Untreated Congenital Adrenal Hyperplasia with 17-alpha Hydroxylase/17,20-Lyase Deficiency Presenting as Massive Adrenocortical Tumor

Congenital adrenal hyperplasia (CAH) with 17alpha-hydroxylase/17,20-lyase deficiency is usually characterized by hypertension and primary amenorrhea, sexual infantilism in women, and pseudohermaphroditism in men. hypertension, and sexual infantilism in women and pseudohermaphroditism in men. In rare cases, a huge adrenal gland tumor can present as a clinical manifestation in untreated CAH. Adrenal cortical adenoma is an even more rare phenotype in CAH with 17alpha-hydroxylase/17,20-lyase deficiency. A 36-year-old female presented with hypertension and abdominal pain caused by a huge adrenal mass. Due to mass size and symptoms, left adrenalectomy was performed. After adrenalectomy, blood pressure remained high. Based on hormonal and genetic evaluation, the patient was diagnosed as CAH with 17alpha-hydroxylase/17,20-lyase deficiency. The possibility of a tumorous change in the adrenal gland due to untreated CAH should be considered. It is important that untreated CAH not be misdiagnosed as primary adrenal tumor as these conditions require different treatments. Adequate suppression of adrenocorticotropic hormone (ACTH) in CAH is also important to treat and to prevent the tumorous changes in the adrenal gland. Herein, we report a case of untreated CAH with 17alpha-hydroxylase/17,20-lyase deficiency presenting with large adrenal cortical adenoma and discuss the progression of adrenal gland hyperplasia due to inappropriate suppression of ACTH secretion.

Estudio preliminar sobre el tratamiento con hormona de crecimiento humana recombinante en el síndrome de Turner / Preliminary study on the recombinant human growth hormone treatment of Turner's syndrome

Introducción: los pacientes con síndrome de Turner presentan una monosomía parcial o total del gonosoma X, disgenesia gonadal, diversos rasgos físicos típicos, baja talla e infantilismo sexual. Objetivo: evaluar el efecto del tratamiento con hormona de crecimiento recombinante sobre la talla en las pacientes con el diagnóstico clínico y cromosómico de síndrome de Turner. Métodos: se realizó un estudio de tipo descriptivo y retrospectivo a pacientes con síndrome de Turner atendidas en consultas externas en el Departamento de Endocrinología Pediátrica del Instituto Nacional de Endocrinología, desde mayo de 2003 hasta mayo de 2004. La muestra estuvo constituida por 19 niñas. Se confeccionaron dos grupos, uno con aquellas pacientes que recibieron tratamiento con hormona de crecimiento recombinante (n= 9) a una dosis de 0,14 UI/kg/día, administrada vía subcutánea entre las 8:30 y 9:30 pm, que se conoció como grupo A. El segundo quedó conformado con las pacientes que no recibieron dicha hormona (n= 10), denominado grupo B. Los datos necesarios para la investigación fueron obtenidos de la revisión de las historias clínicas. Resultados: un incremento de la talla en el grupo A, que inició el estudio con una talla basal media de 131,7 ± 7,5 cm, para alcanzar una talla media, después de un año de tratamiento, de 137,9 ± 7,1 cm, con una velocidad de crecimiento media en ese año de 6,2 ± 2,3 cm/año. La comparación de ambos grupos después de un año de estudio mostró diferencias significativas en la talla media al año (p= 0,0071) y la velocidad de crecimiento media al año (p= 0,0032). Conclusiones: el tratamiento con hormona de crecimiento recombinante durante el primer año resultó efectivo, al acelerar significativamente la velocidad de crecimiento en las niñas con síndrome de Turner. La ganancia de peso corporal resultó adecuada durante el periodo de estudio, pues se logró mantener una valoración nutricional estable sin modificaciones en el canal percentilar. La inducción de la pubertad no cambió el pronóstico de la talla al final del estudio(AU)

