Prevalence of Nonclassic Congenital Adrenal Hyperplasia in Turkish Children Presenting with Premature Pubarche, Hirsutism, or Oligomenorrhoea

Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum of CYP21A2 mutations in NCAH patients. Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL. Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous. Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent

Procoagulant and Anticoagulant Factors in Childhood Hypothyroidism

The aim of this study was to investigate the effects of thyroid hormone deficiencies in childhood on the elements of coagulation proteins. Consecutive 54 children with hypothyroidism and 55 healthy controls aged 1 month–16 years were enrolled. One year after Na-L-thyroxine treatment, the study parameters were reevaluated. Thyroid function tests, procoagulant and anticoagulant proteins were performed for children with hypothyroidism and healthy controls. Significant decreased results were found in children with hypothyroidism in terms of fibrinogen, TT, and anticoagulant proteins including AT, PC, PS, and fPS. Significant increases were found with respect to APTT, fibrinogen, and TT. In the evaluation of posttreatment changes a statistically significant increase was found in vWF, FVIII, AT, PC, PS, and fPS. A positive correlation was found between fT4 and vWF, FVIII, PC, and PS. We would like to emphasize that the coagulation system especially vWF and FVIII, and particularly the anticoagulant system, should be monitored closely in patients followed up for hypothyroidism. Thyroid hormones should be examined and, if necessary, hormone replacement therapy should be administered in patients followed up for a predisposition to coagulation. Additionally, further studies with larger series are needed to investigate the effects of hypothyroidism on the coagulation system

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

Conclusion: We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised

Bilateral Painless Testicular Enlargement: An Unusual Presentation of Sarcoidosis and a Literature Review

Background: Sarcoidosis is a systemic infl ammatory disease characterized by non- seating epitheloid granulomas; whereas it usually involves the lungs and lymph nodes, genitourinary involvement is extremely rare. For this reason, no consensus regarding the diagnostic and management options for testicular sarcoidosis has been reached.Objective: The aim of this case report was to describe an unusual clinical presentation of sarcoidosis. An 8-year-old boy presented with a 6-month history of painless scrotal&nbsp; nlargement and a 2-month history of photophobia, blurred vision, and pain in both eyes. Physical examination revealed tearing, conjunctival hyperemia, and nodular lesions in both eyes as well as bilateral, nontender, irregularly shaped, and very hard testes. Laboratory investigations revealed elevated serum angiotensin-converting enzyme levels, and 8 fl uoro-2-deoxyglucose positron emission tomography (FDG-PET) showed intense FDG accumulation in both testes. Testes biopsy showed non-caseating epitheloid granulomas, staining negative for acid-fast bacilli and fungi; tuberculosis culture was negative. A diagnosis of sarcoidosis was made.Conclusions: This is the fi rst reported case of testicular sarcoidosis in a Turkish child. Frozen section assessment is the most sensitive and reliable method for differentiating testicular masses. The diagnosis of testicular sarcoidosis should be made after excluding other infl ammatory diseases characterized by non-caseating epitheloid granulomas.</p

Horner Syndrome Secondary to Thyroid Surgery

Horner syndrome (HS), caused by an interruption in the oculosympathetic pathway, is characterised by myosis, ipsilateral blepharoptosis, enophthalmos, facial anhydrosis, and vascular dilation of the lateral part of the face. HS is a rare complication of thyroidectomy. A 15-year-old female patient presented with solitary solid and large nodule in the right thyroid lobe. Ultrasound-guided fine-needle aspiration was performed and the cytological examination results were undefined. The patient underwent a total thyroidectomy. On postoperative day 2, she developed right-sided myosis and upper eyelid ptosis. HS was diagnosed. Interestingly, the patient exhibited an incomplete clinical syndrome with the absence of vasomotor symptoms. We herein report a case of HS in a 15-year-old female patient after total thyroidectomy. The possible causes of HS were ischaemia-induced nerve damage and stretching of the cervical sympathetic chain by the retractor during thyroidectomy. Clinicians should be aware of the possibility of this rare but important surgical complication

Can the ratio of metastatic to examined lymph nodes (N ratio) be used as an independent prognostic factor in patients with gastric cancer? Is the hypothetical TRM (tumor-ratio-metastasis) staging system an alternative to the TNM (tumor-node-metastasis) staging system?

