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.

Uremic Leontiasis Ossea: Theoretical Concepts and Practical Considerations.

Leontiasis ossea (LO) in chronic kidney disease patients, also known as Sagliker syndrome, is an exceptionally uncommon uremic complication of long-lasting and severe secondary hyperparathyroidism. The prominent features of uremic LO (ULO) encompass the characteristic clinical trial of massive thickening of maxillary and mandibular bones, widening of interdental spaces, and flattening of nasal bridges and nares. Moreover, during the transformation of craniofacial architecture, significant structural and functional consequences may appear, including upper airway patency, visual and hearing acuity, oral phase of swallowing as well as various neurological and psychiatric disorders. Only few cases of ULO have been reported in the literature until now, making challenging not only the traditional diagnostic procedures but also the optimal therapeutic approach. In this narrative review, we aim to explore the underlying pathophysiological mechanisms, summarize the evidence for adverse outcomes, and highlight the current therapeutic strategies for ULO prevention and treatment, given that precise genetic determinants remain elusive.

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.

Uremic lion face syndrome.

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.

Uremic leontiasis ossea.

Uremic leontiasis ossea is a rare manifestation of renal osteodystrophy clinically characterized by jaw enlargement, widening of the nares, flattening of the nasal bridge, and increased interdental spacing. Computed tomography (CT) findings are particular characteristic and include serpiginous tunneling within the maxillofacial bones and cortical bone resorption. Nuclear medicine scans are also useful for demonstrating hyperplasia of the parathyroid glands. Ultimately, the diagnosis of uremic leontiasis ossea can be made non-invasively through a combination of clinical parameters and imaging findings, as described in this article.

Dramatic alteration of the skull in a uremic patient with leontiasis ossea.

The craniofacial skeleton represents a peculiar target of hyperparathyroidism in patients with end-stage renal disease who exhibit a dramatic pattern of uremic leontiasis ossea. Scant information regarding this condition is available in the renal literature, as the extreme and typical manifestations of leontiasis ossea have been described in only a small series of patients. We herein report a case of significant amelioration of massive modification of the facial appearance of a 30-year-old uremic Chinese woman with severe skeletal deformities who underwent total parathyroidectomy with a forearm autograft concurrently with effective drug treatment. This report may shed light on how to better understand and treat this metabolic derangement.

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.

Intracranial volume, cranial thickness, and hyperostosis frontalis interna in the elderly.

OBJECTIVES: According to the "brain reserve hypothesis," a larger premorbid brain protects against the development of dementia. The aim of this study was to reveal a possible pathophysiology of brain degenerative diseases by studying intracranial bone lesions that act to reduce intracranial volume (ICV), such as hyperostosis frontalis interna (HFI). METHODS: Three hundred and eighty postmenopausal females (aged 60+) who had undergone a head computerized tomography scan (Brilliance 64, Philips Healthcare, Cleveland, OH) at the Carmel Medical Center, Haifa, Israel, before the study were included. The subjects were divided into four groups according to their degree of HFI. Six measurements of the skull and brain were taken. RESULTS: As HFI becomes more severe, the cranial bone thickness and cranial bone volume increase. This process is accompanied by a decrease in ICV. In none of the HFI groups studied there was a significant association between ICV and cranial bone thickness. The inter-relationships between the various thickness parameters are not disturbed by the degree of HFI. CONCLUSION: HFI is accompanied by an increase in thickness of all calvarial bones and reduced ICV. In addition, the thickening process initiated by HFI is synchronized among the calvarial bones. Presence of HFI suggests a decrease in brain volume and has a major clinical significance as it may indicate the beginning of degenerative processes of the brain. In addition, as females age, their skulls tend to develop more robust characteristics.

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.