Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Primary hypothyroidism presenting as multiple ovarian cysts in an adult woman: A case report

A 21-year-old woman was referred because of abdominal pain. On physical examination, her abdomen was distended up to the umbilical region. Ultrasound and computer tomography of the abdomen revealed bilateral multiple ovarian cysts. Laboratory studies revealed increased liver function, total cholesterol and creatine phosphokinase. Further clinical investigations determined that the patient suffered from primary hypothyroidism due to autoimmune thyroiditis. The cysts resolved spontaneously after the simple replacement of a thyroid hormone. Some reports have been published of primary hypothyroidism presenting as ovarian cysts and precocious puberty in prepubertal girls. However, the case presented herein indicates that an ovarian tumor as a result of hypothyroidism may also occur in adult females. To avoid inadvertent surgery to remove an ovarian tumor, it is essential that a patient with multiple ovarian cysts and hypothyroidism be properly managed, as the simple replacement of a thyroid hormone could resolve the ovarian cysts.     

Ovarian cyst in juvenile hypothyroidism

Case report A case of primary hypothyroidism in a pre-pubertal girl presenting with vaginal bleeding and unilateral ovarian cyst is reported. The cyst resolved spontaneously after the institution of thyroid hormone therapy.Conclusion Watchful expectancy is recommended when an ovarian cyst is found in association with primary hypothyroidism and precocious puberty.     

A case of multiple ovarian cysts in a prepubertal girl with severe hypothyroidism due to autoimmune thyroiditis

Some children with profound and long-standing hypothyroidism present with signs of paradoxical sexual maturation. In females, it is characterized by breast development, vaginal bleeding, lack of pubic hair, and delayed bone age. A case of multiple ovarian cysts in a prepubertal girl with severe hypothyroidism due to autoimmune thyroiditis is reported. A 7-year, 8-month-old girl presented with precocious puberty and vaginal bleeding. A pelvic ultrasound revealed markedly enlarged ovaries with numerous cysts which disappeared dramatically after thyroid replacement. When large multiple ovarian cysts with vaginal bleeding are found in a prepubertal girl who has a retarded bone age, the possibility of associated hypothyroidism should be considered. Health care providers should keep this in mind because this constellation of symptoms can be completely reversed with the initiation of thyroid replacement.     

Van Wyk and Grumbach syndrome: an unusual form of precocious puberty

An 8-year-old girl presented with precocious menstruation and growth delay. Laboratory data revealed hypothyroidism and an X-ray of the wrist showed a delayed bone age. The Van Wyk and Grumbach syndrome (VWGS) was diagnosed and thyroid replacement was started with resolution of the symptoms. The association of precocious puberty and/or polycystic ovaries, delayed bone age and hypothyroidism is known as the Van Wyk and Grumbach syndrome. Clinically this syndrome is a diagnostic challenge because hypothyroidism usually leads to pubertal and growth delay, whereas in case of VWGS hypothyroidism it leads to growth delay and precocious puberty. The pathophysiology of VWGS is not yet clear, but the most accepted theory states that the high concentrations of TSH are sufficient to cause activation of the FSH receptor and produce gonadal enlargement. Thyroid replacement therapy results in a resolution of all signs and symptoms. For this reason, conservative management of the ovarian masses is advocated. Our case is unique as this girl did not have breast development or multicystic ovaries (as the other cases in the literature). This may be due to an early recognition and relatively low TSH levels in comparison to other cases.     

Clinical and endocrinologic study of precocious puberty in girls

We describe 30 girls with precocious puberty whom we have seen during the last ten years. Modern procedures such as cerebral computer tomography and abdominal sonography increase diagnostic accuracy so that the incidence of idiopathic precocious puberty is likely to diminish. Abdominal sonography is of value in detecting and monitoring the growth of ovarian cysts and thus exploratory laparotomy can be avoided in those cases in which cysts regress rapidly. A modified classification of precocious is proposed.     

