Precocious pseudopuberty with testicular enlargement

Gonadotropins independent precocious puberty (GIPP) in male is characterized by early appearance of sexual hairs and phallic growth but without testicular enlargement. We report a case of GIPP with testicular enlargement who was diagnosed to have testotoxicosis and successfully managed with spironolactone.     

Hypothyroidism-associated testicular enlargement: is it a form of precocious puberty or not? A case report

In children with untreated hypothyroidism, the onset of puberty is usually delayed, but gonadotropin-independent precocious puberty may occur in children with severe hypothyroidism of long duration. The association of hypothyroidism, delayed bone age and gonadotropin-independent precocious puberty is defined as Van Wyk Grumbach syndrome (VWGS). VWGS has been described mostly in girls, and only seldom in boys. The manifestation of VWGS in boys is only testicular enlargement without substantial Leydig cell stimulation or testosterone secretion. We report a case of testicular enlargement due to obvious hypothyroidism secondary to autoimmune thyroiditis in a boy who presented with obesity. With this case report, we would like to emphasize that VWGS is not a real gonadotropin- independent precocious puberty in boys as it is in girls. Additionally, we would like to emphasize that delayed bone age is a special discriminating feature for differentiation of VWGS from the other causes of precocious puberty.     

Clinical presentation of McCune-Albright syndrome in males

The aims of this study were: (a) to survey gender prevalence and clinical findings at diagnosis in a series of patients who manifested at the time of this study the classical triad of McCune-Albright syndrome (MAS); (b) to investigate whether clinical presentation of MAS in boys may be different from that in girls; (c) to confirm whether boys with MAS may show a peculiar picture of testicular microlithiasis (TM) by testicular ultrasonography (US). Twenty-six patients (10 boys) with the classical clinical manifestations of MAS were recruited for the present study from the database of the Italian Multicenter Study Group on MAS. Age at diagnosis of MAS was significantly lower in girls than in boys (p < 0.025). Whilst there was no difference in the prevalence of skin and bone fibrous dysplasia for the two groups, a significantly higher prevalence of peripheral precocious puberty (PPP) was found in girls (chi2 = 6.5, p < 0.025). Moreover, PPP onset was earlier in females than in males (2.8 +/- 2.3 vs. 6.9 +/- 2.7 years, p < 0.005). In one boy, aged 2.9 years, the first clinical manifestation of MAS was monolateral testicular enlargement in the context of a picture of classical PPP. US scanning of the testes, at the time of the present study, showed bilateral hyperechogeneic multiple spots, compatible with diagnosis of TM, in 6/10 boys. CONCLUSIONS: (a) MAS is slightly more frequent in females. (b) PPP in MAS is significantly more frequent and earlier in girls. (c) PPP in boys with MAS is generally associated with bilateral testicular enlargement, but monolateral macroorchidism may also be seen. (d) TM may be another marker for MAS in males.     

Clinical aspects of testicular microlithiasis in boys: a review

ObjectiveAfter review of the pediatric literature, we report on the prevalence of testicular microlithiasis and its relation with benign and malign entities. We provide a guideline for the management of boys with testicular microlithiasis.Materials and methodsThe databases searched were Medline, Web of Science, Embase and the Cochrane Library. Data on the rates of testicular microlithiasis were collected and from each study information was extracted on the study population according to country, study design, diagnostic method, type of patient, number of patients, age, associated anomalies, additional diagnostic methods and follow-up information. From the 472 articles, we selected 126 articles as potentially relevant, of which 57 were included.ResultsIn asymptomatic boys, the prevalence of testicular microlithiasis is 4.2% and in symptomatic referrals it is 1.6%. The development of a testicular malignancy is occasionally reported after diagnosis of testicular microlithiasis. The management of boys with testicular microlithiasis varies widely. Most authors recommend regular self-examination, and some perform testicular ultrasound and/or screen tumor markers.ConclusionThe prevalence of testicular microlithiasis in boys varies between 1.1% and 4.2%. For follow-up, regular self-examination is advised from the age of 15 years.     

Klinefelter's syndrome associated with precocious puberty due to tumoral secretion of chorionic gonadotropins

A 8 and a half year-old boy presented with precocious puberty related to a malignant thoracic teratoma. He was also shown to have a Klinefelter syndrome. Precocious puberty related mainly to the liver, intracranial or thoracic tumors is rare. It seems to be exclusively observed in boys. The slight testicular enlargement is the main clinical sign. The contrast between high LH and low FSH levels is the most striking biological data. The diagnosis is proved by plasma HCG, beta-HCG and alpha-foetoprotein determination. Our patient is the third one with Klinefelter syndrome; this this association is certainly not fortuitous.     

