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 »  Abstract
 »  Eyes and Pituita...
 »  Eyes and Pituita...
 »  Eye Signs in Pit...
 »  Syndromes Involv...
 »  Miscellaneous Fe...
 » Clinical Approach
 » Conclusion
 »  References
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Table of Contents    
Year : 2019  |  Volume : 67  |  Issue : 4  |  Page : 979-982

Eye Signs in Pituitary Disorders

Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China

Date of Web Publication10-Sep-2019

Correspondence Address:
Dr. Xiaozhe Shi
Department of Ophthalmology, The Affiiated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin - 130000
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.266265

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 » Abstract 

The eye is a vital sense organ and plays a vital role in conveying the underlying physical and mental state of wellbeing of an individual. A comprehensive examination of the eye is often required in patients presenting with systemic complaints. Many endocrine disorders have characteristic manifestations pertaining to the eye, the classical being the exophthalmos in thyrotoxicosis. However, a cursory eye evaluation may lead to the identification of early features that can help in the diagnosis of other endocrine disorders. This is more common in cases of pituitary mass lesions, who often present with the functional hormonal alterations rather than the visual symptoms. The definitive therapy during the late stages of the disease leads to persisting visual disabilities and affects the quality of life. Hence, the endocrinologists and ophthalmologists need to be aware of various ophthalmic features in the pituitary disorders. In this review, we highlight the eye signs in pituitary disorders, along with a brief description of uncommon ocular-pituitary syndromes.

Keywords: Endocrinology, eye, macroadenoma, ophthalmopathy, pituitary disorders
Key Message: The importance of occular signs cannot be undermined. The diagnosis of pituitary lesions both syndromic and nonsyndromic can be suspected very early based on the eye signs. Therefore multidisciplinary approach involving the endocrinologist along with ophthalmologist proves to be essential.

How to cite this article:
Chen Y, Liu Z, Lin Z, Shi X. Eye Signs in Pituitary Disorders. Neurol India 2019;67:979-82

How to cite this URL:
Chen Y, Liu Z, Lin Z, Shi X. Eye Signs in Pituitary Disorders. Neurol India [serial online] 2019 [cited 2021 Jan 27];67:979-82. Available from:

Pituitary gland is the master gland of all the endocrine glands and exerts control over all the hormonal axes. The gland is located deep inside the cranium in a bony cavity called the sella turcica or pituitary fossa. The pituitary fossa is surrounded by vital structures that are relevant in the visual pathway. The disorders of the pituitary gland present either with hormonal dysfunction or due to mass effect because of the enlarged tumor.[1] There exists a long period between the onset of the hormonal dysfunction and diagnosis of the pituitary mass lesions.[2] The problem is compounded further in patients with nonfunctional pituitary adenomas (NFPA), who present only with neuro-ophthalmic features due to the mass effect.[3] The delay in the diagnosis could also be due to the lack of neuro-ophthalmic knowledge of the attending doctors and the cursory examination of the patients, resulting in missing some important initial clues in the presentation.[4]

A comprehensive visual examination includes assessment of the external structures, visual acuity, field of vision, color vision, ocular reflexes, and fundus examination. Few authors have suggested that the temporal field defects are the early signs and predict the suprasellar extension of the pituitary mass lesions.[5] However, the slow growing nature of the tumor results in patients being unaware of the field defects till the late stages. There is a change in the trend of the clinical presentation of pituitary disorders in the last couple of decades due to advanced neuroimaging techniques. The low threshold for the imaging results in identification of the diseases at an early stage of the disease.[6],[7] Vision loss and vision-related quality of life does not improve much in patients undergoing late debulking surgery.[8] Endocrinologists need to be aware of the ophthalmic abnormalities that are encountered in the early stages of the illness and do a detailed evaluation of the patients. In this review, we shall discuss the eye signs in pituitary disorders and highlight few ocular-pituitary syndromes.

