The Neuroradiology Journal 19: 629-632, 2006
www. centauro. it
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence? D. SEIXAS*, M. AYRES-BASTO*, M. FONTOURA**, M.L. SILVA*, J. FONSECA* * Neuroradiology Department, ** Paediatrics Department; São João Hospital, Oporto, Portugal
Key words: internal carotid artery, pituitary gland, malformation, agenesis, congenital hypopituitarism, congenital pituitary hypoplasia
SUMMARY – The CT and MR imaging findings in a case of unilateral agenesis of the internal carotid artery and hypogenesis of the pituitary gland are described in a child with congenital hypopituitarism. The embryological pathogenesis is discussed.
Introduction Congenital absence of the internal carotid artery (ICA) is a very rare vascular anomaly occurring in less than 0.01% of the population 1,2. When the ICA is absent, collateral circulation develops through the circle of Willis to supply the hemisphere involved so that patients may have no symptoms. However, this anomaly is associated with cerebral aneurysms 3 and tortuous and enlarged intracranial vessels, which respectively may account for subarachnoid haemorrhage and neurovascular compression syndromes, such as oculomotor nerve palsy 4 and trigeminal neuralgia 5. It may also be associated with ischemic events 3 or epilepsy 6. Paediatric cases are exceptional, suggesting that initially the collateral pathways are sufficient to support cerebral perfusion 7. Congenital hypopituitarism is an uncommon disorder, often detected clinically because of early growth failure secondary to growth hormone (GH) deficiency, or complex endocrine manifestations secondary to multiple pituitary hormone deficiencies. The clinical and biochemical investigation of growth failure in children may be difficult; magnetic resonance (MR) imaging can help clarify the diagnosis of GH insufficiency (and other hypothalamic-pituitary hormones). Most cases were previously considered idiopathic: MR imaging reveals pituitary stalk interruption in about 60% of these children 8, sometimes with
associated hypoplasia of the anterior pituitary and ectopic posterior pituitary. Midline brain, cranial and facial anomalies are reported in about 10% of anterior hypopituitarism cases 9 . The ICA develops in the fourth embryonic week, and the pituitary primordium develops in the third to fourth week. There is bilateral blood supply to the pituitary gland via the superior and inferior hypophyseal arteries, which arise from both ICAs. We describe a rare case of unilateral ICA agenesis in association with pituitary hypoplasia and congenital hypopituitarism in a child. To the best of our knowledge, there are only five previous published cases of this association, of which two were agenesis of the ICA, the other three cases being ICA hypoplasia 9-14. A possible relationship between them is suggested. Case Report A two-year-old girl was admitted in our pediatric outpatient clinic because of growth failure. She was a first-born child of a non-consanguineous marriage after a term pregnancy (vaginal birth). Her birth weight was 3200 g, her length was 47 cm and her head circumference was 34 cm. On physical examination a small facies, prominent forehead and frontal bossing were noted. Neurological examination was unremarkable. The child was found to have delayed 629
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence?
D. Seixas
Figure 1 Coronal spin-echo T1-weighted MR images showing small anterior pituitary gland and truncated pituitary stalk. No posterior lobe bright spot was identified.
