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.

Effects of Smoking on Diabetic Nephropathy.

Diabetes is a systemic metabolic disease with serious complications that cause significant stress on the healthcare system. Diabetic kidney disease is the primary cause of end stage renal disease globally and its progression is accelerated by various factors. Another major healthcare hazard is tobacco consumption and smoking has deleterious effects on renal physiology. Prominent factors are defined as sympathetic activity, atherosclerosis, oxidative stress and dyslipidemia. This review aims to enlighten the mechanism underlying the cumulative negative effect of simultaneous exposure to hyperglycemia and nicotine.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients.

OBJECTIVES: This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. STUDY DESIGN: Prospective, multicentre study. METHODS: Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. RESULTS: Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=-0.336, p<0.001 and r=-0.258, p<0.001, respectively). CONCLUSIONS: Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.

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.

Evaluation of epicardial fat tissue thickness in patients with Hashimoto thyroiditis.

OBJECTIVE: Hypothyroidism, whether overt or subclinical, has multiple effects on the cardiovascular system. Epicardial fat tissue (EFT) is closely related to cardiovascular disorders and atherosclerosis. Our study aimed to assess EFT thickness and carotid artery intima-media thickness (CIMT) in patients with Hashimoto's thyroiditis (HT) displaying overt and subclinical hypothyroidism (SCH). DESIGN AND PATIENTS: The study included 33 patients with SCH and 24 patients with overt hypothyroidism (OH) with HT as well as 32 healthy controls. EFT thickness, CIMT, thyroid hormone levels and lipid parameters were measured in all subjects. Correlation analysis and linear regression analysis were performed for EFT thickness. RESULTS: Mean EFT thickness was 2·89 ± 0·38, 3·53 ± 0·92 and 4·56 ± 1·61 mm in control, SCH and OH groups, respectively (P < 0·001). EFT thickness of OH patients was high compared with SCH and control subjects (P < 0·01 and <0·001, respectively). CIMT of OH patients was high compared with SCH and control subjects (P < 0·01 and <0·001, respectively). In addition, EFT was significantly thicker in SCH patients than in controls (P < 0·05). Correlation analysis showed that EFT thickness was significantly positively correlated with CIMT, age, body mass index, systolic blood pressure, thyroid-stimulating hormone, total and LDL cholesterol and triglyceride and negatively correlated with free T4. In the regression analysis, EFT thickness retained its independent and positive association with CIMT, patient group (particularly OH) and systolic blood pressure. CONCLUSIONS: Epicardial fat tissue thickness may be a useful indicator of early atherosclerosis in SCH and OH patients with HT.

Serum ischemic modified albumin levels might not be a marker of oxidative stress in patients with hypothyroidism.

Overt hypothyroidism and subclinical hypothyroidism are thought to be associated with atherosclerosis and a chronic ischemic process. Ischemic modified albumin (IMA) is a novel marker of ischemia. We examined serum IMA levels in patients with subclinical and overt hypothyroidism. We recruited patients who presented to our clinic for thyroid disease control. We compared demographic data, fasting blood sugar, serum lipid levels, and the prevalence of metabolic syndrome by the presence of overt, subclinical, and no hypothyroidism. Cobalt binding to albumin capacity was analyzed using a rapid colorimetric technique and compared among the groups. We assessed 11 men and 74 women with a mean age of 39.9 ± 12 years. Of these, 48 (56.5 %) were euthyroid, 24 (28.2 %) had subclinical hypothyroidism, and 13 (15.3 %) had overt hypothyroidism. The groups did not differ significantly in terms of age; body mass index; waist circumference; systolic and diastolic blood pressures; levels of fasting and nonfasting blood sugar, high- and low-density lipoproteins, and triglycerides; and the presence of metabolic syndrome. Mean serum IMA level also did not differ significantly among the groups: 0.20 ± 0.08 absorbance units (ABSU) in the euthyroid participants, 0.18 ± 0.08 ABSU in those with subclinical hypothyroidism, and 0.20 ± 0.09 ABSU in those with overt hypothyroidism (P = 0.754). Mean IMA values did not differ significantly by sex, cigarette use, the presence of metabolic syndrome, or the presence of thyroid autoantibodies. Serum IMA levels did not differ among patients with overt or subclinical hypothyroidism in this case-control study.

Epicardial adipose tissue increased in patients with newly diagnosed subclinical hypothyroidism.

