Endocrinology Pt. 2 Flashcards
What HLA haplotype is seen in 95% of patients with type 1 DM?
DR3 or DR4
What are some environmental triggers for DM type 1?
Viral infections (enteroviruses and rubella)
Early introduction of cow’s milk (controversial)
What autoimmune factors contribute to DM type 1?
- Islet cell antibodies (ICA) are present in 85% of patients
- ICA may be detected in asymptomatic patients 10 years before onset of clinical symptoms
- Other immunologic markers
- Antibodies against insulin and against glutamic acid decarboxylase
What is required for a child to develop type 1 DM?
A combination of ICA, environmental factors, and a genetic predisposition
The classic presentation of DM type 1 includes several weeks of…(3)
Polyuria
Polydipsia
Nocturia
In what percentage of patients is Diabetic ketoacidosis the initial presentation of DM type 1?
25%
Girls who have protracted cases of _____ _________ may have early type 1 DM
monilial vulvovaginitis
What is required to diagnose patients with type 1 DM?
Patients must have hyperglycemia documented by a random blood sugar above 200 mg/dL with polyuria, polydipsia, weight loss, or nocturia
What types of insulin are used to treat DM type 1?
Short-acting
Intermediate-acting
Long-acting
Very long-acting
What is the honeymoon period of DM type 1?
Within a few weeks after initial diagnosis, 75% of patients exhibit a temporary progressive reduction in their daily insulin requirements; this is because of transient recovery of residual islet cell function resulting in endogenous release of insulin in response to carbohydrate exposure
What is the Somogyi phenomenon in DM type 1?
This occurs when the evening dose of insulin is too high causing hypoglycemia in early morning hours, resulting in the release of counter-regulatory hormones (epinephrine/glucagon) to counteract the insulin-induced hypoglycemia; patient then has high blood glucose and ketones in the morning
How do you prevent the Somogyi phenomenon (hyperglycemia in the morning?)
The treatment is to lower the bedtime insulin dose
What are some long term complications of DM type 1?
- Microvascular complications: diabetic retinopathy, nephropathy, neuropathy
- Macrovascular complications (usually seen in adults): atherosclerosis, HTN, heart disease, stroke
- DKA: when ill or noncompliant
Type 2 DM occurs in _-_% of all children with diabetes
2-3%
Which type of diabetes has the strongest hereditary component?
Type 2
What is likely the cause of DM type 2?
Combination of peripheral tissue resistance to insulin and progressive decline in insulin secretion
What is the clinical presentation of DM type 2?
- Obesity
- Acanthosis nigricans
- Asymptomatic to mild DKA
What is the management of DM type 2?
Oral hypoglycemic agents if blood sugar levels are not very high
Insulin therapy may be required
What is the definition of DKA?
Hyperglycemia uually greater than 300 mg/dL with ketonuria and a serum bicarbonate level < 15 mmol/L or a serum pH < 7.3
What are the roles of counter regulatory stress hormones in DM type 2?
Hyperglycemia resulting from insulin deficiency leads to an osmotic diuresis with polyuria and eventual dehydration; counter regulatory stress hormones (glucagon, epinephrine, cortisol, GH) are released and contribute to fat breakdown (lipolysis)
Glucagon stimulates conversion of FFA to ketones and eventually leads to DKA
How does mild DKA present? How does severe DKA present?
Mild: vomiting, polyuria, polydipsia, and mild to moderate dehydration
Severe: severe dehydration, abdominal pain (mimics appendicitis) and rapid and deep (Kussmaul) respirations, and coma
What are the lab findings in type 2 DM?
- Anion gap metabolic acidosis
- Hyperglycemia and glucosuria
- Ketonemia and ketonuria
- Hyperkalemia caused by metabolic acidosis
What are the steps in management of DM type 2?
- Fluid and electrolyte therapy
- Gradual decline in osmolality (minimizes risk of cerebral edema)
- Potassium repletion (potassium acetate and potassium phosphate)
- Regular insulin
- Combination of IVF and insulin should revrese ketogenesis
Why is potassium repletion important in DM type 2?
Important because all patients are potassium depleted, even with a normal serum potassium
Potassium phosphate helps increase levels of 2,3-DPG which in turn shifts the oxygen dissociation curve to tohe right and makes oxygen more readily available to the tissues
What serious complication of DM type 2 usually occurs 6-12 hours into therapy and has a mortality rate of 70%?
Cerebral edema
What factors regulate the hypothalamic pituitary thyroid axis?
Thyroxine (T4), triiodothyronine (T3), TRH, TSH
What is bound to T4 and T3 in circulation
Thyroid binding proteins, including thyroid-binding globulin (TBG) and thyroid binding prealbumin (TBPA)
When are T4 and T3 in their biologically active forms?
When they are unbound
What is the clinical presentation of hypothyroidism?
- Suboptimal growth velocity with delayed bone age
- Goiter
- Myxedema (puffy skin)
- Amenorrhea or oligomenorrhea in adolescent girls
What is the most common metabolic disorder?
