McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS.
Small follicular cysts are commonly found in the ovaries of prepubertal girls, and in most cases, they are of no clinical importance. These cysts are usually self-limiting and resolve spontaneously. However, occasionally, these cysts may enlarge and continue to produce estrogen, resulting in signs of sexual precocity. Here, we report a case of precocious pseudopuberty associated with an autonomous ovarian follicular cyst.
A 5.9-year-old girl initially presented to a local clinic with vaginal bleeding and a large unilateral ovarian cyst. At 6 months after the initial acute episode, the patient visited our hospital as the ovarian cyst had persisted and increased in size. Endocrinological examination showed elevated estrogen levels and suppressed gonadotropin levels on GnRH stimulation test. Also, no skin pigmentation or bone anomaly was noted. Based on these observations, laparoscopic cystectomy was performed, and histologic analysis confirmed the diagnosis of a follicular cyst. After the laparoscopic cystectomy, the patient’s hormone levels returned to normal and no ovarian cyst was detected by ultrasound.
As autonomous ovarian cysts are usually self-limiting disorder, no treatment is necessary. Therefore, surgical management should be deferred as long as possible to avoid the risk of repeat surgery, as pseudoprecocious puberty due to autonomous ovarian cysts can resolve spontaneoulsy and frequently recurs. Precocious pseudopuberty with an ovarian cyst may be due to granulosa cell tumor or may be one symptom of the McCune-Albright Syndrome (MAS). A careful longer-term follow up of patients with autonomous ovarian cysts and/or molecular studies may be necessary in such cases.
Precocious pseudopuberty; Autonomous ovarian follicular cyst; Laparoscopic
McCune-Albright syndrome (MAS) is a rare disorder characterized by the classic triad of precocious puberty, polyostotic fibrous dysplasia and café-au-lait pigmented skin lesions. Cystic change is rare in fibrous dysplasia (FD), especially in McCune-Albright syndrome. There were no reports about cyst degeneration in MAS which resulted in abnormal visual acuity and visual fields. Herein, we report a female patient with MAS associated with sphenoid bone cysts which resulted in visual deterioration to describe the computed tomography (CT) and magnetic resonance (MR) imaging findings of cyst degeneration in McCune-Albright syndrome.
A 20-year-old female presented with right temporal hemianopsia and visual loss in the right eye suddenly. A café-au-lait spot was found on her neck and left shoulder. Endocrinologic examination revealed elevated basal level of serum PRL, FT3 and FT4 with decreased serum TSH. Fibrous dysplasia (FD) generally manifest as round-glass appearance with well defined borders and cystic areas within involved bone were seen as hypointensity on CT. They were showed as hypointense in T1-weighted sequences and as hyperintense in T2-weighted sequences of MRI. After surgery the right temporal hemianopsia improved.
CT combined with MRI is the most effective method to evaluate the extent and complications of fibrous dysplasia in patients with MAS. The treatment of surgery can not cure MAS but relieve the symptom.
Background & objectives
Fibrous dysplasia (FD) is a rare metabolic bone disease and information available from India is limited to only anecdotal case reports. We describe the clinical profile and therapeutic outcome of 25 patients with FD observed over a period of 14 yr in a tertiary care centre from north India.
In this retrospective study patients (n = 25) with diagnosis of fibrous dysplasia based on either classical radiological features and/or histological evidence on bone biopsy, were analyzed. Associated endocrinopathies if any, were evaluated. The diagnosis of McCune Albright syndrome (MAS) was considered when fibrous dysplasia was accompanied by either café-au-lait macules and/or endocrinopathies. The clinical presentation, biochemical parameters and imaging were analysed. Seven patients received bisphosphonate therapy. The final outcome and side effects were noted.
Age of the patients ranged from 7 to 48 yr (mean ± SD, 24.2 ± 11.4 yr) with a lag time between onset of symptoms and presentation ranging from 1 to 20 yr (mean ± SD, 6.6 ± 6.2 yr). The mean duration of follow up was 3.5 ± 2.1 yr. Eighteen (72%) patients had polyostotic disease while the remaining had monostotic FD. Eight patients had endocrinopathies: five had acromegaly, one each had gonadotropin independent precocious puberty (GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright syndrome was observed in 10 (40%) patients. A majority of the patients underwent various minor or major surgical procedures and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all bisphosphonate treated patients with a decrease in subsequent fractures.
Interpretation & conclusions
This series of FD patients from north India shows the varying presentations of this rare disease. Medical treatment with bisphosphonates appears to be potentially rewarding.
