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Type 2 diabetes with recurrent osteoporotic fractures, or Cushings syndrome?

Medrech

ISSN No. 2394-3971

Original Research Article


TYPE 2 DIABETES WITH RECURRENT OSTEOPOROTIC FRACTURES, OR
CUSHINGS SYNDROME?
Blertina Dyrmishi*; Taulant Olldashi; Prof Asc Thanas Fureraj3; Prof Asc Majlinda Ikonomi4;
Dorina Ylli5; Prof Agron Ylli6

1.Endocrinologist, department of Internal Medicine, Hygeia Hospital, Tirana, Albania,


2.Surgeon, Hygeia Hospital, Tirana, Albania, 3. Endocrinologist, UHC Mother Theresa, Tirana,
Albania, 4. Pathologist, Hygeia Hospital, Tirana, Albania, 5. Endocrinologist, UHC Mother
Theresa, Tirana, Albania, 6. Endocrinologist, Head of Endocrine Department, UHC Mother
Theresa, Tirana, Albania

ABSTRACT:
Aim: Presentation of a case with secondary osteoporosis and compressive fracture in Cushings
syndrome.
Clinical Case: A 41 years old male was admitted to our hospital with inability to move the legs,
severe back pain, which started 6 months ago. The patient was bedridden for a month due to
severe pain. He was under treatment for hepatitis B and had been for more than three years under
treatment for diabetes. One year ago he was treated for deep venous thrombosis.
Laboratory data: Loss of circadian rhythm of cortisol, increased free urinary cortisol level, lack
of suppression of cortisol after 1 mg dexamethasone test. DXA: Osteoporosis. Spine x-Ray:
recurrent osteoporotic compressive thoracic fracture. Abdominal MRI showed left adrenal
nodular mass with dimensions 2.5 x 3.3 cm. The patient underwent surgery: Left adrenalectomy.
12 months after surgery the patient continuing the treatment with hydrocortisone, alendronate,
calcium and vitamin D, normal values of blood glucose and blood pressure without treatment
and in DXA an improvement of the bone density was noticed.
Keywords: Cushings syndrome; secondary osteoporosis; osteoporotic compressive fracture
from excessive levels of systemic
Introduction:
Cushings disease was first described in
glucocorticoids (2). Cushings syndrome is
associated with increased risks of
1932 from the American neurosurgeon
Harvey Cushing (1). The incidence of
cardiovascular, metabolic, and respiratory
Cushings syndrome is not exact, because of
disorders,
psychiatric
complication,
the undiagnosed cases with slight
osteoporosis and infection, which all lead to
hypercortisolemia and the lack of data about
increased rates of morbidity and mortality
iatrogenic Cushing (1). Cushings syndrome
(2). The classic features of Cushings
is a serious condition associated with high
syndrome include central obesity, moon
face, and hirsutism (3). Cushings syndrome
rates of morbidity and mortality that result
Dyrmishi B. et al., Med. Res. Chron., 2015, 3 (1), 110-114

Medico Research Chronicles, 2016

Submitted on: February 2016


Accepted on: February 2016
For Correspondence
Email ID:

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Type 2 diabetes with recurrent osteoporotic fractures, or Cushings syndrome?

is an important cause of secondary diabetes,


hypertension, venous thromboembolism and
osteoporosis (4). Patient with Cushing
syndrome have a high incidence of
osteoporotic fractures. 30-50% of patients
experience fractures, particularity in the
vertebral body. The prevalence of
osteoporosis in patients with Cushings
syndrome is 50% (5).
CLINICAL CASE:
A 41 years old male was admitted to our
hospital with inability to move the legs,

severe back pain, which started 6 months


ago, bedridden for a month due to severe
pain. The upper and lower limbs were thin;
he presented a moon face, high blood
pressure and high glucose values. He had
normal motor and sensor function of leg. He
was under treatment for hepatitis B and had
been for more than three years under
treatment for diabetes. One year ago he was
treated for deep venous thrombosis. The
diagnosis of Cushings syndrome was
suspected.

