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1.
Best Pract Res Clin Endocrinol Metab ; 34(6): 101480, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33358481

RESUMO

Klinefelter syndrome (KS) is defined as the presence of one or more extra "X" chromosome in a male patient. It affects approximately 1 in 600 newborn males and the most common chromosomal abnormality, leading to male hypogonadism and infertility. There is a lack of data supporting best practices for KS patients' care. In this paper we review controversial issues in KS research ranging from mechanisms of variation in KS phenotype to abnormalities resulting in reduced sperm production to successful sperm retrieval disparities after testicular sperm extraction (TESE). Translation to live birth and offspring health is also examined. Finally, medical therapies used to optimize the hormonal status and chances of fertility in KS patients are reviewed. We will also discuss the experimental spermatogonial stem cell (SSC) treatments, which are considered the future for TESE negative patients.


Assuntos
Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/terapia , Humanos , Recém-Nascido , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Triagem Neonatal , Recuperação Espermática , Espermatozoides/anormalidades , Espermatozoides/metabolismo , Testículo/metabolismo , Testículo/patologia
3.
Andrologia ; 52(1): e13489, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31777105

RESUMO

A 27-year-old man with nonobstructive azoospermia was diagnosed with Klinefelter syndrome (KS) with a satellite Y chromosome (47, XXYqs) by karyotyping. Genetic analysis revealed azoospermia factor c (AZFc) microdeletion of gr/gr deletion in the Y chromosome. Microdissection testicular sperm extraction (micro-TESE) was performed in bilateral testes. Very few seminiferous tubules were bilaterally observed, and a minute number of spermatozoa obtained from the left testis were cryopreserved. Histologic examination of the left testicular tissue revealed severe tubular atrophy with only Sertoli cells accompanied by Leydig cell hyperplasia. Oocyte harvest was conducted in his wife in two different cycles after ovarian stimulation, and intracytoplasmic sperm injection was performed for 24 oocytes (8 and 16 oocytes respectively) using thawed spermatozoa. Fertilisation was confirmed in total of 19 oocytes (79.2%), with 15 cleaved embryos (62.5%). Two cleavage-stage embryos were cryopreserved at day 2, but no blastocysts developed. Frozen-thawed embryo transfer was performed using two cleavage-stage (day 2) embryos; however, the wife did not conceive. In conclusion, spermatozoa were successfully obtained by micro-TESE from a patient with 47, XXYqs. Despite failure of conception, the fertilisation and cleavage rates were comparable or better than those reported in patients with "typical" KS.


Assuntos
Síndrome de Klinefelter/terapia , Recuperação Espermática , Adulto , Cromossomos Humanos Y/genética , Feminino , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Microdissecção/métodos , Injeções de Esperma Intracitoplásmicas , Resultado do Tratamento
4.
Biochem Genet ; 58(1): 74-101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31273557

RESUMO

Chromosomal microarray (CMA) has emerged as a robust tool for identifying microdeletions and microduplications, termed copy number variants (CNVs). Nevertheless, data regarding its utility in different patient populations with developmental delay (DD), dysmorphic features (DF) and congenital anomalies (CA), is a matter of dense debate. Although regions of homozygosity (ROH) are not diagnostic of a specific condition, they may have pathogenic implications. Certain CNVs and ROH have ethnically specific occurrences and frequencies. We aimed to determine whether CMA testing offers additional diagnostic information over classical cytogenetics for identifying genomic imbalances in a pediatric cohort with idiopathic DD, DF, or CA. One hundred sixty-nine patients were offered cytogenetics and CMA simultaneously for etiological diagnosis of DD (n = 67), DF (n = 52) and CA (n = 50). CMA could identify additional, clinically significant anomalies as compared with cytogenetics. CMA detected 61 CNVs [21 (34.4%) pathogenic CNVs, 37 (60.7%) variants of uncertain clinical significance and 3 (4.9%) benign CNVs] in 44 patients. CMA identified one or more ROH in 116/169 (68.6%) patients. When considering pathogenic CNVs and aneuploidies as positive findings, 9/169 (5.3%) received a genetic diagnosis from cytogenetics, while 25/169 (14.8%) could have a genetic diagnosis from CMA. The identification of ROH was clinically significant in two cases (2/169), thereby, adding 1.2% to the diagnostic yield of CMA (16% vs. 5.3%, p < 0.001). CMA uncovers additional genetic diagnoses over cytogenetics, thereby, offering a much higher diagnostic yield. Our findings convincingly demonstrate the additive diagnostic value of clinically significant ROH identified during CMA testing, highlighting the need for careful clinical interpretation of these ROH.


