Craniometric changes in patients with acromegaly from a surgical perspective

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Object

The objective of this study was to evaluate and analyze morphometric and volumetric changes of the skull due to acromegaly in areas relevant for neurosurgical practice, focusing on the surgical implications.

Methods

On preoperatively acquired CT scans, cephalometric and volumetric measurements were performed on 45 patients with acromegaly (Group A) and 45 control patients (Group B). The authors determined thickness of the cranial vault, inner and outer diameters of the skull, and the diameter of sphenoidal and maxillary sinus, as well as frontal and maxillary sinus volumetry. The morphometric and volumetric CT data of the patients with acromegaly were compared with the data of a control group and correlated with clinical parameters.

Results

Cranial vault thickness differed significantly (p < 0.0001) between the 2 groups. A correlation of the vault thickness with preoperative human growth hormone, insulin-like growth factor–I levels, and duration of clinical history in acromegaly could not be established. The outer anterior-posterior skull diameter of Group A (18.47 ± 0.94 cm) differed significantly (p = 0.0146) from Group B (17.98 ± 0.93 cm) and correlated significantly with preoperative human growth hormone (r = 0.3277; p = 0.0299) and insulin-like growth factor-–I serum levels (r = 0.3756; p = 0.0120). Measurements of the anterior-posterior diameter of the sphenoidal sinus differed significantly (p = 0.0074) between patients with acromegaly and controls. Volumetric analysis of the frontal sinus resulted in a statistically significant difference (p = 0.0382) between patients with acromegaly (14.89 ± 10.85 cm3) and controls (10.06 ± 6.93 cm3).

Conclusions

Significant craniometric changes and volumetric remodelling of the paranasal sinus occur in acromegaly. The bone alterations are of surgical importance for using the transsphenoidal approach. Detailed preoperative diagnostic examination and planning as well as selection of appropriate instruments are mandatory for safe and successful pituitary adenoma removal in patients with acromegaly.

Abbreviations used in this paper: GH = growth hormone; IGF = insulin-like growth factor.

Object

The objective of this study was to evaluate and analyze morphometric and volumetric changes of the skull due to acromegaly in areas relevant for neurosurgical practice, focusing on the surgical implications.

Methods

On preoperatively acquired CT scans, cephalometric and volumetric measurements were performed on 45 patients with acromegaly (Group A) and 45 control patients (Group B). The authors determined thickness of the cranial vault, inner and outer diameters of the skull, and the diameter of sphenoidal and maxillary sinus, as well as frontal and maxillary sinus volumetry. The morphometric and volumetric CT data of the patients with acromegaly were compared with the data of a control group and correlated with clinical parameters.

Results

Cranial vault thickness differed significantly (p < 0.0001) between the 2 groups. A correlation of the vault thickness with preoperative human growth hormone, insulin-like growth factor–I levels, and duration of clinical history in acromegaly could not be established. The outer anterior-posterior skull diameter of Group A (18.47 ± 0.94 cm) differed significantly (p = 0.0146) from Group B (17.98 ± 0.93 cm) and correlated significantly with preoperative human growth hormone (r = 0.3277; p = 0.0299) and insulin-like growth factor-–I serum levels (r = 0.3756; p = 0.0120). Measurements of the anterior-posterior diameter of the sphenoidal sinus differed significantly (p = 0.0074) between patients with acromegaly and controls. Volumetric analysis of the frontal sinus resulted in a statistically significant difference (p = 0.0382) between patients with acromegaly (14.89 ± 10.85 cm3) and controls (10.06 ± 6.93 cm3).

Conclusions

Significant craniometric changes and volumetric remodelling of the paranasal sinus occur in acromegaly. The bone alterations are of surgical importance for using the transsphenoidal approach. Detailed preoperative diagnostic examination and planning as well as selection of appropriate instruments are mandatory for safe and successful pituitary adenoma removal in patients with acromegaly.

Abbreviations used in this paper: GH = growth hormone; IGF = insulin-like growth factor.

Patients with acromegaly are recognizable by the pathognomonic phenotype of somatic overgrowth and craniofacial disproportions. Excessive IGF-I levels cause a periosteal new bone formation resulting in characteristic nasal bone hypertrophy, mandibular overgrowth, maxillary widening, and frontal bossing. Craniometric changes have been analyzed in the literature.3,5,7 Recently our group reported on a reduced intercarotid artery distance (distance between left and right carotid arteries) in acromegaly.4

The vast majority of these patients harbors a pituitary adenoma and potentially may be cured through neurosurgical intervention. Typically a transsphenoidal approach is chosen. However, certain growth patterns with extensive intradural tumor extension necessitate transcranial surgery.6 The aim of the present study was to evaluate and analyze morphometric and volumetric changes of the skull in areas relevant for neurosurgical practice in these patients, focusing on the surgical implications.

