ACTA ENDOCRINOLOGICA (BUC)

Despite an adequate medical treatment of Graves ophthalmopathy (GO), sometimes surgery is required to establish accurate eye movement and avoid severe complications. We present such a woman with Basedow's disease and evolutive exophthalmia despite adequate medical approach. At the admission (2005) she had clinical signs of thyrotoxicosis, TSH = 0.1 mUI/L, FT4 = 4.2 ng/dl and antithyroperoxidase antibodies = 342 UI/ml. Proptosis was 26 mm at the right eye and 25 mm at the left one, with intraocular tension 20 mmHg and NO SPECS score 4. Treatment with methimazole (30 mg/day), propranolol (30 mg/day), and corticotherapy (Metilprednisolone, 3x1g/day iv), improved the hyperthyroidism but not the ocular signs. The euthyroidism was maintained with 5 mg Methimazole daily. In February 2006 a new pulse therapy with Metilprednisolone (1g/day iv 3 days) was started, followed by Prednisone 30 mg /day, without significant improvement of the ocular signs. In June 2006, TSH receptor antibodies were high, TRAb=16.3 U/l, with euthyroid status but evolutive proptosis. The MRI showed an increase of the volume of all intraorbital muscles, a decrease of the optic nerve diameter. The patient had progressive GO with photophobia, palpebral edema, hyperlacrimation and conjunctivitis. The surgical treatment was decided when the proptosis was 25 mm and the intraocular tension was 19 mm Hg for both eyes. The patient was submitted to orbital content decompression through lipectomy and osteotomy of the orbital floor. The postoperative follow-up was uneventful. Two years postsurgery, exophthalmometry was 17 mm at right eye and 18 at the left eye, with an intraocular tension of 13 mm Hg. The MRI showed normal intraorbital muscles and ocular globe; the bicanthal lines were anterior to the posterior pole of the ocular globe. The patient had no limitation of the eyes movements, photophobia or conjunctivitis and a significant esthetic improvement.

Thyrotoxic hypokalemic periodic paralysis (TPP) is a disorder leading to hypokalemia and muscle weakness. It mainly affects the Asian population, and it is rare in the Balkan and Caucasian people. We describe a case of a 34 year-old male presenting with TPP. To our knowledge, this case is the third Turkish patient diagnosed as TPP in the English medical literature. He was admitted to the Emergency Department (ED) with generalized weakness. Initial laboratory analysis showed that serum potassium was 1.6 mmol/L. His serum potassium was normalized after intravenous administration of potassium chloride (KCl) of 80 mmol over 4 h and 40 mg of propranolol administered orally, and then his generalized weakness was recovered. Thyrotoxicosis was treated with propylthiouracil and propranolol.

Adipose tissue is a major store of energy for the human body. Polycystic ovary syndrome (PCOS) patients are more prone to abnormal production of some regulatory proteins secreted from the adipose tissue. This study aims to investigate serum levels of adiponectin and their correlation with metabolic and endocrine indices in PCOS. Patients and methods. This study was conducted on 61 women with PCOS and 17 healthy women whose age and body mass index (BMI) were matched. Adiponectin serum levels were assessed and correlated with parameters of metabolic and hormonal disturbances. Results. In PCOS women, serum levels of insulin, HOMA-IR, testosterone, LH, and LH/FSH were significantly higher, while SHBG was lower than in healthy women. Lower adiponectin was observed in both PCOS groups compared to the control group. Serum levels of adiponectin correlated inversely with BMI (r=- 0.56; p<0.001),WC(r = -0.452;p<0.001), insulin levels (r= - 0.409; p<0.001), HOMA-IR (r= -0.368; p<0.001), and free androgen index (FAI) (r= - 0.53; p<0.001). A positive correlation was found between adiponectin and LH (r= 0.35; p<0.001), LH/FSH ratio (r= 0.33; p<0.001) and SHGB (r= 0.51; p<0.001). Serum adiponectin levels are decreased in women with PCOS compared to the control group. The decrease in adiponectin concentration indicates its potential role in metabolic disorders in the pathogenesis of PCOS, as well as in the development and progression of insulin resistance in PCOS patients.

Context. Therapeutic plasma exchange (TPE) provides time for thyroidectomy in thyrotoxic patients. Objective. TPE is indicated in cases where antithyroid medications cannot be used due to the side effects or attain no adequate hormonal suppression response at the highest dosage and in cases of rapid onset of clinical symptoms. This study presents the treatment results of patients who underwent TPE and were subsequently operated for thyrotoxicosis. Design. The patients who underwent thyroidectomy and TPE between January 1999 and February 2019 were retrospectively analyzed. Subjects and Methods. The files of 27 patients with thyrotoxicosis who performed TPE prior to surgery were analyzed in relation to the demographic and clinical features. Results. We included 15 (55.6%) females, 12 (44.4%) males with a mean age of 44 (23-82) years. The pre-TPE mean free thyroxine (fT4) level was 12 (5-46) pmol/L while free tri-iodothyronine (fT3) level was 34 (17- 141) pmol/L. The post-TPE fT4 level was 6 (3-10) pmol/L while the fT3 level was 21 (12-41). There was one case of an allergic reaction during the procedure. In the postoperative follow-up, there was transient hypocalcemia in 8 (29%) patients, permanent hypocalcemia in 1 (3.7%) patient, and surgical site infection in 1 (3.7%) patient. Conclusion. Preoperative TPE is an alternative treatment option for thyrotoxic patients. This is an especially effective treatment for patients with inadequate response or adverse reaction to antithyroid drugs or patients who need urgent surgery for thyroid storm.