Hypothalamic-pituitary gonadal axis in boys with primary hypothyroidism and macroorchidism

Nine of 15 boys with severe long-standing primary hypothyroidism were found to have macroorchidism. All 15 patients had elevated thyroid-stimulating hormone levels. However, only those patients with testicular enlargement had striking elevations of serum prolactin and gonadotropin values. The response to gonadotropin-releasing hormone in our patients was blunted, in contradistinction to that of children with true precocious puberty. In spite of the elevated levels of luteinizing hormone, the serum testosterone levels were in the prepubertal range, explaining the lack of peripheral manifestations of androgenic effect. Improvement of testosterone secretion followed decreasing prolactin levels with bromocriptine administration, suggesting an inhibitory effect of prolactin on luteinizing hormone action at the Leydig cell. We conclude that testicular enlargement is the result of continuous follicle-stimulating hormone stimulation and that the term "true precocious puberty" is not appropriate in children with hypothyroidism and macroorchidism unless the hypothalamic-pituitary gonadal axis is shown to be at the pubertal stage.     

Image diagnosis in McCune-Albright syndrome

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, precocious puberty and cafè-au-lait skin lesions. Bone lesions are characterized by the presence of fibrous connective tissue with a characteristic whorled pattern and containing trabeculae of immature non-lamellar (woven) bone. They may be solitary (monostotic) or multiple (polyostotic). Commonly involved bones include the femur, tibia, ribs and facial skeleton. In the fibula pseudo-cystic areas and 'ground glass'-like areas, in the femur 'shepherd crook' deformation due to weight on a less resistant bone and secondary to many cortical microfractures, are typical. MRI gives the exact delimitation of the lesions and is especially indicated in the followup of monostotic forms and in the outcome of surgical corrections. Bone scintigraphy with technetium 99 is essential in the follow-up of the disease. Ultrasonography is very useful in ovarian cyst follow-up and in the detection of thyroid and adrenal nodules and testicular microlithiasis.     

Phenotypic testicular abnormalities and pubertal development in boys with McCune-Albright syndrome

Aim of this survey is to review the few available literature data on pathophysiologic and clinical aspects of pubertal development in boys with McCune-Albright syndrome (MAS). On the basis of such analysis, we concluded that:1) peripheral precocious puberty (PPP) is significantly more infrequent in boys than in girls; 2) the most common testicular abnormality at MAS presentation is macroorchidism, that may be either monolateral or bilateral; 3) macroorchidism is not always associated with clinical and biochemical evidence of PPP; 4) testicular microlothiasis is distinctly more frequent in boys with MAS than in those without MAS; 5) the available therapeutic schedules have to be adopted already at MAS presentation only in the cases with PPP.     

Precocious puberty in a 7-year-old boy: A novel case

A 7-year-old boy was referred for evaluation of precocious puberty, evidenced by penile enlargement and pubic hair formation. His testicular size was prepubertal bilaterally. A comprehensive hormonal evaluation showed an elevated serum testosterone value (4.0 nmol/L) and a prepubertal gonadotropin value. A 0.9-cm heterogenous left testicular mass was detected on scrotal ultrasonography. Inguinal exploration was performed with ultrasound-guided open testicular biopsy and orchiectomy. Pathologic evaluation of the orchiectomy specimen showed the unclassified type of a mixed germ cell sex cord stromal tumor (MGCSCST), composed of neoplastic Sertoli cells and seminoma-like germ cells. Isolated previous reports of unclassified MGCSCSTs of the testis are now thought to be reports of sex cord stromal tumors with entrapped non-neoplastic germ cells. In our patient, the germ cells appeared to be neoplastic with aberrant expression of c-kit and placental alkaline phosphatase, a high proliferative rate, and DNA aneuploidy. Postoperatively, the patient's serum testosterone concentrations returned to prepubertal values (<0.2 nmol/L) and puberty was halted. This case represents a novel cause of precocious puberty.     