Introduction: Turner's syndrome patients present with total or partial monosomy of X gonosome, general disgenesia, several typical physical traits, short height and sexual infantilism. Objective: to evaluate the effect of recombinant human growth hormone-based treatment on the height of patients clinically and chromosomally diagnosed as Turner's syndrome subjects. Methods: a retrospective and descriptive study was conducted in Turner's syndrome patients, who had been seen from May 2003 to May 2004 at the pediatric endocrinology department of the National Institute of Endocrinology. The sample was made up of 19 girls divided into 2 groups. Group A comprised patients who were treated with recombinant human growth hormone (n= 9) at a dose of 0.14 IU/kg/day subcutaneously administered from 8:30 to 9:30 pm. Group B included the patients who did not receive this treatment (n= 10). The required data for the research stemmed from the medical history check-ups. Results: increase of the Group A patients' height, whose mean basal height at the beginning of the study was just 131.7 ± 7.5 cm and after one year of treatment, they reached 137.9 ± 7.1 cm, at a rate of average growth of 6.2 ± 2.3 cm/year. The comparison of both groups after one year showed significant differences in mean height (p= 0.0071) and mean growth a year (p= 0.0032). Conclusions: the treatment of these patients with the recombinant growth hormone during the first year was effective, since it markedly accelerated the rate of growth in girls with Turner's syndrome. The body weight gain proved to be adequate in the study period, because it managed to keep steady nutritional assessment without changes in the percentile canal. Inducement to puberty did not alter the final height prognosis at the end of the study(AU)

Congenital adrenal hyperplasia masquerading as periodic paralysis in an adolescent girl

Congenital adrenal hyperplasia is an uncommon diagnosis in routine clinical practice. 21-hydroxylase deficiency, which is its most common subtype, may be diagnosed at birth in a female infant by virilisation or by features of salt wasting in both genders. However, other uncommon subtypes of this condition such as 17-alpha-hydroxylase deficiency, 11-beta-hydroxylase deficiency may present much later in adolescence or adulthood. A high index of suspicion is necessary when evaluating children with hypertension, hypokalaemia, metabolic alkalosis or sexual infantilism.

Dysgerminoma in a nineteen-year-old patient with Swyer's syndrome / Philippine Journal of Obstetrics and Gynecology

Dysgerminomas are the most common type of malignant germ cell tumor. It primarily occurs in women under age thirty. Five percent of cases occur in phenotypic females with dysgenetic gonads.?This paper presents a phenotypically female patient with hypogastric mass and primary amenorrhea. Eight months prior, patient underwent left salpingo- oophorectomy. Physical examination showed? absent secondary sexual characteristics along with normal external female genitalia. Intra-operative findings at that time confirmed the presence of a uterus along with absent right ovary. Hormonal studies revealed increased gonadotropin levels, decreased estrogen and female testosterone levels. Serum LDH was elevated. Karyotyping revealed XY chromosome. Pure gonadal dysgenesis is characterized by abnormal testicular determination. The syndrome, as described by the Swyer in 1955, presents the complete form of "pure" gonadal dysgenesis. This involves the association of the female phenotype, female internal genitalia, normal or tall statue and sexual infantilism with primary amenorrhea. These patients have streak gonads that do not secrete testosterone or Mullerian inhibiting factor, and therefore Mullerian derivatives develop.?

Análise clínica e molecular de pacientes com distúrbios do desenvolvimento gonadal / Clinical and molecular analysis of patients with disorders of gonadal development