Assuntos
Síndrome de Down/diagnóstico , Homozigoto , Síndrome de Klinefelter/diagnóstico , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome de Turner/diagnóstico , Adolescente , Criança , Pré-Escolar , Quebra Cromossômica , Estudos de Coortes , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/genética , Síndrome de Down/genética , Feminino , Humanos , Lactente , Recém-Nascido , Síndrome de Klinefelter/genética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/genética , Síndrome de Turner/genética
5.
J Diabetes Investig ; 11(2): 506-507, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31389187

RESUMO

Klinefelter syndrome (KS) is frequently complicated by diabetes. However, it is severely underdiagnosed due to a lack of reliable screening methods. We diagnosed two patients with KS at the Center for Diabetes and Endocrinology, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan. By comparing the patients with 39 non-KS patients with diabetes, we propose a screening tool for KS in patients with diabetes.


Assuntos
Complicações do Diabetes , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Programas de Rastreamento/métodos , Adulto , Estatura , Complicações do Diabetes/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Síndrome de Klinefelter/sangue , Hormônio Luteinizante/sangue , Masculino , Testosterona/sangue
6.
Best Pract Res Clin Endocrinol Metab ; 34(6): 101479, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33390350

RESUMO

Non-obstructive azoospermia is a distinct diagnosis within male infertility in which no sperm is found in the ejaculate as a result of spermatogenesis failure. Because of the increased prevalence of genetic abnormalities in men with non-obstructive azoospermia, male infertility guidelines recommend screening for karyotype abnormalities and Y chromosome microdeletions in this population. Numerous karyotype abnormalities may be present resulting in impaired spermatogenesis, including: Klinefelter syndrome, translocations, and deletions. Y chromosome microdeletions of the AZFa, AZFb, AZFc subregions all can also result in non-obstructive azoospermia with the possibility of sperm being present if only the AZFc subregion is deleted. While these are the two genetic tests recommended by the guidelines, nearly 50%-80% of non-obstructive azoospermia has no identifiable cause and is deemed idiopathic. Several other genetic defects can lead to non-obstructive azoospermia including Kallmann syndrome, mild androgen insensitivity syndrome, and TEX11. While many additional candidate genes have been proposed, many have yet to be verified or are so infrequent in the population that screening is cost-ineffective. Much research is still required in the genetics of non-obstructive azoospermia and will require multi-institutional initiatives to better understand the genetics of condition.


Assuntos
Azoospermia/genética , Mutação , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Azoospermia/diagnóstico , Azoospermia/epidemiologia , Deleção Cromossômica , Cromossomos Humanos Y/genética , Diagnóstico Diferencial , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Espermatozoides/anormalidades , Espermatozoides/metabolismo
7.
Medicine (Baltimore) ; 98(44): e17838, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689873

RESUMO

RATIONALE: Recurrence of Klinefelter syndrome (KS) in non-twin brothers is very rare. This study examined the inheritance pattern of supernumerary X chromosomes in non-twin brothers. PATIENT CONCERNS: A 16-year-old man presented with small-sized testicles. During his diagnostic work-up, his brother, in his late 20's, also complained of small testes and erectile dysfunction. DIAGNOSIS: Chromosome analysis in peripheral blood revealed non-mosaic 47,XXY karyotype in both brothers. Their mother showed a normal 46,XX karyotype. INTERVENTIONS: To examine the inheritance pattern of supernumerary X chromosomes, quantitative-fluorescence PCR was performed with small tandem repeat markers. It revealed that their supernumerary X chromosomes were inherited from different parents. OUTCOMES: After the diagnosis of KS, 2 brothers started to receive testosterone treatment. CONCLUSION: This case report is the first to report differences in the origins of supernumerary X chromosomes in brothers with KS and furthers the current understanding of the cytogenetic mechanisms in KS.