OBJECTIVE: To investigate whether or not patients with subclinical hypothyroidism (SH) have increased epicardial adipose tissue (EAT). SUBJECTS AND METHODS: Sixty-one patients with newly diagnosed SH and without any known cardiovascular disease were enrolled. Twenty-four subjects matched for age, gender and body mass index without any thyroid dysfunctions were included as a control group. The EAT was measured by echocardiography and thyroid functions were assessed by routine blood examination. RESULTS: Patients with SH had higher EAT values than control subjects (3.6 ± 0.9 vs. 2.8 ± 1.4, p = 0.005). Also, SH patients with thyroid-stimulating hormone (TSH) ≥10 mU/l had higher EAT than those with SH with TSH <10 mU/l and control subjects (p = 0.013). In addition, while there was significant correlation between EAT and TSH (r = 0.31, p = 0.014) in patients with SH, there was no significant relation between EAT and TSH in normal subjects (r = 0.09, p = 0.64). CONCLUSIONS: There was a higher level of EAT in patients with SH compared with normal subjects and a significant correlation between EAT and TSH was found.

Acute adrenal insufficiency associated with tuberculous vertebral osteomyelitis and lymphadenopathy: case report.

A 51-year-old man developed anorexia, dizziness, nausea, vomiting, and weight loss. He had orthostatic hypotension, hyponatremia, hyperkalemia, and hypocortisolemia, and the diagnosis of adrenal insufficiency was made. Magnetic resonance imaging (MRI) showed asymmetrically enlarged adrenal glands. Biopsy of a hypoechoic, enlarged, inguinal lymph node showed caseating granulomas. Lumbar MRI showed vertebral body height loss and abnormal signal in L1 and L2; vertebral biopsy showed chronic, necrotic, caseating granulomatous inflammation consistent with tuberculous osteomyelitis. Clinical improvement occurred with isoniazid, rifampicin, pyrazinamide, and corticosteroids. The differential diagnosis of adrenal insufficiency should include tuberculosis, especially in geographic regions where tuberculosis is endemic.

A woman with thyrotoxicosis- and hyperemesis gravidarum-associated Wernicke's encephalopathy.

Although hyperthyroidism arising from primary thyroid disease is rare in pregnancy, transient gestational hyperthyroidism is not uncommon. This condition can be associated with hyperemesis gravidarum (HG), and Wernicke's encephalopathy. We present the case of a woman with toxic nodular goiter complicating HG-associated Wernicke's encephalopathy. A 38-year-old Caucasian woman, who had received a diagnosis of hyperthyroidism and HG early in her pregnancy, had intrauterine fetal death at Week 16 of gestation. One day after undergoing therapeutic abortion, she was admitted to our clinic with persistent thyrotoxicosis, nausea, and vomiting. A toxic thyroid nodule was detected. She was given antithyroid medication, total parenteral nutrition. On Day 10 of hospitalization, she developed ataxia, aphasia, and somnolence. Cranial magnetic resonance imaging showed increased bilateral thalamic signalization. She was given a diagnosis of Wernicke's metabolic encephalopathy, for which she received thiamine and multivitamin preparations. She responded dramatically on the second day of thiamine therapy. Her consciousness improved rapidly and she began to speak. Her muscle tone was slightly weak and she had paresthesias in both legs. Absorption of thiamine may be particularly impaired in pregnant women with hyperemesis and hyperthyroid disease. Wernicke's encephalopathy should be considered in hyperthyroid women with HG who develop neurological abnormalities.

Parathyroid adenoma with coeliac disease: primary or quaternary hyperparathyroidism?

Coeliac disease is a gluten-sensitive enteropathy of varying severity. Osteomalacia and hypocalcaemia can result from malabsorption of vitamin D and calcium, which, in turn, can lead to secondary hyperparathyroidism. If coeliac disease remains untreated for long, tertiary hyperparathyroidism can also develop through autonomy of the parathyroid glands via chronic stimulation. Primary hyperparathyroidism also has been reported in some cases of coeliac disease. We report the case of an adolescent with coeliac disease presenting with severe hypercalcaemia from a parathyroid adenoma. A 14 year-old girl was admitted to our department for delayed puberty and growth retardation. Laboratory examination revealed iron deficiency anaemia, low 25OH vitamin D level (7 ng/ml), high parathyroid hormone level (PTH) (955 pg/ml), and hypercalcaemia (13.4 mg/dl). Endoscopic biopsy was compatible with gluten enteropathy. Endomysium antibody was positive. A gluten-free diet was started. Her calcium returned to normal after excision of the parathyroid adenoma. After four months of the gluten-free diet, she began to mature, and puberty began with development of breasts and axillary-pubic hair growth. It has been suggested that autonomous four-gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation, and that this should be termed "quaternary hyperparathyroidism". More studies are required to explain the relationship between coeliac disease and hyperparathyroidism.

