Authors: Larrey Kasereka Kamabu, Ronald Oboth, Louange Maha Kataka, Albert Yemba Baruani, Hervé Monka Lekuya, Charles Kahindo Kangitsi
Categories: Case Report, Myasthenia gravis, Graves’ disease, Autoimmune association
Source: Journal of Medical Case Reports
Authors: Larrey Kasereka Kamabu, Ronald Oboth, Louange Maha Kataka, Albert Yemba Baruani, Hervé Monka Lekuya, Charles Kahindo Kangitsi
Myasthenia gravis is a neuromuscular autoimmune condition characterized by the presence of antibodies against acetylcholine receptors. It may present as a generalized disorder or remain limited to specific muscle groups. Myasthenia gravis can occur independently or alongside other autoimmune conditions, including Hashimoto’s thyroiditis and Graves’ disease. Although the co-occurrence of these disorders is recognized, it is an extremely rare clinical phenomenon.
A 20-year-old woman of Muganda ethnicity, with a 2-year history of Graves’ disease confirmed by thyroid scintigraphy, developed a myasthenic syndrome leading to acute respiratory failure. Her condition improved with the administration of Prostigmine. Further investigations, including electrophysiological studies and immunological tests, confirmed a diagnosis of myasthenia gravis. The patient demonstrated a positive response to medical therapy.
This case highlights the importance of recognizing the rare association between myasthenia gravis and Graves’ disease. Accurate diagnosis and effective treatment require a coordinated, multidisciplinary approach, particularly given the challenges posed by overlapping symptoms and the exacerbating effects of hyperthyroidism on myasthenia gravis.
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by the production of autoantibodies that target acetylcholine receptors (AChRs) at the neuromuscular junction, leading to impaired synaptic transmission and fluctuating muscle weakness [1]. The condition may present in a generalized form, affecting multiple muscle groups, or remain localized to specific areas, such as the ocular muscles [2]. MG frequently coexists with other autoimmune diseases, including Hashimoto’s thyroiditis, systemic lupus erythematosus (SLE), and rheumatoid arthritis, suggesting a shared autoimmune pathophysiology [3]. Among these associations, the co-occurrence of MG and Graves’ disease (GD) presents a particularly intriguing interplay between neuromuscular and endocrine dysfunctions [4].
Graves’ disease is an organ-specific autoimmune disorder driven by thyroid-stimulating antibodies (TSAb), which activate the thyrotropin receptor (TSHR) on thyroid follicular cells, resulting in excessive thyroid hormone production [5]. This hyperthyroid state leads to increased metabolic activity, with clinical manifestations including diffuse goiter, weight loss, heat intolerance, and tremors. Thyroid function tests typically reveal suppressed thyrotropin levels alongside elevated serum concentrations of thyroxine (T4) and triiodothyronine (T3) [6]. The condition predominantly affects women, with peak incidence occurring between the ages of 40 and 60 years, and is associated with genetic predisposition and familial clustering [7].
The coexistence of MG and GD is well-documented but remains relatively rare, with an estimated prevalence of 0.14–0.2% among patients with MG [8]. The precise pathophysiological mechanisms underlying this association are not yet fully understood; however, it is hypothesized that genetic susceptibility and shared immunological pathways play a crucial role [8]. Notably, both conditions have been linked to human leukocyte antigen–DR3 (HLA-DR3) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms, which contribute to immune dysregulation [9]. In some instances, MG symptoms may precede, coincide with, or follow the diagnosis of GD, further complicating disease management and treatment strategies [10].
Clinically, the simultaneous occurrence of MG and GD presents a significant diagnostic challenge, as overlapping symptoms—such as muscle weakness, fatigue, and bulbar dysfunction—can be misattributed to either disorder [3]. Furthermore, hyperthyroidism can exacerbate MG symptoms by increasing neuromuscular transmission, leading to a transient worsening of muscle fatigue and weakness [11]. This interplay necessitates a thorough clinical evaluation, including thyroid function tests, electromyography, and antibody assays, to distinguish between the two conditions and inform appropriate treatment strategies [12].