Van Wyk and Grumbach syndrome revisited: imaging and clinical findings in pre- and postpubertal girls

Background In 1960 Van Wyk and Grumbach described a syndrome of juvenile hypothyroidism, precocious puberty and ovarian enlargement. These findings undergo complete regression with thyroid hormone replacement therapy. This diagnosis can be made on the basis of imaging findings and thyroid function analysis, avoiding surgery. Objective To relate the distinctive clinical and imaging features and putative pathophysiological mechanism of a series of patients with Van Wyk and Grumbach syndrome (VWGS). Materials and methods Patients with VWGS diagnosed at two large children’s hospitals over a 6-year period beginning in 1999 were retrospectively reviewed. A literature review was also conducted. Results Five female patients were diagnosed with cystic ovarian enlargement and hypothyroidism at ages ranging from 9 to 17 years. Isosexual precocious puberty was found in prepubescent patients. Associated findings included delayed bone age, ascites, and pleural and pericardial effusions. Ovarian cyst involution occurred following treatment of the hypothyroidism. Conclusion The association of primary hypothyroidism with cystic ovarian enlargement and precocious puberty is important to recognize. In the absence of suspected ovarian torsion, surgery is unnecessary, as cyst regression occurs after appropriate thyroid hormone replacement. Noncompliance with hormone replacement therapy should be considered when cystic ovarian enlargement is noted in patients with a history of hypothyroidism.     

Leydig Cell Testicular Tumour Presenting as Isosexual Precocious Pseudopuberty in a 5 Year-old Boy with No Palpable Testicular Mass

Leydig cell testicular tumors are very rare in children and cause isosexual precocious puberty. Palpable testicular mass or asymmetric testes are common findings on routine examination. We report on a 5-yr-old boy with a Leydig cell tumor of the testis presented with isosexual precocious puberty but no scrotal palpable mass. To our knowledge, this is the first reported Leydig cell tumor in a boy without palpable scrotal mass.     

超声检查在大鼠腹腔镜Fowler-Stephens术后睾丸萎缩中的诊断价值

目的　探讨超声检查包括灰阶影像和能量多普勒在大鼠腹腔镜Fowler Stephens(F S)术后睾丸萎缩中的诊断价值。方法　 30d龄幼年Wistar大鼠行腹腔镜下右侧F S术 (精索血管腹腔内离断 ) ,术后从 9～ 5 4 0d 7个时段 (青春发育前期至中年期 ) ,分别用睾丸触诊和超声检查来判断睾丸萎缩情况 ,并与组织学检查结果进行对比。结果　腹腔镜F S术后该三种检查的睾丸萎缩检出率分别为 6 6 .7%、6 9.4 %和 84 .7% (P <0 .0 5 )。按超声诊断睾丸萎缩可分为三度 (0、Ⅰ、Ⅱ ) ,其相应组织学变化分别为正常或轻度萎缩、重度萎缩和完全萎缩。超声检查对重度和完全睾丸萎缩的检出率为 96 .0 %。用超声检查观察睾丸体积、边界、内部回声均匀情况、微结石和血流信号等指标可最早在术后 9d和 4 5d发现组织学上表现为完全萎缩和重度萎缩的睾丸。而睾丸触诊仅能发现术后 4 5d及其后的完全睾丸萎缩。结论　用超声检测睾丸体积、内部回声均匀于否、微结石和血流下降等指标能无损伤、客观地反映F S手术后不同阶段睾丸萎缩情况。F S术后的常规检查应为超声而非触诊     

LHCGR基因突变(Asp578His)致家族性男性性早熟1例临床特点及基因分析

该文报道1例由LHCGR基因激活性杂合突变导致的家族性男性性早熟(FMPP)患儿的临床特点及基因分析。患儿为男性,婴儿时期出现了外生殖器增长过快、生长加速,伴阴毛及阴茎勃起,结合患儿性征检查、促性腺激素释放激素兴奋试验、血清睾酮检测及骨龄检查等结果,临床诊断为外周性性早熟。随后对患儿及其父母的性早熟相关基因进行检测。基因测序结果提示患儿黄体生成素/绒毛膜促性腺激素受体(LHCGR)基因第11外显子1732GC突变,导致578位氨基酸由天冬氨酸变为组氨酸,该突变是1个未见文献报道的新突变,且父母基因检测结果未见异常。联用第3代芳香化酶抑制剂来曲唑和抗雄激素制剂螺内酯治疗半年后,患儿症状得到控制。该研究结果扩展了LHCGR基因突变谱,为FMPP病因诊断及家系的遗传咨询和产前诊断提供了分子依据。     

Testicular microlithiasis: The importance of self‐examination

Aim: To explore the issue of appropriate management of testicular microlithiasis. We report the third ever case of tumour arising from a testis previously known to have microlithiasis in childhood and review the literature to provide an evidence‐based approach to management of testicular microlithiasis. Methods: Case report and review of previous literature. Results and Conclusions: Although there is a strong association between testicular microlithiasis and testicular malignancy at diagnosis, there are only three reported cases of subsequent tumour development in childhood. Testicular microlithiasis is an increasingly recognised entity. There is insufficient evidence in the current literature to support any regime of clinical surveillance. Self‐examination is the most important factor in the early detection of testicular malignancy.     

