Respiratory failure in Cushing´s disease
Ketoconazole treatment was started at a dose of
200 mg twice daily. The dose was increased to
keep urinary cortisol level within the upper limits
of normal, reaching doses up to 1200 mg/day. As
soon as clinical improvement was observed the
dose was reduced to 800 mg/day. Three months
later, respiratory and muscular symptoms started
to ameliorate and respiratory function tests im-
proved significantly (Tables 1 and 2). Six months
later she underwent transsphenoidal surgery with
removal of a pituitary microadenoma. She devel-
oped post-operative hypocortisolism and was
treated with hydrocortisone for four months. Since
then, the patient has remained well with no fur-
ther treatment.
polysomnogram did not prove OSAS. On the other
hand, clinical estimation of pulmonary embolism
probability was low, as our patient referred a 4-
month history of progressive dyspnea without pleu-
ritic pain and there were no risk factors for venous
tromboembolism (12). Arterial blood gas analysis
showed a ventilatory failure (low PaO2 and high
PaCO2), with a normal alveolar-arterial oxygen gra-
dient. Most patients with no prior cardiac or pul-
monary disease, like our case, who have pulmonary
embolism, have hypoxemia or hypocapnia and an
increased alveolar-arterial oxygen gradient (13).
Treatment of hypercortisolism improves muscle
strength and increases muscle mass (2, 14). We ob-
served an important clinical improvement as well
as amelioration of respiratory function tests a few
months after beginning therapy with ketoconazole.
Although in most cases of Cushing’s disease doses
of 600 to 800 mg/day are enough to bring cortisol
production back to normal (15, 16), we used high-
er doses to maintain normal urinary cortisol levels.
In spite of the high doses used, we did not observe
any side-effects other than an asintomatic transient
liver dysfunction manifested by minor increased
hepatocellular enzymes that did not result in dis-
continuation of the drug.
DISCUSSION
In contrast to many myopathies secondary to he-
reditary, inflammatory, or toxic disorders which are
commonly associated with respiratory failure, Cu-
shing’s myopathy has not been associated with res-
piratory failure as a presenting symptom. Although
the most common finding is a proximal lower-limb
girdle myopathy, some patients experience upper-
limb-girdle weakness (1, 5). Cushing’s syndrome
usually causes profound atrophy of skeletal muscle
without inducing tissue necrosis. Histological find-
ings show type 2 fiber atrophy as the most promi-
nent abnormality although it is not specific (6, 7).
Muscle enzymes are usually normal (8). EMG find-
ings are characterized by an increased number of
low amplitude, short duration, at times poliphasic,
motor unit potentials (9).
In conclusion, we must bear in mind that severe re-
strictive respiratory failure may be secondary only to
Cushing’s myopathy. The measurement of inspira-
tory and expiratory pressures and EMG are useful in
the differential diagnosis with other causes of ven-
tilatory failure. Medical or surgical treatment of the
hypercortisolism can solve the respiratory insuffi-
ciency although it may take months.
In our patient, although proximal lower and upper-
limb girdle myopathy was present, symptoms of
respiratory failure were predominant. Spirometry
and plethysmography showed a restrictive ventila-
tory failure, which was strongly suggestive of neu-
romuscular disease. The profound decrease in MIP
and MEP, the EMG and muscle biopsy results con-
firmed the myopathic disease with involvement of
respiratory muscles.
REFERENCES
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Glucocorticoid action and the clinical features of
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We ruled out other causes of respiratory insufficien-
cy as sleep apnea syndrome or pulmonary embolism.
Type 2 diabetes and Cushing’s syndrome, have been
associated with OSAS in the context of obesity (10).
In addition, central and obstructive apnea have been
described in a small group of patients with Type 1
diabetes and autonomic neuropathy. Autonomic
neuropathy as the sole manifestation of diabetic neu-
ropathy is extremely rare and some degree of in-
volvement of somatic fibers is always present (11). In
our patient sensorimotor polyneuropathy or auto-
nomic involvement were excluded. In addition,
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