skeletal maturation, central hypothyroidism, adrenocortical and GH deficiencies, but no diabetes insipidus. There was no family history of GH deficiency. Brain MR imaging revealed small anterior pituitary gland and truncated pituitary stalk; no posterior lobe bright spot nor post-contrast abnormalities were observed (figure 1). On MR angiogram (three-dimensional time-of-flight technique) the right ICA was not visualized either (figure 2). There was no evidence of associated intracranial aneurysms, enlarged vessels or abnormal collateral channels. All other brain structures were normal. A skull base computerized tomography (CT) scan showed absence of the right carotid canal, confirming the congenital ICA absence (figure 3). A diagnosis of congenital hypopituitarism was made, associated with right ICA agenesis. The patient began hormone replacement therapy with GH, hydrocortisone and thyroxine, which was well tolerated. Discussion During embryogenesis, the cardiovascular system appears in the middle of the third week, when the embryo is starting to be no longer able to satisfy its nutritional requirements by diffusion alone. The ICA develops during the fourth embryonic week and the carotid canal develops in the fifth to sixth week, following the artery that runs through it. So if the ICA fails to develop, the carotid canal will be lacking. Agenesis involves complete developmental failure of an organ and its primordium. Aplasia refers to the defective development of an organ, 630
although its anlage presumably existed at some time. In our case, the ICA abnormality must have occurred before five to six weeks´ gestation as no carotid canal was seen, meaning an early interruption of development or regression at a later stage after an initial period of normal development. The pituitary primordium develops in the third to fourth embryonic week, until the eighth week. Both anterior and posterior lobes of the pituitary are supplied with blood from the bilateral superior and inferior hypophyseal arteries, which arise from the bilateral ICAs. Some authors claim that pituitary stalk interruption and small anterior pituitary gland associated with unilateral ICA agenesis may be explained by an inadequate blood supply to sustain both anterior and posterior pituitary growth during this period 11,15. However, when the pituitary gland begins its development, i.e. in the third week, there is no cardiovascular system yet. Padget’s analysis of the human embryo revealed the full development of this artery by the sixth week 16. Examples of the association of pituitary and vascular abnormalities other than the ICAs are found in the literature: unilateral agenesis of the ICA and pituitary hypoplasia associated with a transsellar intercavernous anastomotic vessel 15,13, pituitary duplication associated with anomaly of the distal basilar artery 17, absence of right common carotid artery, ICA and anterior cerebral artery and pituitary hypoplasia 12. Most of these case reports are even associated with other major malformations, especially of the midline, which point to a more complex explanation of the association of these abnormalities. In this connection and keeping in mind that pituitary vascu-
www. centauro. it
The Neuroradiology Journal 19: 629-632, 2006
Figure 2 MR angiogram (AP view, 3D TOF image) showing absence of flow-related signal of the right ICA with collateral flow to the right middle cerebral artery and anterior cerebral artery via the right posterior communicating artery and anterior communicating artery, respectively.
Figure 3 Axial skull base CT images revealing absence of the right carotid canal. The left carotid canal can be clearly seen (arrows).
631
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence?
larisation is bilateral and that the brain in our child’s case is normal, pointing to good collateral supply, we hypothesize that the explanation for the association between malformations of one of the ICAs and the pituitary gland might be at another level, namely the signaling level. Neural crest cell differentiation and/or migration may play a role in vascular and pituitary development 18. Another possibility must also be considered. Due to the few case reports of the connection between ICA and pituitary malformations, it cannot be excluded that there is no direct relationship between these events. An insult might have disturbed the normal development of structures that merely begin to develop at the same time.
D. Seixas
Conclusion The pathophysiology is still unknown, but ICA underdevelopment and congenital hypopituitarism may have a common explanation. Reports of this extremely rare association, especially imaging findings, could give more insight into its underlying mechanism. To further elucidate this problem, animal embryological studies should be conducted. In the clinical setting, when studying congenital pituitary hypofunction, not only pituitary gland and other midline abnormalities should be sought, but also malformations of the ICAs, as they might be associated with cerebral aneurysms and other major medical conditions.
