Endocrinology Flashcards
What are the causes of nephrogenic diabetes insipidus?
- *Congenital**
- Hereditary nephrogenic DI
Acquired
- Drugs: lithium
- Electrolyte disturbances
>> Hypercalcemia
>> Hypokalemia
- Chronic renal failure
What are the causes of central diabetes insipidus?
- *Congenital**
- Familial Central DI
Acquired
- Trauma
>> Gross Trauma
>> Pituitary surgery
- Autoimmune causes
- Neoplasms
>> Tumours
>> Stalk lesions
>> Histiocytosis X
- Hydrocephalus
- Idiopathic
What are the 2 investigations for diabetes insipidus?
- Water deprivation test to rule out psychogenic polydypsia
- DDAVP to differentiate between central DI (concentrated urine) and nephrogenic DI (no effect)
What is the management for central diabetes insipidus?
DDAVP
What is the management for nephrogenic diabetes insipidus?
- Solute restriction
- NSAIDs
- Thiazide diuretics
How do thiazide diuretics work in treating nephrogenic DI?
Thiazide diuretics act on inhibiting the NaCl cotransporter to inhibit water reabsorption in the distal tubules. The subsequent renal sodium loss causes extracellular volume contraction (as water flows into the relatively hypertonic intracellular compartment), when then leads to lowered GFR and increased proximal tubular sodium and water reabsorption. Hence, less water and solutes are delivered to the distal tubule and collecting duct, and are lost as urine.
What is the physiology behind euvolemic hyponatremia in SIADH?
There is excessive inappropriate isolated water reabsorption in the collecting ductules in SIADH. A similar proportion of water is thus lost in the proximal tubules due to the expanded intravascular volume, but this is accompanied by the secretion of sodium as well. Therefore, the net effect is no change in the intravascular volume, but a loss of sodium from the PCT. The hyponatremia is initially mediated by ADH-induced water retention. The ensuing volume expansion activates secondary natriuretic mechanisms, resulting in sodium and water loss. The net effect is that, with chronic SIADH, sodium loss is as or more prominent than water retention.”
What are the 5 diagnostic criteria for SIADH?
- Hyponatremia with decreased plasma osmolality
- Urine concentration >100mOsm/dL
- Urine Na concentration >20mEq/L
- Normal adrenal, renal and thyroid function
- No signs/evidence of volume depletion
What are the possible causes of SIADH?
- Stress: pain, nausea and post-operation
- CNS conditons: inflammation, hemorrhage, tumour, GBS
- Respiratory infections: TB, pneumonia, empyema
- Neoplasms: lung, pancreas and lymphoma
-
Drugs
>> Vincristine
>> Cyclophosphamide
>> SSRIs
>> Chlorpropamide
>> Carbamazepine
>> Morphine
>> Nicotine
What is the management of SIADH?
- Fluid restriction +/- hypertonic saline
- Vasopressin receptor antagonists: tolvaptan, conivaptan
- Demeclocycline
- Fludrocortisone
- Furosemide
What is cerebral salt wasting (CSW)?
Excessive urinary sodium and subsequent hyponatremia and dehydration in individuals with intracranial disease
What is diabetic ketoacidosis?
A state of severe metabolic derangement that results from both insulin deficiency and increased amounts of counterregulatory hormones such as catecholamines, glucagon, cortisol and growth hormone
- Hyperglycemia (serum glucose at ~16mmol/L or even higher)
- Ketonemia (serum ketones >3mmol/L)
- Acidosis (venous pH <15mEq/L)
What are the common clinical features of diabetic ketoacidosis?
- *From hyperglycemia and osmotic diuresis/electrolyte disturbances**
- Polyuria, polydipsia and polyphagia
- Dehydration
- Abdominal pain
- *From metabolic ketoacidosis**
- Decreased consciousness and lethargy
- Nausea and vomiting
- Fruity-smelling breath
- Kussmaul’s respiration
>> **Must ask for precipitating factors
1. Infections 2. Ischemia 3. Infarction 4. Intoxication 5. Insulin missed**
What is the management for diabetic ketoacidosis?
- Resuscitation and stabilization
-
Fluid resuscitation
>> Beware of pseudohyponatremia due to hyperglycemia
>> Add 3Na+ per 10 glucose over 5.5mmol/L -
Insulin administration
>> DO NOT give insulin if K is <3.3mmol/L
>> Add D5W when glucose <15mM to prevent hypoglycemia -
Electrolytes
>> Replace KCl
>> Essential to avoid hypokalemia
>> Cardiac monitoring if potassium levels normal or low - >> HCO3 is not given unless patient has a pH of <7.0
- Frequent monitoring of
>> Vital signs
>> Electrolytes (esp. Na and K)
>> Glucose
>> Acid-base status
ABG is more useful in monitoring DKA than blood glucose levels
What are the indications for bicarbonate use in DKA?
- Profound acidosis (pH <7.1)
- Associated with hypotension, arrhythmia and/or coma
- Life-threatening hyperkalemia with bradycardia/muscle weakness
What are the common biochemical findings of DKA?