Bisphosphonates; endocrinopathies; fibrous dysplasia; McCune-Albright syndrome
McCune-Albright Syndrome (MAS) is usually characterized by the triad of precocious puberty (PP), fibrous dysplasia, and café au lait spots. Previous treatments investigated for PP have included aromatase inhibitors and the estrogen receptor modulator, tamoxifen. Although some agents have been partially effective, the optimal pharmacologic treatment of PP in girls with MAS has not been identified. The objective of this study was to evaluate the safety and efficacy of fulvestrant (FaslodexTM), a pure estrogen receptor antagonist, in girls with progressive precocious puberty (PP) associated with McCune-Albright Syndrome (MAS).
In this prospective international multicenter trial, thirty girls ≤ 10 years old with MAS and progressive PP received fulvestrant 4 mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal bleeding, rates of bone age advancement, growth velocity, Tanner staging, predicted adult heights, and uterine and ovarian volumes were measured.
Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per year, with a median change in frequency of -3.6 days, (95% confidence interval (CI) -10.10, 0.00; p = 0.0146). Of patients with baseline bleeding, 74% experienced a ≥50% reduction in bleeding, and 35% experienced complete cessation during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively). Average rates of bone age advancement (ΔBA/ΔCA) decreased from 1.99 pre-treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p = 0.0007). No significant changes in uterine volumes or other endpoints or serious adverse events occurred.
Fulvestrant was well tolerated and moderately effective in decreasing vaginal bleeding and rates of skeletal maturation in girls with MAS. Longer-term studies aimed at further defining potential benefits and risks of this novel therapeutic approach in girls with MAS are needed.
McCune Albright syndrome; Peripheral precocious puberty; Estrogen receptor antagonist
McCune-Albright syndrome (MAS) is characterized by the triad of fibrous dysplasia (FD), cafe-au-lait spots and precocious puberty (PP). We report a 14-year-old girl with MAS who has been followed-up for 8 years. She was referred for multiple fractures and vaginal bleeding at age 5.9 years. She had peripheral PP, FD, and osteoporosis and was diagnosed as MAS. The patient was treated with aromatase inhibitors and bisphosphonates. She had no menses during aromatase inhibitor treatment. Her growth rate and bone maturation were in normal ranges while on treatment. She had one new fracture on the seventh year of follow- up in spite of bisphosphonate treatment.
Conflict of interest:None declared.
McCune-Albright syndrome; bisphosphonate; aromatase inhibitor; follow-up
McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly.
Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted.
Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.
Background: Precocious puberty, as early physical development and low final height might lead to psychosocial problems.
Objective: To evaluate etiology and clinical feature of precocious puberty in a cohort of Iranian children.
Materials and Methods: In this case-series study, 44 girls and 8 boys with precocious puberty referred to Endocrine Reserch Centre (Firouzgar), Institute of Endocrinology and Metabolism (Hemmat Campus), were examined in a 10 years period of time.
Results: Mean age of girls and boys was 7.43±1.4 years and 5.8±2.1 years respectively. Most of the patients fell within the age category of 7-7.9 years old (40.9% for girls and 50% for boys). Patients, concerning etiology of precocious puberty were classified in three categories: 42.6% of patients had central precocious puberty (CPP), including idiopathic CPP (87.5%) and neurogenic CPP (12.5%). 23.3% of patients had peripheral precocious puberty (PPP), including congenital adrenal hyperplasia (CAH) (42.8%), ovarian cysts (28.4%), McCune-Albright syndrome (14.2%) and adrenal carcinoma (14.2%). 34.1% of girls and 25% of boys had normal variant puberty including premature thelarche (57%), premature adrenarche (38%) as well as premature menarche (4.7%l).
Conclusion: The most common etiology of precocious puberty in girls was idiopathic central precocious puberty and premature thelarche, while in boys they were neurogenic central precocious puberty and CAH. Therefore precocious puberty in girls is usually benign. In boys, CNS anomalies should first be considered in the differential diagnosis of CPP. Therefore brain Magnetic Resonance Imaging (MRI) is mandatory in all cases.
