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 frontal bone thickness among various age groups - differences between males and females.

Hyperostosis frontalis interna (HFI) represents an abnormality of the frontal cranial bone that is characterized by bilateral, nodular thickening of its inner lamina and may sometimes be associated with neuropsychiatric symptoms such as headaches and depression. The aim was to assess prevalence, sex and age differences of HFI and frontal bone thickness by means of MRI. This retrospective study included 908 subjects who were divided into male and female groups and further subdivided into three groups, youngest (≤45 years), middle-aged (46- 65 years) and the oldest group (65 years). The thickness of the frontal bone was measured on the T2-weighted axial images at the top level of the lateral ventricles as a mean from both sides. We considered 10mm or thicker frontal bone as HFI. The total prevalence of HFI was 8.1%, with a more frequent occurrence in women (p0.05). In males, there was no difference in the frontal bone thickness between different age groups (p0.05), while in females we found differences between the youngest and the oldest group, and also between the middle-aged and the oldest group (p0.05). The female respondents had a thicker frontal bone, which was statistically significant only in the oldest group (p0.001). Frontal bone thickness was age-dependent only in women (Spearman's Rho 0.11; p≤0.01). In women, unlike in men, there is an age-related progression of HFI with increasing prevalence, with 16.4% occurrence in the oldest group.

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.

Etiopathogenesis of hyperostosis frontalis interna: a mystery still.

Hyperostosis frontalis interna is a morphological pattern characterized by single or multiple bony nodules situated on the inner lamina of the frontal bone. It is seldom found in males, but it is a common phenomenon among post-menopausal females in modern societies but relatively rare in antiquity. The etiopathogenesis of the trait is a matter of debate and ranges from genetic predisposition to epigenetic, while endocrine disturbances, aging, and dietary factors are also listed among the causes. We studied the frequency, characteristic features, and etiopathogenesis of the disease in recent cadaveric and dry skull specimens. The frequency of hyperostosis frontalis interna in cadavers and dry skull materials was almost identical, 12.5% and 12.3%, respectively. In cadavers, 87.5% of severe hyperostosis frontalis interna cases were found in females over 65 years-old. Interestingly, in two cadavers we found hyperostotic lesions spreading onto adjacent tissues such as the dura and falx cerebri. We provide some new aspects that may help in better understanding of the etiopathogenesis of hyperostosis frontalis interna. Thereby, we discuss the various etiopathogenesis models found in the literature.

Hyperostosis frontalis interna: what does it tell us about our health?

OBJECTIVES: To examine whether the prevalence and severity of hyperostosis frontalis interna (HFI) has significantly changed during the past 100 years. METHODS: Two female populations, 100 years apart, were studied; 992 historic and 568 present day females. Detection of HFI was carried out via direct observation or CT images (Brilliance 64, Philips Medical Systems, Cleveland, Ohio). HFI was graded according to Hershkovitz et al.'s (1999) 4-scale definition and according May et al.'s (2010c) 3-scale definition. RESULTS: Following correction for age, present day females manifested a significantly higher HFI prevalence compared with historic females (P < 0.05). The risk of developing HFI was found to be approximately 2.5 times greater in present day females compared with females living 100 years ago (P < 0.05). In the young age cohort, present day females manifested a significantly higher prevalence of HFI type B (P < 0.05), whereas in the old age cohort, a significant difference in the prevalence of HFI types C and D was noted between the two groups (P < 0.05). HFI tended to appear at a younger age in the present population. The last two decades has witnessed an increase in HFI prevalence(from 55.6% to 75%). CONCLUSIONS: HFI prevalence has increased during the last century, especially among young individuals, possibly indicating a profound change in human fertility patterns, together with the introduction of various hormonal treatments) and new dietary habits.

Síndrome de Stewar-Treves / Stewart-Treves syndrome

El síndrome de Stewart-Treves es uno de los tumores vasculares más agresivos, siendo su diagnóstico muchas veces tardío. Se define como un tumor maligno de origen lingfático (linfangiosarcoma) que se origina en la extremidad superior afecta de linfedema crónico secundario a mastectomía por neoplasia de mama. Su incidencia del 0,5% de los pacientes con linfedema postmastectomía, apareciendo en una media de 9 años después del inicio del linfedema. Se caracteriza por la presencia de una o múltiples máculas de color rojizo o rojo-púrpura en el miembro superior que tienden a crecer y multiplicarse convirtiéndose en nódulos duros, con tendencia a la ulceración y hemorragias espontáneas. Cursan con metástasis precoces a nivel torácico. Creemos importante que los cirujanos vasculares conozcan esta enfermedad, siendo el diagnóstico precoz y el tratamiento multidisciplinar la única esperanza para estos pacientes

Stewart-Treves Síndrome is one of the most aggresive vascular neoplasm. Sometimes the diagnosis is late. This neoplasm is a lymphatic tumor (lymphangiosarcoma) which appears in an upper limb with chronic lymphedema postmastectomy, arising 9 years after the appearance of lymphedema´s symptoms. The clinical features are one or multiple rose or red-purple macular lesions in the upper limb. The natural evolution of the lesions are growing and becoming a hard nodule with tendency of ulceration and spontaneous hemorrhage. The thoracic metastasis is early. We think is important that the vascular surgeons recognize this pathology, being the early diagnosis and the multidisciplinary treatment the unique opportunity for these patients

Hyperostosis frontalis interna, a genetic disease?: Two medieval cases from Southern Poland.