Congenital hypothyroidism
What is the most common cause of congenital hypothyroidism (90%)?
Thyroid dysgenesis: absent thyroid gland, thyroid hypoplasia, or ectopic thyroid gland
What is thyroid dyshormonogenesis?
What is the most common of these defects?
Multiple inborn errors of thyroid hormone synthesis
Pendred syndrome (organification defect) is most common - associated with sensorineural hearing loss
What maternal factors may lead to transient congenital hypothyroidism?
Use of PTU during pregnancy for maternal Graves’ disease may result in transient hypothyroidism (PTU crosses placenta)
Maternal autoimmune thyroid disease - maternal thyroid blocking antibodies may cross the placenta and block TSH receptors on the newborn thyroid gland
How do most newborns with hypothyroidism present?
Asymptomatic and unremarkable physical examination (T4 is not essential for fetal growth)
Thyroid hormone is essential for normal brain growth during the first __ years of life
2 years
What are classic physical examination findings of congenital hypothyroidism?
Large anterior and posterior fontanelles, protruding tongue, umbilical hernia, myxedema, mottled skin, hypothermia, delayed neurodevelopment, poor growth
What are the 2 classic symptoms of congenital hypothyroidism?
Lethargy and constipation
What is the management of congenital hypothyroidism?
Thyroid hormone replacement should begin immediately with L-thyroxine
What is Hashimoto’s disease?
Autoimmune disorder characterized by lymphocytic infiltration of the thyroid gland, resulting in follicular fibrosis and atrophy and follicular hyperplasia
What are some of the clinical features of Hashimoto’s disease?
- Asymptomatic
- Goiter
- Short stature
- Transient hyperthyroidism
What is measured to diagnose hypothyroidism?
- TSH (neonatal screening tests)
- Increased TSH
- Low T4 level
- Antithyroid antibodies (thyroid antiperoxidase antibodies)
What clinical features of hyperthyroidism are seen in the eye, the skin, and the CNS evaluations?
- Eye: Lid lag and exophthalmos
- Skin: Warm and flushed (presence of vitiligo or alopecia suggests the possible coexistance of other autoimmune polyendocrinopathies)
- CNS: nervousness, fine tremors, history of fatigue and difficulty concentrating in school
What is Graves’ disease?
Autoimmune disorder characerized by produciton of excessive thyroid hormone by the thyroid gland mediated by a TSH look-alike antibody
What antibody is associated with Graves’ disease?
Thyroid-stimulating immunoglobulin (TSI), an IgG antibody that cross reacts with TSH and binds to and stimualtes the TSH receptors in the thyroid gland
What are the laboratory findings in Graves disease?
Increased T3 and T4 levels with suppressed TSH level in the presence of TSI
What is the management of Graves’ disease?
- Antithyroid medications: PTU and methimazole (PTU also impairs peripheral conversion of T4 to T3)
- Subtotal thyroidectomy
- Radioactive iodine
Both _______ and ______ release calcium and phosphorous from bone
Vitamin D; PTH
PTH helps maintain normal serum calcium level by…
Releasing calcium from bone and reabsorbing calcium from the kidneys
How does PTH affect phosphorous in the kidneys?
Increases excretion
What enzyme converts 25-(OH) vitamin D (made in liver) into active vitamin D metabolite (1,25-(OH) vitamin D)?
1ß-hydroxylase vitamin D
What is the main source of calcium absorption and how is it regulated?
Gastrointestinal tract due to 1,25-(OH) vitamin D (most potent form of vitamin D)
Hypocalcemia is serum calcium less than ____ mg/dL or ionized calcium less than ___ mg/dL
8.0 mg/dL; 2.5 mg/dL
What is pseudohypocalcemia? How do you determine hypocalcemia vs. pseudohypocalcemia?
Factitious lowering of total calcium levels as a result of low serum albumin levels (nephrotic syndrome)
Ionized calcium level verifies true hypocalcemia
What are the clinical features of hypocalcemia?
- Tetany
- Carpopedal spasm
- Laryngospasm
- Paresthesia
- Seizures
What can cause early transient neonatal hypocalcemia (younger than 4 days of age)?
Associated with prematurity, IUGR, asphyxia, or infants of diabetic mothers
What can cause late neonatal hypocalcemia (older than 4 days of age)?
- Hypoparathyroidism (maternal hyperparathyroidism)
- DiGeorge syndrome
- Hyperphosphatemia - leads to hypocalcemia by binding to calcium
What are causes of childhood hypocalcemia?
- Hypoparathyroidism (parathyroid failure)
- Pseudohypoparathyroidism (parathyoid resistance)
- Hypomagnesemia (renal and malabsorptive diseases)
- Vitamin D deficiency
What laboratory evaluation is done for hypocalcemia?
- Serum ionized calcium and phosphorous
- Serum magnesium
- Electrocardiogram demonstrating a prolonged QT interval
- PTH level
- Vitamin D level
- Radiograph of wrists or knees to evaluate for rickets
How is hypocalcemia managed?
