented with hypokalemic paralysis. TSH, FT4, TT3 was measured by immunochemiluminescence. Case report 1. Patient O.R, aged 19, presented marked asthenia and lower limbs paralysis, following high carbohydrate meal. He declared 10 kg weight loss on hypocaloric diet and mild sweating. Biochemical data revealed moderate hypokalemia (K+=2.6 mmol/L) and thyrotoxicosis (TSH<0.03 mIU/L, FT4=30 pmol/L, TT3=315 ng/dL). Case report 2. Patient T.A., aged 18, presented 2 episodes of weakness and flaccid paralysis, with hypokalemia, precipitated by effort, without any sign of thyrotoxicosis. Biochemical data revealed severe hypokalemia (K+=1.8 mmol/L) and thyrotoxicosis (TSH<0.03 mIU/L, FT4=24 pmol/L, TT3=190 ng/dL). Treatment with intravenous potassium, thereafter methimazole and propranolol were administered in both cases, with the maintenance of normal kalemia and thyrotoxicosis' control. CONCLUSION: these 2 cases of hypokalemic periodic paralysis occurring in young Caucasian teenagers with mild thyrotoxicosis underlined the importance of thyroid screening in patients with symptomatic hypokalemia, even in the absence of symptoms and signs of thyrotoxicosis.

Case study of appendiceal carcinoid during pregnancy.

The carcinoid tumor of the appendix is one of the most common tumors of the appendix, but one of the rarest anatomic locations of carcinoids. The prognosis is very good, as most tumors are incidentally discovered during surgery for acute or sub-acute appendicitis. The diagnosis is exceptional when combined with pregnancy. We present such a case of a 27-year-old female patient. An emergency appendectomy was performed, and soon after, pregnancy was confirmed. The patient had a tumor smaller than 1 cm in diameter, at the tip of the appendix. The immunochemistry revealed the neuroendocrine profile by positive reaction for chromogranin A and synaptophysin, with a ki-67 profile at an undetectable level. After surgery, the neuroendocrine markers and the octreoscan were negative, consequently indicating a favorable prognosis. Further follow-up is necessary, even though not all the authors recommend it (considering the low index to the associated metastases, especially for small appendiceal tumors). A short review of the literature is presented, starting with this case report.

Pheochromocytoma--from endocrinologist to surgeon.

We report the case an asymptomatic patient who underwent left adrenalectomy for a incidentally discovered large, cystic adrenal tumor. The patient presented no hypertension before or during the intervention. The hystopatological exam revealed a pheochromocytoma, with signs suggesting malignancy. One year after the surgery, the patient is still asymptomatic, the metanephrine levels are normal, and the 1231-metaiodobenzylguanidine scintigraphy showed no metastases. The indications and limits of laparoscopic adrenalectomy are presented.