Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome.

Betatrophin is defined as a new marker in glucose homeostasis and lipid metabolism. We aimed to investigate the role of serum betatrophin in full-blown polycystic ovary syndrome (PCOS) patients and 47-aged healthy women, 51 full-blown PCOS patients were included in this cross-sectional study. Betatrophin concentrations were significantly lower in PCOS group and displayed a positive correlation only with serum tryglyceride in control group (p < .05). A cutoff level (464.5 ng/L) was determined for betatrophin according to Receiver Operating Characteristic curve. Using this value, 64.7% of PCOS patients were classified as below the cutoff and in this group betatrophin was found to correlate negatively with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (p = .038, p = .020, and p = .014, respectively), and positively with total testosterone (p = .041). In the rest of PCOS cases (35.3%) who had betatrophin higher than cutoff, positive correlation was found with low-density lipoprotein cholesterol (p = .009). In conclusion, betatrophin levels are reduced in full-blown PCOS patients who had worse metabolic phenotype.

Hounsfield unit value has null effect on thyroid nodules at 18F-FDG PET/CT scans.

OBJECTIVES: Detection rate of thyroid nodules is increasing with the use of new imaging modalities, especially in screening for malignancies. Positron emission tomography/computed tomography (PET/ CT)-positive thyroid nodules should be differentiated for malignancy to avoid unnecessary operations and further follow-up. Most trials evaluate the role of SUVmax, but there is no definitive information about the utility of Hounsfield unit (HU) values for prediction of malignancy. This study aimed to evaluate the HU values beside SUVmax for detecting malignancy risk of PET/CT-positive thyroid nodules. SUBJECTS AND METHODS: Results of 98 cancer patients who had fine needle aspiration biopsy (FNAB) for thyroid nodules detected on PET/CT between January 2011 and December 2015 were assessed. The FNABs and surgical pathological results were recorded. RESULTS: FNABs revealed benign results in 32 patients (32.7%), malignant in 18 (18.4%), non-diagnostic in 20 (20.4%), and indeterminate in 28 (28.5%). Twenty-four patients underwent thyroidectomy. The mean HU values were not significantly different in benign and malignant nodules (p = 0.73). However, the mean SUVmax was significantly higher (p < 0.001) in malignant ones. Area under curve (AUC) was 0.824 for SUVmax; the cut-off value was over 5.55 (p < 0.001), with 80% sensitivity, 84.5% specificity. CONCLUSIONS: Our current study demonstrated that HU value does not add any additional valuable information for discriminating between malignant and benign thyroid nodules. We also defined a SUV cut-off value of 5.55 for malignant potential of thyroid nodules detected on PET/CT Arch Endocrinol Metab. 2018;62(4):460-5.

Hounsfield unit value has null effect on thyroid nodules at 18F-FDG PET/CT scans

ABSTRACT Objectives: Detection rate of thyroid nodules is increasing with the use of new imaging modalities, especially in screening for malignancies. Positron emission tomography/computed tomography (PET/ CT)-positive thyroid nodules should be differentiated for malignancy to avoid unnecessary operations and further follow-up. Most trials evaluate the role of SUVmax, but there is no definitive information about the utility of Hounsfield unit (HU) values for prediction of malignancy. This study aimed to evaluate the HU values beside SUVmax for detecting malignancy risk of PET/CT-positive thyroid nodules. Subjects and methods: Results of 98 cancer patients who had fine needle aspiration biopsy (FNAB) for thyroid nodules detected on PET/CT between January 2011 and December 2015 were assessed. The FNABs and surgical pathological results were recorded. Results: FNABs revealed benign results in 32 patients (32.7%), malignant in 18 (18.4%), non-diagnostic in 20 (20.4%), and indeterminate in 28 (28.5%). Twenty-four patients underwent thyroidectomy. The mean HU values were not significantly different in benign and malignant nodules (p = 0.73). However, the mean SUVmax was significantly higher (p < 0.001) in malignant ones. Area under curve (AUC) was 0.824 for SUVmax; the cut-off value was over 5.55 (p < 0.001), with 80% sensitivity, 84.5% specificity. Conclusions: Our current study demonstrated that HU value does not add any additional valuable information for discriminating between malignant and benign thyroid nodules. We also defined a SUV cut-off value of 5.55 for malignant potential of thyroid nodules detected on PET/CT Arch Endocrinol Metab. 2018;62(4):460-5

Mean Platelet Volume in Graves' disease: A Sign of Hypermetabolism Rather than Autoimmunity?