Table no 1: Laboratory data.


On
Variable
Admission
Normal range
Sodium
142
136-145 mEq/L
Potassium
4.4
3.5-5.1 mEq/L
Phosphate
2.8
2.5-4.9 mg/dl
Total calcium
8.6
8.5-10.1 mg/dl
Chloride
105
98-107 mEq/L
Magnesium
2.1
1.8-2.4 mg/dl
ALT
68
14-59 U/L
AST
29
15-37 U/L
GGT
67
5-85 U/L
ALP
165
50 -136 U/L
BUN
32
15-39 mg/dl
Creatinine
0.6
0.6-1. 1 mg/dl
Glucose
190
70-106 mg/dl
WBC
14.1 x 10
4.0-10 x 10/l
RBC
5.4 x 10
4.2-5.4 x 10/l
HBG
15.8
12-16 g/dl
Eos
0%
0-5 %
PLT
443 x 10
150 - 350 x 10
TSH
0.61
0.35-4.78 mUi/ml
Cortisol 8 :00
23.9
3.2-22 g/dl
ACTH
12.4
10-60 pg/ml
CLU
730
20.9 - 290 g/24 h
Chromogranin
A
231
< 200 ng/ml
Vitamin D
23
> 30 pg/ml
PTH
25.4
10-65 pg/mL
HbA1c
7%
4 -6 %
HBsAg
> 1000
<1

Dyrmishi B. et al., Med. Res. Chron., 2015, 3 (1), 110-114

Medico Research Chronicles, 2016

Laboratory data:

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Type 2 diabetes with recurrent osteoporotic fractures, or Cushings syndrome?

The laboratory examinations showed a loss of the circadian rhythm of cortisol, increased level of
free urinary cortisol. A one mg over night dexamethasone suppression test was performed; the
plasma cortisol was not suppressed and abdominal magnetic resonance imaging (MRI) was
requested, it showed left adrenal nodular mass with dimensions 2.5 x 3.3 cm.

30
25
20
15

plasma cortisol values


ng/dl

10
5
0
8:00

Lumbar and left femur dual X-ray


absorptiometry (DXA) Z-score values were
low, consistent with osteoporosis: Lumbar
Z-score -3.3 (From -4.4 in L2 to -1.7 in L1),

0:00

4:00

Graphs No 1:24 Hours Cortisol Values

and femoral Z-score -2.6. Spine x-Ray:


recurrent osteoporotic compressive thoracic
fracture.

Figure no 2: Spine x-Ray and DXA

Dyrmishi B. et al., Med. Res. Chron., 2015, 3 (1), 110-114

Medico Research Chronicles, 2016

Figure no 1: MRI showed left adrenal


mass 2.5 x 3.3 cm

12:00 16:00 20:00

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Type 2 diabetes with recurrent osteoporotic fractures, or Cushings syndrome?

hydrocortisone the first days after the


surgery and after that with hydrocortisone
30
mg/day,
calcium,
vitamin
D
supplementation and alendronate for
osteoporosis, since first line treatment of
osteoporosis with teriparatide was not
disponible at that moment.

Figure no 3: Microscopic image of adrenal adenoma


Six month after surgery, the physical
deep vein thrombosis and lately compressive
symptoms and signs of Cushings syndrome
fracture of the thoracic spine. The
disappeared. Blood pressure and glucose
occurrence not at the same time of all the
values without treatment returned within the
typical clinical signs makes the early
normal range. Rapid ACTH stimulation test
diagnosing of Cushings syndrome often
was performed six months and twelve
difficult (6). The physicians should take
months after surgery. The test did not show
carefully the personal history of the patient
changes of cortisol values 60 minutes after
and the signs occurred in different times
the 250 g cosyntropin injection (cortisol
must be connected with each other in order
1.2 ng/dl before test, 1.0 ng/dl 30 minutes
to make the right diagnosing. Our case had
after test and 1.1 ng/dl 60 minutes after test).
been under treatment for three years for
The patient continued the treatment with
diabetes mellitus, he had a history of deep
hydrocortisone, alendronate, calcium and
vein thrombosis an year ago, but a
vitamin D. 12 months after the treatment
Cushings syndrome was never suspected
with bisphosphonates an improvement of the
until he was admitted to our hospital with
bone density was noticed.
inability to move the legs, severe back pain.
The prevalence of osteoporosis in patients
Discussions:
Our case had the classical clinic appearance
with Cushings syndrome is 50% in some
of Cushings syndrome with the occurrence
studies (5). Patient with Cushings syndrome
of secondary diabetes, high blood pressure,
have a high incidence of osteoporotic

Dyrmishi B. et al., Med. Res. Chron., 2015, 3 (1), 110-114

Medico Research Chronicles, 2016

Since the clinical, laboratory and image


dates confirmed the diagnosis of Cushings
syndrome, the patient underwent surgery,
left
adrenalectomy.
Immune
histopathological
examination
of
adrenocortical adenoma confirmed the
diagnosis of Cushings syndrome. The
patient was treated with intravenous

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Type 2 diabetes with recurrent osteoporotic fractures, or Cushings syndrome?

4- Colao A, Petersenn S, Newell Price J,


et al. Pasireotide B2305 Study Group. A
12 month phase 3 study of pasireotide
in Cushings disease. N Engl J Med
2012; 366 (10): 914-924
5- Ju Young Han, Jungjin Lee et al. A case
of Cushing Syndrome Diagnosed by
Recurent Pathologic Fractures in a
Young Woman. J Bone metab. 2012. 19
(2): 153-158.
6- Arnaldi G, Angeli A, Atkinson AB, et al.
Diagnosis
and
complications
of
Cushings syndrome: a consensus
statement. J Clin Endocrinol Metab
2003; 88 (12): 5593-5602.
7- Pereira RM, Carvalho JF, Paula AP, and
al. Guidelies for the prevention and
treatment of glucocortikoid-induced
osteoporosis. Rev Bras Reumatol 2012;
52 (4): 580-593.
8- Rehman Q, Lang TF, Arnaud CD, et al.
Daily treatment with parathyroid
hormone is associate with an increase in
vertebral
cross-sectional
area
in
postmenopausal
women
with
glucocorticoid-induced osteoporosis. Int
2003; 14(1): 77-81.
9- Saag KG, Shane E, Boonen S, et al.
Teriparatide
or
alendronate
in
glucocorticoid-induced osteoporosis. N
Engl J Med 2007; 357: 2028-2039
Medico Research Chronicles, 2016

fractures, where mainly the trabecular bones


are affected. 30-50% of patients experience
fracture, particularly in the vertebral body.
Although the bone mineral density is
improved after the treatment of Cushings
syndrome, it preferred to start alongside the
osteoporosis treatment. In our case the
patient had also compressive fractures and in
this case the chosen treatment would be
teriparatide (8,9), but since its application
was impossible, the treatment with
bisphosphonate drug was started.
Conclusions:
The diagnosis of Cushings syndrome
sometimes is difficult to suspect. Since
osteoporosis and fractures occur frequently
in Cushings syndrome, the diagnosis should
be suspected in young patients and the
treatment of Cushings syndrome is
necessary.
References:
1- Larsen, Kronenberg, Melmed, Polonsky.
Williams test book of endocrinology,
2003.pp 508-509.
2- Newell-Price J, Bertagna X, Grossman
AB, Nieman LK. Cushings syndrome.
Lancet 2006; 13(5); 367:1605-1617.
3- Nieman LK, Biller Mb, Findling JW et
al. The diagnosis of Cushings
syndrome: an Endocrine Society Clinical
Practice Guidelines. J Clin Endocrinol
Metab 2008: 93(5): 1526-1540.

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