Despite the well-established association between MG and GD, reports documenting this coexistence remain scarce, particularly within African medical literature [4, 13, 14]. This case report contributes to the growing body of evidence by providing a detailed clinical account of a patient presenting with both conditions, highlighting the diagnostic and therapeutic challenges involved. Understanding the co-occurrence of MG and GD is crucial for clinicians, as it underscores the necessity of multidisciplinary management strategies that address both neuromuscular and endocrine dysfunctions.
From a clinical perspective, this case emphasizes the importance of considering autoimmune comorbidities in patients diagnosed with either MG or GD, as early recognition can help prevent severe complications such as myasthenic crisis or thyrotoxic storm. Furthermore, the report sheds light on the role of immunomodulatory therapy, including corticosteroids and plasmapheresis, in managing patients with overlapping autoimmune disorders [15]. Given the rarity of documented cases in Africa, this study serves as a valuable reference for healthcare professionals working in regions with limited access to specialized neurology and endocrinology services.
In addition, this case highlights the potential for misdiagnosis in resource-limited settings, where access to confirmatory diagnostic tools such as electromyography and anti-AChR antibody testing may be restricted. By presenting this case, we aim to raise awareness among clinicians regarding the necessity of a comprehensive diagnostic approach, incorporating thyroid function evaluation and neuromuscular assessments in patients presenting with unexplained muscle weakness or hyperthyroid symptoms.
A 20-year-old nulliparous female of Muganda ethnicity, with a 2-year history of psycho-affective distress, presented in 2022 following parental separation and a family history of Graves’ disease (father). Her distress manifested through persistent sadness, mood instability, and emotional numbness, accompanied by increased irritability and feelings of hopelessness. She also reported cognitive difficulties, including excessive worry, intrusive negative thoughts, and trouble concentrating.
Behaviorally, she experienced social withdrawal, sleep disturbances, and changes in appetite. Physically, she complained of fatigue, muscle tension, headaches, and occasional palpitations. These symptoms significantly affected her daily life, contributing to a decline in academic performance and overall well-being.
In June 2022, she was diagnosed with Graves’ disease, a condition known to exacerbate emotional distress through hormonal imbalances affecting mood and psychological stability. She was started on medical treatment with carbimazole (30 mg daily) and propranolol (20 mg daily) to regulate thyroid function and alleviate associated symptoms. Given the interplay between her endocrine condition and psycho-affective distress, a multidisciplinary approach, including psychological support, was considered essential for her overall recovery.
In January 2024, she began experiencing fatigue in her lower limbs, noticeable during walking and stair climbing, which later progressed to involve the upper limbs. In addition, she developed visual difficulties, including variable bilateral ptosis, intermittent diplopia, and challenges with chewing solid foods. On 13 April 2024, she was admitted to the medical ward at Mulago National Referral Hospital owing to an inability to rise from a squatting position.
Examination revealed a nasal voice, bilateral ptosis more prominent on the right, and intermittent diplopia. A vascular, non-compressive goiter with an audible bruit and bilateral exophthalmos were observed. Musculoskeletal examination showed reduced reflexes and scapular muscle atrophy, with an inability to lift the arms above the horizontal plane. Sensory function remained intact, and no abnormalities were noted in the skin, joints, cardiovascular, or respiratory systems.
Approximately 2 hours after admission, the patient experienced acute respiratory failure accompanied by pharyngeal pain, which rapidly progressed to respiratory arrest. Cardiopulmonary resuscitation (CPR), Ambu mask ventilation, and administration of a test dose of Prostigmine were performed, leading to symptom resolution. A working diagnosis of Graves’ disease complicated by myasthenia gravis was established.
