Osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by empty sella syndrome in an adult: A case report

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.

References

Robinson

Michaels

. Empty sella resulting from the spontaneous resolution of a pituitary macroadenoma. Arch Intern Med 1992; 152: 1920–1923.

Borgoni

Giusti

Venturini

. [Primary empty sella syndrome. Report of 6 cases]. Minerva Med 1993; 84: 233–238.

Lenz

Root

. Empty sella syndrome. Pediatr Endocrinol Rev 2012; 9: 710–715.

D'Alessandris

Montano

Bianchi

. Persistence of primary empty sella syndrome despite obesity surgery: report of two unusual cases. Br J Neurosurg 2012; 26: 875–876.

Poggi

Monti

Lauri

. Primary empty sella and GH deficiency: prevalence and clinical implications. Ann Ist Super Sanita 2012; 48: 91–96.

Agrawal

Jain

Garg

. Primary empty sella with isolated ACTH deficiency and microprolactinoma. Gynecol Endocrinol 2012; 28: 568–569.

Degli Uberti

Teodori

Trasforini

. [The empty sella syndrome. Clinical, radiological and endocrinologic analysis in 20 cases]. Minerva Endocrinol 1989; 14: 1–18.

Foppiani

Ruelle

Bandelloni

. Hypopituitarism in the elderly: multifaceted clinical and biochemical presentation. Curr Aging Sci 2008; 1: 42–50.

Piccin

Raimondi

Laspina

. Erythroleukaemia, diabetes insipidus and hypophyseal damage: Two case reports. Leuk Res 2007; 31: 1135–1139.

10.

Del Monte

Foppiani

Cafferata

. Primary “empty sella” in adults: endocrine findings. Endocr J 2006; 53: 803–809.

11.

Durodoye

Mendlovic

Brenner

. Endocrine disturbances in empty sella syndrome: case reports and review of literature. Endocr Pract 2005; 11: 120–124.

12.

Rać

. [Optimized diagnostic performance of brain magnetic resonance imaging in children with idiopathic growth hormone deficiency]. Ann Acad Med Stetin 2006; 52: 25–33. discussion 33–34).

13.

Bettinelli

Rusconi

Ciarmatori

. Gitelman disease associated with growth hormone deficiency, disturbances in vasopressin secretion and empty sella: a new hereditary renal tubular-pituitary syndrome? Pediatr Res 1999; 46: 232–238.

14.

Becejac

Vizner

Berković

. Neuroendocrinological aspects of primary empty sella. Coll Antropol 2002; 26(Suppl): 159–164.

15.

Bianconcini

Bragagni

Bianconcini

. [Primary empty sella syndrome. Observations on 71 cases]. Recenti Prog Med 1999; 90: 73–80.

16.

Ben-Jonathan

Hnasko

. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 2001; 22: 724–763.

17.

Ascoli

Cavagnini

. Hypopituitarism. Pituitary 2006; 9: 335–342.

18.

Lombardo

Lupini

Meola

. Clinical and laboratoristic strategy in late onset hypogonadism. Acta Biomed 2010; 81(Suppl 1): 85–88.

19.

Schmidtova

Kelemenova

Ostatnikova

. Testosterone supplementation therapy as a treatment of hypogonadism. Bratisl Lek Listy 2009; 110: 765–772.

20.

Jackson

Kleerekoper

Parfitt

. Symptomatic osteoporosis in a man with hyperprolactinemic hypogonadism. Ann Intern Med 1986; 105: 543–545.

21.

Allan

Tannenbaum

Sbriscia

. A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats. Endocrine 2007; 32: 41–51.

22.

Kilany

Abou Holw

Abouel-Nour

. Early development of osteoporosis in male smokers with hypoandrogenism due to fascioliasis with or without schistosomiasis added by life style. J Egypt Soc Parasitol 2009; 39: 789–802.

23.

Vandenput

Ederveen

Erben

. Testosterone prevents orchidectomy-induced bone loss in estrogen receptor-alpha knockout mice. Biochem Biophys Res Commun 2001; 285: 70–76.

24.

Daniell

. Osteoporosis after orchiectomy for prostate cancer. J Urol 1997; 157: 439–444.

25.

Wiren

Toombs

Semirale

. Osteoblast and osteocyte apoptosis associated with androgen action in bone: requirement of increased Bax/Bcl-2 ratio. Bone 2006; 38: 637–651.

26.

Jackson

Mittaz-Crettol

Taylor

. Pseudoachondroplasia and multiple epiphyseal dysplasia: a 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution. Hum Mutat 2012; 33: 144–157.

27.

Segesser

Morscher

Goesele

. [Lesions of the growth plate caused by sports stress]. Orthopade 1995; 24: 446–456.

28.

Peralta

Arnold

Currie

. Effects of testosterone on skeletal growth in lambs as assessed by labeling index of chondrocytes in the metacarpal bone growth plate. J Anim Sci 1994; 72: 2629–2634.

29.

Oberbauer

Currie

Krook

. Endocrine and histologic correlates of the dynamics of the metacarpal growth plate in growing rams. J Anim Sci 1989; 67: 3124–3135.

30.

Schwartz

Nasatzky

Ornoy

. Gender-specific, maturation-dependent effects of testosterone on chondrocytes in culture. Endocrinology 1994; 134: 1640–1647.