OBJECTIVE: To evaluate the impact of mean platelet volume (MPV) on predicting disease course among patients with Graves' disease (GD). METHODS: This retrospective study was performed between 2013-2016 at the Outpatient Endocrinology Clinic of Baskent University Faculty of Medicine, Adana hospital on 65 patients with GD. Among participants, 30 cases experienced thyrotoxicosis again during the first six months after discontinuing anti-thyroid drug (ATD) sessions that had been carried out for at least 12 months prior to stopping (Relapse group). We also observed 35 patients who exhibited normal thyroid functions within six months following ATD withdrawal (Remission group). MPV levels and thyroid function tests were recorded and total duration of ATD therapy was calculated for all participants. RESULTS: The mean MPV level that was measured at the time of drug withdrawal did not differ between groups, being 8.0±1.2 fL in the Relapse group vs. 8.0±1.0 fL in the Remission group (p=0.81). However, we found that the relapse MPV was higher than the withdrawal MPV in the Relapse group (9.2±1.3 fL) than it was in the Remission group (8.0±1.2 fL, p=0.00). CONCLUSIONS: Higher relapse MPV in Relapse group but similar MPV levels in both groups at ATD withdrawal may be attributed to hypermetabolism or hyperthyroidism rather than autoimmunity of GD. Abbreviations:BMI: Body mass index GD: Graves' disease MPV: Mean platelet volume TSH: Thyroid-stimulating hormone TRAbs: Thyrotropin receptor antibodies ATD: Anti-thyroid drug fT4: Free thyroxine fT3: Free triiodothyronine CBC: Complete blood count PTC: Papillary thyroid carcinoma.

Stubborn hiccups as a sign of massive apoplexy in a naive acromegaly patient with pituitary macroadenoma.

Pituitary apoplexy (PA) may very rarely present with hiccups. A 32-year-old man with classical acromegaloid features was admitted with headache, nausea, vomiting and stubborn hiccups. Pituitary magnetic resonance imaging (MRI) demonstrated apoplexy of a macroadenoma with suprasellar extension abutting the optic chiasm. Plasma growth hormone (GH) levels exhibited suppression (below <1 ng/mL) at all time points during GH suppression test with 75 g oral glucose. After treatment with corticosteroid agents, he underwent transsphenoidal pituitary surgery and hiccups disappeared postoperatively. The GH secretion potential of the tumor was clearly demonstrated immunohistochemically. We conclude that stubborn hiccups in a patient with a pituitary macroadenoma may be a sign of massive apoplexy that may result in hormonal remission. LEARNING POINTS: Patients with pituitary apoplexy may rarely present with hiccups.Stubborn hiccupping may be a sign of generalized infarction of a large tumor irritating the midbrain.Infarction can be so massive that it may cause cessation of hormonal overproduction and result in remission.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey.

OBJECTIVE: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. METHODS: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. RESULTS: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. CONCLUSION: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Macroprolactinemia, like hyperprolactinemia, may promote platelet activation.

Insulin resistance, which provides a convenient milieu for platelet activation, has been closely associated with atherosclerotic disorders. Although it often accompanies hyperprolactinemia, findings conflict concerning its clinical impact in macroprolactinemia. In order to investigate the relationship between hyperprolactinemia and platelet activation evidenced by ADP-stimulated P-selectin expression on flow cytometry, we studied hyperprolactinemic, macroprolactinemic, and normoprolactinemic subjects. Thirty-four hyperprolactinemic and 44 age- and body mass index-matched euprolactinemic premenopausal women were included. They were matched regarding insulin sensitivity status, waist circumference, blood pressures, and plasma lipids. In order to detect macroprolactinemia among hyperprolactinemic cases, prolactin was measured before and after polyethylene glycol (PEG) precipitation in patients' sera. P-selectin expression was significantly higher in the hyperprolactinemic group (P =0.001), and 41.2% of them exhibited macroprolactinemia. Expression of P-selectin was comparable between the macroprolactin-negative (monomeric hyperprolactinemia; n = 20) and -positive (n = 14) subgroups (P = 0.90). Both subgroups showed greater expression compared with normoprolactinemic controls (P = 0.014 and 0.005, respectively). Platelet activation accompanies the atherosclerotic disorders closely associated with insulin resistance. Among groups matched with regard to insulin-sensitivity markers, both monomeric hyperprolactinemia and macroprolactinemia appeared to promote platelet activation.

