A 59-year-old female patient was admitted to the hospital with a one-day history of sudden onset of right-sided partial ptosis and diplopia on right lateral gaze. The patient had generalized fatigue for over a year. At the age of 30, the patient had symptoms of dyspnoea and painful nodular swellings over her legs. During that time, sarcoidosis was suspected and was confirmed by lung biopsy. For the fear of adverse effects, she had declined steroid treatment. The patient had occasional flares since then until a year later, when she suffered from exacerbation of sarcoidosis in the form of polyarthritis, generalized fatigue, dyspnoea, fever and nodular swelling over legs. The patient again declined steroids and chose to remain on naproxen. Her symptoms had improved over a period of time except the generalized fatigue. She also had diabetes mellitus diagnosed at the same time, which was well controlled with metformin.
A neurological examination revealed a right-sided partial ptosis, and compensatory pseudo- retraction of the left eyelid (Figure 1a). Diplopia was noticed on right lateral gaze due to right lateral rectus weakness. Fluctuations in diplopia and ptosis were noticed during her hospital stay. The patient did not have any bulbar symptoms like dysphagia or dysphonia. But she was having generalized weakness in all her extremities, both proximal and distal, with marked diurnal variation in the form of more weakness during the evening.
During her hospital stay she developed respiratory distress and hypoxemia. A chest CT scan demonstrated a 7 cm necrotic mass in the left anterior mediastinum and bilateral hilar lymphadenopathy (Figure 2). Pulmonary function tests revealed restrictive lung disease and moderately decreased diffusion capacity. Steroids were recommended for the active sarcoidosis, which the patient declined.
An ophthalmology consult revealed no evidence of uveitis or optic neuritis. MG was confirmed by the tensilon test that showed improvement in her ptosis (Figure 1b) and strength in muscles of the upper limb. A confirmatory electrophysiological study with repetitive nerve stimulation (RNS) showed decrement in amplitude of action potentials with further reduction post exercise and recovery after 15 minutes, consistent with MG. Acetylcholine receptor (AChR) binding antibodies were markedly elevated (104.00 nmol/L; normal < 0.30), consistent with MG.
The patient's corrected calcium level was mildly elevated (10.7 mg/dl; normal 8.5–10.4). Other relevant tests with respect to hypercalcemia were, normal renal function tests (blood urea nitrogen 18 mg/dl, normal 7–25; creatinine 0.9 mg/dl, normal 0.7–1.4; phosphorous 3.9 mg/dl, normal 2.5–4.5; magnesium 1.8 mg/dl, 1.7–2.5) and normal intact parathyroid hormone (PTH) levels (33 pg/ml, normal 10 – 69). Other tests like 1,25-dihydroxyvitamin D (OHD), 25-hydroxyvitamin D and 24 hour urinary calcium levels were not measured.
Further tests revealed a high sedimentation rate (ESR) (78 mm/hr; normal 0–30) and increased serum angiotensin converting enzyme (ACE) levels (127 u/l, normal 9–67). These results, in conjunction with the pulmonary function tests, and hilar lymphadenopathy were consistent with active sarcoidosis.
Other relevant investigations including thyroid function tests, muscle enzymes, anti nuclear antibodies, rheumatoid factor, B12 levels, glycosylated hemoglobin levels and rapid plasma reagin tests were normal. MRI of the brain was also normal.
A CT guided fine needle biopsy of the left anterior mediastinal mass showed a predominantly lymphocytic cytokeratin positive thymoma. The patient was started on pyridostigmine with a remarkable improvement in weakness, diplopia and ptosis. Surgical removal of the thymoma with lymphadenectomy was performed. Postoperative surgical pathology demonstrated the presence of stage II A, WHO type B thymoma (Figure 3a). Lymph nodes showed noncaseating granulomas with multinucleated giant cells confirming sarcoidosis (Figure 3b).
The patient was diagnosed with having coexistent thymoma, MG and sarcoidosis.
The patient underwent post thymectomy radiotherapy. After successful counseling she was also started on a high dose of oral prednisone and oral pyridostigmine was continued. She has remained asymptomatic to date, and oral prednisone is being tapered accordingly.