Hyperostosis frontalis interna usually affects postmenopausal women [1], but up to 12% of the whole female population may have this condition, including those of child-bearing age since the disease has also been associated with pregnancy. Men are seldom affected. The real prevalence of the disease may be underestimated because it is often asymptomatic and the diagnosis can only be established following a skull imaging study.

Rarely, the disease is associated with some of the numerous possible manifestations. The clinical examination may reveal certain physical traits: virilization, obesity, epilepsy, facial palsy, or headaches [2]. Patients may be diabetic, therefore also exhibiting the characteristics of this condition: weight loss, polyuria, polydipsia, and polyphagia. Additional features for this condition include fatigability, vertigo, hypertrichosis, and acromegaly [3]. Mental disturbances such as depression, paranoia, or aggressiveness are believed to be caused by intracranial volume decrease [4]. Brain tissue compression, explaining epileptic seizures and dural irritation, may also be encountered [5]. The disease may cause hormonal impairment, such as hyperprolactinemia or ovarian dysfunction.

In the past, hyperostosis frontalis interna was regarded as part of several syndromes, namely Morgagni (hypertrichosis, obesity, virilization, and headaches), Stewart-Morel (neuropsychiatric abnormalities and obesity), and Troell-Junet (diabetes mellitus, acromegaly, and toxic goiter) syndromes [6].

• Fever

  Knies and Le Fever (1941) reported mother and 3 children affected. Thus, the disorder may be dominant, but whether autosomal or X-linked is not known. Lieberman (1967) has observed 5 affected females in 3 generations. [omim.org]

  […] puberty, marked by osteosclerosis of the skull, mandible, clavicles, ribs, and diaphyses of long bones, associated with elevated blood alkaline phosphatase. infantile cortical hyperostosis a syndrome seen in infants under six months of age, marked by fever [medical-dictionary.thefreedictionary.com]

• Fatigue

  Also called Morel's syndrome. hyperostosis frontalis interna Morgagni-Stewart-Morell syndrome A form of osteopetrosis more common in middle-aged ♀, associated with obesity, hirsutism, fatigue, hemiplegia and hemiparesis; HFI affects cranial bones, structurally [medical-dictionary.thefreedictionary.com]

  There may be associated menstrual disorders, virilism, hirsutism, mental disorders, fatigue, somnolence, visual disorders, vertigo, tinnitus, obesity, polyphagia, polydipsia, polyuria, loss of sense of smell, decrease in glucose tolerance, convulsions [whonamedit.com]

  Weakness, obesity, and fatigue are also common, as are vertigo and facial palsy. Due to these symptoms being somewhat generalized, a differential diagnosis must be made. [wisegeek.com]

• Galactorrhea

  Pawlikowski and Komorowski (1983) found hyperostosis frontalis in 43% of women with galactorrhea as compared with a population frequency of 2.5%. (At least 2 other groups reported similar frequencies.) [omim.org]

• Weight Gain

  This may lead to symptoms such as chronic headaches, weight gain, and thyroid irregularities, and is suspected to have multiple causes, including lifestyle, fertility habits, nutrition, and environment. To track the growing prevalence of HFI, Prof. [sciencedaily.com]

• Hypotension

  Definition / general Also called thickened calvarium May be due to intracranial hypotension associated with chronic shunting, as skull lacks the outward pressure needed to expand ( Hum Pathol 1994;25:545 ) Gross description Circumferentially thickened [pathologyoutlines.com]

• Hirsutism

  […] compromising the hypophysis–causing dysmenorrhea, virilism, hirsutism, diabetes insipidus, and glucose intolerance, and cranial nerve foramina–causing vertigo, tinnitus, anosmia, and visual defects [medical-dictionary.thefreedictionary.com]

  Moore The main features of this hereditary syndrome is a trias consisting of 1) hyperostosis frontalis interna, 2) adipositas, and 3) virilism and hirsutism. [whonamedit.com]

  An increase in serum dehydroepiandosterone, its sulphate and testosterone levels and a significant correlation between serum free dehydroepiandosterone and bone mineral content in subjects without any sign of hirsutism or obesity suggested an involvement [ncbi.nlm.nih.gov]

• Hypertrichosis

  Additional features for this condition include fatigability, vertigo, hypertrichosis, and acromegaly. Mental disturbances such as depression, paranoia, or aggressiveness are believed to be caused by intracranial volume decrease. [symptoma.com]

