VCOM Carolinas Research Day 2023

Clinical Case-Based Reports

Myasthenia Gravis in the Setting of Grave’s Disease

Thomas Laux, OMS-III Edward Via College of Osteopathic Medicine-Carolinas Campus, Spartanburg, SC Bon Secours St. Francis, Greenville, SC

Abstract # CBR-11

Abstract

Case Presentation

Conclusions

Context : To distinguish the clinical presentation and laboratory differences between Grave’s disease (GD) and myasthenia gravis (MG) when both present concurrently. The clinical presentation, laboratory workup, and treatment are presented in this case. Report of Case : A 19-year-old male with history of GD presents to the emergency department for slurred speech, generalized weakness, and difficulty swallowing for 2 weeks leading to a 20-pound weight loss. On physical exam the patient was found to have complete ophthalmoparesis with bilateral ptosis, proptosis without lid lag, and he was fatigable with repetitive movements including upward gaze. The initial laboratory work up included a thyroid panel to rule out thyrotoxicosis given the patient’s history of GD, which returned within normal limits. Chest x -ray was clear of obstruction, computed tomography (CT) with contrast showed no thymic enlargement, and swallow study also proved to be unremarkable. Due to the patient’s presentation of fatigable weakness and ptosis rather than lid lag, an autoimmune antibody panel was ordered and revealed a positive acetylcholine receptor (AchR) antibody (AchR-Ab), a positive thyroid peroxidase (TPO) antibody (TPO-Ab), and a positive thyroglobulin (TG) antibody (TgAb), indicating MG. Medical therapy was recommended for treatment of MG, and the patient showed immediate improvement with intravenous immune globulin (IVIG) and pyridostigmine. A port catheter was placed for outpatient plasma exchange and a referral was made for thymectomy. The patient is doing well and is followed in the outpatient neurology office. Comments/Conclusion : Patients with MG demonstrate a 13% coexistence of other autoimmune diseases. Autoimmune thyroid diseases co-occur more frequently than other autoimmune diseases. GD occurs in approximately 5 – 8% of patients with MG [1]. With our patient’s overlapping ocular symptomology and the severity of the ophthalmoparesis, the patient most likely had ocular myasthenia gravis (OMG) which generalized along with Grave’s ophthalmopathy. Given the overlying ocular signs associated with GD and MG diligent diagnostic work up was essential to distinguish the two diseases to facilitate appropriate treatment . Grave’s Disease: Autoimmune disease characterized by antibody stimulation of the thyrotropin receptor (TSHR-Ab) leading to a diffuse goiter and overproduction of thyroid hormone. It is the most common cause of hyperthyroidism and is also associated with ophthalmopathy such as exophthalmos (proptosis) and lid lag (stare sign). These ocular findings are due to the cross activation of TSHR-AB with the IGF-1 receptor in orbital fibroblasts [9] . Activation leads to increased glycosaminoglycans (GAG) and cytokine response, ultimately resulting in periorbital growth and orbital inflammation. Myasthenia Gravis: Is the most common neuromuscular disorder characterized by fatigable motor weakness of skeletal muscle due to an autoimmune antibody-mediated disruption of the post-synaptic AChR. Introduction

HPI: A 19-year-old male with a two- year history of Grave’s disease presented to the emergency department with slurred speech and difficulty swallowing consistent for the past 2 weeks resulting in a 20-pound weight loss. The patient also endorsed fatigue and weakness in his legs which had led to him falling. The patient was currently taking methimazole 20 mg by mouth daily for his Grave’s disease. Neurology Consult: The patient was noted to have complete ophthalmoparesis with bilateral ptosis (figure A), proptosis (figure B), and fatigability with upward gaze. The diagnosis was listed as Grave’s ophthalmopathy with complete ophthalmoparesis. A thyroid panel was ordered to rule out thyrotoxic myopathy considering the patient’s history. And a myasthenia gravis antibody panel was ordered given the patient’s ocular presentation of ptosis rather than lid lag. Labs: B. A.

Diagnostic workup Clinical Presentation ›’‡”–Š›”‘‹†‹• – —‡š’‡…–‡† ™‡‹‰Š– Ž‘••ǡ –ƒ…Š›…ƒ”†‹ƒ ‘” ƒ””›–Š‹ƒ•ǡ •™‡ƒ–‹‰ǡ ƒš‹‡–›ǡ Š›”‘–‘š‹…‘•‹• – ’”‡–‹„‹ƒŽ ›š‡†‡ƒ ‹ˆˆ—•‡ǡ •›‡–”‹…ƒŽ ‘–‡†‡” ‰‘‹–‡” …—Žƒ”ǣ ‡š‘’Š–ŠƒŽ‘• ȋ’”‘’–‘•‹•Ȍǡ Ž‹† Žƒ‰ ȋ•–ƒ”‡ •‹‰Ȍ Initial work up Š›”‘‹† ˆ—…–‹‘ –‡•–ǣ ǡ Ͷ ȋ–‘–ƒŽȌǡ Ͷ ȋˆ”‡‡Ȍǡ ͵ ȋ–‘–ƒŽȌ • Ž‡˜ƒ–‡† ͵ ƒ† Ͷ Ž‡˜‡Ž• ™‹–Š •—’’”‡••‹‘ – ‘ˆ‹”• –Š›”‘–‘š‹…‘•‹• • ‘”ƒŽ – ‡š…Ž—†‡• –Š›”‘–‘š‹…‘•‹• – ”—Ž‡ ‘—– ƒ””›–Š‹ƒ• Antibodies Grave’s Disease