The role of sonography in pediatric gynecology

Sonography has a major role in the evaluation of children with gynecologic disorders. The size, consistency, and origin of pelvic masses and the status of the internal genitalia can be evaluated. Sonography is useful in evaluation of children with precocious puberty because it can demonstrate adult-size ovaries in true precocious puberty, which distinguishes this from premature thelarche and adrenarche. Specific causes of precocious sexual development such as adrenal and ovarian tumors and cysts also can be diagnosed.     

Juvenile Granulosa and Theca Cell Tumor of the Ovary as a Rare Cause of Precocious Puberty: Case Report and Review of Literature

BackgroundThe differential diagnosis for precocious puberty in a young female includes peripheral causes. This case documents a rare cause of peripheral precocious puberty—a juvenile granulosa and theca cell ovarian tumor—and a brief review of the literature for this tumor type.CaseA 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Menarche occurred 5 months after thelarche. A thorough workup revealed a large multicystic left ovary. Other causes of precocious puberty were excluded. She underwent an exploratory laparotomy and left salpingo-oophorectomy. Pathology reported a juvenile granulosa and theca cell tumor of the ovary, FIGO stage 1A. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. A literature review found that early stage disease has an excellent prognosis and that adjuvant chemotherapy is not indicated in this setting.Summary and ConclusionJuvenile granulosa and theca cell tumor of the ovary is a rare cause of peripheral precocious puberty, even more so than juvenile granulosa cell tumor, due to the theca component. Treatment is surgical and an excellent prognosis is possible for early stage disease.     

A case of a naturally conceived pregnancy associated with multiple ovarian cysts in a patient with severe untreated primary hypothyroidism

There are few reports of multiple ovarian cysts secondary to hypothyroidism, and multiple ovarian cysts associated with pregnancy most commonly occur in association with assisted reproductive technologies. Herein, we report a case of a naturally conceived pregnancy occurring 2 years after stopping treatment for primary hypothyroidism. The patient developed multiple ovarian cysts in the first trimester, and laboratory studies and ultrasonography were consistent with hypothyroidism. Herein, we present the case and discuss the importance of prenatal screening for hypothyroidism.     

No Activating Mutations of FSH Receptor in Four Children with Ovarian Juvenile Granulosa Cell Tumors and the Association of These Tumors with Central Precocious Puberty

Study ObjectiveThe stimulation of the follicle-stimulating hormone receptor (FSHR) by circulating FSH or some activating mutations of the FSHR may play a causal role in the development of granulosa cell tumors of ovaries.Study designWe evaluated four patients with ovarian juvenile granulosa cell tumors (age range, 2.4 to 7.2; median, 2.9 years) and five healthy pubertal girls (age range, 16 to 18.5; median, 16.8 years) for activating mutations in exon 10 of the FSHR. The patients were followed and evaluated clinically. Genomic DNA was extracted from the peripheral blood. Exon10 of the FSHR was evaluated for mutations.ResultsAll four patients presented with signs of precocious puberty. One patient, who had markedly accelerated growth velocity and advanced bone age, developed central precocious puberty after the removal of her tumor. Another patient was diagnosed to have a left ovarian cyst without tumor recurrence approximately 3.3 years after the removal of the tumor. Activating mutations were not found, but previously reported polymorphisms (Ser680Asn and Ala307Thr) of the FSHR were detected in three of four patients and in three of five controls. The follow-up period of these four patients ranged from 4.5 to 8.8 years, with a median value of 6.7 years.ConclusionsWe did not find any activating mutation in exon 10 of the FSHR in our patients, and one patient developed precocious puberty after removal of her tumor. The development of ovarian tumors in these patients may have been caused by mutations at other exons of the FSHR and G protein subunits, so the association noted between central precocious puberty and granulosa cell tumors might not be coincidental.     