- If mild: no treatment
- Calcium correction in kids to prevent CNS hyperexcitability
- Calcium supplementation (Oral or IV calcium gluconate)
- Calcitriol (Vitamin D analog) for patients with chronic hypoparathyroidism
What is rickets?
A condition caused by vitamin D deficiency that results in deficient mineralization of growing bones with a normal bone matrix
What are some predisposing factors to Rickets?
- Exclusively breasetfed infants with minimal sunshine exposure
- Fad diets
- Use of anticonvulsant medications
- Renal or hepatic failure
What enzyme is deficient in vitamin-D dependent rickets? What is its inheritance pattern?
1ß-hydroxylase
Autosomal recessive (very rare)
What lab findings are seen in patients with Vitamin D-dependent rickets?
- Increased PTH
- Low vitamin D levels
- Low calcium
- Low phosphorous
- Increased alkaline phosphatase
What causes Vitamin D-resistant rickets?
What is its inheritance pattern?
Renal tubular phosphorous leak, resulting in low serum phosphorous level
X-linked dominant disorder
What are the calcium and phosphorous levels in Vitamin D-resistant rickets?
Normal calcium and low phosphorous
What is oncogenous rickets?
A phosphate-deficient form of rickets caused by a bone or soft tissue tumor; it should be considered in patients who present with bone pain or a myopathy
When does rickets usually occur (2)?
- First 2 years of life
- Adolescence when bone growth is most rapid
Rickets usually involves which parts of the body?
Wrists, knees, and ribs
What are some clinical features of Rickets?
- Weight bearing bones become bowed
- Short stature
- Rachitic rosary (prominent costochondral junctions)
- Craniotabes (thinning of outer skull)
- Frontal bossing, delayed suture closure
What shows the earliest changes of rickets?
Wrist radiographs: distal end of the metaphysis appears widened, frayed and cupped
What laboratory findings are associated with Rickets?
- Low serum phosphorous
- Low to normal serum calcium
- Elevated alkaline phosphatase
- Elevated PTH levels
What is diabetes insipidus?
Inability to maximally concentrate urine because of either low levels of ADH or renal unresponsiveness to ADH
What is ADH?
An octapeptide synthesized in the hypothalamus and transported via axons to the posterior pituitary; increases permeability of the renal collecting ducts to water, leading to increased water reabsorption
What is central vs nephrogenic DI?
Central: ADH deficient
Nephrogenic: ADH resistant
What are the possible etiologies of central DI?
- Autoimmune
- Trauma
- Hypothalamic tumors
- Langerhans cell histiocytosis
- Granulomatous disease (sarcoidosis)
- Vascular (aneurysms)
- Genetic (autosomal dominant)
How is nephrogenic DI inherited?
X-linked recessive disorder
What are the clinical features in children with DI?
Nocturia, enuresis, poor weight gain, polydipsia, and polyuria
Patients with DI present with hypernatremic dehydration and inappropriately dilute urine in the face of increased serum ______ and increased serum osmolality
sodium
An early monring urine specimin with a specific gravity greater than ______ rules out the diagnosis of DI
specific gravity > 1.018
What test can be used to diagnose DI?
How can it be determined whether the DI is central or nephrogenic?
Water deprivation test: Rising serum osmolality in the presence of persistent urine output and an inappropriately low urine osmolality is diagnostic
At the end of the test, if the patient does not respond to administered ADH, the patient has nephrogenic DI
What is the drug of choice for central DI?
DDAVP (synthetic ADH)
Hypoglycemia is a serum glucose less than __ mg/dL or whole blood glucose less than __ mg/dL
40; 45
Why is it important to recognize hypoglycemia early?
Brain is dependent on glucose for proper neurodevelopment
What are the symptoms of hypoglycemia in newborns/infants? In older children?
- Newborns: Lethargy, myoclonic jerks, cyanosis, apnea, or seizures
- Older children: Tachycardia, diaphoresis, tremors, headaches or seizures
What are some high risk conditions associated with transient neonatal hypoglycemia?
Prematurity, history of perinatal asphyxia or fetal distress, and small-for-gestational age and large-for-gestational age infants
Persistent neonatal hypoglycemia is defined as hypoglycemia that persists for longer than __ days
3 days
What is the differential diagnosis for persistent neonatal hypoglycemia?
- Hyperinsulinism (Islet cell hyperplasia; Beckwith-Wiedemann syndrome)
- Hereditary defects in carbohydrate metabolism or amino acid metabolism
- Hormone deficiency (GH and cortisol)
What is the most common cause of hypoglycemia in children 1-6 years of age?
Ketotic Hypoglycemia: hypoglycemia occuring late in the morning in the presence of ketonuria and a low insulin level; inability to adapt to fasting state
What ingestions can lead to hypoglycemia?
- Alcohol (depletes essential cofactors needed for adequate gluconeogenesis)
- Oral hypoglycemic agents