Assuntos
Cromossomos Humanos X , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Adolescente , Adulto , Disfunção Erétil/etiologia , Humanos , Síndrome de Klinefelter/tratamento farmacológico , Masculino , Pais , Reação em Cadeia da Polimerase/métodos , Irmãos , Sequências de Repetição em Tandem , Testosterona/uso terapêutico
8.
Am J Med Genet A ; 179(12): 2374-2381, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31577063

RESUMO

This cross-sectional, retrospective analysis investigated the possible effect of hormonal replacement therapy (HRT) on working memory (WM) and competency/adaptive functioning (CAF) in boys with 47,XXY; the effect of timing of 47,XXY diagnosis on these variables; and the relationship between WM and CAF, if any. A total of 111 boys with 47,XXY, ranging from 6 to 16 years of age (M = 9 years 4 months; SD = 2 years 1 month), were evaluated using the Wechsler Intelligence Scale for Children, and Child Behavior Checklist. Participants were grouped by HRT status and timing of diagnosis. Analysis of variance testing performed on the prenatally diagnosed boys revealed a statistically significant difference in WM for the HRT groups (F[3,84] = 7.467, p = .000174), where WM of the no-HRT group (M = 92.37, SD = 17.83) was lower than that of the early hormonal therapy group (M = 106.39, SD = 12.01; p = .0092). Additionally, there was a positive correlation between low WM capabilities and poor school performance (r = .5106, p = .0027) in the prenatally diagnosed, untreated boys. Our results highlight the potentially positive effects of HRT on WM and CAF in boys with 47,XXY. Further research is required to better determine the underlying relationship among the biological mechanisms of HRT, WM, and CAF outcomes, and timing of diagnosis in boys with 47,XXY.


Assuntos
Adaptação Fisiológica , Terapia de Reposição Hormonal , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/tratamento farmacológico , Síndrome de Klinefelter/genética , Memória de Curto Prazo , Adolescente , Criança , Humanos , Masculino , Classe Social , Testosterona/uso terapêutico
9.
Lupus ; 28(12): 1477-1479, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31551034

RESUMO

We describe a 65-year-old man who presented with arthralgia, reduced body hair and gynecomastia. He showed severe pancytopaenia. Laboratory examination revealed high follicle-stimulating hormone, low testosterone and oestradiol, elevated antinuclear antibodies, anti-dsDNA and ESR levels, as well as low complement levels. An electrocardiogram showed atrial fibrillation. Computed tomography and dual-energy x-ray absorptiometry showed pleural effusion and osteoporosis. Chromosome analysis revealed 47, XXY karyotype. The unifying diagnosis was therefore Klinefelter's syndrome (KS) with systemic lupus erythematosus (SLE), with manifestations of pancytopaenia, atrial fibrillation, serositis and osteoporosis. After immunosuppressive therapy, his physical condition and pancytopaenia improved. Sex hormones and gene escape from X chromosome inactivation may contribute to the pathogenesis of SLE. Clinicians should consider autoimmune processes when patients with KS present with pancytopaenia or additional features of a systemic autoimmune disorder.


Assuntos
Fibrilação Atrial/diagnóstico , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/genética , Lúpus Eritematoso Sistêmico/etiologia , Idoso , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Humanos , Imunossupressores/uso terapêutico , Síndrome de Klinefelter/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Osteoporose/etiologia , Pancitopenia/etiologia , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Serosite/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
11.
Rev Med Chil ; 147(4): 518-521, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344216

RESUMO

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.