References 1 Afifi AK, Godersky JC et Al: Cerebral hemiatrophy, hypoplasia of internal carotid artery, and intracranial aneurysm: a rare association occurring in an infant. Arch Neurol 44: 232-235, 1987. 2 Chen CJ, Chen ST et Al: Hypoplasia of the internal carotid artery with intercavernous anastomosis. Neuroradiology 40: 252-254, 1998. 3 Lee JH, Oh CW et Al: Aplasia of the internal carotid artery. Acta Neurochir 145: 117-125, 2003. 4 Wakai S, Watanabe N et Al: Agenesis of internal carotid artery presenting with oculomotor nerve palsy after minor head injury. Neurosurgery 20: 794-796, 1987. 5 Fukuda M, Kameyama S et Al: Trigeminal neuralgia caused by the vertebral artery associated with primitive trigeminal artery and agenesis of the internal carotid artery. Neurol Med Chir (Tokyo) 38: 367-370, 1998. 6 Wang PJ, Liu HM, et Al: Agenesis of the internal carotid artery associated with symptomatic partial epilepsy. Epilepsia 35: 1337-1341, 1994. 7 Lie TA: Congenital anomalies of the carotid arteries. Excerpta Medica 1968: 35-51. 8 Abernethy LJ: Imaging of the pituitary in children with growth disorders. Eur J Radiol 26: 102-108, 1998. 9 Triulzi F, Scott G et Al: Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients. Pediatrics 93: 409-416, 1994. 10 Blustajn J, Netchine I et Al: Dysgenesis of the internal carotid artery associated with transsphenoidal encephalocele: a neural crest syndrome? Am J Neuroradiol 20: 1154-1157, 1999. 11 Inamo Y, Harada K: Agenesis of the internal carotid artery and congenital pituitary hypoplasia: proposal of a cause of congenital hypopituitarism. Eur J Pediatr 162: 610-612, 2003. 12 Kjelin IB, Curran KB, Geffner ME: Aplasia of right internal carotid artery and hypopituitarism. Pediatr Radiol 29: 586-588, 1999. 13 Mellado JM, Merino X et Al: Agenesis of the internal carotid artery with a trans-sellar anastomosis: CT and MRI findings in late-onset congenital hypopituitarism. Neuroradiology 43: 237-241, 2001. 14 Shulman DI, Martinez CR: Association of ectopic posterior pituitary and anterior pituitary hypoplasia with
632
15 16 17
18
absence of the left internal carotid. J Pediatr Endocrinol Metab 9: 539-542, 1996. Moon W-J, Porto L et Al: Agenesis of internal carotid artery associated with congenital anterior hypopituitarism. Neuroradiology 44: 138-142, 2002. Padget DH: The development of the cranial arteries in the human embryo. Contrib Embryol 32: 207-262, 1948. Huisman T, Fischer U et Al: Pituitary duplication and nasopharyngeal teratoma in a newborn: CT, MRI, US and correlative histopathological findings. Neuroradiology 47: 558-561, 2005. Bergwerff M, Verberne ME, et Al: Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82: 221231, 1998.
Daniela Seixas, MD Alameda Monte Penedo, 8 4475-364 Maia Portugal Tel.: 00351936099363 E-mail: [email protected]
www. centauro. it
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence? D. SEIXAS*, M. AYRES-BASTO*, M. FONTOURA**, M.L. SILVA*, J. FONSECA* * Neuroradiology Department, ** Paediatrics Department; São João Hospital, Oporto, Portugal
Key words: internal carotid artery, pituitary gland, malformation, agenesis, congenital hypopituitarism, congenital pituitary hypoplasia
SUMMARY – The CT and MR imaging findings in a case of unilateral agenesis of the internal carotid artery and hypogenesis of the pituitary gland are described in a child with congenital hypopituitarism. The embryological pathogenesis is discussed.
Introduction Congenital absence of the internal carotid artery (ICA) is a very rare vascular anomaly occurring in less than 0.01% of the population 1,2. When the ICA is absent, collateral circulation develops through the circle of Willis to supply the hemisphere involved so that patients may have no symptoms. However, this anomaly is associated with cerebral aneurysms 3 and tortuous and enlarged intracranial vessels, which respectively may account for subarachnoid haemorrhage and neurovascular compression syndromes, such as oculomotor nerve palsy 4 and trigeminal neuralgia 5. It may also be associated with ischemic events 3 or epilepsy 6. Paediatric cases are exceptional, suggesting that initially the collateral pathways are sufficient to support cerebral perfusion 7. Congenital hypopituitarism is an uncommon disorder, often detected clinically because of early growth failure secondary to growth hormone (GH) deficiency, or complex endocrine manifestations secondary to multiple pituitary hormone deficiencies. The clinical and biochemical investigation of growth failure in children may be difficult; magnetic resonance (MR) imaging can help clarify the diagnosis of GH insufficiency (and other hypothalamic-pituitary hormones). Most cases were previously considered idiopathic: MR imaging reveals pituitary stalk interruption in about 60% of these children 8, sometimes with
associated hypoplasia of the anterior pituitary and ectopic posterior pituitary. Midline brain, cranial and facial anomalies are reported in about 10% of anterior hypopituitarism cases 9 . The ICA develops in the fourth embryonic week, and the pituitary primordium develops in the third to fourth week. There is bilateral blood supply to the pituitary gland via the superior and inferior hypophyseal arteries, which arise from both ICAs. We describe a rare case of unilateral ICA agenesis in association with pituitary hypoplasia and congenital hypopituitarism in a child. To the best of our knowledge, there are only five previous published cases of this association, of which two were agenesis of the ICA, the other three cases being ICA hypoplasia 9-14. A possible relationship between them is suggested. Case Report A two-year-old girl was admitted in our pediatric outpatient clinic because of growth failure. She was a first-born child of a non-consanguineous marriage after a term pregnancy (vaginal birth). Her birth weight was 3200 g, her length was 47 cm and her head circumference was 34 cm. On physical examination a small facies, prominent forehead and frontal bossing were noted. Neurological examination was unremarkable. The child was found to have delayed 629
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence?
