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.     

Ovarian tumors with elevated CA-125 levels and severe juvenile hypothyroidism: A need for increased awareness

A 15-yr-old girl presented with bilateral gross ovarian tumors, clinical features of long-standing unrecognized hypothyroidism and markedly elevated CA-125 levels. Ovarian resection was avoided, as the presentation was consistent with the Van Wyk and Grumbach syndrome; and the patient was treated with replacement of thyroid hormone. Regression of the ovarian tumors occurred 6 months after initiation of the treatment. The authors emphasise the need for increased awareness and screening for hypothyroidism in patients with ovarian tumors, in order to prevent inadvertent operative interventions.     

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.     

Normal ovarian function and assessment of ovarian reserve in the survivor of childhood cancer

Increasingly young people survive cancer in childhood and as a result complications of its treatment are becoming more common and important. Premature ovarian failure is recognized as a complication of radiotherapy to a field that includes the pelvis and alkylating‐agent‐based chemotherapy. Young pre‐pubertal girls are not protected from the effects of gonadal toxic therapy. A young woman, successfully treated for cancer during childhood, may experience regular periods in the presence of a significantly reduced ovarian reserve. There is, however, no reliable measure of ovarian reserve available for the individual woman. Assessment of ovarian function relies on the use of surrogate markers such as follicle stimulating hormone, inhibin‐B, and anti‐mullerian hormone as well as ultrasound assessment of ovarian volume and antral follicle count. We discuss the physiology of normal ovarian function, the effects of cancer treatments on ovarian function and the techniques for evaluation of ovarian reserve in survivors of childhood cancer. Pediatr Blood Cancer 2009;53:296–302. © 2009 Wiley‐Liss, Inc.     

Primary juvenile hypothyroidism concurrent with huge bilateral cystic ovaries: Case report and literature review

Primary hypothyroidism can lead to delayed growth and pseudoprecocious puberty in juvenile patients, which was known as Van Wyk–Grumbach's syndrome (VWGS). There have been very few clinical case reports of primary juvenile hypothyroidism presenting with concurrent huge bilateral cystic ovaries. Here, we report the case of a 14-year-old female patient suffering from primary hypothyroidism in combination with bilateral cystic ovaries. Remarkable improvement of symptoms was observed after one month of hormone replacement therapy and an unnecessary surgical treatment was avoided. A comprehensive literature review of VWGS is summarised here to illustrate the presentation, diagnosis, and treatment of VWGS in pediatric patients. The present study aims to improve the current clinical knowledge of VWGS.     

小儿卵巢肿瘤56例临床分析

目的总结小儿卵巢良恶性肿瘤病理特点,以血清AFP作为指标评价治疗效果及预后。方法回顾性分析本院2005年至今手术治疗56例卵巢肿瘤患儿的肿瘤病理特点、肿瘤与年龄的关系以及治疗前后血清AFP值的变化(按良恶性分组并进行组间及组内比较)。结果 56例患儿中,年龄最小4个月,最大17.6岁;良性39例,恶性17例;良性肿瘤中,以卵巢成熟性畸胎瘤(20/39)及囊肿(19/39)多见;恶性肿瘤中,以卵巢未成熟性畸胎瘤(6/19)发病率高。恶性组血清AFP值术前或术后总体AFP值均显著高于良性组(P<0.01)。良性组手术前后血清总体AFP值的变化无统计学意义(P>0.05),而恶性组术后血清总体AFP值较术前下降,差异有统计学意义(P<0.01)。结论小儿卵巢肿瘤中良性者发病率高于恶性;血清AFP值可能作为良恶性鉴别及评估手术疗效的临床指标。手术是有效治疗小儿卵巢肿瘤、改善恶性卵巢肿瘤患儿预后的重要方法。     

