Atormac
Neurology India
Open access journal indexed with Index Medicus
  Users online: 2258  
 Home | Login 
About Current Issue Archive Ahead of print Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (1,191 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this Article
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed78    
    Printed0    
    Emailed0    
    PDF Downloaded7    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
LETTERS TO EDITOR
Year : 2018  |  Volume : 66  |  Issue : 6  |  Page : 1807-1810

Resolution of primary ovarian insufficiency after corticosteroid administration in a myasthenia gravis patient: Report and minireview of the literature


Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

Date of Web Publication28-Nov-2018

Correspondence Address:
Dr. Yun Jing
Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing - 100730
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.246274

Rights and Permissions



How to cite this article:
Liu X, Li R, Jing Y. Resolution of primary ovarian insufficiency after corticosteroid administration in a myasthenia gravis patient: Report and minireview of the literature. Neurol India 2018;66:1807-10

How to cite this URL:
Liu X, Li R, Jing Y. Resolution of primary ovarian insufficiency after corticosteroid administration in a myasthenia gravis patient: Report and minireview of the literature. Neurol India [serial online] 2018 [cited 2018 Dec 14];66:1807-10. Available from: http://www.neurologyindia.com/text.asp?2018/66/6/1807/246274




Sir,

Myasthenia gravis (MG) is an autoimmune disorder induced by antibodies against components at the neuromuscular junctions.[1],[2] Primary ovarian insufficiency (POI) is a subclass of ovarian dysfunction in which the cause lies within the ovary. The main symptom is the presence of irregular menstrual cycles, and the diagnosis is confirmed by the presentation of increased follicle-stimulating hormone (FSH) and decreased estradiol concentrations in the serum.[3] The simultaneously occurring comorbidity of MG and POI has rarely been reported. We describe the case of a patient with MG in whom POI was resolved after methylprednisolone treatment. To our knowledge, this is the first report of a patient with POI and MG in whom POI remitted after corticosteroid treatment, without the additional administration of hormonal therapy.

A 23-year old woman with an 8-month history of diplopia was admitted to our hospital in March 2015. She also complained of drooping eyelids, fatigability, dysarthria, and dysphagia. She was diagnosed with MG and treated with pyridostigmine bromide and video-assisted thoracoscopic thymectomy in December 2014; however, the muscle weakness persisted despite the treatment. Histological examination of the thymus revealed thymic lymphoid follicular hyperplasia.

Her medical history was notable for 1 year of secondary amenorrhea. Her menarche was at 14 years, and her menses were regular until an year ago. The presence of POI was diagnosed by reduced estradiol and elevated FSH and luteinizing hormone (LH) in June 2014. The ovarian ultrasound showed a small uterus. She had menses once after she was placed on hormone replacement therapy with estrogen and progesterone. However, after taking sex hormones for a month, her myasthenic weakness occurred, and when her hormone replacement therapy was stopped, the menses stopped again. Her family history was unremarkable.

She exhibited external ophthalmoplegia (ptosis and abduction deficit of both her eyes), facial muscle weakness, masseter paresis, as well as dysarthria and myasthenic weakness in her limbs and neck muscles on physical examination; she was tested as being seropositive for anti-acetylcholine receptor antibodies (anti-AChR-Abs). The menopausal levels of gonadotrophins were still present upon biochemical exam: FSH 60.07 mIU/ml, LH 34.46 mIU/L, and estradiol 59.00 pg/ml. Moreover, there was normal T3, T4, and thyroid stimulating hormone (TSH), thyroid function parameters and elevated anti-thyroid antibody titers, namely the thyroglobulin antibody (TGAB) 420.40 IU/ml, and the thyromicrosome antibody (TMAB) 176.60 IU/ml. The pituitary magnetic resonance imaging (MRI) and gynecologic ultrasonic examination did not reveal any abnormalities.