Methods

Study Population

Forty-five consecutive patients referred to our department for primary surgery of a GH-secreting pituitary adenoma were studied prospectively (Group A). All patients showed the characteristic clinical signs of acromegaly and the presence of a pituitary adenoma was neuroradiologically confirmed. Endocrinologically, all patients had elevated sex- and age-adjusted IGF-I levels and pathological GH secretion during an oral glucose tolerance test. A control group (Group B) consisted of 45 patients who were examined with CT scans (Sensation 16, Siemens AG) for a reason other than a disease of the pituitary gland. The controls were age-matched with the patients. Computed tomography scans were acquired preoperatively in all patients. A helical data set was available for 32 in each group.

Data Analysis

Forty-five metric measurements on transversally oriented, orbitomeatally inclined slides were performed with SIENET Sky-VA50B (Siemens AG). Volumetric analysis of 32 frontal and maxillary sinuses was performed using the BrainLAB Workstation (BrainLAB AG). The distances assessed on transversal bone window reconstructions at the Siemens workstation and volumetric assessments are reported in Table 1 and illustrated in Figs. 1 and 2.

TABLE 1:

Assessed craniometric and volumetric measurements*

LocalizationDistance
skull (rt & lt)diameter of frontal skull
diameter of occipital skull
outer diameter longitudinal
inner diameter longitudinal
outer diameter transversal
inner diameter transversal
maxillary sinus (rt & lt)longitudinal diameter
transversal diameter
volume (cm3)
sphenoidal sinuslongitudinal diameter
transversal diameter
frontal sinusvolume (cm3)
* All measurements in centimeters unless otherwise indicated.
Fig. 1.
Fig. 1.

Axial CT scan illustrating the method used for measuring frontal and occipital cranial vault thickness. Measurements were performed on the highest slice where the spur of the sphenoidal wing was still observed. First, a transversal line connecting the spurs and a vertical line at a right angle were drawn. Then a bisecting line was drawn from the intersection toward the frontal skull to determine the frontal vault thickness. For standardized measurement of the occipital vault thickness, a transversal line was drawn orthogonally to the main vertical line where the latter reaches the occipital skull. Where the lateral part of the transversal line touches the bone, the vault thickness was measured at a right angle to a tangent on the outer surface.

Fig. 2.
Fig. 2.

Three-dimensional image showing volume rendering of frontal (red) and maxillary (green) sinuses detailed on the BrainLAB workstation. Figure at lower left shows orientation of the 3D reconstruction.

The morphometric and volumetric CT data of the patients with acromegaly were compared with the data of the control group. Anamnestic data, preoperative human GH and IGF-I values, and secondary diagnoses were determined. The preoperative endocrinological data were assessed immediately preoperatively or prior to medical treatment in those patients who underwent short-term preoperative pretreatment. All patients underwent operations using the transsphenoidal route and histopathological examination confirmed the diagnosis of human GH-producing adenoma.

Statistical Methods

Statistical analysis was performed with JMP statistical discovery software (version 7.0.2, SAS). The mean values of continuous variables in the 2 groups were compared with the 2-sample t-test if the variances did not differ significantly (p < 0.05). We used the Welch test for significantly different variances. Normally distributed data are summarized by their means and SDs. For variables that were not normally distributed we provide medians and ranges. We calculated the Pearson correlation coefficients for the assessment of associations between continuous variables. In the case of human GH, IGF-I, and duration of clinical history, the values were log-transformed to obtain bivariate normal distribution.

Results

Twenty-four patients with acromegaly were female and 21 were male. The control group consisted of 20 females and 25 males. The median age of the 45 patients with acromegaly was 49 years (range 9–80 years), and 52 years (range 8–82 years) in the control group.

Cranial Vault

In the patients with acromegaly (Group A), the mean thickness of the frontal cranial vault was 1.12 ± 0.43 cm. In the control group (Group B), the mean thickness was 0.67 ± 0.27 cm (Fig. 3). The difference between groups was highly significant (p < 0.0001; Fig. 4). In patients with acromegaly, the mean thickness of the occipital cranial vault was 0.75 ± 0.28 cm, whereas in the control group the mean thickness was 0.55 ± 0.14 cm (p < 0.0001). While the outer anterior-posterior skull diameter of Group A (18.47 ± 0.94 cm) differed significantly (p = 0.0146) from Group B (17.98 ± 0.93 cm), no statistical difference could be demonstrated regarding the inner anterior-posterior diameter of the skull (15.80 ± 0.82 cm [Group A] vs 15.97 ± 0.95 cm [Group B]; p = 0.3759).