Myasthenia Gravis ‡‡”ƒŽ‹œ‡† – ˆƒ–‹‰ƒ„Ž‡ ™‡ƒ‡•• –Šƒ– ‹’”‘˜‡• ™‹–Š ”‡•– …—Žƒ”ǣ ’–‘•‹• ȋ‡›‡ Ž‹† †”‘‘’‹‰Ȍ ‡ ’ƒ… –‡•– †”‘’Š‘‹— ȋ ‡•‹Ž‘Ȍ – Š‹•–‘”‹…ƒŽ – ‘ˆ‹”ƒ–‘”› ‹ –Š‘•‡ •‡”‘‡‰ƒ–‹˜‡ Š ƒ–‹„‘†‹‡• – ͺͷΨ Ϊ •M ‘†—Žƒ–‹‰ǡ „‹†‹‰ǡ „Ž‘…‹‰ — – ͺΨ •G ‡‡”ƒŽ‹œ‡† Š •‡”‘‡‰ƒ–‹˜‡ – ͶͲΨ Ͷ – ‡”‘‡‰ ͳ ƒ Ψ –‹˜‡ – ͸Ψ Ϊ Ȁ • Orbital congestion; EOM hypertrophy • Ocular or bulbar symptoms • Thymoma …‡–›Ž…Š‘Ž‹‡ ‹Š‹„‹–‹‘ǣ ’›”‹†‘•–‹‰‹‡ – ƒ—–‹‘ ‹ –Š‘•‡ ™‹–Š — ƒ–‹„‘†‹‡• ȏͶȐ —‘–Š‡”ƒ’‹‡• • Glucocorticoids – ͳ•– Ž‹‡ • Azathioprine or mycophenolate – ƒ‹–‡ƒ…‡ ”‹†‰‡Ȁ”‡•…—‡ ȋ”ƒ’‹†Ȁ•Š‘”– ƒ…–‹‰Ȍ • Plasma exchange (apheresis) • IVIG —”‰‹…ƒŽǣ –Š›‡…–‘› ‡˜‹‡™ †”—‰• –‘ ƒ˜‘‹† ‘” —•‡ …ƒ—–‹‘Ȁ…Ž‘•‡Ž› ‘‹–‘”

Š›”‘–”‘’‹ ”‡…‡’–‘” ȋ ƒ„Ȍȗ – ͸ͲǦͻͲΨ •S –‹—Žƒ–‘”›ǡ „Ž‘…‹‰ǡ ‡—–”ƒŽ ‘Ǧ•’‡…‹ˆ‹… • Š›”‘‹† ’‡”‘š‹†ƒ•‡ ȋ Ȍ • Š›”‘‰Ž‘„—Ž‹ ȋ ‰Ȍ ƒ†‹‘ƒ…–‹˜‡ ‹‘†‹‡ —’–ƒ‡ – Š‹‰Šǡ †‹ˆˆ—•‡ Ž–”ƒ•‘—† Ȁ ǣ ‘”„‹–ƒŽ ‡†‡ƒǡ Š›’‡”–”‘’Š›Ǣ –Š›”‘‹† ‡Žƒ”‰‡‡– ‡–ƒǦ„Ž‘…‡”ǣ •›’–‘ƒ–‹… –Š›”‘–‘š‹…‘•‹• –‹Ǧ–Š›”‘‹†ǣ • ‡–Š‹ƒœ‘Ž‡ – ͳ •– Ž‹‡ • ”‘’›Ž–Š‹‘—”ƒ…‹Ž – ͳ •– Ž‹‡ ‹ ˆ‹”•– –”‹‡•–‡” ‘ˆ ’”‡‰ƒ…› • ƒ†‹‘ƒ…–‹˜‡ ‹‘†‹‡ —”‰‹…ƒŽǣ –Š›”‘‹†‡…–‘› Grave’s ophthalmopathy • Mild: artificial tears • Moderate Ǧ•‡˜‡”‡ǣ ‡–Š›Ž’”‡†‹•‘Ž‘‡ Ϊ ›…‘’Š‡‘Žƒ–‡ • Sight Ǧ–Š”‡ƒ–‡‹‰ǣ ‘”„‹–ƒŽ †‡…‘’”‡••‹‘ Ϊ ƒ–‹Ǧ –Š›”‘‹† ‡†‹…ƒ–‹‘

