Pınar Kocaay

Clinical Review of 95 Patients with 46,XX Disorders of Sex Development Based on the New Chicago Classification

STUDY OBJECTIVE The aim of our study was to determine the etiologic distribution of 46,XX disorder of sexual development (DSD) according to the new DSD classification system and to evaluate the clinical features of this DSD subgroup in our patient cohort. PARTICIPANTS The evaluation criteria and clinical findings of 95 46,XX patients were described by clinical presentation, gonadal morphology, genital anatomy, associated dysmorphic features, presence during prenatal period with/without postnatal virilization, hormonal characteristics, and presence or absence of steroidogenic defects among 319 patients with DSD. RESULTS Types and ratios of each presentation of our 95 patients with 46,XX DSD were as follows: 82 had androgen excess (86.3%): (74 had classical congenital adrenal hyperplasia, 2 had CAH variant possibility of P450-oxidoreductase gene defect), 6 had disorders of ovarian development (6.3%): (1 patient had gonadal dysgenesis with virilization at birth with bilateral streak gonad, 4 patients had complete gonadal dysgenesis, and 1 patient had ovotesticular DSD) and 7 had other 46,XX DSD. Two sisters, who had 46,XX complete gonadal dysgenesis,were diagnosed with Perrault Syndrome with ovarian failure due to streak gonads and associated with sensorineural deafness. CONCLUSION 46,XX DSD are usually derived from intrauterine virilization and CAH is the most common cause of 46,XX DSD due to fetal androgen exposure.

A Novel Heterozygous Mutation in Steroidogenic Factor-1 in Pubertal Virilization of a 46,XY Female Adolescent

BACKGROUND Steroidogenic factor-1 (SF-1) gene (NR5A1) mutations cause disorders of sexual development due to gonadal dysgenesis, particularly in 46,XY individuals. In cases exhibiting this mutation, the phenotype is heterogeneous, and it may vary within a spectrum ranging from complete female appearance to an infertile male. Virilization observed in some cases in the pubertal age group may lead to diagnostic difficulties. CASE The present case report describes the clinical, histopathologic, and genetic characteristics of a 46,XY case, who was born with a female phenotype and raised as a girl, presented with findings of virilization in the pubertal period. She had no germ cells and very few Leydig cells with atrophic testis on biopsy and in whom a novel heterozygous mutation in the SF-1 gene (a heterozygous 7-bp deletion mutation in exon 7 [c.1308-1314del7bp] causing frameshift) was identified. SUMMARY AND CONCLUSION Although the gonads are very dysgentic in patient with SF-1 mutations, sufficient androgen synthesis can cause severe virilization during puberty.

Gonadotropin-Releasing Hormone Analogue Treatment in Females with Moderately Early Puberty: No Effect on Final Height.

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age. Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height. Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold. Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Diagnostic Characteristics and Metabolic Risk Factors of Cases with Polycystic Ovary Syndrome during Adolescence

STUDY OBJECTIVE Polycystic ovary syndrome (PCOS) is a disorder without definite consensus on its diagnosis and management during adolescence. According to Amsterdam-2012 consensus, as physiological characteristics of adolescence may overlap with PCOS signs, it has been indicated that all Rotterdam criteria should be met. In this present study, characteristics of adolescents with different phenotypes who were diagnosed with PCOS were evaluated; and presence of differences for metabolic risk factors between phenotypes were investigated. DESIGN The study was performed on adolescent females. According to phenotypic application models, individuals with all Rotterdam diagnostic criteria [hyperandrogenism (HA), polycystic ovarian morphology (PCOM), and chronic anovulation (CA) on the ultrasonography] were in Group 1 (n = 26); with HA and CA were in Group 2 (n = 10); with HA and PCOM were in Group 3 (n = 7); and with CA and PCOM were in Group 4 (n = 10). RESULTS The most common application complaint (87%) among 53 cases enrolled in the study was menstrual irregularities, and 57% of cases were not obese. When PCOS was evaluated according to phenotypes, it was realized that cases that meet all 3 diagnostic Rotterdam criteria according to the current recommendation in adolescents. (Group 1) was the most common phenotype. Hyperandrogenism was associated with more metabolic abnormalities. CONCLUSION The close monitoring of adolescents, who have 2 diagnostic criteria is advisable among PCOS phenotypes. Potentially Groups 2 and 3 which have hyperandrogenism, in particular should warrant closer follow-up although they do not meet current diagnostic criteria for adolescents.