Introdução: O termo distúrbios do desenvolvimento gonadal (DDG) inclui condições congênitas nas quais o desenvolvimento gonadal é atípico. Estudos feitos em camundongos observaram que alguns genes como o Cbx2 e o Tcf21 interferem na fase inicial do desenvolvimento gonadal, afetando tanto gônadas XX quanto XY. O gene Dhh, por sua vez, codifica o fator de transcrição Dhh, produzido pelas células de Sertoli, que é fundamental para a diferenciação das células de Leydig em gônadas XY. Nos ovários, o gene FOXL2 atua na foliculogênese, sendo fundamental para a formação dos ovários. Objetivos: Analisar clinicamente e pesquisar anormalidades nos genes CBX2, TCF21, DHH e FOXL2 em pacientes portadores de distúrbios do desenvolvimento gonadal 46, XY e 46, XX. Material e Métodos: Foram estudados 60 pacientes (41 com DDG 46, XY e 19 com DDG 46, XX). A análise molecular foi realizada a partir da amplificação gênica por PCR e sequenciamento direto. Resultados: Várias alterações alélicas foram encontradas nos quatro genes, algumas ainda não descritas na literatura. Uma alteração intrônica no gene DHH foi encontrada em um paciente com DDG 46, XY e não foi encontrada em nenhum dos 360 alelos normais estudados (g.IVS2 +29G>A). Estudamos essa variante através da extração do RNA do testículo do paciente afetado, mas não encontramos alteração no RNA; portanto ela parece não ser uma mutação. No gene TCF21, a variante encontrada foi identificada em controles normais. No gene CBX2, das treze alterações encontradas, uma não foi identificada em 206 alelos normais, e há troca de aminoácidos (p.C132R / g.394 T>C). Trata-se de uma variante que pode ter relação com o fenótipo do paciente, portador de DDG 46, XY. No gene FOXL2, das três alterações encontradas, uma não foi identificada em 206 alelos normais; contudo, não há troca de aminoácidos (p.A181A / g.543 C>T). Conclusão: Esse estudo sugere que mutações nos genes CBX2, TCF21, FOXL2 e DHH são causas raras de distúrbios do desenvolvimento...

Introduction: Congenital disorders of gonadal development (DGD) include conditions whose gonadal development is atypical. Studies in mice found that some genes such as Cbx2 and Tcf21 interfere in the initial phase of gonadal development, affecting both XX and XY gonads. Dhh gene, in turn, encodes the transcription factor Dhh, produced by Sertoli cells, which is essential for the differentiation of Leydig cells in XY gonads. In the ovaries, genes as FOXL2 act in folliculogenesis, fundamental to the development of the ovaries. Objectives: To analyze patients with disorders of gonadal development (DGD) 46, XY and 46, XX and research mutations in CBX2, TCF21, DHH and FOXL2 genes. Methods: We analyzed 60 patients (41 DGD 46, XY patients and 19 DGD 46, XX patients). The whole coding region of CBX2, TCF21, DHH and FOXL2 genes were amplified by PCR and direct sequenced. Results: Several allelic variations have been found in the four genes, some not even described by literature. One intronic variation in DHH was described in one patient with 46, XY DGD and it wasnt found in any of the 360 normal control alleles studied (g.IVS2 +29G>A). We studied this variant through RNA extraction from the affected patients testes, but we didnt find any alteration in the RNA, so it doesnt seem to be a mutation. In TCF21 gene, the single variant that was found was identified in normal controls. In CBX2 gene, among the 13 alterations described, one wasnt identified in 206 normal control alleles, and there is aminoacid change (p.C132R / g.394 T>C). This is a variant that may be a mutation, causing the patients phenotype that had 46, XY DGD. In FOXL2, among the 3 variations described, one wasnt indentified in 206 normal control alleles, but there wasnt amino acid change (p.A181A / g.543 C>T).Conclusion: This study suggests that mutations in CBX2, TCF21, FOXL2 and DHH genes are rarely causes of disorders of gonadal development.

Clinical and molecular genetic analysis for 7 patients from 5 pedigrees with 17a-hydroxylase/17, 20 lyase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetic characteristics of 7 patients from 5 families with 17a-hydroxylase/17,20 lyase deficiency (17OHD) and the CYP17A1 mutation in Chinese.</p><p><b>METHODS</b>Clinical features and laboratory data were collected from 5 families with 17OHD. PCR direct sequencing was performed to screen the mutation of CYP17A1 gene of the patients. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to screen the mutations of CYP17A1 gene in 288 healthy individuals from Shandong province.</p><p><b>RESULTS</b>Seven patients (5 of them were 46,XX; 2 were 46,XY) had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. Hormone profile indicated decreased plasma cortisol and sex hormones, and elevated blood adrenocorticotrophic hormone (ACTH). TAC329AA and H373L in exon 6 and D487_F489del in exon 8 were identified from the patients. One heterozygote for D487_F489del was identified in 288 healthy controls.</p><p><b>CONCLUSION</b>The TAC329AA and D487_F489del of the CYP17A1 gene were the most frequent mutations in Chinese with 17OHD.There might be certain frequency of heterozygotes for D487_F489del in Chinese population.</p>