Background. Although diseases such as diabetes, hypertension, obstructive sleep apnea and hyperlipidemia are clearly documented as obesity associated diseases, it is not wellknown whether obesity causes renal pathologies. The aim of the present study was to evaluate the effect of weight loss following laparoscopic sleeve gastrectomy on clinical, renal parameters and urinary Neutrophil gelatinase-associated lipocalin (NGAL) levels in diabetic and non-diabetic obese patients. Methods. Nineteen morbidly obese patients (10 diabetic and 9 non diabetic) who underwent laparoscopic sleeve gastrectomy were evaluated clinically (anthropometric measurements) and biochemically before surgery and at 6 months from surgery. Results. Significant decreases in weight, BMI, FPG, PPG and HbA1c levels were observed in the diabetic group when the baseline and 6th month parameters of the patients were compared. There was also a significant decrease in SBP and DBP. At 6th month following laparoscopic sleeve gastrectomy, renal parameters such as creatinine, mAlb/creatinine, NGAL/ creatinine did not differ in the diabetic group. In the nondiabetic group, serum creatinine levels were significantly decreased, but other renal parameters such as mAlb/creatinine and NGAL/ creatinine were not significantly different. Conclusions. Our findings revealed significant decreases in weight, body mass index and glycemic parameters after sleeve gastrectomy in diabetic and non-diabetic patients, while no significant alteration was noted in renal functions, urinary NGAL and microalbumin levels.

Context. Several enlarged parathyroid glands could be found during thyroid surgery in normocalcemic patients without evidence of primary or secondary hyperparathyroidism, indicating multiglandular parathyroid gland disease (MGD). Objective. Clinical role of various levels of serum ionized calcium (Ca2+) in patients diagnosed with incidental MGD during thyroid surgery remains controversial. The aim of the study was to evaluate the features of PHPT and the clinical role of serum Ca2+ in normocalcemic patients diagnosed with incidental MGD. Study design. A prospective study of patients with normal preoperative Ca2+ to be operated on for thyroid diseases in 2010-2013 and diagnosed with MGD during thyroid surgery. Methods. An analysis of clinical data from 3,561 patients to be surgically treated for thyroid diseases revealed 219 (6%) patients with MGD and normal serum Ca2+. Further data analyses showed patients with MGD and high normal (≥1.25 – 1.3 mmol/L) serum Ca2+ (n = 89) and with moderate-low (1.0 – 1.24 mmol/L) serum Ca2+ (n = 130). Results. Primary hyperparathyroidism was diagnosed intra- and post-operatively in 48 (54%) patients with high-normal serum Ca2+ and in 2 (2%) patients with moderate-low serum Ca2+ (p<0.0001). Parathyroid hormone, serum Ca2+ as well as urine calcium excretion were elevated in 2 (2%) patients with moderate-low serum Ca2+ and in 18 (20%) patients with high-normal Ca2+ at follow-up (p<0.0001). Conclusion. Serum Ca2+ level within the normal range, but higher than 1.25 mmol/L (high-normal) is associated with primary hyperparathyroidism, which should be considered in patients with visually diagnosed MGD, but without clinical symptoms of hyperparathyroidism.

Introduction. Recent studies suggest that nutritional status can modify the association\r\nbetween high iPTH and mortality, especially in diabetics and older hemodialysis patients (HDP).\r\nAim. To assess the impact of mineral metabolism parameters in the survival of HDP\r\nin our area and to evidence the factors that influence iPTH levels in our HDP, which are\r\nyounger and have less frequently diabetic nephropathy as the cause of chronic renal failure\r\nthan in most published studies.\r\nPatients and Methods. A prospective cohort study of 126 HDP was recorded for\r\ndemographic, clinical and laboratory data, and after 24 months, the general mortality. Patients\r\nwere divided in two groups, survivors and non-survivors, and each of groups classified according\r\nto the time on hemodialysis (THD). The groups of non-survivors and survivors with THD more\r\nthan 10 year-period were compared to the groups with less than 10 year vintage, regarding the\r\nalbumin levels, iPTH levels, phosphate-calcium metabolism markers, age and sex.\r\nResults. We observed the better survival only for calcium phosphate product less than 55\r\nmg?/dL? (p=0,02). The iPTH level seems to be conditioned by albumin levels. For THD<10\r\nyears, iPTH levels are greater in survivors (p=0.01); in this subgroup we observed higher levels\r\nof serum albumin (p<0.001), the patients were younger (p<0.001), and had 5-fold lower\r\nfrequency of diabetes. For THD>10 years, iPTH levels are greater in non-survivor patients\r\n(p=0.02), as well as calcium, phosphorus and calcium phosphorus product.\r\nConclusions. Calcium-Phosphorus product is a better indicator for survival in HDP in our\r\narea than immunoreactive PTH levels. Immunoreactive PTH as prognostic factor might be\r\nbetter evaluated in association with calcium phosphorus metabolism parameters and albumin\r\nlevels too, even in younger and lower percent-diabetic HDP groups.

