Endocrine Abstracts

Background: Spondyloenchondrodysplasia (SPENCD) is a rare autosomal recessive skeletal dysplasia characterized by radiolucent spondylar and metaphyseal lesions, representing the persistence of chondroid tissue islands within the bone. Besides skeletal abnormalities and short stature, autoimmune disorders, including systemic lupus erythematosus, Sjögren’s syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud’s disease, and vitiligo, have been reported to occur in this disease. In here, we present a patient with insufficient secondary sex characteristics, despite having normal testosterone levels.

Case: A 21-year-old patient, born at term to healthy parents from same town after an uncomplicated pregnancy, presented with complaints of paleness, arthritis in his right first metacarpophalangeal joint, and arthralgia involving his left knee, both ankles, elbows, and neck at the age of 4. Laboratory examination revealed anemia, hypocomplementemia, hematuria, and proteinuria. ANA, anti-dsDNA antibody, and lupus anticoagulant were positive. Renal biopsy confirmed class IV lupus nephritis. The endocrine work-up was normal. Homozygous mutation in the ACP5 gene led to the diagnosis of SPENCD. Treatment with various immunosuppressive protocols, including hydroxychloroquine, methylprednisolone, cyclophosphamide, and mycophenolate mofetil, resulted in improvement over a 17-year follow-up. When the patient presented to our clinic at the age of 21, clinical and laboratory findings were consistent with activation of lupus, prompting renewed immunosuppressive treatment. During hospitalization, clinical examination suggested hypogonadism. The patient reported a history of erectile dysfunction, decreased libido, absence of morning erections, loss of body hair, and reduced shaving frequency. His height was 146 cm, arm span length was 148 cm, apex-pubis length was 65 cm, and pubis-heel length was 81 cm. Testicular volume was 12 ml for both testes, and penile length measured 7.5 cm. Pubic hair was at Tanner stage 4. Laboratory examination showed a testosterone level of 515 ng/dl (197-669), with FSH, LH, IGF-1, and other anterior pituitary hormones within normal range. Short stature was considered a manifestation of the primary disease. TSH and free T4 values were normal, but anti-TPO and anti-TG values were elevated. Thyroid ultrasound revealed findings consistent with thyroiditis.

Conclusion: Despite normal testosterone levels, inadequate development of secondary sex characteristics and sexual dysfunction may be newly identified features of SPENCD syndrome. ACP5 defect may lead to immune dysregulation. As the patient was under immunosuppressive therapy, lymphopenia and hypogammaglobulinemia were attributed to secondary immunodeficiency. Although FSH and LH levels were normal, autoimmune orchitis will be further evaluated. Resistance at the receptor level by receptor specific autoantibodies may contibute to the pathophysiology.