Correlation between Karyotype and Phenotype in Turner Syndrome

PURPOSE: In spite of the karyotype and phenotype diversity in Turner syndrome patients, there are few reports about such differences in Korea. We reviewed the data of chromosome abnormalities, clinical manifestations, and comorbidities of Turner syndrome patients in Kyungpook National University Hospital to compare them to the recent hypotheses about sex chromosome gene loci related to Turner symptoms. MATERIALS AND METHODS: We identified the cytologic findings of 92 patients with Turner syndrome and the clinical findings of 62 patients among them. RESULTS: 54.3 percent of patients had 45,X while 45.7 percent showed other karyotype combinations (45,X/46,XX, 45,X/46,XX/47,XXX, 46,X,del(Xp), 46,X,del(Xq), 45,X/46,X,del(Xq), 46,X,i(Xq), 45,X/46,X,i (Xq)). The Turner symptoms found included short neck, high arched palate, broad chest, Madelung deformity, short metacarpals, scoliosis, cubitus valgus, low hair line, webbed neck, edematous extremities, pigmented nevus, and sexual infantilism. The specific diseases associated Turner syndrome included renal abnormalities, congenital heart disease, hearing defects, diabetes mellitus, hyperlipidemia, and decreased bone density. The phenotype of the mosaicism group was milder than that of the monosomy group. In the case of 46,X,del(Xp) and 45,X/46,X,del(Xq) groups, all had skeletal abnormalities, but the 46,X,del(Xq) group had none. In the case of 46,X,del(Xp) group, all showed short statures and skeletal abnormalities, but no sexual infantilism was observed. In the case of 46,X,i(Xq) and 45,X/46,X,i(Xq) groups, they all showed delayed puberty and had primary amenorrhea. CONCLUSION: It is important to study karyotype-phenotype correlations in patients with Turner syndrome to obtain interesting information about the genotype-phenotype correlations related to the X chromosome.

Turner's syndrome: diagnosis and management with limited resources

Turner Syndrome or Bonnevie-Ulrich syndrome is a syndrome of gonadal dysgenesis characterized by sexual infantilism, short stature and somatic anomalies. These case reports are meant not only to describe the clinical features of Turners syndrome but also illustrate the challenges faced in the bid to diagnose this medical condition with the available limited diagnostic tools

A case of primary amenorrhea with hypertension due to 17alpha-hydroxylase deficiency / 대한산부인과학회지

17alpha- hydroxylase deficiency is a rare form of congenital adrenal hyperplasia and characterized by the coexistance of hypertension caused by the hyperproduction of mineralocorticoid precursors and sexual abnormalities, such as female pseudohermaphroditism and sexually infantile female with 46,XX karyotype or male pseudohermaphroditism with 46, XY karyotype, due to impaired production of sex hormone. We experienced a case of 17alpha- hydroxylase deficiency (46,XX) presented with primary amenorrhea, sexual infantilism, and hypertension. We report this case with a brief review of the concerned literatures.

Study on the genetic mutations of 17 alpha-hydroxylase/17,20-lyase deficiency in Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the CYP17A1 gene mutations in Chinese patients with 17 alpha-hydroxylase/17, 20-lyase deficiency.</p><p><b>METHODS</b>Clinical data were retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then sequenced. Sequencing results were compared to the established human CYP17A1 sequence.</p><p><b>RESULTS</b>Briefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC-->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA), whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A). The clinical characteristics of 5 cases were all completely combined defects of 17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1 gene mutations that all shifted the reading frame and resulted in truncated protein which lack of the activity center site of P450C17, of which corresponding with their clinical feature.</p><p><b>CONCLUSION</b>Nine alleles have the mutation of 6436-6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this kind of mutation may have racial specificity. More study should be done to have better understanding of the function of the truncated P450C17 enzymes.</p>

A Case of Down-Turner Syndrome / 대한소아내분비학회지

Down-Turner syndrome is a rare disease with the incidence of 1 in 2 million. Although Down syndrome with various Turner's karyotype were reported occasionally since a report in 1962, it was not reported in Korea. We experienced a case of Down-Turner syndrome with 47, X, del(X)(p11.2), +21/ 47, XX, +21, who has clinical features of Down syndrome such as hypotonia, weak Moro reflex, round and wide face, flat occiput, epicanthal folds, upward slanting of the palpebral fissures, low set ears, a simian line on both palms and the brachydactyly of the right little finger with the appearance of Turner syndrome such as the edema of hands, webbed neck. We think it will be necessary to follow up the patient in regard to the aspects such as infertility, sexual infantilism, and primary amenorrhea.