 » Eyes and Pituitary – developmental Links Top

Pituitary gland is developed from the diencephalon portion of the primitive brain. The diencephalon also gives rise to the posterior structures of the forebrain including the thalamus, hypothalamus, and the pineal gland. The optic nerve is attached to the diencephalon and the retina is derived from the optic cup, which itself is a derivative of the diencephalon.[9] The pretectal area derived from the diencephalon controls the pupillary and behavioral responses to changes in the light. Most of the circadian rhythms of the human body are controlled by the regulated release of the hormones. Melanopsin in the retinal ganglion cells could activate the neuroendocrine system, leading to alteration in the secretion of the melanocyte stimulating hormone.[10] Hypothalamo-pituitary derived proopiomelanocortin mediates the ultraviolet radiation-induced stimulation of the Langerhans cells in the retina.[11] Pituitary adenylate cyclase activating polypeptide (PACAP) is a peptide with various functions that has been isolated from the pituitary and hypothalamus. The PACAP molecule has been tightly conserved over the past 700 million years of evolution.[12] In addition to the neurological tissues, the PACAP is seen in the eye, ophthalmic artery and other structures and has a potential role in the regulation of the blood supply to the underlying tissues.[13],[14]

 » Eyes and Pituitary – anatomical Links Top

The ophthalmic presenting symptoms of pituitary enlargement depend on the compression of the neighboring structures. The pituitary fossa is superiorly bound by optic chiasm, cavernous sinuses on both sides, and sphenoid sinus inferiorly.[15] Optic chiasm is the structure where the optic nerves decussate and continue as the optic tracts. Normally, the optic chiasm overlies the pituitary fossa directly. The anatomical variations in their relation include the prefixed (fossa overlying the posterior chiasmal notch) and postfixed (fossa overlying the anterior chiasmal notch) positions. The importance in identifying these variations lies in the fact that the enlarged pituitary may compress the optic nerve, chiasm, or tract depending on their location. There is a characteristic pattern of crossing over of the nasal fibres in the optic chiasm.[16] The inferior nasal fibres cross anteriorly forming the anterior knee of von Willebrand and superior nasal fibres cross posteriorly. The anterior notch of the optic chiasm lies more inferiorly, making it more liable for the compression by the growing pituitary tumor. Cavernous sinuses contain the 3rd, 4th, and 6th cranial nerves along with the maxillary and the ophthalmic branch of the 5th cranial nerve. The involvement of these cranial nerves may present with the pain around the eye, diplopia, ophthalmoplegia, and altered ocular reflexes.[16]

 » Eye Signs in Pituitary Mass Lesions Top

The endocrine symptoms often precede the neuro-ophthalmic symptoms in patients with the pituitary mass lesions.[17] They include alterations in body weight, stature, growth velocity, and progression of puberty. Overlooking these subtle manifestations could also contribute to the delay in the diagnosis of the underlying endocrine disorder. Visual symptoms that are experienced by the patients with pituitary tumors vary with the size of the tumor. The microadenomas (less than 1 cm in diameter) usually do not produce any ocular symptoms. The presence of visual symptoms in pituitary microadenomas should prompt the treating clinician to look for an alternate etiology. The visual signs could be due to raised intracranial pressure, compression of the structures in the visual pathway, and the involvement of cranial nerves in the cavernous sinus.

Macroadenomas usually result in the visual symptoms including the field defects, eye pain, blurring of vision, double vision, and progressive loss of vision.[18] Upper quandrantic bitemporal hemianopia is the classical field defect observed in the early stages of chiasmal compression. This is explained by the location and crossing of nasal fibers, which carry the images of the temporal field. Photophobia is an initial complaint in few patients with large suprasellar masses without other significant visual symptoms.[19] Initial visual fields have shown to be a predictor of visual outcomes in patients with craniopharyngiomas. The visual field defects predict the rate of recurrence and poor postoperative recovery.[20] Diplopia could be the presenting feature occasionally in an elderly patient of bronchial carcinoma with pituitary metastases.[21]

