Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature

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The syndrome is usually seen in association with midline cranial defects, such as transsphenoidal and basal encephaloceles. Although MGS usually presents as an isolated ocular finding, it can be associated with endocrinological abnormalities. We report a case of a 32 year old female with MGS with hyperprolactinemia and growth hormone (GH) deficiency. She was diagnosed with MGS at the age of three and her past medical history was significant for left eye blindness, hyperprolactinemia and GH deficiency. She has received GH replacement and oral contraceptive pills in the past. Our investigations revealed elevated prolactin levels (63mg/l) and borderline low GH levels. Magnetic resonance imaging revealed an abnormality involving the optic chiasm, left optic nerve and compression of the pituitary gland by a basal encephalocele. Genetic studies were positive for a mutation in Paired box 6 gene (PAX6). She is being currently treated with cabergoline for her hyperprolactinemia. Our aims of this report are to highlight the hormonal manifestations of MGS and to review the etiopathogenesis of this rare disorder." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/6-1702/v1", "name": "Case Report: Hyperprolactinemia and growth hormone deficiency associated..." } } ] } Home Browse Case Report: Hyperprolactinemia and growth hormone deficiency associated... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Bhavsar R, Pavlovic M, Razavi A et al. Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.12688/f1000research.12655.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] Ravi Bhavsar https://orcid.org/0000-0002-4611-4025 1 , Maia Pavlovic 1 , Afsoon Razavi 1 , Muhammad Umair 1 , Harsha Senapathi 1 , Issac Sachmechi 1 Ravi Bhavsar https://orcid.org/0000-0002-4611-4025 1 , Maia Pavlovic 1 , [...] Afsoon Razavi 1 , Muhammad Umair 1 , Harsha Senapathi 1 , Issac Sachmechi 1 PUBLISHED 18 Sep 2017 Author details Author details 1 Icahn School of Medicine at Mount Sinai, Queens Hospital Center, Jamaica, NY, 11432, USA Ravi Bhavsar Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Maia Pavlovic Roles: Formal Analysis, Investigation, Methodology, Software, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Afsoon Razavi Roles: Formal Analysis, Investigation, Resources, Software, Validation, Visualization, Writing – Review & Editing Muhammad Umair Roles: Investigation, Methodology, Project Administration, Software, Supervision, Validation, Visualization, Writing – Review & Editing Harsha Senapathi Roles: Investigation, Project Administration, Resources, Software, Supervision, Validation, Visualization Issac Sachmechi Roles: Conceptualization, Investigation, Supervision, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Eye Health gateway. Abstract Morning Glory Syndrome (MGS) is a rare congenital malformation of the optic nerve that is caused by a failure of the closure of the choroidal embryonic fissure in utero . The syndrome is usually seen in association with midline cranial defects, such as transsphenoidal and basal encephaloceles. Although MGS usually presents as an isolated ocular finding, it can be associated with endocrinological abnormalities. We report a case of a 32 year old female with MGS with hyperprolactinemia and growth hormone (GH) deficiency. She was diagnosed with MGS at the age of three and her past medical history was significant for left eye blindness, hyperprolactinemia and GH deficiency. She has received GH replacement and oral contraceptive pills in the past. Our investigations revealed elevated prolactin levels (63mg/l) and borderline low GH levels. Magnetic resonance imaging revealed an abnormality involving the optic chiasm, left optic nerve and compression of the pituitary gland by a basal encephalocele. Genetic studies were positive for a mutation in Paired box 6 gene ( PAX6) . She is being currently treated with cabergoline for her hyperprolactinemia. Our aims of this report are to highlight the hormonal manifestations of MGS and to review the etiopathogenesis of this rare disorder. READ ALL READ LESS Keywords morning glory syndrome, hyperprolactinemia, growth hormone deficiency, basal encephalocele Corresponding Author(s) Ravi Bhavsar ( [email protected] ) Close Corresponding author: Ravi Bhavsar Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2017 Bhavsar R et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Bhavsar R, Pavlovic M, Razavi A et al. Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.12688/f1000research.12655.1 ) First published: 18 Sep 2017, 6 :1702 ( https://doi.org/10.12688/f1000research.12655.1 ) Latest published: 18 Sep 2017, 6 :1702 ( https://doi.org/10.12688/f1000research.12655.1 ) Introduction Morning Glory Syndrome (MGS) was first reported in German literature in 1929, but has been more frequently reported since Kindler named it in 1970 1 . The name was based on the condition’s resemblance to the funnel-shaped excavation of the posterior fundus incorporating the optic nerve to a tropical morning glory flower 1 . It is a rare congenital malformation of the optic nerve that is caused by a failure of the closure of the choroidal embryonic fissure in utero . We report a unique case of a 32 year old female with MGS with hyperprolactinemia and growth hormone (GH) deficiency. Our case highlights the various endocrinological presentations that can present concomitantly with this rare syndrome. Case report A 32 year old woman came to our clinic for the evaluation of amenorrhea and hyperprolactinemia. She was diagnosed with MGS at the age of 3 and at the age of 17 she was diagnosed with hyperprolactinemia and GH deficiency causing her to have a short stature (4ft 1 inch). She had no family history of similar or related issues. She was treated with GH replacement in the past, which led to an increase in her height (5ft) and she received oral contraceptives until the age of 28. Due to hyperprolactinemia and anovulatory cycles, she was treated with cabergoline. At the age of 31, she delivered a healthy baby via in vitro fertilization. Her most recent physical and vital parameters were under normal limits (blood pressure: 110/70 mmHg; pulse: 72 per minute; height: five feet; weight: 126 pounds). Visual acuity to finger counting was 20/20 in the right eye and 20/200 in the left eye. She had hypertelorism and strabismus of the left eye. Laboratory investigations revealed: fasting glucose levels: 87 mg/dl (65–99); Prolactin: 62 mg/l (2–14); GH: 0.2 ng/ml (0.0–10.0); GH arginine stimulation test: <2ng/ml; Insulin-like growth factor 1: 22ng/ml (71–241); luteinizing hormone: 1.3 miu/ml (0.0–4.0); follicle stimulating hormone: 5.0 miu/ml (0.0–5.0); Estradiol: 8.6 pg/ml (12.5–166.0); Dehydroepiandrosterone: 323 ng/dl (31–701); adrenocorticotropic hormone: 33.1 pg/ml (7.2–63.3); thyroid stimulating hormone: 1.48 mIU/L (0.45–4.5); free T4: 1.2 ng/dl (0.58–1.6). Magnetic resonance imaging (MRI) performed at this time revealed an abnormality involving the optic chiasm, left optic nerve and mild compression of the pituitary gland by a basal encephalocele (BE), with a normal sized pituitary gland. Genetic studies were positive for a mutation in Paired box 6 gene ( PAX6 ). She continues to receive 0.5 mg of cabergoline once daily in view of her elevated prolactin levels. Our patient does not have any other symptoms and is being followed up regularly at our clinic. Discussion MGS is a rare congenital malformation of the optic nerve that is caused by a failure of the closure of the choroidal embryonic fissure in utero . It is characterized by an enlarged, funnel shaped optic disk with a central mass of white glial tissue, surrounded by a raised pigmented chorioretinal ring. MGS usually presents as a unilateral malformation without gender predisposition with a median diagnosis of two years. The pathogenesis of MGS is relatively unknown and studies are currently being done to understand the syndrome clearly. MGS usually presents as an isolated ocular manifestation with decreased visual acuity, strabismus, myopia and astigmatism. The most common visual field defect is a central scotoma 2 and MGS is also commonly associated with midline cranial defects, such as transsphenoidal and basal encephaloceles. Transsphenoidal encephalocele or BE have been largely associated with MGS, with 67% of people with BE also having MGS 3 . Cranial defects may present with wide heads, flat noses, cleft lip/palate, hypertelorism, agenesis of the corpus callosum, hypopituitarism, posterior pituitary ectopia, basal and transsphenoidal encephaloceles. BE is a herniation of tissue through the sphenoid bone or cribriform plate of the ethmoid bone 4 . BE may present as a mass in the pharynx, nasal cavity and orbits 4 . Literature suggests that the association of MGS with craniofacial abnormalities may be linked to an embryogenic effect. Kissel et al . theorized that defects in neural crest cells are responsible for the craniofacial malformations 5 . This is the most probable mechanism by which BE occurs, due to