Reminder of important clinical lesson
CASE REPORT
Department of Endocrinology,
Dr RML Hospital, New Delhi,
India
Correspondence to
Dr Bindu Kulshreshtha,
drbindu25@yahoo.co.uk
Accepted 23 December 2015
To cite: Dharmshaktu P,
Aggarwal A, Dutta D, et al.
BMJ Case Rep Published
online: [ please include Day
Month Year] doi:10.1136/
bcr-2015-212803
Bilateral femoral head avascular necrosis with
a very low dose of oral corticosteroid used for
panhypopituitarism
Pramila Dharmshaktu, Anshita Aggarwal, Deep Dutta, Bindu Kulshreshtha
SUMMARY
Avascular necrosis (AVN) of the femoral head is a rare
complication related to glucocorticoid administration and
traditionally has been associated with high doses and/or
prolonged therapy. Occurrence of osteonecrosis with a
physiological replacement dose of glucocorticoids has
not been reported previously. We report a 38-year-old
man with non-secreting pituitary adenoma who
developed bilateral AVN while on a very small dose of
oral prednisolone for secondary adrenal insufficiency
after surgery for pituitary adenoma. The patient was
switched to hydrocortisone. Zolindronic acid was
administered and the patient underwent bilateral core
decompressive surgery resulting in a reduction of hip
pain and improvement. When last evaluated, 2 years
after diagnosis of AVN, the patient was functionally
independent, and was able to do his routine activities
with mild pain. The report intends to highlight the
occurrence of AVN of the femur even with a very small
dose of prednisolone used for treatment of
panhypopituitarism. Glucocorticoids may have to be
continued in the lowest possible dose using the most
physiological preparation such as hydrocortisone when
stoppage is not possible.
BACKGROUND
Avascular necrosis (AVN) is also known as aseptic
necrosis or osteonecrosis. It occurs in approxi-
mately 3–40% of patients receiving corticosteroids
with the most common site of involvement being
the femoral head, resulting in severe morbidity.1 2
This adverse complication is believed to be the
result of limited blood supply to this area with
death of bone tissue in the femoral head, leading to
pain, limited mobility, fractures and in about 80%
of untreated cases collapse of the femoral head
requiring surgical management.1 3 4 We present the
occurrence of AVN in a patient on replacement
doses of prednisolone for panhypopituitarism fol-
lowing surgery for non-functional pituitary
adenoma.
CASE PRESENTATION
A 38-year-old man with persistent headache and
visual disturbances for 3 months was diagnosed to
have non-functioning pituitary adenoma of
26×22×12 mm size on MRI of the pituitary.
Automated perimetry revealed bitemporal hemian-
opia. Surgical resection of the tumour through
trans-sphenoidal pituitary surgery resulted in
improvement in vision and resolution of bitemporal
Dharmshaktu P, et al. BMJ Case Rep 2016. doi:10.1136/bcr-2015-212803
hemianopia. The patient had also received oral
dexamethasone at a dose of 2 mg/day for less than
a month before surgery. He did not follow-up for
2 months either in the surgery or endocrine unit.
Two months after surgery, he presented with per-
sistent fatigue, hypotension, anorexia and weight
loss.
INVESTIGATIONS
On investigative workup, morning cortisol
was<4 mg/dL. Biochemical investigations were sig-
nificant for associated secondary hypothyroidism
and hypogonadism (table 1). Symptoms improved
with initiation of oral prednisolone which
was given at a dose of 7.5 mg and later reduced to
5 mg daily. Levothyroxine was initiated 2 weeks
later, initially at 50 μg/day and later increased to
100 mg/day. Injectable testosterone was also
initiated at a dose of 100 mg 4 weekly as intramus-
cular injections.
Two years after the initiation of hormone
replacement, the patient noticed insidious onset
pain in the medial aspect of bilateral thighs that
gradually worsened with progressive difficulty in
walking leading to limping. X-ray of the bilateral
hip and MRI of soft tissue hips revealed bilateral
AVN of the femoral head (right>left) (figures 1
and 2).
TREATMENT
Oral prednisone was replaced by hydrocortisone as
it is believed to be the more physiological prepar-
ation of glucocorticoids at a lower dose of 10 mg
in the morning (7:00) and 5 mg in the late after-
noon (15:00) with counselling for increasing the
dose during stress. The patient underwent core
Table 1 Hormonal analysis of patient at the time of
presentation
Tests (normal range) Reports
Free T3 (2–4.4 pg/mL) 2.3 mg/mL
Free T4 (0.6–2.2 ng/dL) 0.8 ng/mL
TSH (0.5–5 mIU/L) 2.1 mIU/L
LH (1.8–7.8 mIU/L) 1.4 mIU/mL
FSH (1.55–9.7 mIU/L) 3.2 mIU/mL
Testosterone (4.5–28.2 nmol/L) 0.48 nmol/L
Serum cortisol <4 mg/dL
FSH, follicle-stimulating hormone; LH, luteinising hormone; TSH,
thyroid-stimulating hormone.
1
 Reminder of important clinical lesson
Figure 1 Anteroposterior view of the pelvis showing a flattening of
the outer portion of the right femoral head from avascular necrosis
(arrow), with adjacent joint space narrowing.
decompression surgery, immobilisation and zolindronic acid
5 mg administration along with calcium and vitamin D
supplementation.