Depression, anxiety and quality of life of family caregivers of patients with type 2 diabetes.

OBJECTIVE: It was our aim to investigate the quality of life (QOL) among family caregivers of patients with type 2 diabetes mellitus. SUBJECTS AND METHODS: The Short Form-36 QOL scale, Beck Depression Inventory and State-Trait Anxiety Inventory Form were used to evaluate the presence and degree of depression and anxiety and their association with sociodemographic features of 50 family caregivers of diabetic patients compared to 54 controls. RESULTS: The groups were similar in terms of age, sex, health insurance, educational status and marital and financial status. Beck Depression Inventory scores were significantly higher in family caregivers (p = 0.001) than in controls. Depression as a categorical variable was significantly more frequent among family caregivers of diabetic patients than among controls (p < 0.001). The social function component of the QOL of controls was better than that of family caregivers (p < 0.005). There was no difference between groups in terms of anxiety. CONCLUSION: Family caregivers of diabetic patients appeared to be more prone to depression and tended to have a poorer QOL.

Higher metabolic risk with National Institutes of Health versus Rotterdam diagnostic criteria for polycystic ovarian syndrome in Turkish women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disease with well-established metabolic abnormalities in women of reproductive age. There are various diagnostic criteria to define and establish PCOS. However, data conflict regarding the optimal diagnostic criteria for PCOS and its metabolic consequences. We have evaluated the clinical, endocrine, and metabolic features between main PCOS phenotypes according to different diagnostic criteria. METHODS: In this prospective, case-control study, 175 consecutive women with PCOS, 41 ovulatory women with idiopathic hirsutism, and 109 healthy, nonhirsute, ovulatory controls were enrolled. The following diagnostic criteria were assessed: Hirsutism; ovulatory function; ovarian sonography; gonadotropin, testosterone, dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone, fasting insulin, and lipid levels; oral glucose tolerance test; homeostasis model assessment for insulin resistance (HOMA-IR); body mass index (BMI); waist circumference; and the presence of metabolic syndrome. RESULTS: Of the 175 women meeting the Rotterdam criteria for PCOS, 121 (69%) had both androgen excess and ovulatory dysfunction, thus also meeting the National Institutes of Health (NIH) criteria. The other 54 (31%) had either androgen excess or ovulatory dysfunction. Women meeting the NIH criteria had the largest mean BMI, waist circumference, and HOMA-IR score; the highest mean testosterone, DHEA, triglyceride, and fasting insulin levels; the lowest mean progesterone level; and the greatest prevalence of insulin resistance (HOMA-IR score >3) among the groups. CONCLUSIONS: The NIH criteria identify women at high risk for insulin resistance and metabolic syndrome. The Rotterdam criteria include women who have less severe metabolic implications.

Granulomatous infiltration of a parathyroid adenoma presenting as primary hyperparathyroidism in a woman: a case report.

INTRODUCTION: Hypercalcemia can be associated with vitamin D (1,25(OH)2D3) -mediated granulomatous disorders in addition to primary hyperparathyroidism (PHPT). Although most patients with granulomatous disease-related hypercalcemia are asymptomatic, symptoms and signs of chronic hypercalcemia can occur. There are many reports about co-presentation of a parathyroid adenoma and a granulomatous disorder in the literature. However, granulomatous inflammation within a parathyroid adenoma is very rare. CASE PRESENTATION: A 50-year-old Caucasian woman presented with generalized bone pain and muscular weakness. Biochemical findings suggested PHPT. She underwent excision of an enlarged right inferior parathyroid gland. Histopathological analysis revealed features of a parathyroid adenoma with foci of epithelioid non-caseating granulomas. The etiology of the granulomatous infiltration could not be determined. She is still normocalcemic at the ninth month after surgery and is being followed for the possible manifestation of an occult disease. CONCLUSION: Granulomatous infiltration of a parathyroid adenoma is a rare condition. Pathological examination of the excised adenoma is the only way to diagnose the underlying occult granulomatous disorder. Clinicians should also consider persistent hypercalcemia to be a possible indicator of concomitant parathyroid adenoma.

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.