Aim. To correlate the profile of CFTR gene mutations in patients from Romania with the ethnogenesis of Rumanian people. Patients and methods. One hundred sixty-five patients with clinical diagnosis of CF and elevated values at sweat test were included in the study. Samples of EDTA-anticoagulated blood were obtained by venipuncture, sent to our laboratory and DNA was extracted from leukocytes. For the majority of blood samples we used standardized methods for analysis of at least 18 common mutations. Ten DNA samples were analyzed for 38 CFTR mutations with a kit recently introduced in our program of investigations of CFTR gene mutations.Results. The most frequent mutations in CF patients from Romania are F508del (53.6%), G542X (4.6%), W1282X (2.1%) and CFTRdele2,3(21kb) (1.2%). Other mutations were detected at frequencies less than 1.0%. The profile of the CFTR gene mutations in Rumanian patients appears to be very different from its counterpart profile in Romania’s neighbour countries and rather similar with the profile of mutations in France, Italy and Spain (which, similar to Romania, are Neo-Latin countries). A notable difference between Romania and these Neo-Latin countries is the presence of a Slavic mutation, CFTRdele2,3(21kb) in Rumanian patients; this might reflect the Slavic component in the ethnogenesis of Rumanian people.Conclusion. The profile of the CFTR gene mutations in Rumanian patients confirms the overwhelming evidence regarding the ethnogenesis of Rumanian people from the admixture of Dacians or Getae (the ancient autochtonous inhabitants of the territory of present-day Romania) with Roman (or Romanized) legionnaires and colonists, forming the Daco-Roman population (the basis of Rumanian people), who assimilated the Slavs that entered in the territory of present-day Romania in the VIth century.

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disease characterized by multiple hamartomas in multiple organs. However, there is limited evidence about neuroendocrine tumors (NETs) in patients with TSC, and routine screening of NETs is not recommended in the guidelines. Insulinomas are also an extremely rare disease. According to our knowledge, we presented the 10th TSC patient diagnosed with insulinoma in the literature. Thirty-two years old male patient diagnosed with TSC at the age of 27 due to typical skin findings, renal angiomyolipoma, history of infantile seizures, and cranial involvement was referred to our clinic. The main symptoms of the patient were palpitations, diaphoresis, confusion, and symptoms were improved after consuming sugary foods. Seventy-two hours fasting test was performed, and a low glucose level at 41 mg/dl, a high insülin level at 21.65 μIU/mL, and a high C-peptide level at 7.04 ng/mL were found at the 8th hour. In addition, a 12x7 mm lesion in the pancreatic tail was detected in abdominal imaging. Ga-68 PET-CT (gallium-68 positron emission tomographycomputed tomography) detected an increased uptake of Ga-68 in the pancreatic tail. The patient underwent distal pancreatectomy, and pathological evaluation was consistent with an insulinoma. The patient’s symptoms improved postoperatively. Since in nearly all TSC cases, as in our case, neuropsychiatric abnormalities, such as epilepsy, are one of the main disease manifestations, and these symptoms may be confused with the clinical manifestations of hypoglycemia in insulinoma. Therefore, patients with newly developed neurological symptoms and behavioral defects should be evaluated in terms of insulinoma.

Sarcoidosis, a disease of an unknown etiology, is characterized by the presence of noncaseating granulomas that are most often found in the intrathoracic lymph nodes, lung and in other organs. Hashimoto' thyroiditis is one of the most common organ-specific autoimmune diseases. Although several reports describe the coincidence of sarcoidosis and Hashimoto's thyroiditis, the understanding of the relationship between these two disorders is limited. A 50 year old woman was admitted for cervico-thoracic goiter having a long history of nodular goiter for about 25 years and being suspect of pulmonary sarcoidosis. A chest radiograph and CT scan showed plunging intrathoracic goiter, lymphadenopathy with a pulmonary interstitial infiltrating process. A tracheo-bronchial lung biopsy revealed non-caseating granulomatous lesions consisting of epithelioid cells, confirming sarcoidosis. Angiotensin converting enzyme was high, therefore the patient was diagnosed as having sarcoidosis. The thyroid gland showed signs of goiter, tenderness and nodularity, without latero-cervical adenopathy. Thyroid function tests were normal and thyroid antibodies were positive. For cervico - thoracic goiter, total thyroidectomy with cervical lymph-adenomectomy was practiced. The histopathological exam demonstrated thyroid sarcoidosis, lymph nodes involvement and chronic thyroiditis.