Aim: Lymph node metastasis is the most important prognostic factor in patients with gastric cancer. However, lymph node classification is controversial. We reported the prognostic factors of gastric cancer and the impact of N ratio classification in predicting prognosis and the suitability of TRM classification as an alternative to TNM(tumor-node-metastasis) classification for lymph nodes to avoid stage migration in gastric cancer

SLC4A4 compound heterozygous mutations in exon–intron boundary regions presenting with severe proximal renal tubular acidosis and extrarenal symptoms coexisting with Turner’s syndrome: a case report

Abstract Background Congenital NBCe1A deficiency with the SLC4A4 mutation causes severe proximal renal tubular acidosis, which often comprises extrarenal symptoms, such as intellectual disability and developmental delay, glaucoma, cataract and band keratopathy. To date, almost all mutations have been found to be homozygous mutations located in exons. Case presentation We performed direct nucleotide sequencing analysis of exons and exon–intron boundary regions of the SLC4A4 in a patient presenting with severe renal proximal tubule acidosis, glaucoma and intellectual disability and her parents without these signs. The examination revealed compound heterozygous mutations in exon–intron boundary regions, c.1076 + 3A > C and c.1772 − 2A > T, neither of which have been reported previously. While the former mutation was found in the mother, the latter was found in the father. The transcript of the SLC4A4 gene was almost undetectable, and the patient was also diagnosed with Turner’s syndrome. Conclusions We identified two novel SLC4A4 mutations, c.1076 + 3A > C and c.1772 − 2A > T. When presented in a compound heterozygous state, these mutations caused a phenotype of severe renal proximal tubular acidosis along with glaucoma and mental retardation. This is the first report of congenital proximal renal tubular acidosis carrying compound heterozygous SLC4A4 mutations in exon–intron boundary regions. We suggest that an mRNA surveillance mechanism, nonsense-mediated RNA decay, following aberrant splicing was the reason that the SLC4A4 transcript was almost undetectable in the proband

Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase

Abstract Background Loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase (HADH) cause protein sensitive hyperinsulinaemic hypoglycaemia (HH). HADH encodes short chain 3-hydroxacyl-CoA dehydrogenase, an enzyme that catalyses the penultimate reaction in mitochondrial β-oxidation of fatty acids. Mutations in GLUD1 encoding glutamate dehydrogenase, also cause protein sensitive HH (due to leucine sensitivity). Reports suggest a protein-protein interaction between HADH and GDH. This study was undertaken in order to understand the mechanism of protein sensitivity in patients with HADH mutations. Methods An oral leucine tolerance test was conducted in controls and nine patients with HADH mutations. Basal GDH activity and the effect of GTP were determined in lymphoblast homogenates from 4 patients and 3 controls. Immunoprecipitation was conducted in patient and control lymphoblasts to investigate protein interactions. Results Patients demonstrated severe HH (glucose range 1.7–3.2 mmol/l; insulin range 4.8-63.8 mU/l) in response to the oral leucine load, this HH was not observed in control patients subjected to the same leucine load. Basal GDH activity and half maximal inhibitory concentration of GTP was similar in patients and controls. HADH protein could be co-immunoprecipitated with GDH protein in control samples but not in patient samples. Conclusions We conclude that GDH and HADH have a direct protein-protein interaction, which is lost in patients with HADH mutations causing leucine induced HH. This is not associated with loss of inhibitory effect of GTP on GDH (as in patients with GLUD1 mutations).</p