  Thickening of the inner table of the frontal bone, which may be associated with hypertrichosis and obesity. It most commonly affects women near menopause. [profiles.umassmed.edu]

  Hyperostosis Frontalis Interna: Thickening of the inner table of the frontal bone, which may be associated with hypertrichosis and obesity. It most commonly affects women near menopause. [findexpertmd.com]

  HYPEROSTOSIS FRONTALIS INTERNA Alternative titles; symbols MORGAGNI-STEWART-MOREL SYNDROME ▼ TEXT In addition to thickening of the inner table of the frontal bone, obesity and hypertrichosis may be present. This condition affects mainly females. [omim.org]

• Osteoporosis

  KEYWORDS: Bone thickness; hyperostosis frontalis interna; osteoporosis; postmenopausal women [ncbi.nlm.nih.gov]

  Other findings in the skull are widening of the diploic space, mixed lytic and sclerotic lesions (cotton wool appearance), or large well-defined lytic lesions (osteoporosis circumscripta). Enhancement of the lesions is seen in active disease. [radiologykey.com]

  Castration Affected Skeleton Of Famous Opera Singer Farinelli … Further, the researchers discovered osteoporosis and a condition called hyperostosis frontalis interna, both of which are generally much more ... [educalingo.com]

  Current Osteoporosis Reports. 2021;19(5):494–499. Available from: https://doi.org/10.1007/s11914-021-00695-7 el Demellawy D, Davila J, Shaw A, Nasr Y. Brief review on metabolic bone disease. Academic Forensic Pathology. 2018;8(3):611–640. [ifnmujournal.com]

• Bone Disorder

  […] of androgens in pathogenesis of this metabolic bone disorder. [ncbi.nlm.nih.gov]

  Paget’s disease of the bone: A chronic bone disorder characterized by excessive bone remodeling with replacement of normal bone architecture with a coarsened trabecular pattern. [radiologykey.com]

• Suggestibility

  A review of the literature concerning the Morgagni-Stewart-Morel (MSM) syndrome suggests that the changes in the skull fragment are consistent with this diagnosis. [ncbi.nlm.nih.gov]

  This unique specimen supports earlier suggestions of the possible microevolution of human endocrine regulation, e.g. by sex steroids, and its pathoanatomical impact. [zora.uzh.ch]

  We suggest that the HFI disease process was responsible for the manifestation of these symptoms in this patient. [scholars.northwestern.edu]

• Headache

  Res Clin Stud Headache 3:191–197, 1:STN:280:DyaE3s7ltVKhug%3D%3D, 5527204 CAS PubMed Google Scholar Headache Classification Subcommittee of the International Headache Society. (2004) The International Classification of Headache Disorders: 2nd edition. [thejournalofheadacheandpain.biomedcentral.com]

  We present a novel case of migraine headache in a gentleman with Klinefelter's syndrome and HFI, along with a discussion of possible pathophysiologic mechanisms underlying both the headache and the HFI. [ncbi.nlm.nih.gov]

  It has also been described in association with chronic headaches and rarely with seizures.2 This incidental image finding should not alarm neurologists yet should raise awareness about a possible susceptibility for headaches and seizures as part of the [casereports.bmj.com]

  Results HFI presents in predominantly postmenopausal women, normally ranging in thickness from 0.5–1cm, and has been associated with diabetes, obesity, and chronic headaches. [pulsus.com]

  These factors are obesity, diabetes insipidus, and migraine headaches. [epainassist.com]

• Seizure

  During her current admission, she had an episode suggestive of a seizure and it was thought to be related to concomitant severe hypoglycaemia. Patient denied having a prior history of seizures or any episode of unexplained loss of consciousness. [casereports.bmj.com]

  Individuals with Hyperostosis Frontalis Interna also tend to have frequent bouts of seizures some of which may last for more than a minute followed by loss of consciousness. [epainassist.com]

  Seizures and headaches associated with hyperostosis frontalis interna (HFI) are treated with standard medications.[6] References[edit] ^ INSERM US14. "Morgagni Stewart Morel syndrome". Orphanet. [en.wikipedia.org]

  Literature shows its association with seizure, dementia, obesity, headache and endocrine abnormalities. HFI may be syndromic and non-syndromic. Timely identification of HFI can prevent unnecessary diagnostic tests. [sciedupress.com]

