Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene
A 20-year-old male was admitted to Gulhane School of Medicine, Department of Endocrinology and Metabolism outpatient clinic, with the complaints of fatigue, anorexia, weakness, and absence of penile erection. A detailed medical history taking revealed that the patient had been diagnosed with hypothyroidism and growth hormone (GH) deficiency at the age of 10 and was subsequently started with treatment for both hypothyroidism and GH deficiency. After a 3-year levothyroxine and GH therapy, he himself had stopped the medication and was free of any drug for the past 7 years. He defined that his complaints increased in the last 3 months. He was hospitalized for further evaluation. On physical examination, his blood pressure was 90/50 mmHg and his pulse was 68 beats/min. He was 164 cm tall and weighed 58.5 kg. A eunuchoid appearance with an arm span that was more than 5 cm longer than height, and no facial and minimal axillary hairy were noted. Tanner score of the pubis was 2 and penis length was 5 cm. Right and left testicular volumes were 3.4 ml and 2.5 ml, respectively, on ultrasonography. He had no hyperpigmentation on his skin or oral mucosa. Other physical findings were unremarkable. Laboratory results are shown in .\nOn the 5th day of hospitalization while waiting for magnetic resonance imaging (MRI) appointment, the patient had rapid visual loss in the right eye. Best-corrected visual acuity (VA) was 20/50 in the right eye and 20/20 in the left eye. Dilated funduscopic examination revealed a yellowish elevated lesion near the optic disc, with macular edema and hemorrhage next to the temporal side of the optic disc in the right eye. Fluorescein angiography (FA) showed a hyperfluorescent lesion consistent with CNV [], and optical coherence tomography (OCT) showed a peripapillary lesion with subretinal fluid elevating the neurosensory retina in the macular area []. MRI of the brain revealed a hypoplastic adenohypophysis and a hypoplastic pituitary stalk. An ectopic neurohypophysis was found located in the area of the hypothalamus [, T1 weighted; , T2 weighted]. Because of his visual loss, Department of Ophthalmology did not allow insulin hypoglycemia test. Thyroid morphology was normal on ultrasonography. Thyrotropin releasing hormone stimulation test resulted in a maximum thyroid stimulating hormone (TSH) level of 7.6 μIU/ml by the 30th min. Because of his medical history, clinical and MRI findings, low thyroidal, (free T4) adrenal, (low cortizol) testicular, (low total testosterone) low GH, insulin-like growth factor 1 (IGF-1), and low-normal other pituitary hormone levels [], he was diagnosed as having hypopituitarism.\nFirst, prednisolone 5 mg/day was started; 1 week later, l-thyroxin 50 mg/day was added to the treatment. Since both hypopituitarism[] and CNV could be caused by hypoxia,[] conditions known to cause a hypercoagulable state were explored and an MTHFR C677T homozygous mutation was detected by polymerase chain reaction of genomic DNA.[] For the peripapillary CNV, three intravitreal injections of anti-VEGF antibody (ranibizumab) were administered for persistent fluid collection. Before the start of testosterone gel 50 mg/day treatment, acetyl salicylic acid (ASA) 100 mg/day was also added to the treatment. By the 6th month of follow-up, VA increased to 20/20 and OCT showed peripapillary scar formation and total resolution of the subretinal fluid []. No subsequent thromboembolic event was determined. On the annual control, 1 year after the event, he was still taking L-thyroxin, testosterone gel, prednisolone, and ASA. His vision on the right eye was stable with 20/20 and no thromboembolic event was determined.