Central precocious puberty; Peripheral precocious puberty; Premature thelarche; Congenital adrenal hyperplasia
Endocrine neoplasia syndromes feature a wide spectrum of benign and malignant tumors of endocrine and non-endocrine organs associated with other clinical manifestations. This study outlines the main clinical features, genetic basis, and molecular mechanisms behind two multiple endocrine neoplasia syndromes that share quite a bit of similarities, but one can be inherited whereas the other is always sporadic, Carney complex (CNC) and McCune-Albright (MAS), respectively. Spotty skin pigmentation, cardiac and other myxomas, and different types of endocrine tumors and other characterize Carney complex, which is caused largely by inactivating Protein Kinase A, Regulatory subunit, type I, Alpha (PRKAR1A) gene mutations. The main features of McCune-Albright are fibrous dysplasia of bone (FD), café-au-lait macules and precocious puberty; the disease is caused by activating mutations in the Guanine Nucleotide-binding protein, Alpha-stimulating activity polypeptide (GNAS) gene which are always somatic. We review the clinical manifestations of the two syndromes and provide an update on their molecular genetics
Carney Complex; PRKAR1A; McCune-Albright; GNAS; endocrine neoplasia
McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.
adrenal cortical atrophy; adrenal cortical hyperplasia; Cushing syndrome; GNAS1 mutation; McCune-Albright syndrome
McCune Albright syndrome (MAS) is a rare disorder characterized by precocious puberty, café-au-lait spots, and fibrous dysplasia. Its cause is an activating mutation in the GNAS gene, encoding a subunit of the stimulatory G protein, Gsalpha (Gsα). The action of any mediator that signals via Gsα and cyclic AMP can be up regulated in MAS. We had observed gastritis, gastroesophageal reflux, and anaphylaxis in McCune Albright patients.
As histamine is known to signal via histamine 1 (H1) and histamine 2 (H2) receptors, which couple with stimulatory G proteins, we attempted to mechanistically link histamine responsiveness to the activating GNAS mutation. We hypothesized that responsiveness to histamine skin testing would differ between MAS patients and healthy controls.
Patients and methods
After obtaining informed consent, we performed a systematic review of histamine responsiveness and allergic manifestations in 11 MAS patients and 11 sex-matched, Tanner-stage matched controls. We performed skin prick testing, quantifying the orthogonal diameters of wheals and erythema. We also quantitated G protein mRNA expression.
The peak wheal and flare responses to histamine were significantly higher in MAS patients compared to controls.
This study suggests that MAS patients may be at risk for exaggerated histamine responsiveness compared to unaffected controls.
McCune Albright syndrome; Histamine responsiveness; Wheal and flare; Atopy; Anaphylaxis
Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.
The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.
McCune-Albright syndrome is a rare genetic disorder with typical skeletal and endocrine manifestations. The disease course is complicated by recurrent fractures resulting from polyostotic fibrous dysplasia and the treatment is thus primarily directed at the reduction of the risk of fractures. However, due to the complex mechanism of the skeletal damage the standard antiporotic therapeutics are ineffective. We report here a case of a 31-year-old female, diagnosed with the McCune-Albright syndrome in early childhood. She was suffering from extensive bone involvement, complicated by recurrent fractures despite the treatment with bisphosphonates. In addition, the disease course was complicated by the impairment of several endocrine functions—precocious puberty, hyperestrogenism, and hyperthyroidism for which a total thyroidectomy was performed. During the operation, two enlarged parathyroid glands were removed. This resulted in severe hypocalcaemia in the postoperative period with a need for supplementation with very high calcium and vitamin D doses. After this episode, the patient has remained free of fractures. We discuss here the corrected thyroid function, the supplementation with unconventionally high doses of vitamin D and calcium, and the termination of bisphosphonates treatment as presumable factors contributing to the reduced fracture risk in this patient.
McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).
McCune-Albright syndrome; Fibrous dysplasia; GNAS1; Acromegaly
Patients with McCune-Albright syndrome (MAS), characterized primarily by hyperpigmented skin lesions, precocious puberty, and fibrous dyslasia of bone, carry postzygotic heterozygous mutations of GNAS causing constitutive cAMP signaling. GNAS encodes the α-subunit of the stimulatory G protein (Gsα), as well as a large variant (XLαs) derived from the paternal allele. The mutations causing MAS affect both GNAS products, but whether XLαs, like Gsα, can be involved in the pathogenesis remains unknown. Here, we investigated biopsy samples from four previously reported and eight new patients with MAS. Activating mutations of GNAS (Arg201 with respect to the amino acid sequence of Gsα) were present in all the previously reported and five of the new cases. The mutation was detected within the paternally expressed XLαs transcript in five and the maternally expressed NESP55 transcript in four cases. Tissues carrying paternal mutations appeared to have higher XLαs mRNA levels than maternal mutations. The human XLαs mutant analogous to Gsα-R201H (XLαs-R543H) showed markedly higher basal cAMP accumulation than wild-type XLαs in transfected cells. Wild-type XLαs demonstrated higher basal and isoproterenol-induced cAMP signaling than Gsα and co-purified with Gβ1γ2 in transduced cells. XLαs mRNA was measurable in mouse calvarial cells, with its level being significantly higher in undifferentiated cells than those expressing preosteoblastic markers osterix and alkaline phosphatase. XLαs mRNA was also expressed in murine bone marrow stromal cells and preosteoblastic MC3T3-E1 cells. Our findings are consistent with the possibility that constitutive XLαs activity adds to the molecular pathogenesis of MAS and fibrous dysplasia of bone.