The patient had been treated with 1,000 mg of methylprednisolone daily for 3 days and intravenous immunoglobulin at a dose of 0.4 g/kg/day for 5 days starting from April 5th, 2015. Prednisone was continued at a dose of 1 mg/kg/day for 2 weeks, gradually decreased to 2.5 mg on alternate days, and then withdrawn. After treatment, her myasthenic symptoms remitted. Furthermore, her gonadotrophin levels reached almost complete normalcy after 20 days of corticosteroid treatment [Figure 1]]. Remarkably, her menses restarted on April 12th, 2015 and had been regular until her last visit (August 27th, 2016) without the requirement for any further sex hormone replacement therapy.
Figure 1: Concentrations of sex hormones in the serum before and after methylprednisolone therapy. E2=Estradiol; FSH=Follicle-stimulating hormone; LH=Luteinizing hormone; MP=Methylprednisolone

Click here to view


MG is an autoimmune disorder induced by antibodies against components at the neuromuscular junctions[1],[2] and characterized by skeletal muscle weakness. Anti-acetylcholine receptor (AChR) antibodies are primarily induced by the interaction of lymphocytes, myeloid cells, interdigitating cells, and epithelial cells in the thymi of MG patients. In MG, plentiful of B-cells are present in the medulla and lymphoid follicles of the thymus.

POI is defined as the menopausal range of gonadotropin levels in women before the age of 40 years, in whom amenorrhea should last for 4 months or more.[4] Secondary amenorrhea or oligomenorrhea is the most common symptom and may be accompanied by hot flashes, vaginal dryness, lack of libido, and arthralgia.[5] The mechanisms of POI are various. Genetic abnormalities, FSH receptor gene polymorphisms, enzyme deficiencies, and autoimmune imbalance may be involved. Lymphocytic and plasma cell infiltration in developing follicles indicate the occurrence of an autoimmune mechanism in POI. According to the literature, POI is commonly associated with other autoimmune disorders, most commonly the autoimmune thyroid disease. In view of the patient's negative family history, elevated anti-thyroid antibody titer, and the presence of normal pituitary and ovary, it is speculated that the cause of POI in this case was an autoimmune disorder.

The association of POI with MG is unusual and has been rarely reported. Reviewing literature from 1990 to 2016, we summarized 6 case reports and the current case in [Table 1]. Secondary amenorrhea occurred before or alongside symptoms of MG in 5 of 7 (71%) POI cases. In addition, all patients had generalized MG. A previous study reported that in an MG patient with POI, ovarian insufficiency was relieved after a thymectomy.[6] Chung et al., also reported the presentation of a patient simultaneously suffering from POI and MG, who became pregnant after thymectomy.[7] These studies indicate that the thymus may not only play an important role in MG but also in the genesis of POI. The thymus, as a central immune organ, controls both the development of T cells and the establishment of immunological tolerance to self. A study on autoimmune regulator (AIRE) in mice suggested that uncontrolled thymic expression of ovarian-specific antigens may be a significant factor in the appearance of ovarian autoimmune disease.[8] In the present case, the patient's menses restarted and were regular after corticosteroid treatment, without the requirement of sex hormone replacement therapy, which also strengthens the ‘autoimmune attack’ hypothesis. However, the essential pathogenic mechanisms involved in both the diseases are not completely clear.[12],[13],[14]
Table 1: Summary of current and previous 6 cases of MG accompanied by POI

Click here to view


Another interesting phenomenon in our case was that the sex hormone treatment may have been related to the onset of MG. Li et al.,[9] reported a patient who presented with aggravation of myasthenic weakness and myasthenic crisis after 1 week of estrogen treatment. Vijayan et al.,[10] observed a cyclical variation of acetylcholinesterase (AChE) activity in 3 MG patients, with obvious reduction of the enzyme at the time of menstruation. The study demonstrated that a progressive increase in red cell AChE activity seems to have a bearing on the increasing secretion of estrogens as the menstrual cycle progresses. In immature and adult animals, it was also observed that AChE activity in the central nervous system could be increased by administration of estrogens.[11] Therefore, we presume that the onset and aggravation of MG in our case may have been caused by an enhanced AChE activity related to an increased estrogen titer following the administration of sex hormone therapy.