A Case of Swyer Syndrome Diagnosed in Infant / 대한주산의학회잡지

Swyer syndrome is characterized by a female phenotype, normal to tall stature, sexual infantilism with primary amenorrhea and 46,XY karyotype. The internal genitalia are female with uterus and full vagina, but have no ovaries or testis. Swyer syndrome is often diagnosed when young adults are evaluated for delayed puberty, as menstruation dose not occur naturally. We experienced a case of Swyer syndrome diagnosed incidentally in course of evaluating intrauterine growth retardation and delayed growth in infant. So, we report a case of Swyer syndrome with a brief review of literatures.

A Case of Turner's Syndrome(45,X/46,XX) Associated with Patent Ductus Arteriosus

We described a 65-year-old female of 45,X/46,XX Turner's syndrome associated with patent ductus arteriosus who was admitted due to exertional dyspnea and palpitation. This patient had not spontaneous mensturation and had a short stature without webbed neck and a sexual infantilism. Chromosomal aberrations cause primarily structural defects of cardiovascular system, and a variety of structural aberrations involving the X chromosome can cause partial or complete Turner's syndrome. In Turner's syndrome, bicuspid aortic valve or coarctation of aorta is frequently combined, also aortic root dilatation, partial anomalous venous drainage, hypoplastic left heart, ventricular septal defect, atrial septal defect has been reported. However, this patient had not abnormality in aortic valve and whole aorta. Patent ductus arteriosus in 45,X/46,XX Turner's syndrome have not been reported in Korea. We report this case with a brief review of the literature.

A Case of Anterior Pituitary Agenesis in an Adult Woman / 대한내분비학회지

Dear Author, You have used abbreviations that will need to be defined in the main paper, i.e. PIT1, PROP1 and MRI. This is just for your advice. Pituitary agenesis is an uncommon cause of panhypopituitarism. It has been proposed that breech delivery, or birth trauma, is a major factor causing pituitary agenesis. Recent studies have suggested that genetic defects in the PIT1 or PROP1 gene might be involved in the pathogenesis of pituitary agenesis. In this case we report on the diagnosis of a 33-years old female patient with-growth retardation and sexual infantilism. We diagnosed anterior pituitary hormones deficiencies, with the exception of adrenocorticotropic hormone, by a combined pituitary stimulation test. We observed pituitary agenesis using sella MRI. Involvement of the PIT1 or PROP1 genes in this case remains to be determined. Here we report a case of pituitary agenesis found in an adult woman together with a brief review about this disease entity.

A Case of Dysgerminoma Associated with 46, XY Pure Gonadal Dysgenesis / 대한부인종양콜포스코피학회잡지

Dysgerminoma developed in a 21-year-old phenotypic female patient with 46,XY pure gonadal dysgenesis, Swyer syndrome. This patient presented with pelvic mass associated with abdominal pain and primay amenorrhea. Clinical characteristics showed a typical stigmata of gonadal dysgenesis: primary amenorrhea, sexual infantilism, a small uterus and left streak gonad. A 46,XY karyotype was made by lymphocyte culture. The patient was counseled to undergo operation, chemotherapy and hormon therapy. She underwent bilateral gonadectomy with total hysterectomy, partial omentectomy and multiple pelvic wall random biopsy. Histological examination revealed dysgenetic gonads with dysgerminoma. After surgery, the patient received chemotherapy and also was started on hormone replacement therapy. She is currently alive with no evidence of disease after 19 months from surgery.

