Synchronous jawbone diseases: a multicenter retrospective study.

The aim of this study is to report an original case series of synchronous jawbone diseases. Data of patients seen over 13 years were extracted from the files of three Oral Radiology and Pathology diagnostic centers in Brazil. The clinical, radiographic, and laboratory characteristics were tabulated and analyzed by the authors; the patients were described according to lesion type. Seventy-two synchronous jawbone diseases were included in this study. Florid osseous dysplasia, Gorlin-Goltz syndrome, and cherubism were the most frequent disorders reported in this case series. In addition, the posterior mandible area was the main site of manifestation. Florid osseous dysplasia and Gorlin-Goltz syndrome represented two-thirds of our samples. With the utilization of adequate demographic, clinical, and radiologic information, it is possible to diagnose most of the synchronous lesions of jawbones. Sometimes, however, we need complementary exams, such as histopathologic and biochemical analysis or dosing of calcium, phosphorus, and alkaline phosphatase.

[Early manifestation and progressive multicomponent current of McCune-Albright-Braitsev syndrome in a girl 9 years old: a clinical case and literature review].

McCune-Albright-Braitsev Syndrome (MAB syndrome) is a very rare multisystem disease manifested by fibrous bone dysplasia, coffee-and-milk colored spots, hyperfunction of various endocrine glands and a number of pathologies of other body systems. We present a description of a clinical case of a severe progressive course of MAB Syndrome in a nine-year-old girl. With this diagnosis, the girl is observation of the girl began when she was 2.5 years old, when spots of coffee-and-milk, polyosseous fibrous dysplasia, peripheral premature sexual development against a backdrop of estrogen--secreting ovarian cysts, multinodular goiter were detected. In the process of dynamic observation, it was noted that the child's active growth stopped against a backdrop of deformities of the skeletal system with multiple repeated fractures of the extremities; progression of skull deformity with stenosis of the optic nerve canals and deterioration of visual acuity; development of STH hypersecretion, hypophosphatemic rickets, tachycardia. Appropriate suppressive / replacement therapy was prescribed for each of the endocrine dysfunctions. The article presents algorithms for examining a girl in dynamics, criteria for choosing a component-wise management tactics and a discussion of the features of the course of all manifestations of the Syndrome.

Osteosarcoma of the Mandible in a Patient with Florid Cemento-Osseous Dysplasia and Li-Fraumeni Syndrome: A Rare Coincidence.

Cemento-osseous dysplasia (COD) is the most common benign fibro-osseous lesion of the jaws and generally considered non-neoplastic and self-limited. Here, we present a 30-year old female who noticed a bilateral swelling of her posterior mandible with irregular periapical mineralization and incomplete root resorption on panoramic radiographs. A biopsy revealed florid COD and no further treatment was initiated. 9 years later, she presented with a progressive expansion of her left posterior mandible after being treated for bilateral breast cancer 4 and 8 years before. CT scans showed expansile and densely mineralized lesions in all four quadrants with the left posterior mandible showing a focal penetration of the buccal cortical bone. Biopsies revealed an osteoblastic high-grade osteosarcoma in the left and a COD in the right mandible, notably with cellular atypia in the spindle cell component. The patient underwent segmental resection of the left mandible with clear margins and adjuvant chemotherapy. Subsequent genetic testing identified a heterozygous germline TP53 mutation (p.V173G) which confirmed the clinically suspected Li-Fraumeni syndrome (LFS). 3 years after the resection, the patient is free of disease and the other foci of COD remained stable in size on follow-up imaging analyses. Our case illustrates LFS-related osteosarcoma developing within florid COD. Given the rarity of this coincidence, a causative relation between the two lesions seems unlikely but in patients with tumor predisposition syndromes it might be advisable to closely monitor even benign lesions like COD.

Importância dos aspectos imaginológicos no plano de tratamento da displasia óssea florida: relato de caso / Importance of imaginological aspects in the florid osseous Dysplasia treatment plan: case report