D. Seixas
Figure 1 Coronal spin-echo T1-weighted MR images showing small anterior pituitary gland and truncated pituitary stalk. No posterior lobe bright spot was identified.
skeletal maturation, central hypothyroidism, adrenocortical and GH deficiencies, but no diabetes insipidus. There was no family history of GH deficiency. Brain MR imaging revealed small anterior pituitary gland and truncated pituitary stalk; no posterior lobe bright spot nor post-contrast abnormalities were observed (figure 1). On MR angiogram (three-dimensional time-of-flight technique) the right ICA was not visualized either (figure 2). There was no evidence of associated intracranial aneurysms, enlarged vessels or abnormal collateral channels. All other brain structures were normal. A skull base computerized tomography (CT) scan showed absence of the right carotid canal, confirming the congenital ICA absence (figure 3). A diagnosis of congenital hypopituitarism was made, associated with right ICA agenesis. The patient began hormone replacement therapy with GH, hydrocortisone and thyroxine, which was well tolerated. Discussion During embryogenesis, the cardiovascular system appears in the middle of the third week, when the embryo is starting to be no longer able to satisfy its nutritional requirements by diffusion alone. The ICA develops during the fourth embryonic week and the carotid canal develops in the fifth to sixth week, following the artery that runs through it. So if the ICA fails to develop, the carotid canal will be lacking. Agenesis involves complete developmental failure of an organ and its primordium. Aplasia refers to the defective development of an organ, 630
although its anlage presumably existed at some time. In our case, the ICA abnormality must have occurred before five to six weeks´ gestation as no carotid canal was seen, meaning an early interruption of development or regression at a later stage after an initial period of normal development. The pituitary primordium develops in the third to fourth embryonic week, until the eighth week. Both anterior and posterior lobes of the pituitary are supplied with blood from the bilateral superior and inferior hypophyseal arteries, which arise from the bilateral ICAs. Some authors claim that pituitary stalk interruption and small anterior pituitary gland associated with unilateral ICA agenesis may be explained by an inadequate blood supply to sustain both anterior and posterior pituitary growth during this period 11,15. However, when the pituitary gland begins its development, i.e. in the third week, there is no cardiovascular system yet. Padget’s analysis of the human embryo revealed the full development of this artery by the sixth week 16. Examples of the association of pituitary and vascular abnormalities other than the ICAs are found in the literature: unilateral agenesis of the ICA and pituitary hypoplasia associated with a transsellar intercavernous anastomotic vessel 15,13, pituitary duplication associated with anomaly of the distal basilar artery 17, absence of right common carotid artery, ICA and anterior cerebral artery and pituitary hypoplasia 12. Most of these case reports are even associated with other major malformations, especially of the midline, which point to a more complex explanation of the association of these abnormalities. In this connection and keeping in mind that pituitary vascu-
www. centauro. it
The Neuroradiology Journal 19: 629-632, 2006
Figure 2 MR angiogram (AP view, 3D TOF image) showing absence of flow-related signal of the right ICA with collateral flow to the right middle cerebral artery and anterior cerebral artery via the right posterior communicating artery and anterior communicating artery, respectively.
Figure 3 Axial skull base CT images revealing absence of the right carotid canal. The left carotid canal can be clearly seen (arrows).