GNAS; McCune-Albright syndrome; fibrous dysplasia of bone; gsp oncogene; stimulatory G protein; XLαs
McCune-Albright syndrome (MAS) is typically defined as a triad of precocious puberty (PP), café au lait spots and fibrous dysplasia of bone. PP is the most common endocrinological manifestation of this rare disease and is much more common in girls than in boys. The treatment options for PP associated with MAS have evolved over the last twenty plus years. Therapy in girls typically includes the use of an anti-estrogen, while treatment options in boys include an antiandrogen in combination with an aromatase inhibitor (Al). This article will briefly review the older therapies and explain why they have largely been supplanted by newer approaches. We will discuss current pharmacotherapy options for the treatment of PP in MAS and finally describe potential novel therapies that will hopefully enable optimal care for affected patients.
Treatment; Precocious Puberty; McCune-Albright Syndrome
McCune- Albright Syndrome (MAS) is a rare fibrosseous lesion, characterized by a classic triad of polyostotic fibrous dysplasia (PFD), café –au-lait macules (CALM) and underlying endocrinopathies. We present the oral findings of an interesting case of MAS with relevant review of literature. A 30-year-old male presented to us with swelling of both jaws over a period of two years. Cutaneous examination revealed café - au – lait macule over the back, crossing the midline. Skeletal survey showed expansile, osteolytic, mixed radiolucent- radiopaque lesions in skull and jaw bones. Serum alkaline phosphatase was elevated (388 IU/L), with normal calcium, phosphorus, parathyroid hormone and 25 hydroxy vitamin D levels. Diagnosis of McCune- Albright syndrome was made and he was treated with parenteral bisphosphonates (intravenous Zoledronate 4 mg) and is under follow up for surgical recontouring of the jaws. Early recognition facilitates better treatment and improves prognosis by reducing the morbidity.
Albright's syndrome; fibrous dysplasia of the jaws; fibroosseous lesion; polyostotic fibrous dysplasia
Turner Syndrome (TS) is caused by monosomy or structural abnormalities of the X chromosome, with a prevalence of about 1/2000 females live birth. Most important clinical features of TS are short stature and gonadal failure. Approximately one third of girls with TS may undergo spontaneous puberty. Here we report on the case of a girl with a rare 45X0/47XXX mosaic TS exhibiting a precocious puberty.
The patient was diagnosed with TS at the age of 4 years, upon a diagnostic work-up for dysmorphic features. Chromosome analysis revealed a mosaic karyotype (45X0/47XXX). She presented with normal height and normal growth velocity so that Growth Hormone (GH) therapy was not started. She was referred to our Department at the age of 7 years and 10 months, because of vaginal bleeding. A physical examination revealed a Tanner stage III for breast and Tanner stage III for pubic hair development. Height and weight were within the normal range for age. Psychological evaluation showed moderate global developmental delay, together with emotional and social immaturity and reading difficulties. The growth rate was accelerated. Her bone age was 10 years. Pelvic ultrasound demonstrated increased size for age of both the uterus and the ovaries, with bilateral ovarian follicles. GnRH stimulation test revealed pubertal response of gonadotropins (peak LH 22.5 mIU/ml). MRI of the brain was normal. These clinical, radiologic and laboratory findings were consistent with a diagnosis of idiopathic central precocious puberty; therefore, GnRH analog therapy was started, in order to slow pubertal progression and to preserve adult stature. Furthermore, GH treatment was added to further improve adult height.
Our case highlights the possibility of precocious puberty as an atypical clinical feature of TS. Thus, precocious puberty may occur in TS girls when a dosage compensation by the cell line with more than two X chromosomes allows normal ovarian function. GnRH analog therapy in addition to GH treatment should be recommended in TS girls with precocious puberty in order to slow pubertal progression and to preserve adult stature.
Turner syndrome; Precocious puberty; GnRH analog therapy
The daughter cyst sign is a specific indicator of an uncomplicated ovarian cyst and pathologically represents a stimulated ovarian follicle. This finding must be differentiated from an ectopic pregnancy in a patient who has the potential to become pregnant. We report an uncomplicated ovarian cyst in a 3-year-old female with McCune-Albright syndrome and precocious puberty mimicking an ectopic pregnancy.