A displasia óssea florida (DOFL) é uma lesão fibro-óssea relativamente incomum dos maxilares, que acomete, principalmente, mulheres melanodermas de meia idade e geralmente é diagnosticada em radiografias de rotina. O presente trabalho tem como objetivo relatar o caso de uma paciente de 50 anos de idade, melanoderma, encaminhada ao Curso de Odontologia da Universidade Federal do Ceará para avaliação imaginológica. Clinicamente, não foi observada nenhuma alteração de volume de estruturas faciais ou intraorais. A radiografia panorâmica evidenciou imagens radiopacas circunscritas por halos radiolúcidos, localizadas bilateralmente em região edêntula de corpo mandibular, sugestivas de DOFL. Na tomografia computadorizada de feixe cônico (TCFC), observaram se áreas hiperdensas em regiões mandibulares edêntulas, sem expansão de corticais ósseas vestibulares e linguais, e recobertas por fina espessura de tecido ósseo, típicos da displasia. Diante do diagnóstico clínico-imaginológico de DOFL, a paciente foi encaminhada para tratamento odontológico multidisciplinar. Por meio da TCFC, foi possível se estabelecer um plano de tratamento que consistiu em procedimentos minimamente intervencionistas, considerando os aspectos clínicos e imaginológicos das lesões observadas. Em sumário, o presente trabalho reforça a importância do exame clínico meticuloso aliado à avaliação por meio de TCFC, com fins de embasar um plano de tratamento adequado em casos de DOFL assintomáticos... (AU)

Florid osseous dysplasia (FOD) is a fibrous lesion relatively uncommon of maxillary bones, mainly affects middle-age black women and generally is diagnosed on routine radiographs. This paper aims to report a case of black woman, aged 50 years, referred to Dentistry Faculty of Federal University of Ceará for imaging evaluation. Clinically, there were no facial or intraoral structures alterations. Panoramic radiography showed radiopaque images circumscribed by radiolucent halos, located bilaterally in the edentulous mandibular body region suggestive of FOD. Cone beam computed tomography (CBCT) showed hyperdense areas in edentulous mandibular regions, with no expansion of buccal and lingual cortical bone, and covered by fine thickness of bone tissue, characteristic of FOD. After the clinical-imaging diagnosis of FOD, the patient was referred for multidisciplinary dental treatment. Through the CBCT, it was possible to establish a treatment plan that consisted of minimally interventional procedures considering the clinical and imaging limits of the observed lesions. In summary, the present case emphasizes a meticulous clinical examination along with an evaluation by means of CBCT allowing an adequate treatment plan for asymptomatic FOD... (AU)

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia. / Significado clínico del aumento de los valores séricos de FGF-23 en la displasia fibrosa.

INTRODUCTION AND OBJECTIVE: Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. PATIENTS AND METHODS: Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. RESULTS: FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. CONCLUSION: Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology.

Fibrous dysplasia of bone associated with primary hyperparathyroidism.

OBJECTIVE: Fibrous dysplasia of bone and primary hyperparathyroidism (PHPT) may occur in patients with McCune-Albright Syndrome. A small number of cases with both diagnoses that are not associated with the above-mentioned genetic disorder have been published in the literature. It is uncertain if these disorders are linked in some way. In the present study, we aimed to further explore a potential relationship between PHPT and fibrous dysplasia of bone. METHODS: We conducted a retrospective review of all cases seen at Mayo Clinic, Rochester, Minnesota, between 1976 and 2011 that were diagnosed with both PHPT and fibrous dysplasia of bone. RESULTS: We identified 10 patients who were diagnosed with both PHPT and fibrous dysplasia of bone. Fibrous dysplasia was polyostotic in 7 (70%) cases. It affected the lower extremities in 6 (60%) patients, the skull or facial bones in 4 (40%), and was localized to one rib in 1 patient (10%). In 4 patients, fibrous dysplasia was diagnosed first, between 9 to 50 years before being diagnosed with PHPT. Two cases of fibrous dysplasia were recognized between 2 and 5 years after the diagnosis of PHPT. The remaining 4 patients were diagnosed with both conditions at approximately the same time. CONCLUSION: It remains unclear if the association between fibrous dysplasia of bone and PHPT is more than coincidental, although the possibility of a rare familial genetic syndrome is not completely excluded.

Denosumab treatment for fibrous dysplasia.

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.

[Fibrous dysplasia and McCune-Albright syndrome: case-report and differential diagnose with Paget bone disease]. / Fibrodisplasia óssea e síndrome de McCune-Albright: descrição de um caso clínico e diagnóstico diferencial com doença óssea de Paget.