Analysis of SRY Gene in Korean Patients with Swyer Syndrome and their Family Members / 대한산부인과학회잡지

Individuals affected with Swyer syndrome are phenotypic females with 46, XY karyotype, sexual infantilism, mullerina derivatives, and bilateral streak gonads that may undergo neoplastic transformation. The pathogenesis of this syndrome is uncertain, but may be related to a defect in the regulation or expression of the testicular determining factor which is believed to be located on the short arm of the Y chromosome. Recently, a region termed "SRY", a single copy gene of the Y chromosome was identified as belonging to a testis-determining gene. This gene is Y-specific, highly conserved among mammals, and transcribed only in testis. The predicted amino acid sequence of SRY shares homology with DNA-binding domains of transcription factors such as chromatinassociated, nonhistone proteins HMG 1 and HMG 2. Hence, it was thought that there may be some change in SRY gene of the patients with Swyer syndrome. And it was reported in some cases that there was deletion or mutation in the gene, but no abnormality of SRY gene was observed in other cases. So, it is a new approach to understand the mechanism of the human sexual differentiation to investigate this syndrome in terms of DNA sequence of SRY gene. To verify the presence or absence of SRY, or the change in SRY, we performed polymerase chain reaction and DNA sequencing of the conserved region of SRY gene from four patients with Swyer syndrome and their family members. The results are as follows. 1) Four patients with Swyer syndrome, their father, and two normal male control were positive whereas two female control were negative for the band that represents the coding sequence of SRY. 2) The DNA sequences of SRY gene from four patients with Swyer syndrome, their father, and two normal male control were the same, and there was no deletion or mutation in the gene. In conclusion, there may be complex sex determining cascade including other genes not only on the Y chromosome, but also on the X chromosome or even autosome in human sexual differentiation.

The Changes of the Bone Mineral Density by Treatment Modality in Patients with Turner Syndrome / 대한소아내분비학회지

PURPOSE:Decreased bone mineral density(BMD) has been reported in girls with Turner syndrome. Estrogen therapy is recommanded to improve sexual infantilism and decreased BMD. Short stature is also characteristic finding in patients with Turner syndrome. Treatment modality for short stature has included estrogen, anabolic steroids and growth hormone(GH). Recently GH therapy in GH deficient children could increase BMD in addition to improve short stature. We observed the treatment effects on bone mineral density in patients with Turner syndrome. METHODS: Bone Mineral Density in second to fourth lumbar spine area were measured by dual energy X-ray absorptiometry in 56 girls with Turner syndrome, before and after growth hormone and/or estrogen. All Turner girl was confirmed by clinical and chromosomal examination. RESULTS: 1) There was no significant difference in BMD according to karyotype. 2) The mean BMD of untreated Turner syndrome was 0.752+/-0.122g/cm2. 3) The mean BMD before and after GH treatment were 0.620+/-0.028g/cm2, 0.793+/-0.093g/cm2 respectively. The mean BMD before and after estrogen treatment were 0.761+/-0.125g/cm2, 0.918+/-0.141g/cm2 respectively. In combined group, the BMD were 0.752+/-0.087g/cm2 and 0.939+/-0.134g/cm2. Growth hormone was also effective to improve BMD as well as estrogen. But the changes of BMD were more significant in estrogen and combined group(p<0.05). 4) A significant positive correlation was found between age and BMD(p<0.05). CONCLUSIONS:Estrogen therapy can accelerate epiphysial maturation and compromise final height. Growth hormone therapy in Turner girls was effective for improvement bone mineral density as well as growth improvement. But growth hormone and estrogen combined therapy or Estrogen therapy is more effective to improve bone mineral density in Turner syndrome. Estrogen replacement can be delayed for a while on growth hormone treatment and the appropriated time of estrogen therapy should be elucidated.

A Case of Partial Hypopituitarism and Central Diabetes Insipidus Developed after Tuberculous Meningitis / 대한내분비학회지

Complications related to tuberculous menngitis (TBM) is frequently encountered in medical field during, just after treatment and long time later. Hypothalamo-pituitary dysfunctions such as diabetes incipidus, dwarfism, hypogonadism, growth failure, and hypopituitarism are one of rare complication secondary to TBM and of which obesity with hypogonadism is most commonly documented. Several pathologic mechanics like a granuloma in hypothalamus, or pituitary stalk, organization and progressive scarring of the purulent exudate in the basal cistern or progressive obliterative endarteritis that supplying the hypothalamo-hypophyseal system is well-defined in hypothalamopituitary dysfunction in neurotuberculosis. We recently experienced a diabetic patient with short stature and sexual infantilism who shows polyuria and polydipsia. Detailed endocrinological evaluation showed partial hypopituitarism and central diabetes incipidus secondary to tuberculous meningitis. Polyuria and polydipsia was improved with dDAVP and height increased 5 cm for 11 month with HGH, libido increased with oxadrolone but his extemal sexual characteristics was not changed until now. We present this case with a review of literature.