A timeline table illustrates the sequence of events in the patient’s clinical course (Table 1).Table 1Timeline highlighting the sequence of events in the patient’s clinical courseTimelineSequence of events in the patient’s clinical course2022Experienced psycho-affective distress following parental separationPositive family history of Graves’ disease (father)June: Diagnosed with Graves’ disease; commenced on carbimazole (30 mg daily) and propranolol (20 mg daily)January 2024Onset of fatigue in lower limbs during walking and stair climbing, progressing to the upper limbsDeveloped visual issues (bilateral ptosis, intermittent diplopia)Chewing difficulties with solid foodsApril 202413 April: Admitted to Mulago National Referral Hospital with difficulty standing from a squatting positionExamination - Bilateral ptosis (right side more pronounced)- Intermittent diplopia- Vascular, non-compressive goiter with bruit- Bilateral exophthalmos- Musculoskeletal: reduced reflexes, scapular muscle atrophy, inability to raise arms above horizontal- Sensory function intact- No abnormalities in skin, joints, cardiovascular, or respiratory systemsWithin 2 hours of admission:- Acute respiratory failure with pharyngeal pain and rapid respiratory arrest- Managed with cardiopulmonary resuscitation (CPR), Ambu mask ventilation, and Prostigmine, achieving symptom reversal- Hypothesis: Graves’ disease with myasthenia gravis
On the third day of admission, following three doses of subcutaneous Prostigmine, electrophysiological studies demonstrated a significant reduction in neuromuscular transmission (19–62%) in the orbicularis oculi and abductor pollicis brevis muscles, consistent with a diagnosis of generalized, severe myasthenia gravis.
The patient’s thyroid function tests revealed a suppressed thyroid-stimulating hormone (TSH) level and elevated levels of triiodothyronine (T3) and thyroxine (T4), with mildly raised alkaline phosphatase (ALP), findings consistent with Graves’ disease (Table 2).Table 2Thyroid function testsTestResultsNormal rangeTSH < 0.01 mIU/L0.5–4.0 mIU/LT458 pmol/L10–25 pmol/LT323 pmol/L3.1–5.4 pmol/LALP135 U/L30–120 U/L
Anti-nuclear antibodies (ANA): positive (1:160, homogeneous pattern).Anti-U1 ribonucleoprotein (RNP) positive (9 IU).Anti-DNA antibodies and anti-Sm negative.Anti-acetylcholine receptor positive (16.9 nmol/L; normal < 0.2 nmol/L).
The immunology profile indicates a complex autoimmune overlap syndrome. The strongly positive anti-AChR antibodies confirm myasthenia gravis, while the positive ANA and anti-U1 RNP antibodies suggest a possible coexisting autoimmune connective tissue disorder or a generalized autoimmune predisposition. The absence of anti-DNA and anti-Sm antibodies makes systemic lupus erythematosus (SLE) less likely, but the patient may still exhibit features of other autoimmune conditions, such as Graves’ disease, as suggested by the thyroid function tests.
The full blood count was within normal parameters.
Plain Chest Radiograph: normal.
Thyroid Ultrasound: the thyroid gland was moderately enlarged, measuring 25 mm × 20 mm. Both lobes exhibited a heterogeneous echotexture with increased vascularity on power Doppler imaging. The surrounding tissues appeared normal, and no cervical lymphadenopathy was observed. These findings support a diagnosis of Graves’ disease (Fig. 1).Fig. 1Transverse ultrasound image showing a moderately enlarged 25 mm × 20 mm thyroid gland with reduced echogenicity (B-mode) and an increased vascular pattern on directional power imaging—a phenomenon known as thyroid inferno
Scintigraphic imaging using Tc-99m pertechnetate demonstrated an enlarged thyroid gland (Figs. 2 and 3). The target-to-background uptake was significantly elevated, rendering the submandibular salivary glands minimally visible across all captured images. There was no evidence of retrosternal extension of the thyroid gland. These findings are consistent with a scintigraphic diagnosis of Graves’ disease.Figure 2: anterior view of thyroid scintigraphy with Tc-99m pertechnetate, showing homogeneous increased activity in an enlarged thyroid gland.Figure 3: anterior view with marker Tc-99m pertechnetate, showing no retrosternal extension of the thyroid gland.Fig. 2Anterior view of thyroid scintigraphy with Tc-99m pertechnetate, showing homogeneous increased activity in an enlarged thyroid glandFig. 3Anterior view with marker Tc-99m pertechnetate, showing no retrosternal extension of the thyroid gland
Histopathological examination revealed features indicative of glandular activation, enlarged follicular cells with abundant eosinophilic cytoplasm; hyperplastic follicles exhibiting papillary epithelial infoldings; colloid reabsorption characterized by scalloping at the apical membrane; and varying degrees of follicular collapse and depletion. These findings (illustrated in Fig. 4) support a histopathological diagnosis of Graves’ disease.Fig. 4Hematoxylin and eosin stain at 100× magnification—thyroid parenchyma showing features of thyroid hyperactivity, as seen in Graves’ disease, with scalloping, partial follicular collapse, and follicular depletion
Following successful cardiopulmonary resuscitation (CPR), the patient’s post-resuscitation course was closely monitored for potential complications associated with both the underlying conditions and the resuscitation process.