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity.

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.

The evaluation of thyroid carcinoma in childhood and concomitance of autoimmune thyroid disorders.

Abstract Autoimmune thyroiditis has been suggested as a precancerous condition in some adult studies, but there is still controversy. The importance of autoimmune thyroiditis in childhood thyroid cancer is not yet completely clear. We aimed to evaluate in this study the characteristics of childhood thyroid cancer in patients particularly in terms of coexisting factors including autoimmune thyroid disorders (ATD). Twenty patients diagnosed with primary thyroid cancer were evaluated retrospectively in a Pediatric Endocrinology clinic for 10 years. Patients were followed up for 57.22±11 months. Concomitant conditions (thyroidal and/or extra thyroidal) were determined. Most of the patients (80%) had a coexisting factor. ATDs are the most frequently encountered among them (40%). The ages at the time of diagnosis were older; and the tumor sizes were smaller in patients with concomitant ATDs than without autoimmune thyroid disorders. The follow-up characteristics were similar in both groups. In conclusion, ATDs are frequently encountered in association with thyroid cancer during childhood and adolescence. A thyroid autoimmunity may facilitate the development of a malignant thyroid tumor; on the other hand, increased attention to the thyroid gland may facilitate frequent diagnosis of thyroid cancer. A close follow-up of ATD patients should also include the evaluation of the development of thyroid malignancy.

Three cases of Wolfram syndrome with different clinical aspects.

Abstract Background: Wolfram syndrome is an autosomal recessive disorder caused by mutations in the WFS1 gene. Clinical heterogeneity has been reported both within and between families with WFS1 mutations. Subjects: The first case was diagnosed with insulin-dependent diabetes mellitus with positive for pancreatic autoantibodies and had a ketoacidotic attack in the follow-up period. The second case presented initially with optic atrophy and was diagnosed with behavioral and psychiatric problems at an early age. The third case had early onset insulin-dependent diabetes with multiple anomalies and congenital hypothyroidism. Many of these features have not been reported previously in patients with Wolfram syndrome. In all three patients homozygous mutations in WFS1 were identified. Conclusion: Wolfram syndrome is a disease where the characteristic features may present at different times. A diagnosis of Wolfram syndrome should therefore be considered even in the absence of the full spectrum of clinical features.

A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course.

Unlike other congenital fatty acid oxidation defects, short-chain L-3-hydroxyacyl-CoA (SCHAD, HADH) deficiency is characterised by hypoglycemia with hyperinsulinism in the neonatal or infancy periods. The long-term and detailed clinical progression of the disease is largely unknown with almost 40 patients reported and only a few patients described clinically. We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression.

Evaluation of The Efficacy of Long-Term Growth Hormone Theraphy in Patients with Hypochondroplasıa

Hypochondroplasia is a cause of disproportionate short stature and characterized by minor clinical manifestations. The aim of this study was to evaluate the efficacy of long-term growth hormone (GH) therapy in hypochondroplastic cases with inadequate response to GH stimulation tests. In this study, six patients who had a height standard deviation score of -3.43 before the treatment and a mean age of 7.42 years and who had received GH treatment at a dose of 0.2 mg/kg/week for a mean period of 4.45 years were evaluated. A good response was found in the first year of treatment, but this increase was not found to be sufficient for the patients to achieve an adequate final height.

Acute reversible cardiomyopathy and heart failure in a child with acute adrenal crisis.

Acute adrenal crisis is a life-threatening disorder. Cardiovascular complications of the condition are usually limited to hypovolaemic hypotension and shock. An acute reversible cardiomyopathy and heart failure in association with acute adrenal crisis is rarely reported, particularly in children. A 6-year-old girl with adrenal crisis which was complicated by acute reversible cardiomyopathy is reported. Inotropic and ventilatory support in addition to intravenous hydrocortisone and furosemide therapy were required to achieve cardiovascular stability. The cardiomyopathy resolved over 5 days and she was discharged with normal cardiac and intellectual functions. Cardiomyopathy should be considered in patients with acute adrenal crisis demonstrating any symptoms or signs of heart failure.