Ovarian volume and uterine length in neonatal girls

This study was undertaken to establish reference values for the size of the uterus and ovaries in newborns. We also studied the frequency and follow-up of functional ovarian cysts in healthy neonatal girls. Pelvic ultrasonography was performed on 55 normal newborns. Right and left ovarian volumes positively correlated with birth weight and length, but there was no correlation between uterine length and any of the parameters studied. In a total of 55 newborns, 16 ovarian cysts were detected by transabdominal ultrasound: six neonates (10.9%) had cysts on the left side, ten (18.2%) on the right side, and two (3.6%) had bilateral cysts. All were uncomplicated homogeneous cysts and resolved spontaneously. A higher percentage of cysts was found in the 26 infants weighing 2,500-2,999 g, ten (38.4%) of whom had cysts, than in the 29 infants weighing 3,000 g or more, four (13.7%) of whom had cysts (p < 0.05). Newborns with cysts were followed up, and the cysts resolved spontaneously within 3 months in all but three patients in whom resolution took almost 6 months. Right and left ovarian volumes were positively correlated with birth weight and length, but no significant correlation was found between uterine length and any parameter. In conclusion, ovarian volume was found to be reduced in newborns with relatively low birth weight as well as intra-uterine growth retardation. Functional cysts were more prevalent among low birth weight girls. We suggest that small ovaries and ovarian dysfunction may have a prenatal origin, and further studies on normal and growth-retarded newborns are needed.     

Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents

This paper describes the imaging features of ovarian metastases from adenocarcinoma of the colon in adolescent females. We reviewed retrospectively abdominal and pelvic computed tomographic and pelvic ultrasound examinations, histologic slices, and clinical charts of six adolescent females with ovarian metastases secondary to adenocarcinoma of the colon. One patient had ovarian metastasis at presentation and was presumed to have a primary ovarian tumor. The ovarian metastases were either solid (n=3), complex with both solid and cystic components (n=2), or multilocular cysts (n=1). The ovarian lesions were large, ranging from 6 cm to 18 cm in diameter. Colorectal carcinoma in adolescent females is frequently associated with ovarian metastases. One imaging characteristic differs in adult and adolescent ovarian metastases, although they do have features in common: in adolescents, a smaller proportion of colorectal ovarian metastases are multicystic (17%) compared with the adult series (45%). These lesions are frequently large and may be complex, multicystic, or solid. Although it is a rare disease, the differential dignosis of adnexal masses in adolescent females should include ovarian metastases from adenocarcinoma of the colon.     

Neonatale Ovarialzysten

The detection rate of neonatal ovarian cysts has markedly increased with the widespread use of ultrasonography during pregnancy. Up to now the decision for an invasive therapy has depended primarily on the size of the cyst. Recent insights into the spontaneous postnatal course of ovarian cysts within the 1st year of life have made it possible to prefer a less invasive procedure or at least to postpone any invasive treatment beyond the neonatal period. Having studied the literature published to date, we recommend the following approach: (1) When ovarian cysts are so large that they distend the fetal abdomen to the extent of dystocia of labor primary cesarian section or prenatal aspiration in utero shortly before the time of birth should be performed. (2) All ovarian cysts that are symptomatic in the neonatal period require immediate surgical intervention, preferably by laparoscopy. (3) In the case of ovarian cysts that are asymptomatic in the neonatal period the approach needs to be more tailored to the individual case. (a) Asymptomatic simple cysts with a diameter of more than 5 cm and with no tendency to regress spontaneously should be operated on within the neonatal period, preferably by laparoscopy. (b) In the case of any other asymptomatic neonatal ovarian cyst a wait-and-see policy with ultrasound monitoring can be adopted and continued at least until the end of the neonatal period.     

