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Abstract

We report a case of primary empty sella syndrome (ESS) resulting in osteoporotic fractures and persistent non-fusion of the hand epiphyses, and discuss the potential pathogenesis of this disease. A 41-year-old man presented with pain in the right hand and back after a fall. X-radiographs revealed persistent epiphyses and severe osteoporosis. Serum phosphorus and prolactin levels were above normal levels, and free triiodothyronine, free thyroxine and testosterone levels were below normal limits. Magnetic resonance imaging of the head revealed empty sella. A lumbar bone mineral density examination indicated severe osteoporosis. ESS caused a systemic hormone disorder in this patient, resulting in osteoporotic fractures and persistent non-fusion of the hand epiphyses. Possible causes of this anomaly are chronic or congenital abnormities of the pituitary gland.

Keywords

Osteoporosis empty sella syndrome hyperprolactinaemia hypogonadism pituitary

Introduction

Empty sella syndrome (ESS) was first identified in 1949 in cases of pituitary necrosis in postpartum women, and postmortem studies have found evidence of ESS in about 20% of the population.¹ ESS is thought to arise from an incompetent diaphragma sellae, which allows progressive herniation of the arachnoid membrane with secondary compression and atrophy of the pituitary gland.² Endocrine abnormalities are not uncommon in ESS, including growth hormone deficiency and insulin-induced hypoglycaemia.^3–7 This report presents a rare case of osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by ESS. The patient provided written consent to publish the case report.

Case report

A 41-year-old man was referred to the Department of Orthopaedics, Changzheng Hospital, The Second Military Medical University, Shanghai, China, in November 2009 with pain in his right hand and lower back following a minor accidental fall. The patient weighed 47 kg and was 150 cm tall. He had no history of head injury, seizures, sleep disturbance, visual symptoms, headache or polyphagia, and there had been no perinatal problems. A non-fasting blood sample was taken from the median cubital vein into a procoagulant tube, which was stored at 2–8 ℃ before analysis by an automated analyser. The analyses showed hyperphosphataemia (1.98 mmol/l; normal range 0.81–1.45 mmol/l), hyperprolactinaemia (51.32 µg/l; normal range 1.61–18.77 µg/l) and reduced plasma free triiodothyronine (1.65 ng/l; normal range 2.0–4.4 ng/l), free thyroxine (6.24 ng/l; normal range 7–18.5 ng/l) and testosterone (2 ng/dl; normal range 260–1320 ng/dl). Lumbar bone mineral density examination using dual-energy X-ray absorptiometry revealed severe osteoporosis (T-scores −4.1 to −4.5; a T-score of less than −2.5 indicates osteoporosis). The patient’s karyotype was 46XY with no structural chromosomal abnormalities.

Plain X-radiographs of the right hand revealed a fracture of the 5th metacarpal together with persistent non-fusion of the hand epiphyses including the wrist joint (Figure 1). X-radiographs of the thoracolumbar spine indicated wedging of the T12 vertebra and reduced bone density in multiple vertebrae (Figure 2). Magnetic resonance imaging (MRI) of the head revealed the presence of an empty sella – the pituitary gland was flat without signal intensity defects (Figure 3). Thyroid-stimulating hormone, serum calcium, cortisol, calcitonin and growth hormone levels were below normal range. The patient was treated with a bandage fixation for the 5th metacarpal fracture, kept on bed-rest for the T12 fracture, and given oral painkillers (celecoxib, 200 mg two times per day). Pain was assessed initially and at 3 months with a visual analogue scale; the pain was markedly relieved at 3-month follow-up.

Figure 1.

Plain X-radiographs of the right hand of a 41-year-old man with empty sella syndrome, revealing 5th metacarpal cortical discontinuity and persistent non-fusion of the hand epiphyses including the wrist joint (arrows).

Figure 2.

Plain X-radiograph of the thoracolumbar spine of a 41-year-old man with empty sella syndrome, revealing wedging of the T12 vertebra (arrow) and reduced bone density of multiple vertebrae.

Figure 3.

Magnetic resonance image of the brain of a 41-year-old man, revealing a partially empty sella (arrow). The pituitary gland is flat, without signal intensity defects. There are no obvious brain tissue abnormalities.

Discussion

The present study described a rare case of an adult with osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by ESS. It is well known that endocrine alterations are a common feature of ESS, but the mechanism remains unclear.^8–10

Endocrine abnormalities are not uncommon in ESS, and may be severe.^11–15 A study including 71 cases of primary ESS revealed that 14% of patients had hyperprolactinaemia and 7% had hypogonadism.¹⁵ The pituitary gland is normally inhibited by the hypothalamus prolactin release inhibiting factor (PIF), thought to be dopamine.¹⁶ Dopamine is secreted by neurons in the arcuate nucleus of the hypothalamus, and combines with prolactin receptors in the anterior pituitary to inhibit the secretion of prolactin. ESS affects PIF transport, leading to hyperprolactinaemia,¹⁷ a cause of hypogonadism in both sexes. Hyperprolactinaemia induces hypogonadism by inhibiting gonadotropin releasing hormone secretion and, consequently, follicle-stimulating hormone, luteinizing hormone and testosterone secretion.

Hypogonadism is associated with low plasma testosterone, short stature and testicular atrophy,^18,19 as well as a high incidence of symptomatic osteoporosis.^20–22 Although the mechanism of bone loss in hyperprolactinaemia has not been clearly defined, a study of castrated male rats indicated decreased androgen levels, increased bone resorption, reduction in trabecular bone and cortical thinning.²³ In addition, bone mineral density is decreased in elderly patients and those who have undergone testicular resection.²⁴ Osteoblastic androgen receptors play an important role in promoting osteoblast proliferation and the synthesis and secretion of various cytokines, resulting in formation of bone matrix proteins.²⁵ It is possible that the low plasma testosterone level in the current case was responsible for the reduction in bone density.

Persistent epiphyses are present in multiple epiphyseal dysplasia (Fairbank disease or multiple epiphyseal dysostosis) or pseudoachondroplasia.²⁶ In addition, increased stress to the growth plates caused by taking part in intense sporting activity during growth spurts can influence normal growth.²⁷ The current patient had no history of trauma or surgery, however, and it is possible that a prepubertal absence of androgens resulted in disease.^28,29 Androgens are known to regulate epiphyseal cartilage cell proliferation and differentiation, affecting growth plate cartilage and regulating growth plate closure.³⁰

In conclusion, it is likely that ESS caused a systemic hormone disorder in the current case, resulting in osteoporotic fractures and persistent non-fusion of the hand epiphyses.

Footnotes

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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