Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

PURPOSE: Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. METHODS: Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. RESULTS: Mean frontal bone thickness was 6.75 mm in acromegaly, 4.85 mm in group 1, and 5.1 mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. CONCLUSION: Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.

[Hyperostosis frontalis interna : etiology and differential diagnosis]. / Hyperostose frontale interne : étiologie et diagnostic différentiel.

Hyperostosis frontalis interna was first described in 1719 in association with obesity and hirsutism, forming Morgagni's syndrome. A high prevalence and a lack of studies demonstrating a strong correlation between these different signs currently question the existence of such a syndrome. Hyperostosis frontalis interna predominates in women. The anomaly exclusively involves the inner table and constantly spares the diploe and the external table. The main differential diagnosis of cranial hyperostosis is made between meningioma, osteoma, Paget's disease and fibrous dysplasia. The clinical implication of hyperostosis as well as its etiology are also debated.

L'hyperostose frontale interne a initialement été décrite en 1719, en association avec une obésité et de l'hirsutisme, formant ainsi le syndrome de Morgagni. Une prévalence élevée et un manque d'études confirmant une corrélation entre ces différents signes remettent actuellement en doute l'existence de ce syndrome. L'hyperostose frontale interne prédomine largement chez la femme. L'affection concerne exclusivement la table interne et épargne constamment le diploé et la table externe. Le diagnostic différentiel principal des hyperostoses crâniennes s'établit entre le méningiome, l'ostéome, la maladie de Paget et la dysplasie fibreuse. L'implication clinique de l'hyperostose ainsi que son étiologie sont également débattues.

Hyperostosis Frontalis Interna and a Question on Its Pathology: A Case Report.

BACKGROUND Hyperostosis frontalis interna is a boney overgrowth of the inner side of the frontal bone of the skull caused by overgrowth of the endocranial surface. It is most often found in women after menopause. It is also associated with hormonal imbalance, being overweight, history of headaches, and neurocognitive degenerative conditions. Female gender, advanced age, extended estrogen stimulation, and elevated leptin levels may also play a role. The thickening is usually confined to the frontal bone, but it can spread as far as the anterior parietal and temporal bones. CASE REPORT During a medical school dissection course, an extensive boney overgrowth in the frontal regions covering the inside of the frontal bone of the skull of a 90-year-old female donor, who died of a cerebrovascular infarction, was identified. This boney overgrowth was mainly confined within the frontal region, but there was some boney overgrowth that extended to the temporal bones. The overgrowth in the endocranium of the temporal bone was not as severe as the overgrowth of the frontal bone. The morphology of the overgrowth was rigid, uneven, and bumpy. Based upon the physical characteristics, we concluded that this presentation was consistent with hyperostosis frontalis interna. CONCLUSIONS Our female donor was found to exhibit a phenomenon which could be clinically underdiagnosed due to its internal nature and asymptomatic presentation. Insight into the potential causes of HFI and its identification during clinical evaluation offers a path for future research to better identify and manage cases of HFI.

Manejo de vía aérea en paciente con leontiasis ossea. Reporte de caso / Airway management in a patient with leontiasis ossea. Case report

Leontiasis ossea is an uncommon complication of advanced chronic kidney disease that alters the facial bone and the airway, making its perioperative management more complex. We present a clinical case of a female with Leontiasis ossea presenting a difficult airway which requires parathyroidectomy. Assessment, planning and management of the airway by awake intubation is described.

La leontiasis ossea es una complicación infrecuente de la enfermedad renal crónica avanzada que altera el macizo facial óseo y la vía aérea, complejizando su manejo perioperatorio. Presentamos caso clínico de mujer portadora de leontiasis ossea con vía aérea difícil requiriendo paratiroidectomía. Se describe valoración, planificación y manejo de vía aérea mediante intubación vigil.

Radiological diagnostic features of uremic leontiasis ossea: a case report.

Uremic leontiasis ossea (ULO), which occurs in the craniomaxillofacial region, is a sign of terminal stage osteitis fibrosa cystica or brown tumors and primarily caused by secondary hyperparathyroidism induced by renal failure. Pathophysiological changes include osteoclasts or osteoblasts proliferation, bone resorption, bone decalcification, and connective tissue proliferation. In this paper, we report a case of a 24-year-old female patient, who was diagnosed with ULO and presented with multiple facial swellings. Imaging features included zonal patterns with alternating rings of hypo- and hyperattenuated craniomaxillofacial bones, and diffused mixed sclerotic tissues with lytic changes in CT imaging. T1 weighted image and T2 weighted image in MRI were characterized by alternating rings of low and intermediate signal intensity patterns. To the best of our knowledge, this case is the first example of pathologically proved ULO with maxillofacial MRI.

Uremic lion face syndrome / Face Leonina na Síndrome Urêmica

Abstract Mineral bone disorder is a common feature of chronic kidney disease. Lion face syndrome is rare complication of severe hyperparathyroidism in end-stage renal disease patients, which has been less commonly reported due to dialysis and medical treatment advances in the last decade. The early recognition of the characteristic facial deformity is crucial to prompt management and prevent severe disfigurement. The authors present a rare case of severe hyperparathyroidism presenting with lion face syndrome and bone fractures.