Fig. 3.
Fig. 3.

Scatterplot showing the difference in frontal vault thickness between patients with acromegaly (Group A) and controls (Group B). Dashed horizontal lines in graph represent standard deviation, solid line represents the mean value.

Fig. 4.
Fig. 4.

Axial bone window CT scans show markedly increased frontal bone thickness in a patient with acromegaly (upper) in contrast to the frontal bone of a patient from the control group (lower).

There was a statistically significant difference (p = 0.0411) between the outer lateral-lateral (right side to left side) diameter in patients with acromegaly (14.49 ± 0.66 cm) compared with controls (14.20 ± 0.66 cm). However, this difference was not as great as the difference in the outer anterior-posterior skull diameter. There was no difference (p = 0.6057) in the inner lateral-lateral diameter between Group A (13.52 ± 0.83 cm) and Group B (13.43 ± 0.66 cm).

A correlation of the vault thickness with preoperative GH, IGF-I levels, and duration of clinical history in acromegaly could be established neither at the frontal bone (r = 0.039, p = 0.8021; r = 0.1362, p = 0.3780; and r = −0.047, p = 0.7934, respectively) nor at the occipital bone (r = 0.2806, p = 0.0650; r = 0.2413, p = 0.1145; and r = 0.019, p = 0.9133, respectively). The anterior-posterior length of the skull in patients with acromegaly correlated significantly with preoperative human GH (r = 0.3277, p = 0.0299) and IGF-I serum levels (r = 0.3756, p = 0.0120) as well as with duration of clinical history (r = 0.2939, p = 0.500). A correlation of these parameters with the laterallateral diameter could not be established (human GH r = −0.1590, p = 0.3082; IGF-I r = −0.1361, p = 0.3839; and duration of clinical history r = −0.1705, p = 0.2683).

Sinus Diameter

The sinuses showed a marked difference in longitudinal expansion. Measurements of the anterior-posterior diameter of the sphenoidal sinus differed significantly (p = 0.0074) between patients with acromegaly (3.31 ± 0.62 cm) and controls (2.92 ± 0.71 cm). Human GH (r = 0.240, p = 0.1251) and IGF-I (r = 0.093, p = 0.5569) at presentation were not correlated with the anterior-posterior sinus diameter. Similarly, the anterior-posterior diameter of the maxillary sinus was significantly longer (p = 0.0042) in the acromegaly group (4.22 ± 0.30 cm) than in the control group (4.06 ± 0.24 cm). Preoperative human GH values (r = 0.115, p = 0.4590) and duration of clinical history (r = 0.212, p = 0.1624) did not correlate with maxillary sinus length.

The width of the evaluated sinuses did not differ significantly between patients with acromegaly and controls. The lateral-lateral diameter of the sphenoidal sinus was 3.53 ± 1.03 cm in Group A and 3.30 ± 0.63 cm in Group B (p = 0.2199). The lateral-lateral diameter of the maxillary sinus was 2.33 ± 0.27 cm in Group A and 2.40 ± 0.24 cm in Group B (p = 0.1766).

Sinus Volumetry

Volumetric analysis of the maxillary sinus resulted in a measurement of 19.47 ± 7.02 cm3 in the patients with acromegaly. The maxillary sinus was only slightly smaller in the control group with a volume of 17.64 ± 4.19 cm3 (p = 0.2117). Furthermore, duration of clinical history (r = −0.131, p = 0.5134) and preoperative hormone levels (human GH r = 0.058, p = 0.7521; IGF-I r = 0.127, p = 0.4897) were not correlated with the maxillary sinus volume. However, a positive correlation between maxillary sinus volume and the variables tumor diameter (r = 0.374, p = 0.0348) and patient age (r = −0.474, p = 0.0061) was noted.