Pituitary apoplexy is a condition characterized by sudden bleeding into the enlarged pituitary gland. The classical ophthalmic features include the sudden loss of vision and ophthalmoplegia. This is due to the involvement of the 3rd and 4th cranial nerves and also the pressure on the optic nerve. Pituitary apoplexy should be considered in a patient with an abrupt neuro-ophthalmological presentation in the background of long standing headache.[22] Early surgery for apoplexy results in better recovery of the vision. The recovery of ophthalmoplegia is observed even if the surgical decompression is delayed.[23] Visual findings could be the initial manifestations of the intracranial tumors, including the pituitary tumors.[24]

 » Syndromes Involving the Eyes and Pituitary Gland Top

The structures of the eye and pituitary gland are derived from the primitive neuroectoderm, giving rise to a possibility of certain congenital syndromes. Jung syndrome and Peters-plus syndrome have overlapping features and are reported from the Arab nations.[25] The syndromes involving the chromosome 22 such as the Di-George syndrome and Cats eye syndrome have short stature as a common manifestation.[26] The short stature could be due to growth hormone deficiency or associated malnutrition. The Cat-eye syndrome is also known as Schmid Fraccaro syndrome, which has a characteristic facial appearance.[27] The details about the important syndromes involving the eyes and the pituitary gland and their characteristic features are given in [Table 1].[28],[29],[30],[31],[32]
Table 1: Clinical features of oculopituitary syndromes

Click here to view

 » Miscellaneous Features Top

Optic atrophy at the time of presentation is very difficult to treat and previous reports have shown only less than one-third recovery. Most of the pituitary mass lesions progress to result in optic atrophy if the compression on the nerve is not relieved early.[33] The presence of ophthalmic features in patients with normal pituitary or microadenomas should prompt the treating endocrinologist to look for any alternate causes. Previous reports suggest the presence of idiopathic intracranial hypertension in a patient of microprolactinoma leading to the visual field defects.[34] Craniopharyngioma is the most common tumor involving the hypothalamo-pituitary region and is often treated by the radiotherapy.[35] Most of the ophthalmic structures lie in the radiation field and get affected. They include an increased risk of cataract formation and cranial nerve damage leading to diplopia.[36]

 » Clinical Approach Top

In view of the abovementioned facts, an endocrine screening is warranted in all patients with anterior segment anomalies. Vision-related quality of life is affected by the presence of pituitary tumors, and transsphenoidal surgery improves this aspect of life significantly.[37] A close interaction between ophthalmologist and endocrinologist helps in the rapid diagnosis and accurate assessment of the condition. This helps in identifying the correct therapeutic approach and minimizes the postsurgical ophthalmic morbidity. All patients with unexplained pituitary hormonal dysfunction should be evaluated in detail by the ophthalmologist for the identification of a syndromic diagnosis. This helps in the proper screening and genetic counselling of the prospective parents.

 » Conclusion Top

In conclusion, our review shows that eye signs play an important role in the early identification of the pituitary lesions. The subtle nature of the findings emphasizes the importance of having a team approach to diagnostics that include endocrinologist, neurosurgeon, neurologist, neuro-ophthalmologist, and neuroradiologist.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

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Potok MA, Cha KB, Hunt A, Brinkmeier ML, Leitges M, Kispert A, et al. WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth. Dev Dyn 2008;237:1006-20.  Back to cited text no. 9
Bertolesi GE, Hehr CL, McFarlane S. Melanopsin photoreception in the eye regulates light-induced skin colour changes through the production of α-MSH in the pituitary gland. Pigment Cell Melanoma Res 2015;28:559-71.  Back to cited text no. 10
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Taylor M, Couto-Silva AC, Adan L, Trivin C, Sainte-Rose C, Zerah M, et al. Hypothalamic-pituitary lesions in pediatric patients: Endocrine symptoms often precede neuro-ophthalmic presenting symptoms. J Pediatr 2012;161:855-63.  Back to cited text no. 17
Kitthaweesin K, Ployprasith C. Ocular manifestations of suprasellar tumors. J Med Assoc Thai 2008;91:711-5.  Back to cited text no. 18
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Jedraszak G, Braun K, Receveur A, Decamp M, Andrieux J, Rabbind Singh A, et al. Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: A family report. Ann Endocrinol 2015;76:629-34.  Back to cited text no. 27
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  [Table 1]


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