Resumo O distúrbio mineral e ósseo é uma característica comum da doença renal crônica. A síndrome da face leonina é uma complicação rara do hiperparatireoidismo grave em pacientes com doença renal terminal, que tem sido menos relatada devido aos avanços na diálise e tratamento médico na última década. O reconhecimento precoce da deformidade facial característica é crucial para estimular o tratamento precoce e prevenir a desfiguração severa. Os autores apresentam um caso raro de hiperparatireoidismo grave, apresentando síndrome da face leonina e fraturas ósseas.

Total parathyroidectomy with autotransplantation for a rare disease derived from uremic secondary hyperparathyroidism, the uremic leontiasis ossea.

SUMMARY: We described six uremic leontiasis ossea (ULO) patients who underwent total parathyroidectomy with autotransplantation. ULO demonstrated more a systemic disease than a simple craniofacial deformation. The surgery seemed an effective treatment to alleviate secondary hyperparathyroidism and to improve patients' quality of life. ULO may have a high postoperative recurrence tendency. INTRODUCTION: ULO is a rare disease derived from uremic secondary hyperparathyroidism (SHPT). Previous studies mostly focused on the craniofacial deformations. This study aims to investigate the systemic features of the disease and the surgical outcomes. METHODS: The present study retrospectively assessed six ULO patients who underwent total parathyroidectomy (TPTX) with autotransplantation (AT). Follow-up data were recorded. The follow-up status was considered as "effectiveness" if serum intact parathyroid hormone (iPTH) levels were <150 pg/mL in the first 3 days after surgery, or as "recurrence" if serum iPTH gradually increased >300 pg/mL during follow-up in patients whose status was initially considered as "effectiveness". RESULTS: Craniofacial deformations, short stature, thoracocyllosis, spine malformations, osteodynia, and muscle weakness were observed in all patients. Abnormal pulmonary functions were observed in five patients. After surgery, one patient died from respiratory failure. Surgery was effective in the remaining five patients with relieved osteodynia and stopped craniofacial deformation. A mean follow-up of 7.6 (4 to 12) months was available. Three patients suffered from recurrence of hyperparathyroidism originating from autografts. CONCLUSIONS: Our data suggests that ULO is not only a simple disease with craniofacial malformations but is a severe systemic disease leading to increased surgical risks. TPTX with AT seems an effective treatment to relieve SHPT and to improve quality of life. ULO may have a high postoperative recurrence tendency.

The spectrum of orofacial manifestations in renal osteodystrophy: diagnostic challenges of an uncommon presentation.

Renal osteodystrophy refers to a spectrum of bone diseases caused by pathologic alterations in the metabolism of calcium, phosphate, and bone in the context of end-stage renal disease and secondary hyperparathyroidism. Radiographic alterations affecting the jaw and facial skeleton are common and among the earliest signs of renal bone disease. Renal osteodystrophy also shares clinical, histologic, and radiologic similarities with several benign fibro-osseous conditions affecting the craniofacial region, and its recognition is critical to prevention, choice of therapy, and overall prognosis. The aim of this article is to review the craniofacial manifestations of renal osteodystrophy, describe the work-up of a patient with macrognathia and facial disfigurement caused by renal bone disease, discuss the challenges in arriving at a definitive diagnosis, and highlight an interdisciplinary approach to evaluation and timely diagnosis in overall management.

Synchronous Paget disease of bone and hyperparathyroidism: report of a case with extensive craniofacial involvement.

Paget disease of bone (PDB) and hyperparathyroidism (HPT) are metabolic osseous disorders which affect ≥2% of the population. As these diseases may share clinical, radiographic, biochemical, and histopathologic features, knowledge of their phenotypic overlap may provide diagnostic utility and improve clinical outcome. Scant information is available in the dental literature regarding patients concurrently affected with both pathologies. We present an unusual case report of a 63-year-old woman coaffected with primary HPT, attributed to a functional oxyphilic parathyroid adenoma, and PDB. Bone scintigraphy revealed pagetoid lesions of the skull, humeral head, spine, sacrum, and hemipelvis. Salient craniofacial features noted were bony involvement of the calvarium and midface, resulting in extensive maxillary overgrowth, hearing loss, telecanthus and consequent visual impairment, nasal deformity, and leontiasis ossea. The patient underwent a partial parathyroidectomy and bisphosphonate administration was to be initiated upon extraction of the remaining dentition.

Hyperostosis frontalis interna and androgen suppression.