A case report of the cascade filtration system: a safe and effective method for low-density lipoprotein apheresis during pregnancy.

Women with familial hypercholesterolemia (FH) should be treated effectively during pregnancy, as elevated low-density lipoprotein cholesterol (LDL-C) levels may result in life-threatening consequences. Hydroxymethylglutaryl-coenzyme A reductase inhibitors are contraindicated during pregnancy, therefore LDL apheresis should be considered in the management of such pregnant cases. There are five different methods of selective LDL apheresis: heparin-induced extracorporeal LDL precipitation, double filtration plasmapheresis, direct adsorption of lipoproteins, dextran sulfate adsorption, and LDL immunoadsorption. The cascade filtration system is another modern and effective method for the extracorporeal elimination of LDL-C, although it is not as selective as the methods mentioned above. Herein, we present the case of a pregnant woman with heterozygous FH and extremely elevated LDL-C levels who has been successfully treated with the cascade filtration system until delivery. As far as we can ascertain, LDL apheresis with the cascade filtration system during pregnancy has not yet been reported in the literature.

Lanreotide autogel and insulin sensitivity markers: report of 5 acromegalic patients and literature review.

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors. DESIGN: Prospective clinical trial with six months of follow-up. SETTING: A tertiary endocrinology clinic. MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index. RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR. CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect.

A new perspective in diagnosing polycystic ovary syndrome.

Recently, the term of "possible" polycystic ovary syndrome (PCOS) has been used for defining cases in which biochemical evaluations are incomplete but clinical phenotypes are suggestive of PCOS. The aim of this study was, by using Rotterdam 2003 criteria, to detect possible PCOS cases and compare their characteristics and insulin sensitivity status with confirmed PCOS subjects. One-hundred-eighteen women who admitted with complaints and symptoms suggesting PCOS were included. Insulin sensitivity status of the cases was calculated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Cases fulfilling Rotterdam 2003 criteria were defined as confirmed PCOS, whereas indeterminate subjects as possible PCOS. Confirmed PCOS was detected in 70 (59.3%) and possible PCOS in 48 (40.7%) cases. Confirmed PCOS was most prevalent among subjects with hirsutism and menstrual dysfunction; 32 (80.0%) vs. 8 (20%), (p=0.000). Body mass index and HOMA-IR values did not differ between groups: confirmed PCOS versus possible PCOS; 25.46+/-5.55 kg/m(2) vs. 26.75+/-7.55 kg/m(2), 3.37+/-4.12 vs. 3.21+/-2.50, (p>0.05). Family history of type-2 diabetes mellifus was similar within both groups (p>0.05). Many PCOS patients seem to be undiagnosed due to inadherence to diagnostic work-up and/or to not fulfill Rotterdam 2003 criteria. These criteria may not be sufficient to cover the entire spectrum of PCOS.

Incidental papillary microcarcinoma of the thyroid.

Papillary microcarcinoma (PMC) is a thyroid tumor measuring 10mm or less in maximum diameter and comprise up to 30% of all papillary thyroid cancers. Most of them are detected incidentally and defined as incidental papillary microcarcinoma (IPC

Wegener's granulomatosis with a possible thyroidal involvement.

Wegener's granulomatosis (WG) is an autoimmune disorder characterized by the involvement of many organ systems. In patients with refractory disease, the efficacy of cyclophosphamide, corticosteroids and infliximab has been reported recently. Even in cases with serological response, disease progression has still been observed. Herein, we report a case of WG, most likely accompanied with subacute granulomatous thyroiditis while the patient was on cyclophosphamide, corticosteroid and infliximab therapy. As far as we know, this is the first time that such a copresentation has been observed, suggesting that mechanisms other than T-cell-mediated cytotoxicity may be important in the pathogenesis of granulomatous thyroiditis.