Ovarian masses in the newborn

Prenatal sonography uncovers many fetal ovarian masses that previously would have gone unrecognized. This challenges clinicians to learn the natural history of these asymptomatic lesions so as to provide the best care postnatally. Spontaneous resolution of simple ovarian cysts is expected by about 6 months of age, which is attributed to predicted changes in the postnatal hormonal milieu. After birth, levels of human chorionic gonadotropin (HCG) and estrogen plummet. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) rise until about 3 months of age and then fall as the "gonadostat" matures. Although symptomatic cysts demand intervention, simple asymptomatic cysts less than 5 cm in diameter should be left alone but reassessed sonographically. If simple cysts are larger than 5 cm in diameter the risk of torsion may be significant, and intervention often is advocated. However, the risk of torsion versus the likelihood of resolution is not well established. The therapeutic goal for a clinician managing a newborn with a simple ovarian cyst is to maximize ovarian salvage. Aspiration alone may be a reasonable option. The laparascopic approach to the neonatal ovarian cyst provides a view of both ovaries and allows aspiration, unroofing, cystectomy, or ovariectomy. The sonographically complex cyst usually represents adnexal torsion but could be a neoplasm and warrants intervention because the morbidity from untreated neonatal adnexal torsion can be significant beyond loss of the ovary (eg, hemorrhage, peritonitis, intestinal obstruction, or a wandering tumor).     

胎儿腹腔囊性占位的生后治疗及转归

目的 分析产前诊断胎儿腹腔囊性占位的病因、随访、预后及转归,指导产前会诊咨询工作.方法 收集2006年4月至2009年4月产前发现胎儿腹腔囊性占位的病例32例,分析病因、就诊年龄、占位大小、手术治疗效果及随访情况,总结预后与转归.结果 32例患儿,男女比例为7:25,女性占绝对多数.新生儿期就诊23例,其余生后3个月内就诊.就诊时囊性占位较产前明显增大者7例(21.9%).病因包括卵巢囊肿、畸胎瘤、肠源性囊肿、肾上腺来源性占位及胆总管囊肿.27例经Ⅰ期手术预后良好.2例经Ⅱ期手术恢复良好.2例未行手术预后良好.1例因恶性肿瘤死亡.结论 胎儿腹腔囊性占位以女性多见,以卵巢囊肿最多见.肠重复畸形、囊性畸胎瘤亦是常见病因.多数患儿因产前发现肿块在新生儿早期就诊.巨大腹腔囊性肿块造成消化道梗阻症状是早期就诊的主要原因.腹腔囊性占位的胎儿多数预后良好,转归满意.

Abstract：

Objective To summarize our experience with prenatal diagnosis of the fetus with cystic abdominal mass, and retrospectively analyze their clinical outcome after birth. Methods From April 2006 to April 2009, 32 fetuses were diagnosed with cystic abdominal mass in prenatal tests.Their clinical data including etiology, age at diagnosis, mass size, surgical treatment and follow-up were retrospectively analyzed. Results The 32 cases included 7 males and 25 females. Twenty three (71.9%) patients visited doctors in the neonatal period. The other patients (71.9%) visited doctors in the first 3 months after birth. The chief compliant was intestinal obstruction caused by abdominal mass. Seven patients' (21.9%) cystic abdominal masses enlarged after birth. The origins of the cystic abdominal masses were ovarian cysts, teratorna, enterogenous cysts, adrenal tumors and common bile duct cysts. Among the 32 patients, 27 patients underwent one stage tumor resection, and 2 were performed 2 stage surgery. Two patients didn't receive any surgery. And 1 patient with malignant tumor died. All patients recovered eventually from surgery. Conclusions Cystic abdominal mass in female fetus is more common than that in male fetus. The most common origin of cystic abdominal mass in female fetus is ovarian cysts. Intestinal duplication and cystic teratoma is also the common origins. Most neonates visit doctors for prenatal diagnosis of cystic abdominal mass. The prognosis of the majority of fetus with abdominal cyst is good.     

Massive ovarian oedema: An unusual abdominal mass in infancy

We describe a 13‐month‐old female who presented with vaginal bleeding, breast and pubic hair development and an abdominal mass. She underwent emergency laparotomy and left‐sided salpingoopherectomy. Histological examination of the resected ovary revealed massive ovarian oedema, a rare non‐neoplastic enlargement of the ovary. Consideration of this diagnosis in patients with an abdominal mass and endocrine disturbance may allow conservative surgery and preservation of fertility. Pediatr Blood Cancer 2009;53:217–219. © 2009 Wiley‐Liss, Inc.     