  Although most patients with HFI show no clinical symptoms, a few have been reported to show diverse and non-specific symptoms, including－but not limited to－cognitive decline, epileptic seizure, and endocrine disorder. [jstage.jst.go.jp]

• Frontal Headache

  They can include a frontal headache, mental impairment, and depression. Weakness, obesity, and fatigue are also common, as are vertigo and facial palsy. Due to these symptoms being somewhat generalized, a differential diagnosis must be made. [wisegeek.com]

  Mitra Assadi Khansare, Hyperostosis Frontalis Interna, Causing Frontal Lobe Dysfunction and Refractory Headaches,American academy of nuerology, nuerology.org ,2014 16. [medicalandresearch.com]

  Frontal headache, asthenia, forgetfulness, vertigo, nervousness, obesity and poor vision were rather characteristic of this group. There was a high degree of morbidity with frequent remission and exacerbation of symptoms. [amjmed.com]

  Khansare MA, Duome M, Mintz A: Hyperostosis frontalis interna, causing frontal lobe dysfunction and refractory headaches. Neurol Genet. 2014, 82:222. [cureus.com]

• Apathy

  The neuropsychological testing confirmed significant frontal lobe dysfunction manifested as apathy and impairment in abstract reasoning, cognitive inflexibility and executive dysfunction. [n.neurology.org]

  It is has been established that HFI can cause vast psychiatric disturbances, e.g aggressiveness, paranoia or depression.[16] Psychological testing has confirmed that HFI causes significant frontal lobe dysfunction manifested as apathy and impairment in [medicalandresearch.com]

• Forgetful

  Our patient had headache refractory to analgesics because of hyperostosis frontalis externa and there was associated symptoms of intermittent forgetfulness, and depressive symptoms. [medicalandresearch.com]

  Frontal headache, asthenia, forgetfulness, vertigo, nervousness, obesity and poor vision were rather characteristic of this group. There was a high degree of morbidity with frequent remission and exacerbation of symptoms. [amjmed.com]

A conventional radiological evaluation may offer some information about the extent and localization of the abnormality. The bone deposition process is often confined to the frontal bone but sometimes extends to parietal bones. However, frontal bone areas related to venous channels and superior sagittal sinus are spared [2]. Suture lines represent clear boundaries for the development of this pathological process. Lesions may be flat or nodular, isolated or confluent [2]. The external contour of the skull remains normal, therefore the clinical examination could exclude other entities, such as Paget's disease or leontiasis ossea.

Magnetic resonance imaging (MRI) and computed tomography (CT) offer more detailed clues regarding both the bone proliferation and the status of the brain tissue and dura mater. The lesion border characteristics, along with its shape and location, are elements on which four disease types (A to D) have been defined [2].

If doubt persists, a histological evaluation is able to shed light on the case by describing thick lamellar bone deposition, predominantly on the inner table of the frontal bone [7]. The pattern of bone deposition differs markedly when compared with patterns seen in Paget's disease, endosteal osteoma, or osteosarcoma. The bone changes are normally less than 1 cm thick in hyperostosis frontalis interna.

• Hyperprolactinemia

  Since hyperprolactinemia was found in many of these cases, the authors suggested that this and other features of the syndrome such as hirsutism, diabetes, and menstrual troubles may be related to hyperprolactinemia. ▼ REFERENCES Gegick, C. [omim.org]

  The disease may cause hormonal impairment, such as hyperprolactinemia or ovarian dysfunction. [symptoma.com]

  Cited by Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis? Mutlu U, Telci Caklili O, Barburoglu M, Yarman S. Mutlu U, et al. [pubmed.ncbi.nlm.nih.gov]

  In one study (n=36), 72% of patients who had acromegaly had HFI, and of those, 19 had hyperprolactinemia [10]. The acromegalic patients who had hyperprolactinemia also had higher evidence of HPI than those in the normal control groups. [amjcaserep.com]

and 60 who received different treatments or none at all. [ncbi.nlm.nih.gov]

Diagnosis considers a combination of clinical features including obesity,[4] virilism, and mental disturbances.[5] Treatment[edit] Treatment is based upon the symptoms, and generally includes medication, diet and lifestyle modification for weight control [en.wikipedia.org]

Other than this, treatment is purely supportive for Hyperostosis Frontalis Interna. This article does not provide medical advice. See disclaimer [epainassist.com]

Best practice management of HFI begins with patient counseling about the diagnosis and outlining a plan of treatment of headache pain. Treatment is mainly supportive. [amjcaserep.com]