Assuntos
Síndrome de Klinefelter/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Adulto , Humanos , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Radiografia Torácica , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico , Tomografia Computadorizada por Raios X
12.
Horm Res Paediatr ; 91(5): 293-310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31302655

RESUMO

Tall stature and/or accelerated growth (TS/AG) in a child can be the result of a primary or secondary growth disorder, but more frequently no cause can be found (idiopathic TS). The conditions with the most important therapeutic implications are Klinefelter syndrome, Marfan syndrome and secondary growth disorders such as precocious puberty, hyperthyroidism and growth hormone excess. We propose a diagnostic flow chart offering a systematic approach to evaluate children referred for TS/AG to the general paediatrician. Based on the incidence, prevalence and clinical features of medical conditions associated with TS/AG, we identified relevant clues for primary and secondary growth disorders that may be obtained from the medical history, physical evaluation, growth analysis and additional laboratory and genetic testing. In addition to obtaining a diagnosis, a further goal is to predict adult height based on growth pattern, pubertal development and skeletal maturation. We speculate that an improved diagnostic approach in addition to expanding use of genetic testing may increase the diagnostic yield and lower the age at diagnosis of children with a pathologic cause of TS/AG.


Assuntos
Acromegalia/diagnóstico , Transtornos do Crescimento/diagnóstico , Puberdade Precoce/diagnóstico , Acromegalia/etiologia , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/etiologia , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Puberdade Precoce/etiologia
13.
Acta Otolaryngol ; 139(6): 479-486, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035849

RESUMO

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS. OBJECTIVES: This study examined the causative genes in three Chinese probands with congenital hearing loss. MATERIAL AND METHODS: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy. RESULTS: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis. CONCLUSIONS: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.


Assuntos
Surdez/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Síndrome de Klinefelter/genética , Miosina VIIa/genética , Síndromes de Usher/genética , Criança , China , Implantes Cocleares , Surdez/congênito , Feminino , Auxiliares de Audição , Humanos , Síndrome de Klinefelter/diagnóstico , Masculino , Multimorbidade , Mutação , Prognóstico , Amostragem , Síndromes de Usher/diagnóstico
14.
Rinsho Shinkeigaku ; 59(5): 253-257, 2019 May 28.
Artigo em Japonês | MEDLINE | ID: mdl-31061299

RESUMO

A 69-year-old man was admitted because of subacute development of lower limb weakness from one month ago. He showed central obesity, gynecomastia, dorsal fat pad ("buffalo hump"), and proximal muscle weakness in the lower extremities (manual muscle test 4). Needle EMG, muscle MRI and labolatry screening including CPK were negative for neuromuscular diseases, except for the hypogenitalism accidentally detected in MRI. Although blood corticol was in normal range, the levels of serum ACTH and 24-hour urinary free cortisol excretion were high, and the dexamethasone suppression tests were positive. Brain MRI showed a small pituitary mass with gadolinium enhancement, and ACTH measurement from petrosal sinus sampling after CRH stimulation lead to the diagnosis of definite Cushing disease. Moreover, he also showed low testosterone and elevated LH and FSH. Chromosome banding revealed 47 XXY in 22 in 30 cells, leading to the diagnosis of mosaic Klinefelter syndrome. The supplementation with testosterone was partially effective for his weakness. The surgical resection of pituitary microadenoma resulted in the full recovery. Either Klinefelter syndrome or mild Cushing disease alone was insufficient as a cause of the muscle weakness in this patient. It is plausible that the mild elevation of cortisol accompanied by the lack of tesstelone may underlie the weakness, probably linked to impaired balance between muscle anabolism and catabolism.


Assuntos
Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Doenças Musculares/etiologia , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico , Doença Aguda , Adenoma/complicações , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/sangue , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Bandeamento Cromossômico , Hormônio Foliculoestimulante/sangue , Humanos , Hidrocortisona/urina , Hormônio Luteinizante/sangue , Imagem por Ressonância Magnética , Masculino , Debilidade Muscular/etiologia , Doenças Musculares/diagnóstico , Doenças Musculares/terapia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Testosterona/administração & dosagem , Testosterona/deficiência , Resultado do Tratamento
15.
J Pak Med Assoc ; 69(4): 567-571, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31000864