Although hyperostosis frontalis interna (HFI) has been documented in the medical literature for over 300 years, its etiology remains undetermined. It is generally assumed to be associated with hormonal disturbances of the gonads. The aim of this study was to examine the association between androgen deprivation and development of HFI in males. Two groups of males over 60-years old were compared: a control group that included 180 healthy males, 45 suffering from benign prostatic hypertrophy (BPH) and a study group of 127 males with prostate cancer: 67 who received complete androgen block treatment, and 60 who received different treatments or none at all. CT head scans were used to identify and classify HFI (Brilliance 64, Philips Medical Systems, slice thickness 3 mm x 1.5 mm). It was found that males who received a complete androgen block manifested significantly higher prevalence of HFI compared to healthy males. However, no significant difference in HFI prevalence was found between males suffering from BPH and healthy males or males with prostate cancer who had not received a complete androgen block. A positive association between length of hormonal treatment and manifestation of HFI was shown. It can be concluded that BPH does not promote development of HFI; males who are hormonally treated for prostate cancer are at a higher risk of developing HFI compared to healthy males; the longer the duration of hormonal treatment, the higher the risk of developing HFI.

Leontiasis ossea: a paleopathologic case report.

We describe the archeological and imaging findings of a unique specimen (skull and mandible) with leontiasis ossea (LO) that is on display in the National Museum of Anthropology and History in Mexico City. The specimen shows diffuse and irregular periosteal bone proliferation, which produces a grossly nodular appearance involving the neurocranium and the facial skeleton. Plain radiography and helical computed tomography revealed generalized hyperostosis obliterating the maxillary and sphenoidal sinuses and 2 exuberant bony masses arising from the maxilla with encroachment of the anterior nasal aperture.Currently, LO is a purely descriptive term applied to a variety of osseous conditions that have in common hyperostosis of craniofacial bones leading to a leonine appearance. Clinicians who see such lionlike facies should consider the main causes of LO, which include renal osteodystrophy, Paget disease and, as most likely in this specimen, fibrous dysplasia.

Leontiasis ossea and post traumatic cervical cord contusion in polyostotic fibrous dysplasia.

Leontiasis ossea (leonine facies) or cervical canal stenosis are rare complications of polyostotic fibrous dysplasia (PFD). This case report documents dramatic leontiasis ossea in PFD as well as post traumatic cervical cord contusion due to hyperextension injury in a patient with generalized PFD involving the cranio-facial bones, axial skeleton and entire spine with secondary cervical canal stenosis. Cervical cord contusion has not been reported earlier in PFD.

[Cranial hyperostosis as a metastasic adenocarcinoma presentation form]. / Hiperostosis craneal como forma de presentación de un adenocarcinoma metastásico.

Hyperostosis is a volume-unit osseous increase of very diverse etiology. We present the case of a 68-year woman with a cranial hyperostosis debuting with frontal protrusion, headache and neurologic symptoms. Image proves demonstrated a hyperostosis in the calotte and meningeal enhancement, without intracerebral lesions nor malignant cells in the cerebrospinal fluid. Analytic data were unspecific. Cranial biopsy showed huge neoplastic infiltration in bone and meninges. Primary site remained unknown after a CAT and a mammography.

Hyperostosis frontalis interna: case report and review of literature.

Hyperostosis frontalis interna (HFI) has been reported in high frequency among post-menopausal elderly women. Although it was widely discussed in the past, this entity is rarely mentioned in the current pathology literature. We report a postmortem case of a 56 yr-old post-menopausal woman with irregular thickening of the internal surface of the frontal bone. Histology revealed an organized trabecular pattern with overall thickening of the cancellous bone. The periosteum and cortical bone were unaffected. The finding was considered to be unrelated to her death. HFI should be recognized as a benign entity and distinguished from other disorders that involve the frontal skull bone, such as Paget's disease, acromegaly, and malignancy. The etiology of HFI is unknown, but current hypotheses implicate hormonal stimulation.

Maxillary brown tumor and uremic leontiasis ossea in a patient with chronic renal insufficiency.

Findings of renal osteodystrophy in cranial bones are not uncommon and include osteomalacia, osteosclerosis, erosion of the cortical bone, brown tumors and resorption of the lamina dura. However, massive thickening of the cranial vault and facial bones, called uremic leontiasis ossea, have been reported very rare. In the present article, we describe the case of an uncooperative female patient with a brown tumor, involving the left maxillary sinus and massive thickening of the cranial vault and facial bones, secondary to severe secondary hyperparathyroidism during 8 years of regular hemodialysis treatment.

[82-year old patient with hyperostosis frontalis, prognathism, makroglossia and cutis gyrata. Acromegaly]. / 82-jährige Patientin mit Hyperostosis frontalis, Prognathie, Makroglossie und Cutis gyrata. Akromegalie.

We present a 82 year old female patient with typical acral enlargement. There were no signs of visceromegaly. Magnetic resonance imaging of the pituitary region showed a macroadenoma. Oral glucose tolerance test revealed missing suppression of the Human Growth Hormone (HGH), which could be achieved with a long acting somatostatin analog. A HGH suppressive therapy with a long acting dopamine agonist (Cabergolin) was induced. The patient died one year later following cardiovascular complications.