Two cases of thickening of the internal tables of the frontal bones (hyperostosis frontalis interna, (HFI)) have been examined. These were two female skeletons from the 16th century Dominican Church in Raciborz (Southwest Poland). The similarity of their morphological and metrical traits indicates that they could be related, and suggests that HFI is likely to have a genetic base. These two skeletons are the subject of an analysis which may possibly throw some new light on the controversial and continually disputed nature of this illness.

Brief communication: unusual finding at Pueblo Bonito: multiple cases of hyperostosis frontalis interna.

Hyperostosis frontalis interna (HFI) is a disease characterized by excess bone growth on the internal lamina of the frontal bone and, occasionally, other cranial bones. Although the disease is fairly common in modern populations, its etiology is poorly understood. Hyperostosis frontalis interna has been identified in antiquity, primarily in the Old World, but with a much lower frequency than in modern groups. The purpose of the present study is to report multiple cases of HFI at Pueblo Bonito (Chaco Canyon, New Mexico). Twelve out of 37 adults with observable frontal bones exhibited HFI, ranging from mild to severe, including 11 females and one male. This is the first published case report of HFI in archaeological remains from the New World having a frequency comparable with modern groups. Most archaeological cases of HFI are isolated, so comparative data for multiple cases at one site are rare. The results of this study emphasize the importance of looking for HFI in archaeological remains, although it is rarely observed. Possible genetic and environmental factors for the high frequency of HFI at Chaco Canyon are considered, but additional research is needed to discover the etiology and to better understand why HFI sometimes occurs at modern frequencies in ancient populations.

Hyperostosis frontalis interna: forensic issues.

The use of pathological conditions in age and sex determination, important factors in personal identification, is not widespread in anthropology and legal medicine. Hyperostosis frontalis interna (HFI) is a bone condition that mainly affects the inner table of the frontal bone. Although there are numerous publications on the subject, at the present time its etiology remains obscure. Several associations of symptoms, whose incidence varies according to the population studied, have been described. Age and gender appear to be linked with the preponderance of this condition, as does the presence of behavioral disturbances. The aim of our study, based on a series of 1532 autopsies, was to define the incidence and the associations observed with other pathological conditions. Thirteen cases of HFI were identified (0.8% of autopsies), 12 women and one man whose mean age was 59.15 years (range: 42-79 years). All had behavioral disturbances and most were under psychiatric care. This study emphasizes the value of this condition in medico-legal identification.

Why do we fail in aging the skull from the sagittal suture?

The controversy over the reliability of ectocranial suture status (open vs. closed) as an age estimation stimulated the pursuit of Meindl and Lovejoy's suggestion (Meindl and Lovejoy [1985] Am. J. Phys. Anthropol. 68:57-66) for large scale analysis. The extent of the sagittal suture closure was assessed in 3,636 skulls from the Hamann-Todd and Terry collections. The debate over whether cranial suture ossification represents a pathologic or an age-predictable pathologic process also stimulated a comparison with age and two stress markers, hyperostosis frontalis interna and tuberculosis. Sagittal suture closure was found to be age-independent and sexually biased. The wide confidence intervals (for age) appear to preclude meaningful application of suture status for age determination. No correlation was found with the tested biological stressors.

Endocranial hyperostosis in Sangiran 2, Gibraltar 1, and Shanidar 5.

Sangiran hominid 2 (S-2), Gibraltar hominid 1 (G-1), and Shanidar hominid 5 (SH-5) exhibit previously undescribed bilateral, paramedian hyperostosis of the endocranial frontal squama that spares the frontal crest, sagittal sinus, and ectocranial surface. The hyperostosis is localized to the frontal (usually the middle third) and parietal and is consistent with a diagnosis of hyperostosis calvaria interna (HCI), inclusive of hyperostosis frontalis interna. The hyperostosis in these specimens is compared to fossil hominids from Indonesia and Europe and to modern human cases of HCI. The three cases of HCI reported here documented the existence and frequency of HCI in fossil hominids and push the antiquity of the disease back to nearly 1.5 million years. The relatively great incidence of HCI in fossil hominids adds another confounding factor to the problematical issue of the taxonomic significance of cranial vault thickness.

[Paget's disease, ankylosing vertebral hyperostosis and hyperostosis frontalis interna]. / Rapports de la maladie de Paget avec l'hyperostose vertébrale ankylosante et l'hyperostose frontale interne.

Ankylosing vertebral hyperostosis and internal frontal hyperostosis have a frequency of 5% and 8% respectively. In Paget's disease, these two disorders are found with a frequency of 40% and 19.1% respectively. This frequency is not due to chance. There exists a link between the 3 diseases. Ankylosing vertebral hyperostosis is thusa new pathological association in Paget's disease. It is even the most frequent of these associations. It seems Paget's disease induces hyperostosis and not the contrary. The authors suggest the theory that cortical and periostal hypervascularisation in pagetoid bone favour the development of these hyperostoses.

Gerontological aspects of hyperostosis frontalis interna.

Authors discuss hyperostosis frontalis interna observed in a large number of aged persons, on the basis of age and sex distribution as well as its clinical and roentgenomorphological analysis. In various forms of the ossification of the frontal bone no significant difference was found between the localisation of hyperostosis and the clinical symptoms. On other hand, there is a direct correlation between the extension and severity of hyperostosis and the frequency of occurence of the associated symptoms (obesity, hypertension). They found the aetiological classification more adequate than the morphological categorization of Moore. Their cases are discussed 1. as partial phenomenon of the Morgagni's syndrome; 2. as independent alteration, showing no other symptoms; 3. as transitionary forms inserted between the two groups mentioned above. They discuss also the question of senile, compensatory hyperostosis frontalis interna. On the basis of the study of a large autopsy material they support the opinion that there is a direct connection of this form with old age.