A case of luteinizing thecoma with sclerosing peritonitis: Revisiting a link with anti‐epileptic drugs

Luteinizing thecoma with sclerosing peritonitis (LTSP) is a rare ovarian tumor of unclear etiology and pathogenesis. The diagnostic entity was proposed in 1994, but a number of earlier reports described possible cases, and some suggested an association with anti‐epileptic drugs (AEDs). In presenting a new case we review the literature of previous cases to evaluate the possibility of such a link. When cases in reproductively immature patients are considered, evidence for an association between LTSP and AEDs is strongly suggested despite the rarity of the condition. Pediatr Blood Cancer 2010;54:470–472. © 2009 Wiley‐Liss, Inc.     

Inflammatory myofibroblastic tumor of the conjunctiva: Response to chemotherapy with low‐dose methotrexate and vinorelbine

Inflammatory myofibroblastic tumor (IMT) is an unusual entity that mainly affects children and young adults, and for which standardized therapies for inoperable cases are still lacking. We report on a 12‐year‐old patient with an extremely rare and inoperable conjunctival location that was treated with chemotherapy using low‐dose methotrexate plus vinorelbine, achieving complete tumor remission. This regimen is usually well tolerated and may be considered as the treatment of choice for cases of unresectable advanced IMT. Pediatr Blood Cancer 2010;54:483–485. © 2009 Wiley‐Liss, Inc.     

Ovarian cysts in infants and children

The etiology of ovarian cysts varies with the developmental stage and hormonal milieu of the patient. In general, most ovarian cysts are functional in nature and usually resolve without treatment. Treatment is indicated if the diagnosis is in question, the cyst persists, or the patient is symptomatic. Laparoscopy has become the approach favored by most pediatric surgeons for the treatment of ovarian cysts. All surgical procedures for ovarian cysts should spare functional ovary as much as is technically possible. Simple cysts should be fenestrated. Complex or functional cysts should be excised, with preservation of the remaining ovary.     

Percutaneous drainage as the treatment of choice for neonatal ovarian cysts

Background Involution of neonatal ovarian cysts occurs usually by 12 months. Persisting cysts larger than 4 cm are prone to torsion. Two modes of therapy are advocated: surgery and percutaneous US-guided cyst aspiration.Objective To compare ovarian preservation following the use of US-guided aspiration or conventional surgery for the treatment of large asymptomatic neonatal ovarian cysts, and to suggest alternative treatment when intrauterine ovarian torsion occurs.Materials and methods The study population comprised 25 baby girls with an ovarian cyst, 5 with a simple cyst and 20 with a complex cyst. Of these 25 infants, 8 had surgery and 17 had US-guided cyst aspiration.Results In the surgical group of 8, 6 underwent oophorectomy, and in 2 the ovary was saved. In the aspirated group of 17, the ovary was saved in 10, and was lost in 5. At the time of this report one patient was still in the follow-up period, and one was lost to follow-up.Conclusion US-guided aspiration of large neonatal cysts preserves ovarian tissue in a higher percentage of patients than surgery. It is safe, effective, and repeatable. We recommend US-guided aspiration of asymptomatic large ovarian cysts for salvage or for decompression if intrauterine ovarian torsion occurs. Surgery should be reserved for patients with acute torsion, intestinal obstruction and intestinal volvulus.     