Fibrous dysplasia of bone or Jaffe Lischtenstein's disease is a genetic, non-inheritable disease of bone development, characterized by bone pain, deformities and fracture, mainly observed in yo ung adults. The frequency is equal between sexes. Mutations in the gene coding the Gsα, GNAS complex, results in osteoblastic differentiation defects, and bone resorption. The disease can have a monostotic or polyostotic form, or be associated with café-au-lait skin spots and precocious puberty (McCune-Al bright syndrome). The normal bone and bone marrow is replaced with abnormal benign intramedullary fibro-osseous tissue, and can involve any bone in the body. The vertebral involvement is rare. Radiological and pathological findings can be diagnostic. Biphosphonates and calcium, vitamin D and phosphorus supplements have been used in fibrous dysplasia treatment. Osteosarcoma is a rare, but serious malignant complication. We report the case of a 68 year old woman with a history of hypofisectomy, with a progressive low back pain, without systemic or neurological symptoms. The bone scan, the ra di o graphs and the computed tomography findings revealed polyostotic fibrous dysplasia, with vertebral and mandibular involvement. In this paper we compared fibrous dysplasia of bone with Paget bone disease.

Alternative indications for bisphosphonate therapy.

Bisphosphonates are currently used in the treatment of osteoporosis (postmenopausal and steroid-induced), hypercalcemia of malignancy, Paget's disease of bone, multiple myeloma, and skeletally related events associated with metastatic bone disease in breast, prostate, lung, and other cancers. There are, however, numerous other conditions where a decrease in bone remodeling by bisphosphonates might aid in disease management. The focus of this review will be to discuss a select group of conditions for which bisphosphonate therapy may be efficacious. In this review we present several cases where bisphosphonates have been used as a primary or adjunctive treatment for giant cell lesions of the jaws. Use of bisphosphonate therapy for giant cell tumors of the appendicular skeleton, pediatric osteogenesis imperfecta, fibrous dysplasia, Gaucher's disease, and osteomyelitis will be discussed. Finally, we will review previous in vivo studies on the use of bisphosphonates to augment integration and to treat osteolysis surrounding failing orthopedic implants.

Fibrous dysplasia of bone and McCune-Albright syndrome.

Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by bone pain, bone deformities and fracture, involving one or several bones. It is caused by mis-sense mutations occurring post-zygotically in the gene coding for the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This mutation results in osteoblastic differentiation defects, and bone resorption is often increased. The bone lesions may be associated with endocrine dysfunctions and café-au-lait spots; this is known as McCune-Albright syndrome. Patients with polyostotic fibrous dysplasia often have renal phosphate wasting. The disease, however, has a wide clinical spectrum, so many patients are asymptomatic. Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in the treatment of fibrous dysplasia to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.

[Fibrous dysplasia of bone]. / Dysplasie fibreuse des os.

Fibrous dysplasia of bone is a congenital non hereditary benign bone disease, where normal bone is replaced by a fibrous-like tissue with immature osteogenesis. Prevalence is difficult to estimate, due to frequent asymptomatic lesions. Bone lesions are mono- or polyostotic and may be associated with bone pain and fragility, leading to fractures. In some patients or bone sites, they are hypertrophic, responsible for neurological complications. Imaging and, when necessary, histology are the cornerstones of the diagnosis. A common molecular defect, i.e. activating mutations of the GNAS gene, encoding the a subunit of the Gs protein in target cells, is responsible for bone cell alterations as well as for the involvement of other cells/tissues bearing the same molecular defect (melanocytes, endocrine cells). These mutations affect only somatic cells and are therefore not hereditary: antenatal diagnosis is not appropriate for this disease and genetic counselling is not very useful, except for reassuring the patients. The conventional therapeutic approach is essentially symptomatic (pain killers) and orthopaedic (prevention and treatment of bone complications). Recent publications have focused attention on pamidronate, which rapidly relieves bone pain in most patients, and progressively increases bone mineralization in osteolytic areas in about half of the patients. Tubular phosphate wasting is common and should be treated with phosphate supplement and calcitriol. The prognosis should improve with therapeutic advances, but this remains to be properly evaluated.

Medical therapy in adults with fibrous dysplasia of bone.