Volumetric analysis of the frontal sinus resulted in a statistically significant difference (p = 0.0382) between patients with acromegaly (14.89 ± 10.85 cm3; Fig. 5) and controls (10.06 ± 6.93 cm3). Within the group of patients with acromegaly, no statistically significant association of frontal sinus volume with duration of clinical history (r = 0.028, p = 0.8899) and tumor diameter (r = 0.266, p = 0.1418) was detected. A slight correlation was found between preoperative hormone levels and size of the frontal sinus (GH r = 0.289, p = 0.1089; IGF-I r = 0.342, p = 0.0554). However, this correlation did not reach statistical significance.

Fig. 5.
Fig. 5.

Axial bone window CT scan shows an impressively enlarged frontal sinus in a patient with acromegaly.

Discussion

Patients with acromegaly are characterized by a pathognomonic phenotype. The excess of human GH and IGF-I has ubiquitous effects on all tissues throughout the body. This excess results in the clinical features of acral enlargement, colon polyps, cardiovascular problems, sleep apnea, visceromegaly, and endocrine and metabolic alterations. In more than 95% of patients, acromegaly is derived from a pituitary adenoma.10

The shape and size of the head changes during the lifetime of not only patients with acromegaly, but also in healthy patients.3 Using lateral radiographs, Macho9 showed in his study of 353 patients that the viscerocranium increases up to the 4th decade of life and thereafter decreases, while the height of the neurocranium progressively decreases during an adult life. However, the effects of acromegaly on the patient's head are much more striking. The viscerocranium is affected in terms of prognathism, malocclusion, maxillary widening, widened tooth gap, and nasal bone hypertrophy. At the neurocranium, the phenomenon of frontal bossing is well known because it gives a characteristic appearance to affected patients. Further, mucosal changes both in the nose and the paranasal sinuses in terms of mucosal hypertrophy and polyposis are reported occurrences in acromegaly.14 It is logical to assume that these morphological alterations have repercussions in microsurgical therapy. The transsphenoidal route is direct and safe for the majority of pituitary adenomas and thus represents the standard approach for pituitary surgery. In acromegaly, however, two issues related to the pathological anatomical alterations have to be taken into consideration when considering pituitary surgery.

First, the reduced intercarotid artery distance in the C5 and C4 segment narrows the habitual working space,4,12 increasing the risk of a potentially life-threatening vascular complication. Therefore, we have recommended bone window CT scan of the cranial base during preoperative diagnostics in patients with acromegaly scheduled for transsphenoidal surgery.4 In difficult cases, additional use of neuronavigation can be considered. Magnetic resonance imaging depicts the course of carotid arteries well. However, the chronic excess of human GH and IGF-I significantly distorts bone anatomy, which is better visualized by CT. Additionally, drilling of bone is often required for transsphenoidal exposure. Therefore, it is justified to add a CT scan to the preoperative workup. In acromegaly, it is important to know the position and proximity of the internal carotid arteries before surgery; even then, a very narrow intercarotid working space does not preclude the transsphenoidal intervention.4

Second, our data show that the anterior-posterior diameter of the sphenoid sinus is extended in patients with acromegaly compared with the control group. This diameter elongates the depth of the working corridor through the transsphenoidal route (Fig. 6). Saeki et al.13 studied morphological differences of the nasal cavity between patients with and without acromegaly and also found a narrower and deeper operating access in human GH-secreting adenomas. Osseous changes and pathological cartilaginous overgrowth of viscerocranium and neurocranium have implications for the selection of instruments for surgery.11

Fig. 6.
Fig. 6.

Sagittal bone window CT scan showing voluminous sphenoidal sinus (arrow) in a patient with acromegaly. The increased anteroposterior diameter lengthens the transnasal working distance to the floor of the sella turcica. Note the increased thickness of the cranial vault and the prominent frontal sinus.

One-stage complete transsphenoidal resection is achievable in most pituitary adenomas. In selected cases, however, adenomas are more amenable to a transcranial approach. The degree of vertical intracranial extension as well as an irregular and multilobular configuration are important predictors of incomplete transsphenoidal resection.6 Pituitary adenoma removal is then performed through a pterional or frontolateral approach. In this context, the reported increase of frontal sinus volume and thickness of the cranial vault are of surgical interest. The issue might be not to injure the enlarged frontal sinus to prevent a CSF fistula or secondary infection. In addition, increased effort during craniotomy can be anticipated due to the almost double thickness of the frontal vault in patients with acromegaly compared with those patients without this condition.

Increase of cranial vault diameter and sinus volume also influences the required radiation dose. However, these changes are without clinical relevance in the era of modern radiation algorithms with correction of incompatibility based on individual CT examinations. An association of acromegaly and Chiari malformation has been reported in the literature.1,2,8 A hypothesis for this association might be that the bony overgrowth reduces posterior fossa volume.2 At least supratentorially, we could not confirm this phenomenon: both the outer anterior-posterior and lateral-lateral skull diameters increased but not the corresponding inner diameters, thus the intracranial volume itself does not appear to diminish.