the failure of closure of the anterior neuropore, which normally occurs by 4 weeks in utero 5 . The embryological findings support the neurologic and craniofacial manifestations seen with MGS. Hormonal dysfunctions are seen with approximately 50–60% of BE patients. GH deficiency (66.7%), hypogonadotropic hypogonadism, hypothyroidism, hyperprolactinemia (13.3%) and diabetes insipidus are the most common hormonal disorders reported 3 . Eustis et al . postulated that the dysplastic optic discs in association with endocrine abnormalities are products of reduced trophic stimulation of the pituitary gland caused by abnormal hypothalamic control or an abnormal portal hypophysial system 6 . Table 1 lists several cases of MGS associated with endocrinopathies that have been reported in literature. Table 1. Cases of Morning. Glory Syndrome associated with different endocrinopathies that have been reported in the literature. Abbreviations: M: Male, F: Female, ADH: Anti-Diuretic Hormone, GH: Growth Hormone, TSH: Thyroid Stimulating Hormone, PRL: Prolactin, LH: Luteinizing Hormone, NP: Not Performed. Author, year Age (year) Sex Endocrine abnormalities Optic abnormalities Reference First exam Follow up Pollock JA, 1968 21m M ADH NP + 9 Pollock JA, 1968 12 M GH, TSH (10) GH, TSH PRL (12) + 9 Pollock JA, 1968 20 F GH, ADH, gonadotropin (20) NP + 9 Pollock JA, 1968 48 M ADH(8) ADH, TSH (48) + 9 Wiese GM et al , 1972 28 M GH, gonadotropin (20) GH gonadotropin, PRL (28) - 10 Manelfe C et al, 1968 57 M TSH (57) NP + 11 Larsen JL et al, 1979 16 F GH, ADH (16) NP - 12 Ellyin F et al, 1982 12 M GH, PRL ↑ (12) NP - 13 Ellyin F et al, 1982 16 F PRL ↑ NP - 13 Nishi Y et al, 1982 12 M GH (9) GH, ADH, gonadotropin (12) + 14 Takezawa N et al, 1986 7 M GH (4) GH (4) + 15 Durham et al, 1988 33 M Gonadotropin, cortisol (18) Gonadotropin, cortisol, TSH, ADH (33) + 16 Rice JF et al, 1989 15 F GH, gonadotropin (15) NP - 17 Kobayashi et al, 1990 6 M GH (3) GH (6) + 18 Morioka et al, 1995 11 F GH, ADH (9) GH, ADH, gonadotropin, PRL (11) + 19 Eustis et al, 1994 4 months F NP GH, TSH + 6 Eustis et al, 1994 3 months M NP GH, gonadotopin + 6 Present case 17 F GH,PRL GH,PRL,LH Studies by Asakura et al . suggest that MGS may be associated with a heterozygous Prokineticin receptor 2 ( PROKR2 ) gene mutation 7 . The PROKR2 pathway plays a vital role in early pituitary development and the development of gonadotropin releasing hormone neurons. This could possibly explain the pituitary malformation and the hormonal imbalance seen in our case report Hormonal disorders are common in patients with BE induced MGS, possibly due to malformed cranial structures, which exert pressure on the pituitary gland causing gland compression, thereby restricting production of hormones, such as GH and prolactin at healthy rates. Genetic studies performed on our patient revealed a mutation in the PAX6 gene. PAX6 gene mutations are commonly implicated in congenital ocular malformations. PAX6 gene is responsible for activating genes involved in the formation of the eyes, brain, spinal cord, and pancreas during embryonic development 8 . As far as MGS is concerned, the PAX6 protein is an excellent resource to study in patients, as it is responsible for ocular embryogenesis and regulating the expression of other genes involved in the other structures of the eye. MGS is a complex disease, but can be diagnosed best through a fundus examination and radiological studies, such as CT scans and cranial MRI scans. The white glial tissue mass in the malformation causes the pupil to look a whitish-color (leukokoria), which is a classic and telling symptom. The diagnostic measures should be accompanied by a complete physical and ophthalmological examination and appropriate laboratory investigations to rule out hormonal dysfunction. There are still under 100 cases of MGS reported worldwide. It is still a very rare medical anomaly that has not been greatly researched until more recent decades. Treatments are directed towards preventing and treating possible existing complications associated with the syndrome such as hormone replacement for hormonal imbalance and suitable correction lenses for myopia and astigmatism. Conclusion Our case aims to highlight the endocrinological manifestations of MGS. Although the association of MGS with pituitary hormonal imbalance is relatively well known, the diagnosis was established much later in our case. Early recognition of these features through physical examination and lab investigations should prompt appropriate intervention. Consent statement Written informed consent was obtained from the patient for the publication of the patient’s details. Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Acknowledgements Our team presented this case as an abstract (#1349) at the American Association of Clinical Endocrinologists meeting in 2014. The considerable interest received regarding the case promoted the authors to write this article. F1000 recommended References 1. Kindler P: Morning glory syndrome: unusual congenital optic disk anomaly. Am J Ophthalrnol. 1970; 69 (3): 376–384. PubMed Abstract | Publisher Full Text 2. Beyer WB, Quencer RM, Osher RH: Morning glory syndrome. A functional analysis including fluorescein angiography, ultrasonography, and computerized tomography. Ophthalmology. 1982; 89 (12): 1362–7. PubMed Abstract | Publisher Full Text 3. Oyakawa Barcelli Y, García Durruti P, Enes Romero P, et al. : Morning glory syndrome associated with transsphenoidal encephalocele and panhypopituitarism. Endocrinol Nutr. 2014; 61 (4): 222–224. PubMed Abstract | Publisher Full Text 4. Hope-Ross M, Johnston SS: The Morning Glory syndrome associated with sphenoethmoidal encephalocele. Ophthalmic Paediatr Genet. 1990; 11 (2): 147–53. PubMed Abstract | Publisher Full Text 5. Kissel P, Andre JM, Jacquier A: The Neurocristopathies. New York, NY: Mas-son Publishing; 1981. Reference Source 6. Eustis HS, Sanders MR, Zimmerman T: Morning glory syndrome in children. Association with endocrine and central nervous system anomalies. Arch Ophthalmol. 1994; 112 (2): 204–207. PubMed Abstract | Publisher Full Text 7. Asakura Y, Muroya K, Hanakawa J, et al. : Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation. Clin Pediatr Endocrinol. 2015; 24 (1): 27–32. PubMed Abstract | Publisher Full Text | Free Full Text 8. Guerra-Junior G, Spinola-Castro AM, Siviero-Miachon AA, et al. : Absence of mutations in Pax6 gene in three cases of morning glory syndrome associated with isolated growth hormone deficiency. Arq Bras Endocrinol Metabol. 2008; 52 (8): 1221–7. PubMed Abstract | Publisher Full Text 9. Pollock JA, Newton TH, Hoty WF: Transsphenoidal and transethmoidal encephaloceles. A review of clinical and roentgen features in 8 cases. Radiology. 1968; 90 (3): 442–53. PubMed Abstract | Publisher Full Text 10. Wiese GM, Kempe LG, Hammon WM: Transsphenoidal meningohydroencephalocele. Case report. J Neurosurg. 1972; 37 (4): 475–8. PubMed Abstract | Publisher Full Text 11. Manelfe C, Starling-Jardim D, Touibi S, et al. : Transsphenoidal encephalocele associated with agenesis of corpus callosum: value of metrizamide computed cisternography. J Comput Assist Tomogr. 1978; 2 (3): 356–61. PubMed Abstract | Publisher Full Text 12. Larsen JL, Bassøe HH: Transsphenoidal meningocele with hypothalamic insufficiency. Neuroradiology. 1979; 18 (4): 205–9. PubMed Abstract | Publisher Full Text 13. Ellyin F, Khatir AH, Singh SP: Hypothalamic-pituitary functions in patients with transsphenoidal encephalocele and midfacial anomalies. J Clin Endocrinol Metab. 1980; 51 (4): 854–6. PubMed Abstract | Publisher Full Text 14. Nishi Y, Muraki K, Sakoda K, et al. : Hypopituitarism associated with transsphenoidal meningoencephalocele. Eur J Pediatr. 1982; 139 (1): 81–4. PubMed Abstract | Publisher Full Text 15. Takezawa N, Sato M, Yanagisawa T, et al. : [Pituitary dwarfism associated with morning glory syndrome and transsphenoidal encephalocele: a case report]. No To Hattatsu. 1987; 19 (6): 492–6. PubMed Abstract | Publisher Full Text 16. Durham LH, Mackenzie IJ, Miles JB: Transphenoidal Meningohydroencephalocoele. Br J Neurosurg. 1988; 2 (3): 407–409. PubMed Abstract | Publisher Full Text 17. Rice JF, Eggers DM: Basal transsphenoidal encephalocele: MR findings. AJNR Am J Neuroradiol. 1989; 10 (5 suppl): S79. PubMed Abstract 18. Kobayashi S, Miyazaki M, Miyagi O, et al. : [A case of transsphenoidal meningoencephalocele]. No Shinkei Geka. 1990; 18 (11): 105–70. PubMed Abstract 19. Morioka M, Marubayashi T, Masumitsu T, et al. : Basal encephaloceles with morning glory syndrome, and progressive hormonal and visual disturbances: case report and review of the literature. Brain Dev. 1995; 17 (3): 196–201. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 18 Sep 2017 ADD YOUR COMMENT Comment Author details Author details 1 Icahn School of Medicine at Mount Sinai, Queens Hospital Center, Jamaica, NY, 11432, USA Ravi Bhavsar Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Maia Pavlovic Roles: Formal Analysis, Investigation, Methodology, Software, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Afsoon Razavi Roles: Formal Analysis, Investigation, Resources, Software, Validation, Visualization, Writing – Review & Editing Muhammad Umair Roles: Investigation, Methodology, Project Administration, Software, Supervision, Validation, Visualization, Writing – Review & Editing Harsha Senapathi Roles: Investigation, Project Administration, Resources, Software, Supervision, Validation, Visualization Issac Sachmechi Roles: Conceptualization, Investigation, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 18 Sep 2017, 6:1702 https://doi.org/10.12688/f1000research.12655.1 Copyright © 2017 Bhavsar R et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Bhavsar R, Pavlovic M, Razavi A et al. Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.12688/f1000research.12655.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 18 Sep 2017 Views 0 Cite How to cite this report: Garcia-Filion P. Reviewer Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r27942 ) The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-27942 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 03 Jan 2018 Pamela Garcia-Filion , The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA, USA Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.13701.r27942 Is the background of the case’s history and progression described in sufficient detail? Partly Comment: The background fails to describe the ophthalmic diagnostic characteristics of Morning Glory Syndrome. ... Continue reading READ ALL Is the background of the case’s history and progression described in sufficient detail? Partly Comment: The background fails to describe the ophthalmic diagnostic characteristics of Morning Glory Syndrome. Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Comment: Case describes only a patient with decreased visual acuity, and nothing specific to Morning Glory. Authors don’t provide information about the clinical eye exam to establish the 3 defining clinical features: i.e., enlarged disc, chorioretinal pigmentary changes around the optic disc, a glial tuft overlying the disc. Decreased visual acuity is insufficient to establish diagnosis. There is no opthalmoscopic findings, no funduscopic findings. The MR findings don’t match those of Morning Glory. Additionally, the MR details don’t mention whether the scan involved orbital cuts. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Comment: The discussion is the best part of the case report. The relevance is questionable since the case is unlikely to be Morning Glory Syndrome. Is the case presented with sufficient detail to be useful for other practitioners? No Commentary: Detail is insufficient and this case absolutely shouldn’t be available to clinicians. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Garcia-Filion P. Reviewer Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r27942 ) The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-27942 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Martins TGdS. Reviewer Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r26768 ) The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-26768 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Oct 2017 Thiago Gonçalves dos Santos Martins , Departamento de Oftalmologia, Universidade Federal de São Paulo, São Paulo, Brazil Approved VIEWS 0 https://doi.org/10.5256/f1000research.13701.r26768 The background of the case’s history and progression is described in sufficient detail. The case is presented with sufficient detail The authors should consider a differential diagnosis. The coloboma of optic disk, which is a differential diagnosis, ... Continue reading READ ALL The background of the case’s history and progression is described in sufficient detail. The case is presented with sufficient detail The authors should consider a differential diagnosis. The coloboma of optic disk, which is a differential diagnosis, is characterized as excavation, normally in inferior part, without glial tissue typically present in Morning Glory syndrome. Coloboma of the optic nerve is a congenital anomaly of the optic disc in which there is a defect of the inferior aspect of the optic nerve. The issue stems from incomplete closure of the embryonic fissure while in utero. A varying amount of glial tissue typically fills the defect, manifests as a white mass. Although both optic nerve colobomas and morning glory disc anomaly (MGDA) involve mutations of the PAX6 gene, these two separate diseases represent two distinct causes. An optic nerve coloboma is easily differentiated from morning glory anomaly. Colobomas affect only the inferior aspect of the nerve as it represents an incomplete closure of the embryonic fissure, whereas MGDA encompasses all aspects of the nerve and represents more generally a dysgenesis of the mesoderm. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Martins TGdS. Reviewer Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r26768 ) The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-26768 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 18 Sep 2017 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 18 Sep 17 read read Thiago Gonçalves dos Santos Martins , Universidade Federal de São Paulo, São Paulo, Brazil Pamela Garcia-Filion , The Vision Center at Children's Hospital Los Angeles, Los Angeles, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2018 Garcia-Filion P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Jan 2018 | for Version 1 Pamela Garcia-Filion , The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA, USA 0 Views copyright © 2018 Garcia-Filion P. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Is the background of the case’s history and progression described in sufficient detail? Partly Comment: The background fails to describe the ophthalmic diagnostic characteristics of Morning Glory Syndrome. Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Comment: Case describes only a patient with decreased visual acuity, and nothing specific to Morning Glory. Authors don’t provide information about the clinical eye exam to establish the 3 defining clinical features: i.e., enlarged disc, chorioretinal pigmentary changes around the optic disc, a glial tuft overlying the disc. Decreased visual acuity is insufficient to establish diagnosis. There is no opthalmoscopic findings, no funduscopic findings. The MR findings don’t match those of Morning Glory. Additionally, the MR details don’t mention whether the scan involved orbital cuts. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Comment: The discussion is the best part of the case report. The relevance is questionable since the case is unlikely to be Morning Glory Syndrome. Is the case presented with sufficient detail to be useful for other practitioners? No Commentary: Detail is insufficient and this case absolutely shouldn’t be available to clinicians. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Garcia-Filion P. Peer Review Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r27942) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-27942 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2017 Martins T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Oct 2017 | for Version 1 Thiago Gonçalves dos Santos Martins , Departamento de Oftalmologia, Universidade Federal de São Paulo, São Paulo, Brazil 0 Views copyright © 2017 Martins T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The background of the case’s history and progression is described in sufficient detail. The case is presented with sufficient detail The authors should consider a differential diagnosis. The coloboma of optic disk, which is a differential diagnosis, is characterized as excavation, normally in inferior part, without glial tissue typically present in Morning Glory syndrome. Coloboma of the optic nerve is a congenital anomaly of the optic disc in which there is a defect of the inferior aspect of the optic nerve. The issue stems from incomplete closure of the embryonic fissure while in utero. A varying amount of glial tissue typically fills the defect, manifests as a white mass. Although both optic nerve colobomas and morning glory disc anomaly (MGDA) involve mutations of the PAX6 gene, these two separate diseases represent two distinct causes. An optic nerve coloboma is easily differentiated from morning glory anomaly. Colobomas affect only the inferior aspect of the nerve as it represents an incomplete closure of the embryonic fissure, whereas MGDA encompasses all aspects of the nerve and represents more generally a dysgenesis of the mesoderm. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Ophthalmology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Martins TGdS. Peer Review Report For: Case Report: Hyperprolactinemia and growth hormone deficiency associated with Morning Glory Syndrome; with a review of the literature [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2017, 6 :1702 ( https://doi.org/10.5256/f1000research.13701.r26768) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/6-1702/v1#referee-response-26768 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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