UNLABELLED: In open studies, bisphosphonate therapy (pamidronate, alendronate) reduced bone pain associated with fibrous dysplasia of bone and was associated to some radiological improvement. Calcium, vitamin D, and phosphorus supplements may be useful in patients with deficiency. We are awaiting results from controlled trials testing bisphosphonates. INTRODUCTION: Fibrous dysplasia of bone (FD), a rare disease caused by osteoblastic lineage differentiation defects, is associated with bone pain, fracture, and bone deformity, but few therapeutic options are available. MATERIALS AND METHODS: We reviewed published data on the treatment of FD with bisphosphonates (pamidronate, alendronate), calcium, vitamin D, and phosphorus. We also present new results on FD therapy with a more potent bisphosphonate, zoledronic acid, given intravenously at the dose of 4 mg every 6 months. RESULTS: Pamidronate therapy, given intravenously every 6 months at a dose of 180 mg in adults, relieved bone pain, decreased bone resorption, and improved the radiological aspect (filling of lytic lesions and/or thickening of cortices) in approximately 50% of patients. BMD in affected sites was also significantly increased after pamidronate treatment. Those results have been obtained only in open studies, without controls, by several research groups. In a series of nine patients on long-term pamidronate treatment, but resisting to this medication and switched to intravenous zoledronic acid, no substantial improvement was observed. There is some biological rationale supporting the use of calcium and vitamin D in patients with deficiency to improve FD lesions by limiting secondary hyperparathyroidism. Phosphorus supplementation may prevent mineralization defects in those patients who have both FD and renal phosphate wasting. However, we are lacking clinical evidence for the efficacy of such supplements. CONCLUSIONS: Bisphosphonate treatment reduces increased osteoclastic activity in FD and probably improves bone pain, but their use should be better studied in randomized controlled trials.

Treatment of fibrous dysplasia of bone with intravenous pamidronate: long-term effectiveness and evaluation of predictors of response to treatment.

Fibrous dysplasia (FD) of bone is a rare but potentially severe bone disease that often entails fractures, deformities, and bone pain. An activating mutation of the alpha subunit of Gs proteins leads to differentiation abnormalities of the osteoblastic lineage, which are responsible for development of fibrous tissue in the medulla and increased osteoclastic activity. This increased bone resorption has been the rationale to use bisphosphonates in our center since 1988. So, we have analyzed the largest series, so far, of patients treated with the bisphosphonate pamidronate and sought predictors of response to treatment. We have treated 58 patients (41 adults and 17 under 18 years of age) with FD in an open study, using intravenous (IV) pamidronate 180 mg every 6 months and calcium and vitamin D supplements, in combination with oral phosphate and calcitriol in patients with FD who also had renal phosphate wasting. Patients were followed up with biannual visits, for an average 50 months, with pain assessment, annual radiographs of affected bones, measurement of biochemical markers of bone turnover, and annual bone mineral density measurements in the case of affected hips. We found that pain intensity significantly decreased with treatment in the 44 patients who had bone pain at baseline, biochemical markers of bone turnover were significantly reduced, and about 50% of patients had improvement of bone lesions on radiographs, evidenced by filling of osteolytic lesions and/or cortex thickening. Bone mineral density was substantially increased in the 12 patients who had hip FD. There was no significant clinical or biological predictor of positive radiographic response to pamidronate treatment. Long-term treatment with pamidronate was safe, in particular among the 12 patients who were followed up for more than 8 years. Despite the lack of a control group, our results suggest that intravenous pamidronate improves radiological aspect in half of the patients with FD, decreases bone turnover, and may decrease pain intensity.

Cherubism in siblings: a case report.

Cherubism is a non-neoplastic bone disease characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. Cherubism may appear in solitary cases or in many members of the same family, often in multiple generations. On radiography, the lesions exhibit bilateral multilocular radiolucent areas. Histopathologic evaluation reveals proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since the first description of this condition in 1933, almost 200 cases have been reported. We describe cherubism in 2 siblings and briefly review the literature on this subject.

Renal osteodystrophy in dialysis patients: diagnosis and treatment.

This article reviews the clinical, biological, radiological, and pathological procedures and their respective indications for the practical diagnosis of the following various histological patterns of renal osteodystrophy: osteitis fibrosa due to parathyroid hormone (PTH) hypersecretion: osteomalacia or rickets due to native vitamin D deficiency and/or aluminum overload; and adynamic bone disease (ABD) due to aluminum overload and/or PTH secretion oversuppression. Our advice regarding bone biopsy is to restrict it to patients with symptoms and hypercalcemia, especially those who have been previously exposed to aluminum. In other cases, we propose relying merely on the determination of the plasma concentrations of calcium, protide, phosphate, bicarbonate, intact PTH, aluminum, 25(OH)D3, and alkaline phosphatase (total and bony if hepatic disease is associated) to choose the appropriate treatment. Because of the danger of the desferrioxamine treatment necessary to chelate and remove aluminum, the suspicion of aluminic bone disease (osteomalacia or ABD) will always be confirmed by a bone biopsy. In the case of nonaluminic osteomalacia, correction of the vitamin D deficiency by native vitamin D or 25(OH)D3, and of the calcium deficiency and acidosis by alkaline salts of calcium and if necessary sodium bicarbonate are sufficient to cure the disease. In the case of nonaluminic ABD, the stimulation of PTH secretion by the discontinuation of 1alpha hydroxylated vitamin D and the induction of a negative calcium balance during dialysis by decreasing the calcium concentration in the dialysate will allow an increase of the CaCO3 dose to correct for hyperphosphatemia without inducing hypercalcemia. For hyperparathyroidism, i.e., plasma intact PTH levels greater than two- or four-fold the upper limit of normal levels (according to the absence or presence of previous aluminum exposure), the treatment will consist in increasing the CaCO3 dose to correct for hyperphosphatemia together with a decrease of the calcium concentration in the dialysate if the dose of CaCO3 is so high that it induces hypercalcemia. When the hyperphosphatemia has been corrected and there is still a low or normal corrected plasma calcium level, 1alpha(OH)D3 in an oral bolus 2 or 3 times a week should be given at the minimal dose of 1 microg. When the PTH level stays above 400 pg while hypercalcemia occurs and hyperphosphatemia persists, surgical subtotal parathyroidectomy is recommended or the injection of calcitriol into the big nodular hyperplastic parathyroid glands under sonography control in high surgical risk patients. Special recommendations are given for children.