RESUMO

This study was designed to investigate the hormonal, seminal changes and chromosomal aberrations in cases of male infertility. A total of ten infertile families from Khyber Pakhtunkhwa of Pakistan were included in the study. The families were clinically evaluated by standard criteria; diagnosis of azoospermic and oligospermic males was confirmed. Seminal, hormonal, ultra sonographic and histopathological examinations were carried out for all the affected participants of the study. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Hormones were altered in six families. Ultrasonographic abnormal finding was observed in six families. Karyotyping analysis revealed numerical aberration in family G (0X) and family I (XXY). The remainingfamilies had no structural or numerical aberration. Y chromosome microdeletion analysis revealed AZFc deletion in both the affected participants of the family C. The remaining families were found normal for microdeletion. The occurrence of chromosomal anomalies and Y chromosome microdeletions among infertile males strongly suggests the need to include these two tests in routine investigations of male in fertility cases.


Assuntos
Azoospermia/genética , Hipogonadismo/genética , Infertilidade Masculina/genética , Oligospermia/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adolescente , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Proteína 1 Suprimida em Azoospermia/genética , Família , Humanos , Infertilidade Masculina/diagnóstico , Síndrome de Klinefelter/diagnóstico , Masculino , Pessoa de Meia-Idade , Linhagem , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Adulto Jovem
16.
Rev. méd. Chile ; 147(4): 518-521, abr. 2019. graf
Artigo em Espanhol | LILACS | ID: biblio-1014254

RESUMO

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.


Assuntos
Humanos , Masculino , Adulto , Timoma/patologia , Neoplasias do Timo/patologia , Síndrome de Klinefelter/patologia , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico , Radiografia Torácica , Tomografia Computadorizada por Raios X , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia
17.
Vnitr Lek ; 65(1): 51-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30823838

RESUMO

Acromegaly is a rare disorder usually caused by a benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF1) levels accompanying this disease is associated with complications such as cardiomyopathy, diabetes mellitus, sleep apnoea and arthropathy. Incidence of acromegaly is 3-4 patients per million per year. Klinefelter syndrome (KS) is the most common sex chromosome disorder occuring in about 1/500 live male births. Common physical features include particularly small testes, among other symptoms are tall stature, reduced muscle tone, delayed pubertal development, lack of secondary male sex characteristics and gynecomastia. We present a 32-year-old man suffering from both acromegaly and 47, XXY Klinefelter syndrome. The patient with typical acromegalic features. Laboratory tests revealed high level of GH which was not suppressed after glucose administration, high level of IGF1, low testosterone concentration with high concentation of luteinizing hormone and follicle stimulating hormone. A magnetic resonance imaging scan revealed a 25 × 18 × 18 mm macroadenoma involving the pituitary gland. A diagnosis of acromegaly was established. After this examination trans-sphenoidal resection was performed. Histopathologic and immunohistochemical findings revealed growth hormoneproducing pituitary adenoma. The presence of infertility with clinical features such as small testes, lack of secondary male sex characteristics and laboratory findings revealed hypergonadotropic hypogonadism that could not be explained by the diagnosis of acromegaly. A chromosomal karyotyping revealed a 47, XXY, confirming the diagnosis of KS. Testosterone replacement therapy wasn´t begun because of patient disagreement Postoperatively elevated plasma concentration of GH and IGF1 levels persist. Treatment by somatostatin analogues (lanreotid) was initiated at dose 120 mg every 28 days. Control magnetic resonance imaging of the sella demonstrated a residue of pituary adenoma size 14 × 14 × 7 mm. The patient is currently undergoing endoscopic revision of the residue. acromegaly - growth hormone - IGF1 - Klinefelter syndrome - testosterone.


Assuntos
Acromegalia , Adenoma , Síndrome de Klinefelter , Neoplasias Hipofisárias , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/genética , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/genética , Adulto , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética
18.
Andrologia ; 51(6): e13272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30907014

RESUMO

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.