A Case of Precocious Pseudopuberty Associated With Ovarian Follicular Cyst

A case of precocious pseudopuberty associated with a follicular cyst in the ovary is described. A five-year-and-month-old Japanese girl had breast enlargement, areolar pigmentation and intermittent genital bleeding. On laparotomy, bilateral ovarian cysts were found. The left cyst (4.0 times 4.0 times 3.5 cm) was far larger than the right (1.5 times 1.3 times 1.3). The fluid in the left cyst contained a high concentration of estrogens. Therefore, the main cause of the precocious puberty was thought to be the left cyst. It was clearly detected by ultrasonography and computed tomography only when the signs of precocious puberty were remarkable and the serum estrogen level was increased; however, the right one could not be detected throughout the observation. We consider that in the case of intermittent puberty a functioning ovarian cyst can be identified more easily when the signs of precocious puberty are remarkable and the serum estrogen level is increased.     

Central precocious puberty

Diagnosis of the central origin of precocious puberty is easy in boys on the enlargement of the testes. In girls, conversely, diagnosis of central precocious puberty (CPP) may be difficult, as isolated development of the breast may initially be the only feature. Differentiation of CPP and premature thelarche is nevertheless essential, as CPP always requires neuroradiologic investigations to look for an intracranial space-occupying lesion and may indicate inhibitory treatment. CPP is usually idiopathic in girls and tumor-related in boys. Early secretion of sex steroids increases the rate of growth and bone maturation and may lead to final short stature. LHRH analogues represent a breakthrough in the treatment of CPP.     

Ultrasound demonstration of testicular microlithiasis in pediatric patients: is there an association with testicular germ cell tumors?

Background

There is suggestion that testicular microlithiasis predicts risk of testicular malignancy, especially testicular germ cell tumors. This association remains uncertain.

Objective

We retrospectively reviewed testicular germ cell tumor occurrence in patients with testicular microlithiasis to assess this association and determined the prevalence of testicular microlithiasis in symptomatic boys.

Materials and methods

This study was IRB and HIPAA compliant. Two-thousand six-hundred twenty-five testicular US exams performed on 2,266 children (younger than 19 years of age) in our institution from 2000 through 2011 were reviewed for presence of testicular microlithiasis and masses. Testicular microlithiasis was defined as presence of five or more testicular microcalcifications on a single US image. Incidence of testicular germ cell tumors was calculated in a group of patients with testicular microlithiasis and in a control group without testicular microlithiasis. Relative risk, odds ratio, 90% and 95%CI were calculated.

Results

Eighty-seven patients out of 2,266 had testicular microlithiasis. One child was found to have both testicular germ cell tumor and testicular microlithiasis. In 2,179 children without testicular microlithiasis, 8 had testicular germ cell tumors. Incidence of testicular microlithiasis was 3.8%. Incidence of testicular germ cell tumors in testicular microlithiasis patients was 1.2%, and 0.38% in non-testicular microlithiasis patients. Relative risk of testicular germ cell tumors in testicular microlithiasis patients vs. non-testicular microlithiasis patients was 3.13 (90%CI: 0.55–17.76; 95%CI: 0.40–24.76), odds ratio 3.16 (90%CI: 0.55–18.32; 95%CI: 0.39–25.5).

Conclusion

There is no association between testicular microlithiasis and testicular germ cell tumors. We had hoped to do a meta-analysis, but only two studies had a sufficient case control group of non-testicular microlithiasis patients.     

Central precocious puberty in 48,XXYY Klinefelter syndrome variant

We report the first case of central precocious puberty in a patient with 48,XXYY Klinefelter syndrome variant. We also report clinical characteristics, growth pattern, endocrine data and pathological testicular findings. The patient did not receive medical care for his precocious pubertal development, because of adequate height prognosis, and reached normal height for both his target height and Klinefelter patients. Since precocious puberty seems to occur in Klinefelter syndrome and its variants, we advise karyotype analysis in boys with mental retardation, gynecomastia, small testes and precocious onset of puberty.     

Undulating course of precocious puberty]

The normal course of precocious puberty is progredient resulting eventually in full sexual maturation. In few cases a transient form of the disease has been recorded, characterized by a temporary appearance of signs of sexual maturation. We report on a female patient with an undulating course of the disorder: after precocious initiation of puberty, a temporary interruption and subsequent resumption of sexual maturation occurred. Presently, the patient is successfully treated with an LHRH-analogon. Within the framework of this case problems in diagnosis and treatment of precocious puberty are being discussed.