The patient was admitted to the intensive care unit (ICU) for continuous monitoring of vital signs, neurological status, and respiratory function.
Special attention was given to cardiac function and potential neurological deficits due to hypoxic injury.
Over the following days, the patient exhibited progressive clinical improvement, with stabilization of cardiac function, neurological status, and muscle strength.
Thyroid function was closely monitored and managed to prevent thyrotoxic crises, which could exacerbate myasthenia gravis (MG) symptoms. The patient responded well to antithyroid medications and beta-blockers.
Neuromuscular function improved with anticholinesterase therapy (Prostigmine). There was no evidence of myasthenic crisis or recurrence of severe muscle weakness.
The patient remained hemodynamically stable, with no further cardiac events or respiratory distress during the hospital stay.
After 11 days of hospitalization, the patient was deemed stable and discharged with a comprehensive outpatient management plan.
Post-discharge, the patient was placed under regular outpatient follow-up with neurology and endocrinology teams to ensure ongoing management of myasthenia gravis and Graves’ disease.
The post-cardiopulmonary resuscitation period was uneventful, and the patient showed significant clinical improvement by the time of discharge. She remains under regular review to monitor for relapse or complications, with an overall favorable prognosis given the early diagnosis and multidisciplinary management approach.
The co-existence of myasthenia gravis (MG) and Graves’ disease presents a complex clinical scenario requiring tailored management strategies. In this case, the diagnosis of Graves’ disease preceded the onset of MG by 2 years, aligning with literature indicating that hyperthyroidism precedes MG in approximately 40–50% of cases. Conversely, MG is diagnosed first in 30–35% of cases, while both conditions are identified simultaneously in 20–25% [16]. It remains uncertain whether MG was present at the initial diagnosis of Graves’ disease in this patient, as no immunological investigations for MG were conducted at that time.
The patient’s family history revealed Graves’ disease in her father. The prevalence of concurrent MG and hyperthyroidism varies, with estimates suggesting that 2–3% of individuals with hyperthyroidism have MG, and 2–17.5% of MG patients experience thyrotoxicosis. Epidemiologically, both conditions exhibit a female predominance, with incidence peaking between 20 and 40 years of age [13, 14].
This patient presented with generalized myasthenia, although hyperthyroidism is more frequently associated with spino-bulbar forms of MG [4]. In Graves’ disease, ocular manifestations such as exophthalmos and superior eyelid retraction are typical. The co-occurrence of ptosis or nystagmus should prompt consideration of MG [17]. The patient exhibited both exophthalmos and ptosis, supporting the diagnosis of concurrent Graves’ ophthalmopathy and MG. The disproportionate association between thyroid eye disease and MG may stem from cross-reactivity against shared epitopes or autoantigens in the thyroid and ocular muscles in genetically predisposed individuals [6].
The thymus plays a significant role in MG, with frequent thymic abnormalities, including follicular hyperplasia in 65% of cases and thymoma in 10–15% [14]. While thymic hyperplasia has also been reported in Graves’ disease without MG, this patient did not exhibit an enlarged thymus, likely owing to prior antithyroid treatment. A chest radiograph showed no mediastinal widening suggestive of thymic enlargement; however, computed tomography (CT) imaging, the preferred modality, was not performed [13].
Thyroid scintigraphy, ultrasonography, and functional tests confirmed Graves’ disease in this patient. Immunologically, ANA positivity in the absence of lupus-specific symptoms was attributed to MG [13]. Positive anti-TSH receptor antibodies, observed in a quarter of MG cases, and strongly positive anti-AChR antibodies corroborated the diagnosis of MG.