Assuntos
Aneuploidia , Infertilidade Masculina/epidemiologia , Síndrome de Klinefelter/epidemiologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/epidemiologia , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Testes Genéticos/métodos , Necessidades e Demandas de Serviços de Saúde , Humanos , Incidência , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Estudos Prospectivos , Arábia Saudita/epidemiologia , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Contagem de Espermatozoides
19.
Bone ; 123: 103-114, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30914274

RESUMO

INTRODUCTION: The FSH receptor (FSHR) has been found to be expressed in human bone cells and bone marrow-adipocytes, and highly-debated mouse studies have suggested extra-gonadal effects of gonadotropins on glucose, adipocyte and bone homeostasis. These putative effects could be direct or indirectly mediated by endocrine factors released from bone-cells or adipocytes. Here, we investigated whether gonadotropins are linked with glucose- and lipid-metabolism in hypergonadotropic men. METHODS: Single centre, cross-sectional study of 307 men with idiopathic infertility and 28 men with Klinefelter syndrome (KS). OUTCOME: associations between serum LH and FSH with soluble-RANKL (sRANKL), osteoprotegerin (OPG), osteocalcin, fasting glucose and insulin, sex steroids, and body composition. Expression of FSHR was studied in human-derived adipocyte-cell-models (hMADS, TERT-hWA) and FSH stimulation of RANKL expression and secretion in hMADS in vitro. RESULTS: Serum FSH was not directly linked with glucose- and lipid-metabolism. However, FSH was inversely associated with sRANKL in both infertile men and KS men (p = .023 and p = .012). Infertile men with elevated FSH (>11 U/L) had significantly lower sRANKL (p = .015). sRANKL was positively associated with fat percentage, fasting insulin, and glucose (all p < .05). Men with prediabetes had higher sRANKL (p = .021), but lower testosterone (p < .0001) and Inhibin B (p = .005). The FSHR was expressed in the investigated human derived adipocytes, and 3-6 h treatment with FSH markedly increased RANKL release (p < .05). CONCLUSION: KS and infertile men with prediabetes have low Inhibin B, and testosterone but elevated RANKL compared with non-prediabetic men despite comparable levels of serum gonadotropins. Serum FSH and sRANKL was inversely associated in both infertile and KS men, but the increased release of RANKL from FSH treated adipocytes suggest a direct effect of FSH on RANKL production in some tissues. Further studies are required to clarify whether FSH targets RANKL in the skeleton. ClinicalTrial_ID:NCT01304927.


Assuntos
Adipócitos/metabolismo , Hormônio Foliculoestimulante/metabolismo , Infertilidade Masculina/metabolismo , Síndrome de Klinefelter/metabolismo , Ligante RANK/metabolismo , Adipócitos/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Coortes , Estudos Transversais , Hormônio Foliculoestimulante/farmacologia , Humanos , Infertilidade Masculina/complicações , Infertilidade Masculina/diagnóstico , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Masculino
20.
Andrologia ; 51(5): e13253, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30746732

RESUMO

BACKGROUND: Klinefelter syndrome(KS), affecting 1 in 500-1,000 newborn males, is the most common sex chromosome aneuploidy among males with primary hypogonadism. Isochromosome Xq on the other hand is a rare variant of Klinefelter syndrome, accounting approximately 0.3% of all KS and associated with normal height and androgenisation compared to classical KS. Here, we present a case of isochromosome Xq variant of KS with similar clinical and cytogenetic findings with the few cases reported before. MATERIALS AND METHODS: A 25-year-old male patient referred to our clinic with complaint of infertility. He is the son of a consanguineous couple who are first cousins and there was no family history of reproductive difficulty. In physical examination synophrys, prominent ear and small testicles noted. The patient's spermiogram showed azoospermia and scrotal USG revealed testicular atrophy. RESULTS: Karyotype analysis using G-banding resulted as 47,X,i(X)(q10),Y, and STR analysis showed no deletion in AZF and SRY loci of interest. CONCLUSION: Although several isochromosome Xq variant of KS cases can be found in literature, it is our duty to emphasise the importance of karyotyping for patients with reproductive difficulty who may not have all features of classical Klinefelter syndrome.


Assuntos
Cromossomos Humanos X/genética , Isocromossomos/genética , Síndrome de Klinefelter/genética , Adulto , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Masculino
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