Conclusions

Significant craniometric changes and volumetric remodelling of the paranasal sinus occur in acromegaly. The bone alterations are of surgical importance for the transsphenoidal approach. Detailed preoperative diagnostic examination and planning as well as selection of appropriate instruments are mandatory for safe and successful pituitary adenoma removal in patients with acromegaly.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Ebner, Bültmann, Nägele, Honegger. Acquisition of data: Kürschner. Analysis and interpretation of data: Ebner, Kürschner, Honegger. Drafting the article: Ebner. Critically revising the article: Honegger. Reviewed final version of the manuscript and approved it for submission: Ebner, Nägele, Honegger. Statistical analysis: Dietz. Administrative/technical/material support: Ebner, Bültmann, Nägele, Honegger. Study supervision: Ebner, Honegger.

Acknowledgment

The authors thank Dr. F. Paulsen, Department of Radiooncology, Eberhard-Karls-University Tübingen, for professional and courteous advice regarding radiooncologic implications.

References

  • 1

    Agostinis CCaverni LMontini MPagani GBonaldi G: “Spontaneous” reduction of tonsillar herniation in acromegaly: a case report. Surg Neurol 53:3963992000

    • Search Google Scholar
    • Export Citation
  • 2

    Ammerman JMGoel RPolin RS: Resolution of Chiari malformation after treatment of acromegaly. Case illustration. J Neurosurg 104:9802006

    • Search Google Scholar
    • Export Citation
  • 3

    Dostálová SSonka KSmahel ZWeiss VMarek J: Cephalometric assessment of cranial abnormalities in patients with acromegaly. J Craniomaxillofac Surg 31:80872003

    • Search Google Scholar
    • Export Citation
  • 4

    Ebner FHKuerschner VDietz KBueltmann ENaegele THonegger J: Reduced intercarotid artery distance in acromegaly: pathophysiologic considerations and implications for transsphenoidal surgery. Surg Neurol 72:4564602009

    • Search Google Scholar
    • Export Citation
  • 5

    Farmand MKünzler ADe Giacomi BThe effects of pituitary adenoma on the facial skeleton in cases of acromegaly. Samii M: Surgery of the Sellar Region and the Paranasal Sinuses BerlinSpringer1991. 341345

    • Search Google Scholar
    • Export Citation
  • 6

    Honegger JErnemann UPsaras TWill B: Objective criteria for successful transsphenoidal removal of suprasellar nonfunctioning pituitary adenomas. A prospective study. Acta Neurochir (Wien) 149:21292007

    • Search Google Scholar
    • Export Citation
  • 7

    Künzler AFarmand M: Typical changes in the viscerocranium in acromegaly. J Craniomaxillofac Surg 19:3323401991

  • 8

    Lemar HJ JrPerloff JJMerenich JA: Symptomatic Chiari-I malformation in a patient with acromegaly. South Med J 87:2842851994

  • 9

    Macho GA: Cephalometric and craniometric age changes in adult humans. Ann Hum Biol 13:49611986

  • 10

    Melmed S: Acromegaly. The Pituitary ed 2Malden, MABlackwell Publishing2002. 419454

  • 11

    Rhoton AL Jr: The sellar region. Neurosurgery 51:Suppl 1S335S3742002

  • 12

    Sacher MSom PMShugar JMLeeds NE: Kissing intrasellar carotid arteries in acromegaly: CT demonstration. J Comput Assist Tomogr 10:103310351986

    • Search Google Scholar
    • Export Citation
  • 13

    Saeki NIuchi THiguchi YUchino YMurai HIsono S: Bone CT evaluation of nasal cavity of acromegalics—its morphological and surgical implication in comparison to nonacromegalics. Endocr J 47:SupplS65S682000

    • Search Google Scholar
    • Export Citation
  • 14

    Skinner DWRichards SH: Acromegaly—the mucosal changes within the nose and paranasal sinuses. J Laryngol Otol 102:110711101988

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Article Information

Contributor Notes

Address correspondence to: Florian H. Ebner, M.D, Department of Neurosurgery, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Street 3, Tuebingen, Germany 72076. email: florianebner@virgilio.it.
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Figures
  • View in gallery

    Axial CT scan illustrating the method used for measuring frontal and occipital cranial vault thickness. Measurements were performed on the highest slice where the spur of the sphenoidal wing was still observed. First, a transversal line connecting the spurs and a vertical line at a right angle were drawn. Then a bisecting line was drawn from the intersection toward the frontal skull to determine the frontal vault thickness. For standardized measurement of the occipital vault thickness, a transversal line was drawn orthogonally to the main vertical line where the latter reaches the occipital skull. Where the lateral part of the transversal line touches the bone, the vault thickness was measured at a right angle to a tangent on the outer surface.