Given the autoimmune nature of both conditions and their potential for mutual exacerbation, a multidisciplinary approach was essential in managing the patient’s condition. Upon admission, she presented with acute respiratory failure, pharyngeal pain, and rapid respiratory arrest. Emergency intervention was initiated with cardiopulmonary resuscitation (CPR) and Ambu mask ventilation, successfully restoring respiratory function. The administration of Prostigmine, an acetylcholinesterase inhibitor, resulted in symptom reversal, confirming the suspicion of coexisting myasthenia gravis (MG) and Graves’ disease [18].
Once stabilized, the patient was admitted to the intensive care unit (ICU) for continuous monitoring of vital signs, neurological status, and respiratory function. Special attention was given to cardiac function and the prevention of potential neurological deficits due to hypoxic injury. To address her Graves’ disease, she was maintained on carbimazole (30 mg daily) to suppress excessive thyroid hormone production and propranolol (20 mg daily) to control hyperadrenergic symptoms such as palpitations and tremors [22].
Throughout her hospitalization, her thyroid function was closely monitored to prevent thyrotoxic crises, which could further exacerbate her MG symptoms. Neuromuscular function improved with the continued administration of Prostigmine, and there was no recurrence of severe muscle weakness or evidence of a myasthenic crisis. For long-term management of MG, corticosteroids such as prednisone were considered, though initiated cautiously owing to their potential to transiently worsen symptoms [19]. In refractory cases, immunosuppressants such as azathioprine or mycophenolate mofetil were considered [20]. The possibility of thymectomy was also discussed, given its potential benefit in generalized MG [21].
For severe exacerbations, plasmapheresis or intravenous immunoglobulin (IG) was available as an option to rapidly reduce circulating autoantibodies and improve muscle strength [21]. Given the interrelationship between MG and Graves’ disease, achieving euthyroidism promptly was emphasized, as thyrotoxicosis can impair neuromuscular transmission and worsen MG symptoms [23]. The patient’s thyroid function was closely monitored to guide appropriate adjustments in antithyroid medication and to assess the need for alternative definitive treatments such as radioactive iodine therapy (RAI) or thyroidectomy [23].
Over the course of 11 days, the patient demonstrated steady clinical improvement, remained hemodynamically stable, and experienced no further respiratory distress or cardiac complications. Given her positive response to treatment, she was discharged with a comprehensive outpatient management plan, including continued antithyroid therapy, beta-blockers, and acetylcholinesterase inhibitors. In addition, psychological support was recommended to address the psycho-affective distress associated with her chronic illness and personal circumstances. Close follow-up was scheduled to ensure continued symptom control and to prevent disease exacerbation. A multidisciplinary approach involving neurologists, endocrinologists, and intensive care specialists was crucial in optimizing the patient’s management and ensuring long-term stability [23].
The prognosis for co-morbid MG and Graves’ disease varies. In approximately 40% of cases, MG improves while hyperthyroidism worsens; in 20%, thyrotoxicosis is controlled but MG persists [24]. Both conditions impact neuromuscular function, with thyroid hormones and synthetic replacements exacerbating neuromuscular blockade through direct effects on the neuromuscular junction. This relationship likely explains the onset of MG symptoms in this patient during a period of excessive thyroid hormone levels. Promptly achieving euthyroidism, often via radical treatment, is essential.
This patient was administered a low dose of corticosteroids to mitigate the risk of transient MG exacerbation associated with steroid initiation. In addition, radioactive iodine therapy was provided. The patient demonstrated improvement and remains under regular follow-up.
The co-occurrence of MG and Graves’ disease is not coincidental and should be considered in clinical practice. MG should be suspected in patients with Graves’ disease presenting with ptosis, nystagmus, or persistent myogenic symptoms despite thyroid hormone regulation. Radiological imaging, particularly in conjunction with immunoassays, is critical in diagnosing these conditions and identifying associated thymic pathology, such as thymoma. Prompt recognition and targeted management are essential for optimizing patient outcomes.