Key-words: Acute limb ischemia - diabetic ketoacidosis - pituitary apoplexy - supraventricular
tachycardia - uncontrolled diabetes
Introduction
Pituitary apoplexy (PA) is a rare life-threatening condition arising from acute ischemia
or hemorrhage of the pituitary gland.[[1 ]],[[2 ]] PA commonly occurs in the presence of pituitary adenomas, especially in nonfunctioning
adenomas.[[1 ]] The incidence of PA in adenomas is underreported, as many cases may remain “clinically
silent.” Common presenting symptoms of PA include headache, nausea-vomiting, visual
impairment, ophthalmoplegia, altered sensorium, and panhypopituitarism. Precipitating
factors described for PA include hypertension, diabetes mellitus, pregnancy, radiation,
etc.[[2 ]] Relative rarity and wide spectrum of nonspecific symptoms seen in PA, makes it
a diagnostic challenge.
Diabetic ketoacidosis (DKA) is a common but serious complication of uncontrolled diabetes
mellitus. Underlying pathophysiologic cause for DKA is severe insulin deficiency.
Hence, DKA is more common in type-1 diabetes mellitus, either as an initial manifestation
or resulting from subsequently increased insulin requirement.[[3 ]] The spectrum of clinical presentation seen in DKA is nonspecific and vary greatly
depending on the severity of the condition. Common symptoms in DKA include polyuria,
polydipsia, nausea-vomiting, lethargy, breathlessness, altered sensorium. Supraventricular
tachycardia (SVT) and acute limb ischemia (ALI) are extremely rare complications seen
in DKA.[[4 ]],[[5 ]] There are only a couple of published case reports on association between DKA and
PA. Herein, we report the case of a young woman, known case of pituitary adenoma,
presenting as DKA – complicated with SVT and ALI, secondary to PA.
Case Report
A 20-year-old woman was rushed to the emergency room with complaints of progressively
worsening headache, lethargy, breathlessness, and altered sensorium for 3 days. Due
to the severity of symptoms, she was brought in a wheelchair. On arrival, she was
found to be tachypnoeic, tachycardic (heart rate 180 beats/min), and drowsy. She had
a Glasgow comma scale [GCS] of E3M6V4, with no gross focal deficits (quick assessment).
Electrocardiogram revealed an underlying SVT as shown in [[Figure 1 ]]. Emergency cardiology opinion was taken, and she was immediately started on injection
Adenosine for cardioversion, after unsuccessful carotid massage. She also sequentially
required injection diltiazem and injection amiodarone to get cardioverted. Meanwhile,
arterial blood gas analysis revealed severe metabolic acidosis with the following
readings: pH 7.083, pCO2 17.9 mmHg, pO2 47 mmHg, and HCO3 5.3 mmol/L. Random blood
glucose was 746 mg/dl, and urine was strongly positive for ketone bodies. She was
diagnosed to have DKA. Endocrinology team was consulted, and she was started on insulin
infusion along with hydration. She received corrective measures for her metabolic
derangements.
Figure 1: A 12-lead electrocardiogram taken at the time of arrival in the emergency room. Electrocardiogram
shows a heart rate of 180 beats/min, regular RR intervals, narrow QRS complexes with
few p-waves buried within, and pseudo s waves (red arrow mark). These findings are
highly suggestive of atrioventricular node re-entrant tachycardia
Within 1 h of being in the emergency room, the patient showed significant neurological
deterioration. Repeat detailed neurological assessment revealed GCS of E2M5V1, with
gross left-sided hemiparesis (Grade 2/5) and right ophthalmoplegia. In view of her
rapidly worsening neurological status and fragile cardiopulmonary condition, she was
intubated – ventilated. Simultaneously, she was found to have rapidly worsening renal
function leading to acute renal shutdown. After correction of intracellular compartment
fluid deficit, she was started on infusion of inotropes and diuretics. Emergency computed
tomography (CT) brain (plain) revealed heterogeneous, mixed density, ill-defined lesion
in right suprasellar-parasellar region measuring 4.6 cm × 3.8 cm in the largest dimension
– suggestive of pituitary adenoma with apoplexy [[Figure 2 ]]. She was then transferred from the emergency room to intensive care unit (ICU)
for further management.
Figure 2: Emergency computed tomography brain (plain) images (a and b) showing heterogenous,
mixed density, ill-defined lesion in right suprasellar-parasellar region
On detailed inquiry regarding past medical history, parents revealed that the patient
had menstrual irregularities and episodes of severe headache about 2 years ago. She
had consulted an outside physician and had undergone an magnetic resonance imaging
(MRI) brain imaging as shown in [[Figure 3 ]]. No hormonal profiling or visual testing was done. The physician had put her on
hormone-stabilizing medications (no records available) for few months. This relieved
her symptoms to significant extent. She had no history of diabetes, though her parents
say she had complaints of polyuria and polydipsia in the last 2–3 months which was
not evaluated.
Figure 3: Contrast-enhanced magnetic resonance imaging brain done 2 years ago at an outside
hospital. Coronal (a) and sagittal (b) sections show a lobulated, heterogeneously
enhancing mass lesion, with areas of nonenhancing cystic/necrotic degeneration, located
in sellar-parasellar-suprasellar region. Sellar enlargement and right cavernous sinus
invasion seen
Considering the emergency CT brain findings and the past medical history, the patient's
hormonal profiling was done. Her cortisol (8 pm) on arrival to the hospital was 31.8
μg/dl (range 5–25 μg/dl); prolactin was 193 ng/ml (range 0–20 ng/ml); human growth
hormone was 30.5 ng/ml (range 0–7 ng/ml); insulin-like growth factor 1 was 231 ng/ml
(range 117–323 ng/ml); and free T3 was 4.55 pg/ml (range 1.4–4.4 pg/ml), free T4 was
2.88 ng/dl (range 0.8–2 ng/dl), thyroid stimulating hormone was 0.84 μIU/ml (range
0.3–5 μIU/ml). She was started on injection hydrocortisone supplementation in view
of apoplectic status. Owing to the poor general condition, emergency neurosurgical
intervention was put on hold.
Within 2–4 h of admission to the ICU, the patient's right leg was found to be cyanosed
and cold. Peripheral pulsations in the right leg were not felt from femoral level
and below. Emergency Doppler study revealed thrombosis and complete obstruction of
right lower limb vasculature, starting from common femoral artery and below, suggestive
of ALI. Due to her then fragile status and extensive nature of the clot (no arterial
flow restoration was possible as the veins were also blocked), she was not taken up
for emergency vascular interventional procedure. Instead, she was started on anticoagulant
therapy (low molecular weight heparin) and observed. On day 2 of admission, glycated
hemoglobin done was 15.4%-suggestive of undiagnosed diabetic status.
The patient's overall condition started improving from day 4 of admission. DKA was
corrected, and acute kidney injury resolved. Her GCS improved to E4M6Vet, with spontaneous
movement of right upper limb. She had residual left hemiparesis (Grade 2/5) and right
complete ophthalmoplegia. She got extubated on day 6 of admission. In view of the
gangrenous changes that had developed in the right leg, right hip disarticulation
was done on day 9 [[Figure 4 ]]. An MRI brain (Plain and contrast) was done at this point as patient's kidney function
normalized, and further neurosurgical plan of action was to be decided [[Figure 5 ]]. In view of the large size and significant mass effect of the lesion, patient underwent
right frontotemporal craniotomy and radical decompression of the sellar-suprasellar
lesion under image guidance. She withstood the procedure well. Histopathological examination
confirmed the lesion to be a nonfunctioning pituitary adenoma with apoplexy. [[Figure 6 ]] shows the microscopic images of the tumor. Despite the hardships of left hemiparesis
and right hip disarticulation, patient is recovering well. She is in neurorehabilitation
phase. On insulin therapy for newfound diabetic status. Anti-Glutamic acid decarboxylase
and other antibody testing are planned for defining the type of diabetes in the subsequent
outpatient follow-ups.
Figure 4: Portable X-ray pelvis and both hips-anteroposterior view showing postdisarticulation
status of right hip
Figure 5: Contrast-enhanced magnetic resonance imaging brain done during the present hospitalization.
Lobulated dumbbell shaped mass lesion is seen in sellar-parasellar-suprasellar region.
Lesion appears mixed hypo- and hyper-intense on T1 weighted images (a), heterogeneously
hyperintense on T2 weighted images (b) with tiny diffuse cystic spaces at the margin
of central necrotic area, and heterogeneous contrast enhancement (c and d). Size of
the lesion appears significantly increased compared to previous magnetic resonance
imaging brain in Figure 3. Findings suggestive of apoplexy in the pituitary macroadenoma
Figure 6: Photomicrographs of the surgical specimen. H and E staining showing monomorphic cell
proliferation with round nuclei and chromophobe cytoplasm, indicating pituitary adenoma
(red arrow), as well as intra-tumoral hemorrhage/necrosis (black arrow). Immunohistochemistry
analysis done for various hormones show negative results, confirming nonfunctional
status of the adenoma
Discussion
PA has a wide range of presentations, and hence, remains a diagnostic challenge. Common
reported pathophysiological mechanisms leading to PA in adenomas are: (1) reduced
blood supply due to tumor overgrowth or compression of vascular structures or other
systemic factors; (2) sudden surge in blood flow due to conditions like malignant
hypertension; (3) pituitary gland stimulation in pregnancy or hormonal therapy such
as bromocriptine; and (4) anticoagulant states.[[2 ]] Although diabetes induced microvasculopathy has been theoretically incriminated
in the pathophysiology of PA, available clinical data does not support the same.[[2 ]] DKA, on the other hand, has been reported to precipitate apoplectic episodes.[[2 ]] There are only two case reports available of PA presenting as a DKA [[Table 1 ]]. Jiang et al.[[6 ]] reported an apoplectic GH-secreting adenoma with DKA, while Camara-Lemarroy et
al.[[4 ]] reported a nonadenomatous PA with DKA.
Table 1: List of available case reports on the rare clinical association between pituitary
apoplexy, diabetic ketoacidosis, and acute limb ischemia
SVT is a broad terminology used to describe arrhythmias above or involving atrioventricular
node (AVN).[[11 ]] SVTs are a rare, reported complication of DKA. Factors precipitating SVTs in DKA
could be either the severe acidosis or the accompanying electrolyte abnormalities
such as hypomagnesemia or hypophosphatemia.[[7 ]],[[8 ]],[[9 ]] Our case had AVN re-entrant tachycardia precipitated possibly by severe acidosis,
as the magnesium (2 mg/dl) and phosphorus (2.9 mg/dl) levels were normal. Vagal maneuvers
and adenosine (AVN blocker) are the mainstay of treatment for SVTs in emergency conditions.[[11 ]] Additional usage of antiarrhythmic medications is required in refractory cases.
There are only three case reports available of DKA complicated by SVTs in young patients
with type 1 diabetes [[Table 1 ]].
DKA has been reported to lead to a prothrombotic state, resulting rarely in devastating
arterial or venous thrombotic episodes.[[5 ]],[[10 ]] Many postulated underlying mechanisms include dehydration and resulting hyperosmolarity/hypercoagulation
state, activation of endothelium, increased platelet aggregation, and impaired fibrinolysis.
Various reported vascular thrombotic conditions involved iliac artery, femoral artery,
brachial artery, or mesenteric artery. ALI resulting from such a thrombotic episode
is seldom seen [[Table 1 ]].[[5 ]],[[10 ]]
Our case report documents an amalgamation of the above-mentioned rare clinical associations.
It highlights the worst clinical possibilities that can occur in a patient with neglected
pituitary adenoma and an uncontrolled diabetes mellitus (diagnosed/undiagnosed). A
watchful eye for the unfolding clinical scenario and an appropriate early treatment
can salvage even the rarest and gravest of the cases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