The Changes of the Bone Mineral Density in the Girls with Turner Syndrome, using Recombinant Human Growth Hormone

PURPOSE: Estrogen deficiency causes sexual infantilism in Turner syndrome, which could decrease the bone mineral density(BMD) since birth. This decreased BMD might be contributed by the decreased growth hormone(GH) secretion. To improve the decreased BMD, estrogen therapy is recommended, especially after the pubertal age, but estrogen therpay during childhood can accelerate the epiphyseal fusion, resulting in shorter final height. There is a possibility that GH therapy not only ameliorates the final height, but also improve the decreased BMD, because GH is known to be involved in the normal bone metabolism. We observed whether GH therapy, given to improve the growth velocity, can change the BMD in the girls with Turner syndrome. METHODS: Thirteen prepubertal girls with Turner syndrome, who were confirmed by clinical and chromosomal examinations, were given GH(1 U/kg/week, daily, subcutaneous) for one year. During GH therapy, BMDs were mesured by DEXA(dual energy X-ray absorptiometry at trochanter and lumbar spine between the second and fourth vertebra. Growth velocity significantly increased during GH therapy and bone age were significantly advanced during this period. RESULTS: 1) The BMD of femur neck was significantly increased from 0.59+/-0.09 gm/cm2 before therapy to 0.73+/-0.07 gm/cm2 and 0.81+/-0.06 gm/cm2 at 6 and 12 months of therapy, respectively(p<0.01, Fig. 2). 2) The BMD of 2nd lumbar spine did not change during GH therapy. 3) The BMD of 3rd lumbar spine was decreased with marginal significance from 0.73+/-0.09 gm/cm2 before therapy to 0.66+/-0.09 gm/cm2, 0.65+/-0.05 gm/cm2 after 6 and 12 months of therapy, respectively(p=0.05). 4) The BMD of 4th lumbar spine was significantly decreased from 0.75+/-0.06 gm/cm2 before therapy to 0.69+/-0.10 gm/cm2, 0.64+/-0.08 gm/cm2 after 6 and 12 months of therapy, respectively(p<0.01, Fig. 2). 5) There was no significant correlation between the changes of the BMD and Bone or chronological age at initial GH therapy. Conclusion : The positive effect on BMD of GH therapy seems to be dependent on the specific area of skeletal system, where GH might exerts its effect, regardless of the existence of estrogen effect. The BMDs of another areas of skeletal system, where GH does not exert its effect, did not change with GH therapy and rather decreased by probably unknown mechanisms and GH therapy. These unknown mechanisms partially might involve the estrogen defect on BMD, This should be remained to be clarified with more patients and longer duration of study.

A Case of Turner's Syndrome(46, XXqi) Associated with Large Atrial Septal Defect and Mitral Valve Prolapse

We descrive a 23-year-old female of 46, XXqi Turner's syndrome associated with large atrial sepatal defect(secundum type) and mitral valve prolapse who was admitted due to amenorrhea, sexual infantilism and exertional dyspnea. This patient had only one spontaneous menstrual period at the age of 15 and had a short stature without webbed neck. Chromosomal aberrations cause primarily structural defects of cardiovasculaqr system, and a variety of structural aberrations involving the X chromosome and cause partial or complete Turner's syndrome. In Turner's syndrome, bicuspid aortic valve or coarctaton of aorta is frequently combined, also aortic root dilatation, partial anomalous venous drainage, hypoplastic left heart and ventricular septal defect, atrial septal defect has been reported. However, this patient had not abnormalities in aortic valve and whole aorta. Atrial septal defect simultaneously with mitral valve prolapse in 46 XXqi Turner's syndrome have not been reported in Korea. We report this case with a brief review of the literature.