Imaging

Treatment

Discussion: The patient most likely had ocular myasthenia gravis evident from his ptosis rather than lid lag which then generalized along with Grave’s ophthalmopathy. GD occurs in approximately 5 – 8% of patients with MG. Patients with MG demonstrate a 13% coexistence of other autoimmune diseases with autoimmune thyroid diseases co-occur more frequently [1]. This validates the need for a high degree of clinical suspicion and further work-up with patients presenting with overlapping autoimmune symptomology. With a positive MG antibody panel, this will now change the perioperative management for the patient. Also, certain drugs must be carefully evaluated before use to prevent worsening of his condition or worse, promoting an exacerbation. Even though there were no evidence of a thymoma in this patient, it is recommended in nonthymomatous patients positive for AchR-Ab to undergo thymectomy. Removing the thymus plus prednisone has shown more effective than prednisone alone [5]. Table 2 : Presentation, Workup, and Treatment Differences in Grave’s Disease and Myasthenia Gravis *Specific for Grave’s disease Ϊ ‹‰Š Š ƒ–‹„‘†› –‹–‡”• ƒ”‡ ‘”‡ •’‡…‹ˆ‹… ˆ‘” †‹ƒ‰‘•‹•ǡ „—– ’Žƒ•ƒ …‘…‡–”ƒ–‹‘ ’‘‘”Ž› …‘””‡Žƒ–‡• –‘ †‹•‡ƒ•‡ •‡˜‡”‹–› ȏͳͲȐ „„”‡˜‹ƒ–‹‘•ǣ Ͷ αŽ‘™Ǧ†‡•‹–› Ž‹’‘’”‘–‡‹ ”‡…‡’–‘”Ǧ”‡Žƒ–‡† ’”‘–‡‹ ͶǢ — α —•…Ž‡Ǧ•’‡…‹ˆ‹… –›”‘•‹‡ ‹ƒ•‡Ǣ α ‡š–”ƒ‘…—Žƒ” —•…Ž‡•ǡ α ‡Ž‡…–”‘…ƒ”†‹‘‰”ƒǡ α ‡Ž‡…–”‘›‘‰”ƒ’Š› ƒ–ƒ ‹ –Š‹• –ƒ„Ž‡ ™‡”‡ …‘ŽŽ‡…–‡† ˆ”‘ ”‡ˆ‡”‡…‡• ȏ͵ǡ Ͷǡ ͳͳǦͳ͵Ȑ

Thyroid Panel ™‹–Š ”‡ˆŽ‡š Ͷǡ –‘–ƒŽ Ͷǡ ˆ”‡‡ ͵ǡ –‘–ƒŽ

Result ͳǤ͵͵ ͸Ǥͺ ͲǤͺ ͲǤͻ͸ ε͸ͲͲ Ȁ ͺͲǤͺ Ȁ Result ͳͷ ‘ŽȀ ʹͲΨ ͶͺΨ

‘”ƒŽ ‘”ƒŽ ‘”ƒŽ ‘”ƒŽ Positive Positive

Interpretation

Š›”‘‹† ’‡”‘š‹†ƒ•‡ ƒ–‹„‘†› ȋ Ǧ Ȍ Š›”‘‰Ž‘„—Ž‹ ƒ–‹„‘†› ȋ ‰Ǧ Ȍ AChR Panel Š ǡ ‘†—Žƒ–‹‰ ƒ–‹„‘†› Š ǡ „‹†‹‰ ƒ–‹„‘†› Š ǡ „Ž‘…‹‰ ƒ–‹„‘†›

Interpretation High/Positive High/Positive †‡–‡”‹ƒ–‡

Imaging: • X-ray, neck and chest: unremarkable • Swallow study: unremarkable Table 1 : Laboratory Values from Patient’s Thyroid Panel and Myasthenia Gravis Antibody Panel Abbreviations ǣ Š α ƒ…‡–›Ž…Š‘Ž‹‡ ”‡…‡’–‘”Ǣ α –Š›”‘‹† •–‹—Žƒ–‹‰ Š‘”‘‡

References

• Computed tomography with contrast: no thymic enlargement Treatment: The patient was given 30 g IVIG daily and 30 mg of pyridostigmine to take three times daily. He showed immediate improvement in symptoms of ophthalmoplegia and muscle fatigue and was discharged with oncology follow up to place a port catheter to receive outpatient plasma pheresis daily for five days. The patient was then referred to surgery for thymectomy.

Please scan the provided QR code.

I would like to thank Dr. Paul LaPenna for connecting me to this patient with such a unique presentation. Acknowledgements

25

2 0 2 3 R e s e a r c h R e c o g n i t i o n D a y