Endocrinology

Table of Contents

1. Introduction
2. Endocrine System
3. Disorders of Water Balance
4. Growth Disorders
5. Gonad Disorders
6. Adrenal Gland Disorders
7. Pancreas Disorders
   1. Diabetes Mellitus
   2. Diabetic ketoacidosis
   3. Hypoglycemia
   4. Quickchecks
8. Thyroid disorders
9. Parathyroid Disorders
10. Multiple Endocrine Neoplasia (MEN)

Hypoglycemia

Hypoglycemia occurs when the body's glucose level (blood sugar) is too low. Glucose is the predominant energy source for cells. In order for the brain to survive, it requires a continuous supply of glucose. Hypoglycemia occurs as a result of the body releasing too much insulin into the blood stream and the body's glucose being used up too quickly.

The rate of glucose turnover is 8 mg/kg/minute in newborns, 6-8 mg/kg/min in children ; 4-6 mg/kg/min in adolescents and about 2-4 mg/kg/min in adults. Infants have smaller glycogen reserves and their stores are depleted sooner. Therefore, infants and children are more likely to develop hypoglycemia than adults. Hypoglycemia occurs most commonly in newborns.

Hypoglycemia also commonly occurs in people with diabetes mellitus either due to their being over insulinized, too little food, or too much exercise. It can also be caused by factitious hypoglycemia, drug ingestion, alcohol, pancreatic tumors (insulinomas and other beta cell disorders), non-beta cell tumors, sepsis, inborn errors of metabolism, liver disease or after gastric bypass surgery

Hypoglycemia can be overt, nonspecific or subtle . This diagnosis maybe difficult to make especially in the neonate and in infancy. There are discrepancies in the diagnostic criteria for various ages; however, most agree that if the blood glucose is less than 40 mg/dl, this is considered hypoglycemic.

There are many causes of hypoglycemia and the causes vary according to the age group.

Signs and symptoms of hypoglycemia:

In newborns, signs of hypoglycemia include cyanosis, poor feeding, apnea, irritability, apathy, limpness, apathy or seizures. These signs are very non-specific and are indistinguishable from sepsis. In newborns, infants, children and adults, symptoms might include tremors, irritability, lethargy, cyanosis, apnea, tachypnea, and eating difficulties. In older children and adults, moderately severe hypoglycemia might mimic mania, psychosis, drug or alcohol intoxication.

Causes

Causes may vary, according to the age group.

PERMANENT AND/OR RECURRENT HYPOGLYCEMIA

• Hyperinsulinemia. The most common cause of persistent hypoglycemia in infants and young children is B-cell dysfunction. In the face of hypoglycemia (glucose less than 40 mg/dl), the insulin level should be less than 5 μU/ml. If the insulin level is greater than 10 μU/ml, further diagnostic evaluation is warranted. A glucagon stimulation test can be both diagnostic and therapeutic in making the diagnosis of hyperinsulinism. After a dose of glucagon, the blood sugar will increase to greater than 40 mg/dl above the basal. The differential diagnosis is nesidioblastosis, β-cell adenoma, β-cell hyperplasia. To distinguish these entities, a combination of CT Scan, ultrasound are required.
• Syndromes associated with endocrine deficiency
  • Beckwith-Wiedemann Syndrome. Syndrome of macroglossia, viseromegaly, and omphalocele. In these infants, islet cell hyperplasia has been demonstrated. Hyperinsulinism and hypoglycemia are usually self-limited. The etiology is an abnormality of a region of the short arm of chromosome 11. The abnormality is of paternal origin, with affected individuals either having duplication or paternal disomy for this region with the loss of maternal chromosome contribution.
  • septo -optic dysplasia
  • mid-line brain defects (cleft lip/palate)
  • anencephaly
• Clinical manifestations of Beckwith Wiedeman Syndrome include umbilical hernia, increased birth weight and postnatal gigantism, earlobe fissures and grooves, craniofacial anomalies, enlarged liver, kidneys and other organs. A significant number of patients have somatic asymmetry. The syndrome is associated with a number of malignancies such as Wilms's tumors, hepatoblastoma, adrenocortical carcinoma and rhabdomyosarcoma. Persistent hypoglycemia occurs frequently in the neonatal period especially in the first few days of life. Hypoglycemia should be recognized and treated as soon as possible.
• Pituitary insufficiency - microphallus
• Adrenal insufficiency due to Addison's Disease. Can be associated with hyperpigmentation, hypoparathyroidism, chronic mucocutaneous moniliasis or other endocrinopathies. Adrenoleukodystrophy should also be ruled out.
• Congenital glucagon deficiency
• Inborn errors of metabolism
• Defects in amino acid metabolism - methylmalonic aciduria
• Defects in gluconeogenesis - glycogen storage disease, glucose-6-phosphate deficiency, hereditary fructose intolerance, galactose 1-phosphate aldolase deficiency
• Defects in Fatty acid oxidation- carnitine deficiency, carnitine acyl transferase deficiency, HMG CoA Lyase deficiency or short, medium or long chain acyl CoA dehydrogenease deficiency.