631
Agenesis of the Internal Carotid Artery and Hypogenesis of the Pituitary Gland: Cause, Consequence or Coincidence?
larisation is bilateral and that the brain in our child’s case is normal, pointing to good collateral supply, we hypothesize that the explanation for the association between malformations of one of the ICAs and the pituitary gland might be at another level, namely the signaling level. Neural crest cell differentiation and/or migration may play a role in vascular and pituitary development 18. Another possibility must also be considered. Due to the few case reports of the connection between ICA and pituitary malformations, it cannot be excluded that there is no direct relationship between these events. An insult might have disturbed the normal development of structures that merely begin to develop at the same time.
D. Seixas
Conclusion The pathophysiology is still unknown, but ICA underdevelopment and congenital hypopituitarism may have a common explanation. Reports of this extremely rare association, especially imaging findings, could give more insight into its underlying mechanism. To further elucidate this problem, animal embryological studies should be conducted. In the clinical setting, when studying congenital pituitary hypofunction, not only pituitary gland and other midline abnormalities should be sought, but also malformations of the ICAs, as they might be associated with cerebral aneurysms and other major medical conditions.
References 1 Afifi AK, Godersky JC et Al: Cerebral hemiatrophy, hypoplasia of internal carotid artery, and intracranial aneurysm: a rare association occurring in an infant. Arch Neurol 44: 232-235, 1987. 2 Chen CJ, Chen ST et Al: Hypoplasia of the internal carotid artery with intercavernous anastomosis. Neuroradiology 40: 252-254, 1998. 3 Lee JH, Oh CW et Al: Aplasia of the internal carotid artery. Acta Neurochir 145: 117-125, 2003. 4 Wakai S, Watanabe N et Al: Agenesis of internal carotid artery presenting with oculomotor nerve palsy after minor head injury. Neurosurgery 20: 794-796, 1987. 5 Fukuda M, Kameyama S et Al: Trigeminal neuralgia caused by the vertebral artery associated with primitive trigeminal artery and agenesis of the internal carotid artery. Neurol Med Chir (Tokyo) 38: 367-370, 1998. 6 Wang PJ, Liu HM, et Al: Agenesis of the internal carotid artery associated with symptomatic partial epilepsy. Epilepsia 35: 1337-1341, 1994. 7 Lie TA: Congenital anomalies of the carotid arteries. Excerpta Medica 1968: 35-51. 8 Abernethy LJ: Imaging of the pituitary in children with growth disorders. Eur J Radiol 26: 102-108, 1998. 9 Triulzi F, Scott G et Al: Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients. Pediatrics 93: 409-416, 1994. 10 Blustajn J, Netchine I et Al: Dysgenesis of the internal carotid artery associated with transsphenoidal encephalocele: a neural crest syndrome? Am J Neuroradiol 20: 1154-1157, 1999. 11 Inamo Y, Harada K: Agenesis of the internal carotid artery and congenital pituitary hypoplasia: proposal of a cause of congenital hypopituitarism. Eur J Pediatr 162: 610-612, 2003. 12 Kjelin IB, Curran KB, Geffner ME: Aplasia of right internal carotid artery and hypopituitarism. Pediatr Radiol 29: 586-588, 1999. 13 Mellado JM, Merino X et Al: Agenesis of the internal carotid artery with a trans-sellar anastomosis: CT and MRI findings in late-onset congenital hypopituitarism. Neuroradiology 43: 237-241, 2001. 14 Shulman DI, Martinez CR: Association of ectopic posterior pituitary and anterior pituitary hypoplasia with
632
15 16 17
18
absence of the left internal carotid. J Pediatr Endocrinol Metab 9: 539-542, 1996. Moon W-J, Porto L et Al: Agenesis of internal carotid artery associated with congenital anterior hypopituitarism. Neuroradiology 44: 138-142, 2002. Padget DH: The development of the cranial arteries in the human embryo. Contrib Embryol 32: 207-262, 1948. Huisman T, Fischer U et Al: Pituitary duplication and nasopharyngeal teratoma in a newborn: CT, MRI, US and correlative histopathological findings. Neuroradiology 47: 558-561, 2005. Bergwerff M, Verberne ME, et Al: Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82: 221231, 1998.
Daniela Seixas, MD Alameda Monte Penedo, 8 4475-364 Maia Portugal Tel.: 00351936099363 E-mail: [email protected]