Treatment includes surgery to remove diseased section of bone. What causes a protruding forehead? They can be hormonal disorders, genetic or inherited syndromes, or others. [amasyadsyb.biz.tr]

Some authors have observed that prognosis did not seem to be affected by HFI, and the clinical outcome was in accordance with the psychiatric diagnosis. [hindawi.com]

The etiology of HFI is uncertain: it may be an unknown genetic predisposition, a common environmental exposure, or special metabolic diseases. [ncbi.nlm.nih.gov]

Little is known about the etiology and clinical presentation of HFI. [scholars.northwestern.edu]

The etiology is unknown. The condition is generally of no clinical significance and an incidental finding. It is typically bilateral and symmetrical and may extend to involve the parietal bones. [radiopaedia.org]

The epidemiology of HFI shows that it is relatively common in postmenopausal women but very rare in men. Men affected by this pathology suffer from diseases, syndromes or treatments causing androgen deficiency. [ncbi.nlm.nih.gov]

[…] light on the past through the analysis of human and non-human skeletal materials, mummified remains and preserved tissue Integrates scientific advances in multiple fields that contribute to the understanding of ancient and historic diseases, such as epidemiology [books.google.com]

Aims: To determine the epidemiology of hyperostosis frontalis interna in Uyo using computed tomograms of the skull. [ajol.info]

We present a novel case of migraine headache in a gentleman with Klinefelter's syndrome and HFI, along with a discussion of possible pathophysiologic mechanisms underlying both the headache and the HFI. [ncbi.nlm.nih.gov]

Arch Neurol 61:1366–1368, 10.1001/archneur.61.9.1366, 15364681 Article PubMed Google Scholar Ahkenazi A, Silberstein SD (2006) Hormone-related headache: pathophysiology and treatment. [thejournalofheadacheandpain.biomedcentral.com]

With more than1,500 images, the authors have assembled an accessible resource and review that presents over 170 core topics using the imaging findings as a platform to discuss pathophysiology, clinical presentation, and disease management. [books.google.com]

Since HFI identification, 300 years ago, studies have endeavored to reveal its prevalence, pathophysiology, and etiology (Moore, 1955 ; Perou, 1964 ; Antón, 1997 ; Hershkovitz et al., 1999 ). [onlinelibrary.wiley.com]

Timely identification of HFI can prevent unnecessary diagnostic tests. We report a case of non-syndromic HFI in an elderly female who presented with headache. DOI: https://doi.org/10.5430/crim.v4n1p57 Refbacks There are currently no refbacks. [sciedupress.com]

Prompt diagnosis helps to prevent a misdiagnosis and prevent the patient from undergoing many unnecessary diagnostic tests [1]. [amjcaserep.com]

Migraine headaches can be treated with preventive and abortive medications. The frequent bouts of seizures can be controlled with standard anticonvulsant medications. [epainassist.com]

The headaches proved to be refractory to multiple preventative medications and nerve blocks. She also had progressive difficulty with concentration, visual and verbal memory as well as organizational skills. [n.neurology.org]

1. Raikos A, Paraskevas GK, Yusuf F. Etiopathogenesis of hyperostosis frontalis interna: a mystery still. Ann Anat. 2011;193(5):453–458.
2. Hershkovitz I, Greenwald C, Rothschild BM, et al., Hyperostosis frontalis interna: an anthropological perspective. Am J Phys Anthropol. 1999;109:303-325.
3. Crispin JC, Alcocer-Varela J. Rheumatologic manifestations of diabetes mellitus. Am J Med. 2003;114:753–757.
4. Devriendt W, Piercecchi-Marti MD, Adalian P, et al . Hyperostosis frontalis interna: forensic issues. J Forensic Sci. 2005;50(1):143–146.
5. Chaljub G, Johnson RF III, Johnson RF Jr, et al. Unusually exuberant hyperostosis frontalis interna: MRI. Neuroradiol 1999;41:44–45.
6. Nikolić S, Djonić D, Zivković V, et al. Rate of occurrence, gross appearance, and age relation of hyperostosis frontalis interna in females: a prospective autopsy study. Am J Forensic Med Pathol. 2010;31(3):205–207.
7. Chen OI, Murthy AS. Benign hyperostotic mass of the frontal bone. J Craniofac Surg. 2012;23(1):e27–e30.