Ovarian hyperstimulation syndrome in preterm infants

Ovarian cysts are a relatively frequent finding in fetuses and neonates. In preterm infants, a simultaneous occurrence of estradiol-producing ovarian cysts and edematous swelling of the vulva, the thighs and the lower abdominal wall was described by Sedin and co-workers in 1985 for the first time. This ovarian hyperstimulation syndrome occurred at a postconceptional age that slightly preceded the expected time of delivery. We report on four extremely low birth weight infants who were observed in the neonatal ward with ovarian cysts and stimulation of the external and internal genitalia, beginning at a postconceptional age of 35 to 39 weeks. The serum concentration of estradiol was within or above the range of the preovulatory peak of adults in all patients. Other causes of edema in preterm infants were excluded. The findings receded during 5 - 9 weeks. It is supposed, that in some cases the physiologically high concentration of gonadotropins in preterm infants stimulates the ovaries to produce ovarian cysts as well as to secrete high amounts of estradiol. This induces a transient stimulation of the external and internal genitalia as in idiopathic or transient precocious puberty.     

Multicystic ovaries in primary hypothyroidism

Nine of 12 girls diagnosed consecutively as having severe and longstanding primary hypothyroidism were found to have multicystic ovaries when evaluated by pelvic ultrasound examination. The cysts resolved rapidly with thyroid replacement therapy. The patients had either elevated or high normal plasma luteinizing hormone levels which decreased markedly after thyroid therapy. Five of seven patients tested with luteinizing hormone-releasing hormone had attenuated gonadotropin responses; the other two reacted normally. The pathogenesis of the cysts remains uncertain. Use of pelvic ultrasound scan has documented a high frequency of multicystic ovaries in girls with primary hypothyroidism.     

Primary amenorrhea-galactorrhea with hyperprolactinemia and huge pituitary enlargement in juvenile primary hypothyroidism.

We report a girl with juvenile primary hypothyroidism revealed by growth retardation and a syndrome of primary amenorrhea-galactorrhea with hyperprolactinemia and suprasellar pituitary enlargement. Resolution of the pituitary enlargement and the amenorrhea-galactorrhea syndrome occurred after thyroid hormone replacement. No similar observation has been reported earlier in juvenile hypothyroidism.     

Isosexual Pseudoprecocious Puberty in a 2½-Year-Old Girl Presenting with Intense Skin Pigmentation

BackgroundOvarian follicular cyst producing estradiol is a rare cause of isosexual pseudoprecocious puberty. Intense pigmentation of breast papillae, areolae, and labia minora is also rarely reported in the literature.CaseWe describe a 2½ year old girl presenting with signs of precocious puberty and advanced bone age due to a large follicular cyst. Estradiol and Dehydro-epiandrosterone sulfate (DHEAS) levels were remarkably elevated. Hyperpigmentation was also noted. Salpingoophorectomy resulted in regression of precocity and depigmentation, but DHEAS serum levels remained elevated.Summary and ConclusionHigh levels of circulating estradiol due to an ovarian follicle can induce precocious puberty and pigmentation of the skin which regresses after surgical removal of the cyst. Elevated DHEAS levels may be the initiating event causing the formation of the large follicular cyst.     

Adnexal masses in infancy and childhood

The presentation of adnexal masses in childhood differs from that in adult women. Children may present with poorly localized symptoms or precocious puberty. Ovarian cysts occur throughout development; ovarian tumors are less frequent but occur in all age groups. Congenital malformations may present with signs or symptoms of an adnexal mass. Occasionally adnexal findings may suggest the presence of an underlying syndrome. Assessment of the patient's developmental, hormonal, and pubertal status is necessary to ensure an accurate diagnosis. Treatment options must consider risks to ovarian function and future fertility.     

Vaginal bleeding in a young girl due to primary hypothyroidism

When vaginal bleeding occurs in young girls, it is always of clinical importance. The diagnosis should be made with some urgency, so that an appropriate therapy will be given in time. We present a rare case of a 6-year-old girl with primary hypothyroidism, who presented with a history of cyclical vaginal bleeding and precocious puberty while her bone age was delayed. Thyroxine therapy was commenced soon after diagnosis, the bleeding consequently stopped and there was no recurrence after six-month of follow-up.     