Daughter cyst; ovarian cyst; ovarian follicle; ectopic pregnancy
The clinical outcomes of seven girls presenting with
pseudosexual precocity caused by isolated autonomous ovarian follicular cysts are presented. Six of the seven girls, aged 11 months to 6.9 years, had a unilateral ovarian cyst detected by ultrasound at the
first acute episode. Plasma oestradiol was raised in only five of the
cases, but all had a low response to luteinising hormone releasing
hormone stimulation. Follow up lasted for up to eight years with
recurrent episodes of variable frequency and severity in all seven
patients. Evidence of McCune-Albright syndrome appeared later in only
three patients. It could not be predicted from the initial symptoms or
the clinical course. Mutations of the Gsα protein leading
to activation were investigated in the lymphocytes and ovarian and bone
tissues of four patients. Only one patient showed a mutation in bone
tissue. Close follow up with repeated searches for skeletal lesions
remains necessary since the distribution of somatic mutations cannot be
assessed by molecular studies. Most patients with recurrent ovarian
cysts require a conservative approach.
McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder, characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone and café-au-lait macules. The most common endocrine dysfunction is gonadal hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders, although the majority of cases have been reported in young females. Atypical presentations of MAS, with only one or two of the classic symptoms, have been previously described, but remain particularly challenging due to the lack of a diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the gene of the α-subunit of the stimulatory G-protein is limited; thus, diagnosis is based on clinical judgment. In the present study, a male with polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with atypical MAS, was reported. The pituitary adenoma was effectively treated with radiotherapy and the patient underwent surgery for the polyostotic fibrous dysplasia, with marked improvements observed in appearance.
McCune-Albright syndrome; fibrous dysplasia; growth hormone-secreting pituitary adenoma
Fibrous dysplasia (FD) is a developmental disease of bone in which there is replacement of normal spongiosa and filling of the medullary cavity of affected bones by an abnormal fibrous tissue that contains trabeculae of poorly calcified primitive bone formed by osseous metaplasia. Fibrous dysplasia is a common benign bone disease existing in monostotic and polyostotic forms. It is sometimes associated with aneurysmal bone cysts, and it is a component of McCune-Albright and Mazabraud syndromes.
We describe here a 4-months old Austrian infant who presented with a hard bulging painless mass of (5 x 3 cm) of the right parietal bone. Radiographs showed a large irregular osteolytic lesion. T1-weighted MR image showed significant expansile lesion associated with a dense zone of calcification in the diploic space. To the best of our knowledge this is the first clinical report of an infant with early presentation of monostotic fibrous dysplasia of the right parietal bone.
Fibrous dysplasia of the skull is a painless progressively expanding destructive bone swellings produce cosmetic deformities. The clinical course may be unpredictable, with sudden appearance of symptoms, some of which can be important and irreversible. In our present patient, the possibility that an early surgical correction might positively interfere with the natural history of the lesion has to be evaluated by taking into account the obvious difficulties that will be encountered in reconstructing the skull after a wide excision of the pathologic bone.
The cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype.
11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed.
Ovarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP.
We will discuss a potential role of percutaneous vertebroplasty (PVP) in the management of patients with severe fibrous dysplasia of the spine with multiple cervical lesions and C2–C3 pathologic fractures that may not be a good surgical candidate. Polyostotic fibrous dysplasia involvement of the cervical spine is rare. Review of literature indicates only few reported cases of surgical management with one case of mortality indicating increased risks associated with surgical intervention. While PVP is commonly used for the treatment of osteoporotic thoracolumbar vertebral compression fractures, its role in vertebral stabilization for fibrous dysplasia has not been reported. A 35-year-old man with McCune–Albright syndrome and severe polyostotic fibrous dysplasia of C2 and C3 vertebrae presented with severe neck pain, radiculopathy, quadriparesis and myelopathy. The lesion had pathologic fractures, and there was an os odontoideum with cervical cord atrophy at the C1 level. After discussing need for aggressive surgical management and potential complications, we offered PVP due to surgical risks involved. PVP was performed with a posterolateral transpedicular approach without complication. The patient had remarkable improvement in clinical relief of neck pain and improvement of myelopathic symptoms at 1-year follow-up. We present a case that illustrates a potential use of PVP in the management of a patient with symptomatic spinal fibrous dysplasia with associated pathologic fractures who was poor surgical candidate.
Percutaneous vertebroplasty; Polyostotic; Fibrous dysplasia
McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.
Fibrous dysplasia; McCune-Albright syndrome; Acromegaly