Ovarian cyst torsion in a patient with congenital lipoid adrenal hyperplasia

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia, characterized by lack of synthesis of all gonadal and adrenal steroid hormones. Ovarian cysts can develop as complications of CLAH. However, the precise mechanism of development and natural history of such cysts in patients with CLAH have not yet been determined. We recently treated a 14-year-old female patient with CLAH and ovarian cyst torsion. As a neonate, she presented with vomiting, skin pigmentation, and electrolyte imbalance. At that time, her serum adrenocorticotropic hormone concentration was elevated, while 17-hydroxypregnenolone level was normal, as were her normal female external genitalia. Mutation analysis showed that she was homozygous for p.Q258X in the StAR gene. She underwent spontaneous puberty and menstruation. At 14 years of age, she received salpingo-oophorectomy because of ovarian cyst torsion presenting as acute pelvic pain. Ovarian cysts are important clinical manifestations in 46,XX patients with CLAH, although onset time and severity can vary depending on individuals. Thus, patients with CLAH should be carefully monitored for ovarian complications to preserve as much ovarian function as possible.     

Preserving female fertility following cancer treatment: Current options and future possibilities

Children and women of reproductive age are increasingly surviving cancer diagnoses, and therefore long‐term quality‐of‐life issues are of greater importance at the time of diagnosis. Cancer therapies including radiation and chemotherapy can be detrimental to fertility, and therefore many patients are motivated to preserve fertility prior to cancer treatment. The only highly successful method in preserving fertility to date is embryo cryopreservation, which may not be appropriate for some patients due to age, delay in treatment, cancer type and stage, as well as availability of an acceptable sperm donor. Alternative methods including oocyte cryopreservation and ovarian tissue banking may also preserve fertility while providing additional flexibility to patients. In vitro ovarian follicle maturation following tissue banking is one potential approach that would not require a delay in cancer therapy for ovarian stimulation, would not require an immediate sperm donor, and does not carry the risk of reintroducing malignant cells following tissue transplantation. In vitro follicle culture systems have resulted in successful live births in the mouse. However, many challenges must be addressed in translating the system to the human. This review summarizes current approaches to fertility preservation and discusses recent developments and future challenges in developing a human in vitro follicle culture system. Pediatr Blood Cancer 2009;53:289–295. © 2009 Wiley‐Liss, Inc.     

Ovarian cysts in newborns

Before the introduction of ultrasonography (US), ovarian cysts in newborns were thought to be rare. With the extended use of real-time US, prenatal detection has increased. There is still considerable controversy regarding the best treatment of these neonatal findings. A total of 27 instances in 24 consecutive newborns of antenatally-diagnosed ovarian cysts were reviewed for US data, management, and outcome to assess the ante- and postnatal evolution of the cyst and establish appropriate therapy. The cysts detected during pregnancy were studied by repeated postnatal US studies. In 10 children (2 with bilateral cysts) the cyst evolved spontaneously toward regression. Fourteen patients were operated upon; 10 had complex and 4 (in 1 bilateral) had simple cysts. Cystectomy was employed when possible to preserve the ovarian parenchyma (3 cases); in the remaining cases oophorectomy was performed. Histologically, the cysts were of follicular origin or necrosis made a diagnosis impossible. US was found to be a helpful diagnostic tool for simple ovarian cysts, but could not reliably distinguish between benign and malignant tumors if a sonographically complex lesion was present. Based on our experience, surgical management of ovarian cysts should be reserved to complex masses. Simple cysts can be monitored safely by close US follow-up; surgery is indicated if the cyst fails to regress after several months or becomes symptomatic. Accepted: 9 March 2000     

Familial small cell carcinoma of the ovary

Ovarian tumors have a low incidence in childhood, accounting for 1% of malignancies within the ages of 0–17 years. Small cell carcinoma of the ovary is a rare histology and historically has a poor prognosis. We report a case of an 11‐year‐old female diagnosed with small cell carcinoma of the ovary and hypercalcemia (SCCOHT). There was a strong family history of the disease, a reduction in the age of onset in the proband, and the absence of BRCA mutations. This case suggests the phenomenon of genetic anticipation in an ovarian cancer. Pediatr Blood Cancer 2009; 53:1334–1336. © 2009 Wiley‐Liss, Inc.