ENDOCRINE EMERGENCIES IN PICU

KARNATAKA PEDICON 2006

Dr. Vaman Khadilkar,

Pediatric Endocrinologist, Pune

Introduction:
Endocrine emergencies in a child often manifest in an occult manner and resemble more
commonly seen acute conditions such as sepsis or CNS infection or renal failure. A high index of
suspicion is necessary to recognize an endocrine emergency. Once suspected appropriate tests
can be arranged to reach the diagnosis. In this chapter an overwiew of when to suspect an
endocrine emergency, which tests to order and how to manage the child in ICU is discussed.
Long term diagnosis, management and outcome of specific condition is not discussed as it is
beyond the scope of this text.

When to suspect Pediatric Endocrine problem in ICU setting

A high index of suspicion is necessary to diagnose endocrine problem in a sick child admitted to
PICU. It is possible to overlook a probable endocrine pathology when all the attention is diverted
to the management of other problems such as sepsis or shock.

Pointers to the diagnosis of endocrine disease are:

Laboratory indicators

 Electrolyte imbalance
o Hyponatremia associated with hyperkalemia
o Hypernatremia
o Hypocalcemia associated with hyperphosphatemia
o Hypercalcemia

 Glucose imbalance
o Hypoglycemia
o Hyperglycemia
o Ketone bodies in the urine and serum

 Acid base disturbance

o Metabolic acidosis with hyponatremia, hyperkalemia
o Hypoglycemia with metabolic aciodisis
o Alkalosis with hypocalcemia

Clinical indicators

1. Short stature
2. Inappropriate tall stature
3. Obesity
 4. Hypertension
5. Goiter
6. Genital abnormalities
7. Hyper-pigmentation or hypopigmented patches
8. Acanthosis nigricans
9. Midline craniofacial defects
10. Polyuria despite dehydration
11. Urine output well over 2-3 liters per day

Some Select Endocrine Emergencies:

Diabetic ketoacidosis

Introduction: Diabetes in childhood in increasingly reported from the western world and also
from India. As many as 50% of children with diabetes present with DKA as their first
presentation. Diabetic ketoacidosis needs early recognition and prompt management in an ICU
setup to prevent morbidity and mortality. When diagnosed early and treated in a systematic
manner DKA has a good prognosis. Pathophysiology: There is relative or absolute insulin
deficiency and elevated levels of stress hormones with increased serum osmolarity due to
hyperglycemia and ketosis. Acidosis shifts the oxygen dissociation curve to the left leading to
tissue hypoxia and shock. Osmotic diuresis leads to dehydration and sodium and potassium is
lost in the urine. Hypoinsulinemia leads to ketosis and lactic acidosis. Some degree of cerebral
oedema is always present due to hyperosmolirity, acidosis and electrolyte imbalance.

Management: The principles of management of DKA in a child are prompt recognition of the
problem, adequate but cautious fluid replacement, provision of insulin, treatment of associated
infections, careful monitoring of glucose, electrolytes, vitals and blood gases in an intensive care
unit and prevention of complications in particular cerebral edema. During the management of
DKA first priority is to replenish fluids. The initial fluid should be an isotonic solution like
normal saline. Subsequent fluid can be normal or half normal dextrose saline or ringer lactate
solution. It is important not to infuse hypotonic fluid as it increases the chance of cerebral edema.
The speed of fluid replenishment is a critical factor in determining cerebral edema and hence
overzealous fluid replacement in too short a time is best avoided. Insulin infusion is the gold
standard of insulin delivery. Subcutaneous insulin should be avoided because acidosis leads to
cutaneous vasoconstriction and insulin does not get absorbed in a reliable manner from
subcutaneous sites. Studies have shown that there is not much benefit of giving intravenous
bolus of insulin at the beginning of therapy either. Since insulin deficiency is the primary
pathology in type 1 diabetes and particularly in DKA, it is best not to titrate insulin infusion with
the blood glucose level but to titrate the amount of glucose that is infused so that adequate
amount of insulin and substrate (glucose) is provided to the child. It is also necessary to saturate
insulin-binding sites on the tubing by running about 50 ml of insulin infusion through the tubing
before starting the infusate. It is important not to stop insulin infusion early based on the glucose
value alone. It must ideally be continued for about 12-24 hours after acidosis has resolved and
ketone bodies have disappeared. If the blood glucose continues to fall, glucose concentration of
the infusate can be increased from 5% to 10% mixed with half normal saline instead of normal
saline so that osmolality of the infusate is maintained. With adequate insulin and glucose, lactate
gets converted into bicarbonate in liver thus resolving acidosis. Measurement of ketone bodies in
the urine can be tricky. Ketodiastics, which are routinely used for measurement of ketones in the
urine do not measure betahydroxybutarate but are sensitive to acetone and acetoacetic acid. In
the initial phase of DKA as there is more betahydroxybutarate in the urine the test may be
weakly positive and as the patient improves and more of acetone and acetoacetic acid starts
coming out in the urine the test becomes strongly positive giving a false impression of
deterioration of the patient's condition. There is no role for routine use of bicarbonate in DKA.
Metabolic acidosis, which is often profound, should not be treated with bicarbonate as it usually
settles down with adequate fluid and insulin therapy. When fluid and insulin are provided
ketones and lactic acid are metabolized to bicarbonate thus correcting the acidosis. Bicarbonate
on the other hand worsens cerebral acidosis, leads to hypernatremia and hypokalemia and this
leads to poor oxygen delivery to the tissues due to shift of the oxygen dissociation curve.
Cerebral edema is the most dangerous complication of DKA and is often precipitated by
overzealous fluid replacement. Therefore slow rehydration over 36 hours is recommended.
Isotonic and not hypotonic fluids should be used for rehydration. Other complications include
electrolyte imbalances and hypoglycemia, these can be prevented by careful monitoring.

Fluids

Volume: Total fluids replaced is a combination of maintenance + deficit + ongoing losses.

Maintenance: 1500 ml/m2/day at all ages
Deficit: 5-10% generally 10% is assumed as the clinical signs of dehydration are less
pronounced.
Ongoing losses: Urine output + loss in the vomitus and gastric aspirate

Type:Calculate the total fluid for a period of 36 hours. Initial fluid should be normal saline or
ringer lactate. In the first 1-2 hrs the fluid is given at a rate of 10-20 mls per kg to stabilize the
circulation. When the blood sugar drops to 200 mg%, add 5% dextrose to the fluid so that risk of
hypoglycemia is reduced. Total fluid replacement should be divided as 1/3 in the first 6 hours,
next third in the next 12 hours and next third in the next 18 hours (Total 36 hours)

Electrolytes

Potassium:Total body potassium is always depleted. Potassium replacement should be started

after the initial hour (after the rapid fluid correction is over). It can be started even earlier if the
initial potassium is lower than 3 mmol/l. In places where urgent electrolytes are not available
Electrocardiogram should be used to monitor T wave abnormalities. Amount of potassium
administration should be 20-30 mmol/l of fluids infused. Ideally potassium should be replaced as
half phosphate and half chloride, but this is a problem in India as phosphate containing infusate
is not available.

Bicarbonate: Only when the serum pH <7.0, there is symptomatic hyperkalemia and poor
myocardial contractility and insulin resistance, bicarbonate may be used with caution only as
slow infusate and never as bolus. WHEN GIVEN IT SHOULD BE GIVEN AS A SLOW IV
INFUSION OVER A PERIOD OF 2-4 HOURS and NEVER AS BOLUS Half correction is
recommended.
Insulin therapy: Infusion is made as 50 units of short or ultrashort acting insulin (e.g. regular
insulin or Lispro) in 500 ml of normal saline and initial 50-60 ml is run off through the tubing to
saturate binding sites. Infusion is then given through an infusion pump. INSULIN INFUSION
MUST BE CONTINUED UNTIL ACIDOSIS RESOLVES and NOT when sugars are
controlled. Half hour before the infusion is discontinued subcutaneous regular insulin is given in
a dose of 0.25 iu/kg. The dose of insulin infusion is 0.1 unit/kg/hr.

Monitoring Schedule:

Initial investigations: Glucose, electrolytes, blood gas, creatinine, serum osmolarity, blood
count and culture. Subsequent schedule: Glucose: 1-2 hourly Electrolytes: 1-2 hourly, ABG: At
2,4,6,12 and 24 hours Consciousness: (Using a scale like Glasgow coma) should be monitored 2
hourly

Complications of fluid and electrolyte therapy:

Brain edema
Hypokalemia
Hypocalcemia
Hypoglycemia
Alkalosis

How to suspect brain edema ? Deterioration in the level of consciousness in a child who was
improving, bradycardia and other signs of raised ICT and convulsions point to the possibility of
brain edema.

Prevention of brain edema:

Slow rehydration over 36-48 hours
Use of isotonic solutions for rehydration
Avoid hypotonic or hypertonic solutions (such as bicarbonate bolus)
Early detection by vigilance

Treatment of Developing Brain Edema

Manitol 20% i.v. in a dose of 0.5 to 1 gm/kg may be repeated every 15 minutes if necessary
Reduce rate of fluid input
Nurse the child in bed-up position
Assisted ventilation

Hypoglycemiaiii
Introduction: Hypoglycemia is a common problem encountered in PICU and NICU.
Hypoglycemia is diagnosed when blood glucose drops to below 40 mg./dl (2.2 mmol/l) in a
neonate and to 50 mg/dl (2.7 mmol/l) thereafter. Hypoglycemia is not a diagnosis by itself but
is a manifestation of a variety of metabolic and endocrine disorders. It can be symptomatic
or asymptomatic. The serum or plasma level of blood glucose tends to be 12-15 percent higher
than the whole blood glucose. Contrary to the general belief asymptomatic hypoglycemia is as
dangerous as symptomatic variety and should be investigated and treated with the same
seriousness as the symptomatic form.

Etiolgoy:
Etiology can broadly be divided into those caused by substrate deficiency such as malnutrition,
malabsorption, poor hepatic stores etc, decreased production or release of glucose such as defects
of the counter-regulatory hormone secretion and hereditary metabolic defects and finally
excessive utilization such as hyperinsulinemia.

Clinical features:
Clinical features of hypoglycemia are usually non-specific especially in the neonatal period. In
neonate these include, lethargy, jitteriness, apnea, cyanosis, respiratory distress, poor feeding,
hypothermia, myoclonic jerks or convulsions. In older children adrenergic hormone release in
response to hypoglycemia dominate the symptoms in the form of sweating, tremors, hunger,
pallor, tachycardia and shakiness followed by symptoms of neuroglycopenia in the form of
sleepiness, lethargy, visual difficulty, ataxia, behavioral abnormalities and frank convulsions or
unconsciousness. In cases where hypoglycemia is prolonged and severe, permanent brain
damage results.

Investigations:
The most important investigation for the etiological diagnosis is the collection of 'critical
sample'. Blood sample taken during the episode of hypoglycemia is the critical sample. The next
immediate urine sample should also be analyzed. Following tests should be done on urine and
blood.

Blood tests:

 Glucose
 Acetone
 Cortisol
 Growth hormone
 Insulin
 Free fatty acids
 Lactate and Pyruvate

Urine tests:

 Ketone bodies
 Reducing substance
 Amino acids and organic acids

Approach to diagnosis of hypoglycemia:

Broadly speaking hypoglycemia can be divided into 2 categories: Ketotic and Non Ketotic
depepending upon the presence or absence of ketones in the serum and or urine. Non-Ketotic
hypoglycemia is usually caused by either hyperinsulinism or by â oxidation defects such as
carnitine deficiency. Ketotic hypoglycemia can be due to many more causes. Presence of
hepatomegaly in Ketotic hypoglycemia suggests glycogen storage disease (such as glucose 6
phosphatase deficiency) and other metabolic defects and specific enzyme assays are necessary
for the diagnosis. In Ketotic hypoglycemia without hepatomegaly endocrine deficiencies such as
growth hormone deficiency, adrenal failure and hypothyroidism should be suspected.

Treatment:
Immediate management consists of intravenous bolus of 10% dextrose in a dose of 2-2.5ml per
kg slowly after collecting the 'critical sample'. Blood glucose is checked after 5 minutes and if
there is no improvement in the blood glucose concentration, another bolus of 10% dextrose in
given. The concentration of dextrose should not exceed 10%. Twenty five (25%) dextrose
SHOULD NOT BE USED. Hypertonic solutions like this can cause permanent brain damage and
must be avoided.
The bolus is then followed by intravenous infusion of dextrose that will give a glucose
concentration of 4-8 mg/kg/minute. In cases of refractory hypoglycemia, Hydrocortisone can be
used in a dose of 5 mg/kg/24 hours in 8 hourly devided doses. Intramuscular growth hormone in
a dose of 1 mg(3 iu) can be used in unresponsive cases.
Af and if the critical sample has not been useful in making the diagnosis, a hypoglycemia
provocation by starvation under controlled environment can be undertaken by admitting the child
to special endocrine units.

Hypocalcemia
Hypocalcemia, like hypoglycemia is more common in neonatal period and infancy although it
can occur at any time of life. The symptoms of hypocalcemia are caused by disturbance in
neuromuscular excitability due to reduction in the extracellular calcium pool.

Hypocalcemia in the neonatal period:

Hypocalcemia which is common in the neonatal period is mainly seen two forms: early and late.
Early neonatal hypocalcemia is typically seen in sick, low birth weight and preterm neonates
usually before 72 hours of life. It is caused by transient inability of the parathyroid glands to
respond to dropping calcium. Other causes such as transfusion of blood containing high
phosphate also contribute to this variety of hypocalcemia.
Hypocalcemia beyond the neonatal period: This is usually seen after first 2 weeks of life in
apparently healthy newborn and is associated with hyperphosphatemia. This is caused by
transient relative hypoparathyroidism

Investigations:
Total and ionic Calcium, serum protein
In places where ionic calcium is not available serum proteins are very important to get a correct
idea about the true calcium. The correction used for 1 gm of albumin is 0.8 mg of calcium. e.g if
albumin is less by 1 gm, add 0.8 mg to the measured calcium value.
Phosphosus and alkaline phosphatase
Parathyroid hormone
Vitamin D level (25 OH D3 is usually sufficient)
Wrist and chest x rays are useful for the diagnosis of rickets, Hyperparathyroidism, renal
osteodystrophy etc.
Management:

In crisis 1-2 ml/kg of 10% cal gluconate is given by intravenous infusion over 5 min under
cardiac monitoring. This is then followed by i.v. calcium infusion in a dose of 50-75 mg/kg/day
of elemental calcium. The dose is reduce to ½ after 24 hrs. Oral calcium can be given in the dose
of 100 to 200 mg per kg day in the newborn. Oral calcium and phosphate should preferably be
given in a proportion of 2:1 for better absorption.
In neonates and children with transient or permanent hypoparathyroidism, 1-25 (OH2) vitamin
D3 may be necessary to improve the calcium levels rapidly. In cases of resistant hypocalcemia,
after the sample is collected for calcium, phosphorus, alkaline phosphatase, PTH and Vitamin D,
1-25 (OH2) vitamin D3 may be given in a dose of 0.25 to 4 mcg in 3-4 divided doses orally.
There is however no role of 1-25 (OH2) vitamin D3 in routine management of hypocalcemia.
Typically in hypoparathyroid patients the hypocalcemia is very severe, phosphate is significantly
elevated and hypocalcemia is resistant to routine management of calcium infusion and regular
vitamin D3 supplements.

Addisonian crisis
Adrenal failure is usually gradual but manifests acutely due a precipitating cause such as
infection, stress or trauma. Irrespective of the etiology of adrenal cause the manifestations of
acute adrenal failure are similar.

Clinical features
After an initial period of failure to thrive, patient may suddenly present with vomiting, lethargy,
anorexia, and dehydration. Circulatory collapse may be fatal. The patient suddenly becomes
cyanotic, the skin is cold, and the pulse is weak and rapid. The blood pressure falls, and
respirations are rapid and labored. In the absence of immediate and intensive therapy, the course
can be fatal. The presenting manifestations may be those of hypoglycemia, particularly in the
neonate with congenital adrenal hyperplasia. Patients with adrenocortical insufficiency are
deficient in gluconeogenic substrates; the hypoglycemia may therefore be associated with ketosis
and confused with ketotic hypoglycemia.
Clinical signs such as hyperpigmentation or hypopigmented patches, ambiguous genitalia,
asthenic appearance, muscular hypertrophy (in X linked 21p deletions), midline craniofacial
defects and achalasia, alacrimia (in case of triple A syndrome) should increase the suspicion of
adrenal insufficiency in an acutely ill child.

Laboratory: Typically the Sodium is low and potassium is high. Neonates can tolerated a very
high level of potassium and levels upto 9-10 mmol/l can also be tolerated for a short period of
time. Hypoglycemia and metabolic acidosis are common accompaniments. In an older child, X
ray of the chest may show a small heart suggesting hypovolemia. Plain x-ray of the abdomen
may show calcified adrenals in case of adrenal hemorrhage. CT scan and MRI may be helpful.
Measuring cortisol, ACTH, 17 hydroxyprogesterone, Aldoseterone and renin levels during crisis
are useful in making the definitive diagnosis.

Management: injection hydrocortisone in a dose of 5 mg per kg in 6 hourly doses should be

given after collecting the blood for endocrine assays. Even in children with salt wasting crisis
this dose of hydrocortisone will prevent salt loss due to its mineralocorticoid action in high dose.
Patient can be maintained later on a dose of 12-15 mg/m2/day of hydrocortisone and 100 mcg
per m2 of fludrocortisone (Both available in India by Samarth Pharma ltd). After the patient is
out of ICU a detailed investigation into the etiology of adrenal pathology should be undertaken.

Thyroid stormiv :
Thyroid storm is rare in children. It is an acute, potentially life threatening syndrome of thyroid
hormone excess which is often precipitated by stress such as infection or surgery. This represents
decompensated state of hyperthyroidism that results from increased serum levels of free thyroid
hormone however free thyroid hormone levels can not differentiate between thyroid storm and
hyperthyroidism. There is hypercatabolic and hyperdynamic state characterized by
vasodilatation, increased cardiac output, heart failure, arrythmia, diarrhoea, nausea, vomiting,
abdominal pain, hyperthermia and CNS disturbances.

Differential diagnosis of this condition includes sepsis, malignant hyperthermia,

pheochromocytoma, cocain intoxication and pancreatitis. Laboratory evaluation shows grossly
suppressed TSH ( Third or fourth generation assay is necessary), elevated total and free thyroid
hormones, hyperglycemia, increased alkaline phosphatase, increased liver transaminase and
leukocytosis.

Early diagnosis with high index of suspicion is necessary as mortality can be high in this
condition. Aggressive supportive care and treatment of underlying precicpitating cause is
necessary. Treatment consists of controlling temperature with acetaminophen, fluids and cooling
the body. Salicylates are avoided as they displace thyroid hormone from binding proteins.
Propylthyouracil (PTU) in the dose of 5-10 mg per kg per day is the medication of choice.
Lugols idodine which gives total idodine of 135 mg/ml is used in a dose of 0.1 to 0.3 ml (10-40
mg) three times daily diluted with water or milk. It should be given 2 hours after PTU to avoid
worsening of symptoms. Beta blockers such as propranolol are important to control adrenergic
symptoms. Corticosteroids such as hydrocortisone and dexamethasone are useful as they prevent
the conversion of t4 to t3 and may also prevent adrenal crisis in a patient with co existing
undiagnosed hypoadrenalism.

Pheochromocytomav :
Hypertensive crisis in PICU can be caused by Pheochromocytoma. The treatment consists of
removal of the tumour and exquist blood control is manadatroy before opertion can be
undertaken. Hypertension should be controlled prepoperative with á adrenergic blockers such as
phenoxybenzamine in a dose of 0.5 - 1 mg/kg/12 hours or prazocin in a dose of 0.1-0.4
mg/kg/day in 6 hourly divided doses. Sodium nitroprusside can also be used as infusion at a rate
of 1 mcg/kg/min. â blockers such as propranolol may be used to control tachycardia and
arrhythmia after á blockade is established. Use of beta blockers without prior use of alpha
blockers can lead to severe hypertension. Alpha blockers are used 2 weeks prior to surgery to
minimize the risk of hypertensive crisis that may occur during intubation, induction of anesthesia
and tumour handling. Hypovolemia should be corrected with volume expanders post operatively
and by replacing fluid losses.

Blood pressure should be monitored closely during surgery and hypertension should be treated
with sodium nitroprusside or phentolamine. Tachycardia and arrhythmia is controlled by use of
beta blockers. If both adrenal glands are removed hydrocortisone should be used. Blood pressure
may not return to normal until 2-3 days of surgery. Hypoglycemia should be prevented by close
glucose monitoring.

Perioperative management of Diabetes Insipidusvi,vii,viii,ix:

Brain tumour surgery especially in the area of pituitary and hypothalamius can lead to diabetes
insipidus in the perioperative and postoperative period. The commonest tumour in pediatric
practice that is associated with this complication is craniopharyngioma.

As cortisol has a permissive role on water clearance, DI often manifests only after adequate
cortisol replacement is done. DI can be a temporary phenomenon; hence administration of
DDAVP postoperatively should be monitored with extreme caution for the fear of water
intoxication. DI usually manifests within 6-12 hours of surgery, lasts for 1-2 days and then
recovers for 1-2 days only to return in the majority of patients in 3-5 days. The transient recovery
is due to lysis and release of antidiuretic hormone (ADH) stored in neuronal cells containing
ADH. This triphasic response needs effective management by meticulous assessment of fluid
input and output, and regular monitoring of electrolytes. In the immediate postoperative period,
hourly urine output should not exceed 100-150 ml/m2. The urine output can be controlled by
using DDAVP. In some patients, due to injury to the hypothalamus a permanent state of adipsic
DI leading to chronic hypernatremia and hyperosmolality may develop, which is difficult to
manage. As the patient has no thirst, a fixed schedule of replacement, and a flexible schedule for
DDAVP varying according to the environmental temperature in needed.

Syndrome of Inappropriate ADH:

In children who are acutely unwell with conditions such as pneumonia or meningitis, syndrome
of inappropriate ADH is observed. This leads to excessive water reabsorption for the distal
convoluted tubule leading to hyponatremia, hypocalemia and swelling. Water intoxication is
seen clinicallly as edema, altered sensorium and even convulsions. In contrast to adrenal failure,
here the sodium is low but the potassium is not high. The urine output is inappropriately low for
the clinically edematous child. Diagnosis is made by combined assessment of urinary and serum
osmolarity. Serum osmolarity is usually below 265 mmol/l and the urine osmolarity is high at the
same time, usually above 800 mmol/l.

SIADH is treated by fluid restriciton to about two third of the maintainance amount and other
supportive care. If brain oedema is severe and fluid overload is very significant frusemide can be
used. Hypertonic saline can be used to correct hyponatrmia. When used it should be used over 2-
3 hours as infusion.

Cerebral salt wasting x:

In acute and rarely chronic brain injury an increase in urinary sodium excretion is seen with
increased urinary volume. The urinary loss of sodium is often>100 meq/l. It could be because of
increased secretion of atrial natriuretic peptide. It differs from SIADH by increased urinary
volume, dehydration and increased urinary loss of sodium. ADH levels are low in cerebral salt
wasting while they are high in SIADH.

Management consists of volume by volume replacment of fluids with normal saline and if
needed 3% saline. Oral supplementation of sodium chloride will be needed. Some researchers
have successfully used mineralocorticoids to treat this condition although it may not always be
effective.

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