OUTCOME AND FOLLOW-UP
The patient reported significant improvement in pain. When last
evaluated, 2 years after diagnosis of AVN, the patient was func-
tionally independent, and was able to do his daily activities with
mild pain without analgesics. On further follow-up, he contin-
ued to require a low dose of oral hydrocortisone at a dose of
5 mg/day.
Figure 2 MRI of the bilateral hip showing avascular necrosis of femoral heads with the right side affected more than the left side.
2 Dharmshaktu P, et al. BMJ Case Rep 2016. doi:10.1136/bcr-2015-212803
DISCUSSION
AVN is one of the devastating complications of glucocorticoid
therapy occurring in up to 40% of patients.1 The association
between glucocorticoid use and osteonecrosis was first described
in patients with a renal transplant who were on immunosuppres-
sion as part of the transplant regimen.1 5 Causes of AVN apart
from trauma include conditions associated with hypercoagulable
states, systemic lupus erythematosus, acute lymphoblastic leu-
kaemia, alcoholism and organ transplantation.5 These condi-
tions put the patient at higher risk for developing AVN prior to
the initiation of glucocorticoids. Most patients with AVN are
incapacitated and may eventually require hip replacement.
Corticosteroids affect almost every body system and its long-
term use is associated with various well-established side effects,
including AVN.6 7 Corticosteroids are also given as replacement
therapy as our patient with hypopituitarism. The mechanism of
steroid-induced AVN is due to a complex interplay and imbal-
ance of bone resorption and formation, impairment of vascula-
ture within bone and apoptosis.4 5
Powell et al8 reviewed 66 cases of steroid-induced AVN and
found that the most commonly associated administered route
included intravenous steroids followed by oral and rarely intra-
muscular, intra-articular injections and inhaled steroids.
Karkoulias et al9 reported aseptic femoral head necrosis in a
patient receiving long courses of inhaled and intranasal corticos-
teroids. The occurrence of AVN after steroid use appears to be
dose related. A majority of the studies have shown an increased
risk of AVN in patients receiving >20 mg/day of prednisone.
A meta-analysis of 22 studies conducted by Felson and
Anderson10 suggested a 4.6-fold increase in incidence of AVN
with every 10 mg/day increase in prednisone therapy in the first
6 months of corticosteroid therapy.10 Patton et al11 also noted

that the mean linear trend of higher daily prednisolone dose
was also statistically significant for the development of osteo-
necrosis. However, Dimant et al12 failed to find a correlation
between peak dose, duration or cumulative dose of steroid and
osteonecrosis.
Most cases of AVN due to oral prednisolone have been with
doses ranging from 10 to 200 mg/day over a prolonged period
ranging from 14 days to 20 years. We could come across only
two cases of steroid-induced osteonecrosis where lower doses
had been used. O’Brien and Mack13 reported AVN of the
femoral head with oral prednisolone 5 mg/day over a prolonged
duration of 10 years. However, this patient also received
intra-articular cortisone injection. Another case was reported by
Spencer et al14 where AVN of the femoral head occurred after
10 years of oral prednisone at 4 mg/day. This patient had also
received intravenous methylprednisolone injection previously.
As compared to these two patients, our patient developed AVN
of the femoral head over a period of only 2 years. He also
received supraphysiological doses of steroids for a short dur-
ation almost 2 years prior to the occurrence of AVN. It is diffi-
cult to say whether it was the cumulative doses of steroids that
precipitated AVN in this particular case. Another unusual obser-
vation in our patient was bilateral involvement of femoral
heads. Anecdotal case reports of steroid-induced bilateral
AVN have been reported.8 15 Havel et al15also reported
steroid-induced bilateral osteonecrosis of lateral femoral epicon-
dyles with oral steroids.
The occurrence of osteonecrosis with such a low dose of cor-
ticosteroid was surprising. Tokuhara et al16 examined the rela-
tionship between osteonecrosis and steroid dose in white
rabbits and they observed that low levels of steroid metabolising
hepatic activity may increase responsiveness to steroids and
further risk of steroid-induced osteonecrosis even with low
steroid dose.
Hip replacement was not considered in our patient in view of
improvement with conservative management, zolindronic acid
Learning points
▸ Any patient with hip pain even on a replacement dose of
glucocorticoid should be evaluated to rule out avascular
necrosis (AVN).
▸ Stoppage of glucocorticoids may not always be possible.
▸ In such situations, glucocorticoids need to be continued in
the lowest possible dose using the most physiological
preparation, viz hydrocortisone.
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Dharmshaktu P, et al. BMJ Case Rep 2016. doi:10.1136/bcr-2015-212803
Reminder of important clinical lesson
and core decompression surgery. Bisphosphonates (alendronate)
have been shown in two different studies to be helpful in delay-
ing collapse of the femoral head and hence delaying the need
for hip replacement.17
This report intends to highlight the occurrence of AVN of the
femur even with a very small dose of glucocorticoid used for
treatment of secondary hypocortisolism.
Acknowledgements The authors would like to thank the patient for his
cooperation and pray for his good health.
Contributors PD and AA have clinically worked up the patient under the guidance
of DD and BK. PD has written the case report under the guidance of BK and DD.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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