TRANSIENT HYPOGLYCEMIA

• Infant of the diabetic mother. Infants are at risk for hypoglycemia if they are born to mother with gestational diabetes or diabetes mellitus . During pregnancy, metabolic changes result in beta cell hypertrophy with increased insulin secretion. Insulin does not cross the placenta. Therefore, in order for the fetus to metabolize maternal substrates, it must use its own Insulin production. This metabolic environment primes the fetal islets. Shortly after birth, serum glucose is utilized by hyperinsulinism. Because of hyperinsulinism, the newborn is unable to mobilize glucose and adequate fuel sources. Other contributing factors may be suppression of glucagon secretion
• Maternal drug treatment - can occur after the use of terbutaline, oral hypoglycemic agents, or propranolol. This may be the result of increased pancreatic insulin secretion in response to the glucose concentration
• Preterm AGA infants. Small for gestational infants have functionally immature gluconeogenic and glycogenolytic enzyme systems and limited glycogen stores.
• Neonates experiencing perinatal stress, hypoxia, cold-stressed neonates, neonatal sepsis, after umbilical artery catheter placement, following maternal ethanol ingestion, or after exchange transfusion are also at risk for hypoglycemia. Hypoglycemia is a result of decreased substrate availability, decreased rate of gluconeogenesis or free fatty elevation.
• Ketotic hypoglycemia is the most common form of hypoglycemia beyond infancy. It usually occurs between the ages of 6 months and 5 years of age. Hypoglycemia typically occurs after illness in the face of decreased oral intake. The classic history is that the child was difficult to arouse in the morning, or was comatose or had a convulsion after being ill with limited food intake the night before. These children may have a history of small for gestational age or transient neonatal hypoglycemia. Glycogen storage disease (particularly type 1) and disorders of gluconeogenesis such as fructose-1,6-diphosphate deficiency are commonly associated with hypoglycemia. The diagnosis is confirmed by elevated ketones, ketonuria, suppressed insulin levels and elevated counter regulatory hormones. To avoid further episodes it is recommended that the child have frequent feedings of high protein, high carbohydrate meals during illness.
• Factitious hypoglycemia. A form of Munchausen by proxy. Either the care giver or the child, administers exogeneous insulin or oral hypoglycemic agents. These children present with hypoglycemia. However, in the face of hypoglycemia, the insulin level is elevated with a low/suppressed C-Peptide.
• Disorders of substrate deficiency Maple Syrup Urine disease, glycogen storage disease, or gluconeogenesis (fructose-1,6-diphosphatase deficiency, pyruvate carboxylase deficiency or phosphoenolpyruvate deficiency) or fatty acid oxidation (carnitine deficiency) can also cause hypoglycemia. These are associated with hepatomegaly, metabolic acidosis. Hypoglycemia has also been associated with congenital hypopuitarism,or adrenal insufficiency.

Making the diagnosis:

Take a good history. Was the infant cold or stressed? Is sepsis suspected?

Perform a thorough physical examination. Are there dysmorphic features, proturbent tongue, umbilical hernia? Is hepatomegaly present? Is there evidence of microphallus or prolonged jaundiced? Was the infant SGA, AGA or LGA? Is a cleft lip or palate present to suggest hypopituitarism?

Draw blood for cortisol, growth hormone, insulin, glucose, thyroid test, lactate, pyruvate.

Note: draw blood samples for the appropriate test prior to administrating glucose or allowing the patient to eat.

Obtain urine for glucose and ketones. Based on these test results, further definitive test may need to be done such as a glucagon stimulation test (if hyperinsulinism or glycogen storage disease is suspected) or provocative testing to evaluate the pituitary gland axis.

CT ccan of the abdomen, or ultrasound. Is hepatomegaly present? If hyperinsulinism is present, is there a mass lesion present or diffuse

Treatment

Treat the underlying medical condition.

Give glucose.

• In diabetics give glucose tablets, candy or glucose containing foods (if patient is able to tolerate orals).
• IV bolus glucose D10 should be used if the patient is unable to tolerate oral feedings, followed by an infusion of D5 or D10 dextrose. Glucose infusion rate (GIR) = ( dextrose % concentration X ml/kg/d). The glucose utilization of healthy infants is 5 to 8 mg/kg/min. In the case of hyperinsulinism, rates of greater than 15- 20 mg/kg/min are required.
• In some cases the plasma glucose cannot be raised or maintained by glucose infusion alone. In the case of nesidoblastosis, a trial of diazoxide or hydrocortisone may be required. In the case of islet cell adenoma, or nesidoblastosis, a near or total pancreactomy needs to be performed.

Child. A glucagon stimulation test is both diagnostic as well as therapeutic. In particular, it will help to differentiate between hyperinsulinism and glycogen storage defects. To perform the test, check the blood sugar before and 30 minutes after glucagon administration. The dose of glucagon depends on the weight of the infant or child.

Infant. In an infant, give Glucagon infant 50ug/kg IV, IM or SC (maximum dose is 1 MG) or 30 ug/kg in children. In response to glucagon, the blood sugar will increase more than 40 mg/dl in the case of hyperinsulinism. Glucagon will also increase the blood sugar in an infant or child but not to the degree that it is increased in hyperinsulinism.