Overall, we report an unusual case diagnosed with the simultaneous presence of MG and POI. These comorbidities were thought to share a common pathogenesis of an autoimmune attack. It is interesting that sex hormone replacement may induce the onset of MG, and regular menses restarted after the initiation of corticosteroid treatment in the present case. Therefore, we suggest that immunosuppressants may contribute to the treatment of POI in some cases, and therefore, extra care should be taken while using hormonal therapy to treat MG patients.

Acknowledgments and funding

This study was funded by Beijing Municipal Science and Technology Commission grant (No. Z131107002213155) and the foundation of Beijing Tongren Hospital, Capital Medical University (No. 2015-YJJ-ZZL-004).

The authors thank all the staff members of Myasthenia Gravis Research Center of Beijing Tongren Hospital, including the neurologists, thoracic surgeons, intensive care unit physicians, clinical laboratory physicians and nurses for their professional efforts.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jayam TA, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: A review. Autoimmune Dis 2012;2012:874680.  Back to cited text no. 1
    
2.
Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B. Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 2014;48-49:143-8.  Back to cited text no. 2
    
3.
De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet 2010;376:911-21.  Back to cited text no. 3
    
4.
Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009;360:606-14.  Back to cited text no. 4
    
5.
Vujovic S, Brincat M, Erel T, Gambacciani M, Lambrinoudaki I, Moen MH, et al. EMAS position statement: Managing women with premature ovarian failure. Maturitas 2010;67:91-3.  Back to cited text no. 5
    
6.
Çakır ED, Özdemir Ö, Eren E, Sağlam H, Okan M, Tarım ÖF. Resolution of autoimmune oophoritis after thymectomy in a myasthenia gravis patient. J Clin Res Pediatr Endocrinol 2011;3:212-5.  Back to cited text no. 6
    
7.
Chung TK, Haines CJ, Yip SK. Spontaneous pregnancy following thymectomy for myasthenia gravis associated with premature ovarian failure. Asia Oceania J Obstet Gynaecol 1993;19:253-5.  Back to cited text no. 7
    
8.
Jasti S, Warren BD, McGinnis LK, Kinsey WH, Petroff BK, Petroff MG. The autoimmune regulator prevents premature reproductive senescence in female mice. Biol Reprod 2012;86:110.  Back to cited text no. 8
    
9.
Li Y, Xiao B, Xiao L, Zhang N, Yang H. Myasthenia gravis accompanied by premature ovarian failure and aggravation by estrogen. Intern Med 2010;49:611-3.  Back to cited text no. 9
    
10.
Vijayan N, Vijayan VK, Dreyfus PM. Acetylcholinesterase activity and menstrual remissions in myasthenia gravis. J Neurol Neurosurg Psychiatry 1977;40:1060-5.  Back to cited text no. 10
    
11.
Moudgil VK, Kanungo MS. Induction of acetylcholinesterase by 17- estradiol in the brain of rats of various ages. Biochem Biophys Res Commun 1973;52:725-30.  Back to cited text no. 11
    
12.
Tsirigotis M, Craft IL. Benign thymoma and resistant ovary syndrome. Br J Obstet Gynaecol 1994;101:350-2.  Back to cited text no. 12
    
13.
Ryan MM, Jones HR. Myasthenia gravis and premature ovarian failure. Muscle Nerve 2004;30:231-3.  Back to cited text no. 13
    
14.
Dong JD, Wang XS, Jin I. Primary ovarian insufficiency in a MG patient. J Clin Neurol 2011;24:117.  Back to cited text no. 14
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow