Scott Med J OnlineFirst, published on January 5, 2015 as doi:10.1177/0036933014565586
Case Report
A successfully treated case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis
Scottish Medical Journal 0(0) 1–4 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933014565586 scm.sagepub.com
Yi-Chen Wang1, Li-Chao Gao1, Hui Xu2, Xiao-Zhang Qu1, Ye Wang1, Xiao-Qian Lou1 and Hui Guo3
Abstract Introduction: This study aimed to report a rare case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis. Case presentation: Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. It often leads to hypoglycaemia, but in this case the patient was complicated with hyperosmolar hyperglycaemic state. The patient received prompt medical treatment, which effectively prevented the occurrence of possible acute kidney failure and other complications. Conclusion: This is a complicated and rare case. Our report provides some indications for the timely diagnosis and the standardised treatments for a patient who has hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.
Keywords Hyperosmolar hyperglycaemic state, hypopituitarism, rhabdomyolysis
Introduction Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. The condition often leads to hypoglycaemia. Here, we report a case of a 23-year-old Chinese male who was admitted to our hospital in a hyperosmolar hyperglycaemic state (HHS) combined with hypopituitarism and rhabdomyolysis. HHS sometimes induces rhabdomyolysis and temporal acute kidney injury. The mortality rate of HHS ranges from 10% to 50%1 due to the high incidence of coexisting disease. Age (>65 years), degree of hyperosmolarity (>375 mOsm/L),2 hemodynamic instability,3 a low Glasgow coma scale score on admission and precipitation by infection4 are powerful predictors of a fatal outcome. Rhabdomyolysis is defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various non-traumatic
causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia. Therefore, it is crucial to establish a timely diagnosis and standardised treatments.
Case presentation A 23-year-old Chinese man was admitted to our hospital because of drowsiness. Two months prior, he had undergone surgery to remove a germinoma located in the sella region. He also received Gamma-knife radiosurgery after another month. During the previous two 1
Physician, The Second Part of First Hospital, Jilin University, China Researcher, Basic Medical College, Jilin University, China 3 Professor, The Second Part of First Hospital, Jilin University, China 2
Corresponding author: Hui Guo, The Second Part of First Hospital, Jilin University, Changchun 130031, China. Email: [email protected]
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
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Scottish Medical Journal 0(0)
weeks, he had suffered general fatigue and anorexia. He took dexamethasone (3 mg) for a day as treatment, but his symptoms did not change. After two days, the symptoms became more serious, and he could not move due to lower limb muscle pain and weakness. Five hours before his admission, he became drowsy. On admission, his blood pressure was 130/80 mmHg, his pulse rate was 102 beats/min, his respiratory rate was 33/min and his body temperature was 37.1 C. An oropharyngeal examination revealed an extremely dry oral mucosa. A chest and abdominal examination revealed no abnormalities. Muscle strength of the upper limbs was grade 3, and that of the lower limbs was grade 0. The pathologic reflex was not drawn out. Blood tests revealed severe hyperglycaemia, electrolyte abnormalities, elevated myoglobin, leukocytosis (Table 1) and hypopituitarism (Figure 1). His calculated plasma osmolarity was 427 mOsm/L. On admission, hypopituitarism, HHS and rhabdomyolysis were diagnosed. After fluid resuscitation (0.9% NaCl) and insulin infusion, the patient’s blood sugar levels gradually decreased. By the second day of hospitalisation, his blood sugar levels had decreased from 574 mmol/L to 196 mmol/L, his osmolarity decreased from 427 to 355 mOsm/L and his consciousness was restored; however, his muscle strength had not improved. His myoglobin levels were still over
3000 ng/mL (Figure 2). On the third day of hospitalisation, his muscle strength improved (the upper limbs were grade 5 and the lower limbs were grade 2), he stopped complaining of any muscle pain and osmolarity decreased to normal (314 mOsm/L). On the eighth day of hospitalisation, his muscle strength was restored to normal, and his myoglobin levels decreased to 226.1 ng/mL. He could walk unaided, but his appetite was still altered. After a day of administering hydrocortisone (10 mg) replacement therapy, on the 10th day of hospitalisation his appetite was remarkably increased and he was discharged.
Discussion Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary. This may result from disorders involving the pituitary gland, hypothalamus or surrounding structures. In this case, surgery and radio-surgery treatment led to hypopituitarism. In previous cases wherein patients with diabetes mellitus experienced complications of hypopituitarism, they required little or no insulin and frequently exhibited normal or low levels of glucose even without insulin treatment, known as the Houssay phenomenon.5 In this case, the patient had HHS, a very rare medical condition, with many
Table 1. Laboratory findings on admission. Peripheral blood
Blood chemistry
White blood cell
10,290/mL
Red blood cells Haemoglobin
541 104/mL 14.8 g/dL
Platelets Coagulation PT APTT Fibrinogen PT-INR TT PTA Urine ions 24 h K 24 h Na 24 h Ca
11.3 104/mL 13 s 36 s 334 mg/dl 1.01 18 s 99%
Urinalysis
AST ALT LDH Total protein Albumin Blood urea nitrogen
180.00 IU/L 95.00 IU/L 270.00 IU/L 6.40 g/dL 4.09 g/dL 28.01 mg/dL
Creatinine Glucose Myoglobin Sodium Potassium Chloride Calcium
1.02 mg/dL 574.67 mg/dL >3000 ng/mL 189.00 mEq/L 3.50 mEq/L 141.08 mEq/L 4.46 mEq/L
Gravity pH Protein Occult blood Sugar Ketones Red blood cells 4.40/hpf Serological test HbA1c Arterial blood gas pH PO2 pCO2 HCO3 Base excess
1.005 5.50 1+ 3+ 4+ ( ) 4.40/hpf 9.60% 7.44 72.00 mmHg 45.00 mmHg 30.60 mmol/L 5.20 mmol/L
38.67 mmol/24 h 9.80 mmol/24 h 1.19 mmol/24 h
ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; PT, prothrombin time; APTT, activated partial thromboplastin time; PT-INR, prothrombin time-international normalised ratio; TT, thrombin time; FDP, fibrinogen/fibrin degradation products; PTA, prothrombin activity; HbA1c, haemoglobin A1C.
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
Wang et al.
3
Figure 1. Function of pituitary-target gland axis. Diagram shows the regulation of thyroid, adrenocorticoids and sex hormones in the patient. Downward arrows indicate down-regulation of the hormones. Numbers in parentheses indicate normal ranges of hormone concentrations. TSH, ACTH, LH and FSH are secreted from anterior pituitary gland. FT3: free triiodothyronine; FT4: free thyroxine; TSH: thyroid stimulating hormone; FSH: follicle-stimulating hormone; LH: luteinizing hormone; ACTH: adreno-cortico-tropic-hormone; PRL: Prolactin; E2: estradiol; PROG: progesterone; TESO: testosterone
Figure 2. Patient’s blood chemistry. After fluid resuscitation (0.9% NaCl) and insulin infusion, the patient’s serum sodium and chloride levels gradually decreased, then maintained at stable levels (a, b). His myoglobin levels decreased from over 3000 to 226.1 ng/mL by the seventh day (c). His serum potassium was significantly lower than normal on the second day (2.1 mEq/L), then rose to normal and remained stable (d).
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
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potential causes. First, the man had taken too much dexamethasone over the previous two weeks, which might have caused hyperglycaemia. Second, he had polyuria at a level of over 3000 mL per day. The initiating event in HHS is glycosuria diuresis. Glycosuria impairs the concentrating capacity of the kidneys, further exacerbating water loss. Under normal conditions, the kidneys act as a safety valve to eliminate glucose above a certain threshold and prevent further accumulation. However, decreased intravascular volume or underlying renal disease decreases the glomerular filtration rate, causing the glucose level to increase. The loss of more water than sodium leads to hyperosmolarity. Moreover, because the gravity of his urine was less than 1.005, he might have had complications from diabetes insipidus. Third, it is believed that diabetes complicated with hypopituitarism and its symptoms is aggravated by insulin resistance. The Livingstone group reported that there are interactions between sex steroids and insulin in tissues. At physiological levels, testosterone and oestradiol are thought to be involved in maintaining normal insulin sensitivity.6 Rhabdomyolysis may be defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various nontraumatic causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia.7 HHS is a rare cause of rhabdomyolysis. The exact mechanism of rhabdomyolysis in HHS remains unclear. The electrogenic sodium pump is inhibited by HHS, acidosis, hypernatremia and potassium deficiency, as well as by decrease in intramuscular energy supply due to insulin deficiency. This results in a fall in the transmembrane potential, thereby contributing to the development of rhabdomyolysis.8 Hyperosmolar states may also elevate the intracellular calcium concentration. A persistently high intracellular calcium level may bring about the activation of neutral proteases and subsequent leakage of muscle enzymes. Singhal et al.9 concluded that serum sodium, serum osmolarity and blood glucose are the major determinants for the occurrence of rhabdomyolysis in the diabetic state. According to Gabow et al.,10 hypokalaemia
and hypophosphataemia are important predisposing factors for rhabdomyolysis. In conclusion, we can say that it is very important to make a timely diagnosis of HHS for a patient who has hypopituitarism, and to initiate the standardised treatments for hypopituitarism and HHS. Our report provides useful indications for the treatment of the disease. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician 2005; 71: 1723–1730. 2. MacIsaac RJ, Lee LY, McNeil KJ, et al. Influence of age on the presentation and outcome of acidotic and hyperosmolar diabetic emergencies. Intern Med J 2002; 32: 379–385. 3. Pinies JA, Cairo G, Gaztambide S, et al. Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state. Diabetes Metab 1994; 20: 43–48. 4. Chu CH, Lee JK, Lam HC, et al. Prognostic factors of hyperglycemic hyperosmolar nonketotic state. Chang Gung Med J 2001; 24: 345–351. 5. Hadithi M, Toorians A and Heine R. The Houssay phenomenon, another clue to Sheehan’s syndrome in a diabetic. Diabetes Med 2002; 19: 795. 6. Livingstone C and Collison M. Sex steroids and insulin resistance. Clin Sci (Lond) 2002; 102: 151–166. 7. Gangopadhyay KK and Ryder RE. Nontraumatic rhabdomyolysis: an unusual complication of diabetic hyperosmolar nonketotic (HONK) state. J R Soc Med 2006; 99: 200. 8. Izumi T, Shimizu E, Imakiire T, et al. A successfully treated case of hyperosmolar hyperglycemic state complicated with rhabdomyolysis, acute kidney injury, and ischemic colitis. Intern Med 2010; 49: 2321–2326. 9. Singhal PC, Abramovici M, Ayer S, et al. Determinants of rhabdomyolysis in the diabetic state. Am J Nephrol 1991; 11: 447–450. 10. Gabow PA, Kaehny WD and Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore) 1982; 61: 141–152.
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
Case Report
A successfully treated case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis
Scottish Medical Journal 0(0) 1–4 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933014565586 scm.sagepub.com
Yi-Chen Wang1, Li-Chao Gao1, Hui Xu2, Xiao-Zhang Qu1, Ye Wang1, Xiao-Qian Lou1 and Hui Guo3
Abstract Introduction: This study aimed to report a rare case of hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis. Case presentation: Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. It often leads to hypoglycaemia, but in this case the patient was complicated with hyperosmolar hyperglycaemic state. The patient received prompt medical treatment, which effectively prevented the occurrence of possible acute kidney failure and other complications. Conclusion: This is a complicated and rare case. Our report provides some indications for the timely diagnosis and the standardised treatments for a patient who has hypopituitarism complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis.
Keywords Hyperosmolar hyperglycaemic state, hypopituitarism, rhabdomyolysis
Introduction Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary gland. The condition often leads to hypoglycaemia. Here, we report a case of a 23-year-old Chinese male who was admitted to our hospital in a hyperosmolar hyperglycaemic state (HHS) combined with hypopituitarism and rhabdomyolysis. HHS sometimes induces rhabdomyolysis and temporal acute kidney injury. The mortality rate of HHS ranges from 10% to 50%1 due to the high incidence of coexisting disease. Age (>65 years), degree of hyperosmolarity (>375 mOsm/L),2 hemodynamic instability,3 a low Glasgow coma scale score on admission and precipitation by infection4 are powerful predictors of a fatal outcome. Rhabdomyolysis is defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various non-traumatic
causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia. Therefore, it is crucial to establish a timely diagnosis and standardised treatments.
Case presentation A 23-year-old Chinese man was admitted to our hospital because of drowsiness. Two months prior, he had undergone surgery to remove a germinoma located in the sella region. He also received Gamma-knife radiosurgery after another month. During the previous two 1
Physician, The Second Part of First Hospital, Jilin University, China Researcher, Basic Medical College, Jilin University, China 3 Professor, The Second Part of First Hospital, Jilin University, China 2
Corresponding author: Hui Guo, The Second Part of First Hospital, Jilin University, Changchun 130031, China. Email: [email protected]
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
2
Scottish Medical Journal 0(0)
weeks, he had suffered general fatigue and anorexia. He took dexamethasone (3 mg) for a day as treatment, but his symptoms did not change. After two days, the symptoms became more serious, and he could not move due to lower limb muscle pain and weakness. Five hours before his admission, he became drowsy. On admission, his blood pressure was 130/80 mmHg, his pulse rate was 102 beats/min, his respiratory rate was 33/min and his body temperature was 37.1 C. An oropharyngeal examination revealed an extremely dry oral mucosa. A chest and abdominal examination revealed no abnormalities. Muscle strength of the upper limbs was grade 3, and that of the lower limbs was grade 0. The pathologic reflex was not drawn out. Blood tests revealed severe hyperglycaemia, electrolyte abnormalities, elevated myoglobin, leukocytosis (Table 1) and hypopituitarism (Figure 1). His calculated plasma osmolarity was 427 mOsm/L. On admission, hypopituitarism, HHS and rhabdomyolysis were diagnosed. After fluid resuscitation (0.9% NaCl) and insulin infusion, the patient’s blood sugar levels gradually decreased. By the second day of hospitalisation, his blood sugar levels had decreased from 574 mmol/L to 196 mmol/L, his osmolarity decreased from 427 to 355 mOsm/L and his consciousness was restored; however, his muscle strength had not improved. His myoglobin levels were still over
3000 ng/mL (Figure 2). On the third day of hospitalisation, his muscle strength improved (the upper limbs were grade 5 and the lower limbs were grade 2), he stopped complaining of any muscle pain and osmolarity decreased to normal (314 mOsm/L). On the eighth day of hospitalisation, his muscle strength was restored to normal, and his myoglobin levels decreased to 226.1 ng/mL. He could walk unaided, but his appetite was still altered. After a day of administering hydrocortisone (10 mg) replacement therapy, on the 10th day of hospitalisation his appetite was remarkably increased and he was discharged.
Discussion Hypopituitarism is a clinical syndrome in which there is a deficiency in hormone production by the pituitary. This may result from disorders involving the pituitary gland, hypothalamus or surrounding structures. In this case, surgery and radio-surgery treatment led to hypopituitarism. In previous cases wherein patients with diabetes mellitus experienced complications of hypopituitarism, they required little or no insulin and frequently exhibited normal or low levels of glucose even without insulin treatment, known as the Houssay phenomenon.5 In this case, the patient had HHS, a very rare medical condition, with many
Table 1. Laboratory findings on admission. Peripheral blood
Blood chemistry
White blood cell
10,290/mL
Red blood cells Haemoglobin
541 104/mL 14.8 g/dL
Platelets Coagulation PT APTT Fibrinogen PT-INR TT PTA Urine ions 24 h K 24 h Na 24 h Ca
11.3 104/mL 13 s 36 s 334 mg/dl 1.01 18 s 99%
Urinalysis
AST ALT LDH Total protein Albumin Blood urea nitrogen
180.00 IU/L 95.00 IU/L 270.00 IU/L 6.40 g/dL 4.09 g/dL 28.01 mg/dL
Creatinine Glucose Myoglobin Sodium Potassium Chloride Calcium
1.02 mg/dL 574.67 mg/dL >3000 ng/mL 189.00 mEq/L 3.50 mEq/L 141.08 mEq/L 4.46 mEq/L
Gravity pH Protein Occult blood Sugar Ketones Red blood cells 4.40/hpf Serological test HbA1c Arterial blood gas pH PO2 pCO2 HCO3 Base excess
1.005 5.50 1+ 3+ 4+ ( ) 4.40/hpf 9.60% 7.44 72.00 mmHg 45.00 mmHg 30.60 mmol/L 5.20 mmol/L
38.67 mmol/24 h 9.80 mmol/24 h 1.19 mmol/24 h
ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; PT, prothrombin time; APTT, activated partial thromboplastin time; PT-INR, prothrombin time-international normalised ratio; TT, thrombin time; FDP, fibrinogen/fibrin degradation products; PTA, prothrombin activity; HbA1c, haemoglobin A1C.
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
Wang et al.
3
Figure 1. Function of pituitary-target gland axis. Diagram shows the regulation of thyroid, adrenocorticoids and sex hormones in the patient. Downward arrows indicate down-regulation of the hormones. Numbers in parentheses indicate normal ranges of hormone concentrations. TSH, ACTH, LH and FSH are secreted from anterior pituitary gland. FT3: free triiodothyronine; FT4: free thyroxine; TSH: thyroid stimulating hormone; FSH: follicle-stimulating hormone; LH: luteinizing hormone; ACTH: adreno-cortico-tropic-hormone; PRL: Prolactin; E2: estradiol; PROG: progesterone; TESO: testosterone
Figure 2. Patient’s blood chemistry. After fluid resuscitation (0.9% NaCl) and insulin infusion, the patient’s serum sodium and chloride levels gradually decreased, then maintained at stable levels (a, b). His myoglobin levels decreased from over 3000 to 226.1 ng/mL by the seventh day (c). His serum potassium was significantly lower than normal on the second day (2.1 mEq/L), then rose to normal and remained stable (d).
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
4
Scottish Medical Journal 0(0)
potential causes. First, the man had taken too much dexamethasone over the previous two weeks, which might have caused hyperglycaemia. Second, he had polyuria at a level of over 3000 mL per day. The initiating event in HHS is glycosuria diuresis. Glycosuria impairs the concentrating capacity of the kidneys, further exacerbating water loss. Under normal conditions, the kidneys act as a safety valve to eliminate glucose above a certain threshold and prevent further accumulation. However, decreased intravascular volume or underlying renal disease decreases the glomerular filtration rate, causing the glucose level to increase. The loss of more water than sodium leads to hyperosmolarity. Moreover, because the gravity of his urine was less than 1.005, he might have had complications from diabetes insipidus. Third, it is believed that diabetes complicated with hypopituitarism and its symptoms is aggravated by insulin resistance. The Livingstone group reported that there are interactions between sex steroids and insulin in tissues. At physiological levels, testosterone and oestradiol are thought to be involved in maintaining normal insulin sensitivity.6 Rhabdomyolysis may be defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of muscle cell contents into the plasma. Apart from crush injuries, various nontraumatic causes may also be implicated such as alcohol, drug overdose, hypokalaemia, hypophosphataemia and hypothermia.7 HHS is a rare cause of rhabdomyolysis. The exact mechanism of rhabdomyolysis in HHS remains unclear. The electrogenic sodium pump is inhibited by HHS, acidosis, hypernatremia and potassium deficiency, as well as by decrease in intramuscular energy supply due to insulin deficiency. This results in a fall in the transmembrane potential, thereby contributing to the development of rhabdomyolysis.8 Hyperosmolar states may also elevate the intracellular calcium concentration. A persistently high intracellular calcium level may bring about the activation of neutral proteases and subsequent leakage of muscle enzymes. Singhal et al.9 concluded that serum sodium, serum osmolarity and blood glucose are the major determinants for the occurrence of rhabdomyolysis in the diabetic state. According to Gabow et al.,10 hypokalaemia
and hypophosphataemia are important predisposing factors for rhabdomyolysis. In conclusion, we can say that it is very important to make a timely diagnosis of HHS for a patient who has hypopituitarism, and to initiate the standardised treatments for hypopituitarism and HHS. Our report provides useful indications for the treatment of the disease. Declaration of conflicting interests None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician 2005; 71: 1723–1730. 2. MacIsaac RJ, Lee LY, McNeil KJ, et al. Influence of age on the presentation and outcome of acidotic and hyperosmolar diabetic emergencies. Intern Med J 2002; 32: 379–385. 3. Pinies JA, Cairo G, Gaztambide S, et al. Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state. Diabetes Metab 1994; 20: 43–48. 4. Chu CH, Lee JK, Lam HC, et al. Prognostic factors of hyperglycemic hyperosmolar nonketotic state. Chang Gung Med J 2001; 24: 345–351. 5. Hadithi M, Toorians A and Heine R. The Houssay phenomenon, another clue to Sheehan’s syndrome in a diabetic. Diabetes Med 2002; 19: 795. 6. Livingstone C and Collison M. Sex steroids and insulin resistance. Clin Sci (Lond) 2002; 102: 151–166. 7. Gangopadhyay KK and Ryder RE. Nontraumatic rhabdomyolysis: an unusual complication of diabetic hyperosmolar nonketotic (HONK) state. J R Soc Med 2006; 99: 200. 8. Izumi T, Shimizu E, Imakiire T, et al. A successfully treated case of hyperosmolar hyperglycemic state complicated with rhabdomyolysis, acute kidney injury, and ischemic colitis. Intern Med 2010; 49: 2321–2326. 9. Singhal PC, Abramovici M, Ayer S, et al. Determinants of rhabdomyolysis in the diabetic state. Am J Nephrol 1991; 11: 447–450. 10. Gabow PA, Kaehny WD and Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore) 1982; 61: 141–152.
Downloaded from scm.sagepub.com at University of Otago Library on November 2, 2015