  • View in gallery

    Three-dimensional image showing volume rendering of frontal (red) and maxillary (green) sinuses detailed on the BrainLAB workstation. Figure at lower left shows orientation of the 3D reconstruction.

  • View in gallery

    Scatterplot showing the difference in frontal vault thickness between patients with acromegaly (Group A) and controls (Group B). Dashed horizontal lines in graph represent standard deviation, solid line represents the mean value.

  • View in gallery

    Axial bone window CT scans show markedly increased frontal bone thickness in a patient with acromegaly (upper) in contrast to the frontal bone of a patient from the control group (lower).

  • View in gallery

    Axial bone window CT scan shows an impressively enlarged frontal sinus in a patient with acromegaly.

  • View in gallery

    Sagittal bone window CT scan showing voluminous sphenoidal sinus (arrow) in a patient with acromegaly. The increased anteroposterior diameter lengthens the transnasal working distance to the floor of the sella turcica. Note the increased thickness of the cranial vault and the prominent frontal sinus.

References
  • 1

    Agostinis CCaverni LMontini MPagani GBonaldi G: “Spontaneous” reduction of tonsillar herniation in acromegaly: a case report. Surg Neurol 53:3963992000

    • Search Google Scholar
    • Export Citation
  • 2

    Ammerman JMGoel RPolin RS: Resolution of Chiari malformation after treatment of acromegaly. Case illustration. J Neurosurg 104:9802006

    • Search Google Scholar
    • Export Citation
  • 3

    Dostálová SSonka KSmahel ZWeiss VMarek J: Cephalometric assessment of cranial abnormalities in patients with acromegaly. J Craniomaxillofac Surg 31:80872003

    • Search Google Scholar
    • Export Citation
  • 4

    Ebner FHKuerschner VDietz KBueltmann ENaegele THonegger J: Reduced intercarotid artery distance in acromegaly: pathophysiologic considerations and implications for transsphenoidal surgery. Surg Neurol 72:4564602009

    • Search Google Scholar
    • Export Citation
  • 5

    Farmand MKünzler ADe Giacomi BThe effects of pituitary adenoma on the facial skeleton in cases of acromegaly. Samii M: Surgery of the Sellar Region and the Paranasal Sinuses BerlinSpringer1991. 341345

    • Search Google Scholar
    • Export Citation
  • 6

    Honegger JErnemann UPsaras TWill B: Objective criteria for successful transsphenoidal removal of suprasellar nonfunctioning pituitary adenomas. A prospective study. Acta Neurochir (Wien) 149:21292007

    • Search Google Scholar
    • Export Citation
  • 7

    Künzler AFarmand M: Typical changes in the viscerocranium in acromegaly. J Craniomaxillofac Surg 19:3323401991

  • 8

    Lemar HJ JrPerloff JJMerenich JA: Symptomatic Chiari-I malformation in a patient with acromegaly. South Med J 87:2842851994

  • 9

    Macho GA: Cephalometric and craniometric age changes in adult humans. Ann Hum Biol 13:49611986

  • 10

    Melmed S: Acromegaly. The Pituitary ed 2Malden, MABlackwell Publishing2002. 419454

  • 11

    Rhoton AL Jr: The sellar region. Neurosurgery 51:Suppl 1S335S3742002

  • 12

    Sacher MSom PMShugar JMLeeds NE: Kissing intrasellar carotid arteries in acromegaly: CT demonstration. J Comput Assist Tomogr 10:103310351986

    • Search Google Scholar
    • Export Citation
  • 13

    Saeki NIuchi THiguchi YUchino YMurai HIsono S: Bone CT evaluation of nasal cavity of acromegalics—its morphological and surgical implication in comparison to nonacromegalics. Endocr J 47:SupplS65S682000

    • Search Google Scholar
    • Export Citation
  • 14

    Skinner DWRichards SH: Acromegaly—the mucosal changes within the nose and paranasal sinuses. J Laryngol Otol 102:110711101988

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