Recurrent fetal complex ovarian cysts with rupture followed by simple cyst in the neonatal period with no adverse sequelae

Fetal ovarian cysts are the most frequent type of abdominal tumors in female fetuses with prenatal detection rate of more than 30%. The etiology of fetal ovarian cysts is unclear, but hormonal stimulation as well as presence of maternal diabetes, hypothyroidism, Rh iso-immune hemolytic disease and toxemia has been generally considered responsible for the disease. Complications of fetal ovarian cysts include compression of other viscera, cyst rupture, hemorrhage and, most frequently, ovarian torsion with consequent loss of the ovary. Management is controversial with several options described in the literature, including watchful expectancy, antenatal aspiration of simple cysts to prevent torsion and ovarian loss and finally, resection of all complex cysts in the neonatal period. To date, no case report has described recurrent complex cysts with rupture in the fetal period and recurrence of simple cyst in neonatal period. By presenting this case, we wanted to show that surgical intervention in case of prenatally diagnosed fetal ovarian cyst should be considered postnatally and only in symptomatic or complicated cases.     

Ovarian cyst in a premature infant treated with spironolactone

We describe the late occurrence of an ovarian cyst in a premature infant, the second of a set of monochorionic diamnionic twins, during treatment with spironolactone. Spironolactone is commonly used in the management of neonatal chronic lung disease in combination with other diuretics because of its potassium-sparing effect. It has progestational activity and has been reported to cause gynecomastia. It is used widely for its antiandrogenic properties in the treatment of female hirsutism and hyperandrogenism and it has a role in the management of familial male-limited precocious puberty. However, the estrogenic influence induced during therapy may significantly alter the hormonal milieu in newborn females, resulting in the formation of ovarian cysts. Simple ovarian lesions <5 cm merit close ultrasonographic surveillance for resolution while larger complex masses may warrant surgical intervention.     

Gonadoblastoma in a 46XX Female with Isosexual Precocious Puberty

A five and a half year-old female presented with increased breast tissue. There was no sign of virilization. Gonadoblastoma was diagnosed histologically. Karyotyping did not detect any Y chromosome remnant. Signs of precocious puberty regressed promptly with excision of the tumour. The child continued to develop normally after six years. This is a rare case of gonadoblastoma in a genetically and phenotypically normal female presenting in childhood as precocious puberty.     

Diagnosis and management of precocious puberty in atypical presentations of McCune-Albright syndrome: a case series review

BackgroundMcCune-Albright syndrome is a rare syndrome, classically defined as the triad of precocious puberty, fibrous dysplasia of bone, and café au lait lesions. Partial or atypical presentations of McCune-Albright syndrome, with only one or two of the classic symptoms, have been described in the literature and remain particularly challenging due to lack of diagnostic phenotype. In these patients, the utility of analysis of mutations in the gene of the α subunit of the stimulatory G-protein is limited and so the diagnosis is often based on clinical judgment. Three atypical cases of suspected McCune-Albright syndrome with gonadotropin-independent precocious puberty are presented.CasesCase #1: A 5-year-old female presented with painlesss vaginal bleeding and was found to have café au lait lesions. She was diagnosed with gonadotropin independent precocious puberty with eventual progression to gonadotropin dependent precocious puberty which was successfully treated with both letrozole and gonadotropin-releasing hormone agonist therapy. Case #2: A 3-year-old female presented with painless vaginal bleeding and was found to have café au lait lesions. She was diagnosed with gonadotropin independent precocious puberty and was successfully treated with letrozole. Case #3: A 5-year-old female presented with fibrous dysplasia and was found to have evidence of uterine and ovarian enlargement on ultrasound. She was diagnosed with gonadotropin-independent precocious puberty and was successfully treated with letrozole.Summary and ConclusionAlthough different in presentation, all three atypical cases of suspected McCune-Albright syndrome with gonadotropin-independent precocious puberty were successfully treated with aromatase inhibitors. This small case series shows the utility and efficacy of aromatase inhibitors in the setting of atypical cases of suspected MAS with gonadotropin-independent precocious puberty.