Prevention of osteitis fibrosa, aluminium bone disease and soft-tissue calcification in dialysis patients: a long-term comparison of moderate doses of oral calcium +/- Mg(OH)2 vs Al(OH)3 +/- 1 alpha OH vitamin D3.

Since 1980, moderately large doses of oral calcium (80 +/- 35 mmol/day as CaCO3 +/- calcium polystyrene sulphonate), in association if necessary with Mg(OH)2 (2.5 +/- 1 g/day), with a reduction in the dialysate Mg concentrations from 0.75 to 0.375 mmol/24 h, have replaced A1(OH)3 as phosphate binders in our centre. A1(OH)3 was previously given to our haemodialysis patients in association with small doses of Ca CO3 (less than or equal to 3 g/day) and if necessary with 1 alpha OH vitamin D3. To compare the long-term efficacy of this new approach with the former one in the prevention of renal osteodystrophy and soft-tissue calcification, 32 current patients were selected on the basis of at least 24 months of treatment in our centre and availability of a yearly bone survey (profile of lumbar spine and anteroposterior view of the pelvis, shoulders and hands). A group of 30 patients treated before 1980 were then selected on the same criteria and matched for age, sex, and duration on dialysis. Linear calcifications of the anterior and posterior walls of the aorta in front of L2, L3, L4 and on the lateral walls of the iliac and femoral arteries were measured and the para-articular calcifications and subperiosteal resorptions of the hands evaluated. The initial extent and the subsequent increase of the ocular and para-articular calcification were comparable in the two groups. Plasma alkaline phosphatase was stable in the normal range in both groups, as was plasma concentration of calcium. Plasma phosphate was slightly elevated (1.7 mmol/l) but stable and comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Scintigraphic manifestation of fibrous dysplasia.

Scintigraphic manifestations of fibrous dysplasia were analyzed in 59 lesions of 26 patients (12 monostotic, 14 polystotic). Bone imaging with Tc-99m MDP revealed a high percentage of increased uptake of radioisotope in the lesions of fibrous dysplasia. Four (14%) of 29 cystic lesions and two (7%) of 30 lesions with the appearance of ground glass showed no increase in radioisotope uptake, although roentgenograms showed marked changes. Therefore, care must be taken in the diagnosis of fibrous dysplasia with bone imaging alone. Nuclear methods, however, are indispensable in evaluating the dynamic aspects of bone mineral behavior and in demonstrating disease where none was suspected, or in visualizing polyostotic involvement in those cases where only monostotic disease was suspected clinically. It is concluded that both scintigrams and roentgenograms are complementary procedures in the diagnosis of fibrous dysplasia.

The McCune-Albright syndrome.

The presence of polyostotic fibrous dysplasia of bone, hyperpigmented skin macules, and precocious sexual development in children is known as the McCune-Albright syndrome. To date, a complex combination of multiple endocrinopathies including goiter, hyperthyroidism, acromegaly, Cushing syndrome, hyperprolactinemia, sexual precocity, hyperparathyroidism, and hypophosphatemic hyperphosphaturic rickets have been described in association with this syndrome. Even though the pathogenetic mechanisms involved in the development of the endocrinopathies is unknown, it was assumed for many years that hypothalamic dysfunction was the cause in most cases. The overwhelming amount of data now permits the development of an alternate hypothesis; one of hyperfunctioning endocrine organs working with relative autonomy from hypothalamic control.