KETONEMIA
- *Renal function**
- Hyponatremia
- Normakalemia/Hyperkalemia with low total body potassium
- Creatinine increased
- BUN increased
- Plasma osmolality increased
- *Arterial Blood Gas**
- Metabolic acidosis: decreased pH and with decreased HCO3
- Secondary respiratory alkalosis by compensation
- *Bone Profile**
- PO4 decreased
- *Urine**
- Glucosuria
- Ketonuria
What is the target glucose range in children?
Infants: 6-10mmol/L
Children: 4-10mmol/L
Adolescents: 4-7mmol/L
What are the complications of DM Type 1?
- *Short-term complications**
- Hypoglycemia
- Hyperglycemia
- Diabetic ketoacidosis
- *Long-term complications**
- Microvascular: retinopathy, neuropathy, nephropathy
- Macrovascular: metabolic syndrome
- Increased risk for other autoimmune diseases
What are the risk factors for Type II DM?
- Obesity
- Female gender
- Positive family history
- Certain ethnic groups
What is the management for Type II DM in children?
- Diet
- Physical activity: 60min of moderate-intense exercise per day
- Weight loss
- Oral hypoglycemics (Metformin as it does not cause hypoglycemia)
- Insulin
What are the goals for HbA1C in children with Type I DM?
<6 years: <8.5%
6-12 years: <8%
>12 years: <7%
What is the Somogyi phenomenon?
Rebound hyperglycemia afrer an incident of hypoglycemia
- Secondary to the release of counterregulatory hormones as a natural response to hypoglycemia
- Commonly reported at night as there is a greater likelihood of unrecognized and untreated hypoglycemia when the child is sleeping
- Suspect when a child whose blood sugar is in excellent control (and thus prone to hypoglycemia) begins to have intermittent high blood glucose in the morning
- BG should be checked between 2-3AM on several nights to determine whether the hypoglycemia is occurring
What is the dawn phenomenon?
A rise of blood glucose that occurs during the early morning hours (5-8AM), particularly among patients who have normal blood glucose levels
- Normal increase of morning cortisol levels
- Cumulative effect of increased nocturnal growth hormones
- Insulinopenia due to the length of time since the last insulin injection
What are the indications for further investigations in short stature?
- Very short: height <3rd centile
- Slow growth velocity
- Growth arrest
- History or physical examination findings suggestive of endocrine or other systemic disorders
What are the 4 questions to ask when evaluating a child with short stature?
- Was there IUGR? If yes, what was the cause?
- Is the growth proportionate?
- Is the growth velocity normal?
- Is bone age delayed?
What are the possible causes of short stature in children?
- *IUGR present**
- Chromosomal abnormalities: Down’s, Turner’s, Russell-Silver, Noonan
- Congenital infections
- Teratogen exposure
- Placental insufficiency
- *No IUGR with disproportionate growth (U/L ratio)**
- Rickets
- Skeletal dysplasia, e.g. Achondroplasia
- Scoliosis
- Mucopolysaccharidoses
- *No IUGR, proportionate growth with normal growth velocity**
- Constitutional growth delay (delayed bone age for chronological age)
- Familial short stature (normal bone age for chronological age)
No IUGR, proportionate growth with slow growth velocity
- Endocrine
>> Growth hormone deficiency
>> Hypercortisolism/Cushing’s
>> Hypopituitarism (look for midline defects/visual field defects)
>> Hypothyroidism/Hyperthyroidism
>> Adrenal insufficiency
- Chronic illnesses
>> Congenital cyanotic heart diseases
>> Respiratory: asthma, cystic fibrosis
>> GI: celiac disease, IBD
>> Renal: chronic renal failure, recurrent UTI
>> Chronic infections
- Malnutrition
- Psychosocial: child neglect, child abuse
What are the causes of congenital growth hormone deficiency?
- Idiopathic
- Genetic mutations
- Embryologic CNS malformations (look for the associated following:)
>> Midline facial anomalies
>> Neurological defects
>> Micropenis in males
>> Hypoglycemia - Perinatal asphyxia
What are the causes of acquired growth hormone deficiency?
- Cranial infection
- Trauma
- Tumours: e.g. craniopharyngioma (look for visual field defects)
- Iatrogenic causes
>> Cranial irradiation
>> Previous surgery
What are the risk factors for (especially acquired) growth hormone deficiency?
- Intracranial infection
- Head trauma
- *- Intracranial bleed
- Previous head surgery or irradiation
- Breech delivery**
- Positive family history
What does growth hormone mainly mediate?
- Chondrocyte proliferation
- IGF-1 release (works on long bones and the liver)
When is GH stimulation testing indicated?
- Height <3rd centile
- Decreased growth velocity
- Delayed bone age
- Delayed puberty
- Midline craniofacial anomalies
- Episodes of hypoglycemia
What are the indications for growth hormone therapy?
- Positive GH stimulation tests for GH deficiency on two separate occassions
- Growth velocity <3rd percentile
- Height <<3rd centile
- Bone age X-ray shows unfused epiphyses/delayed bone age
- Chromosomal/Genetic syndromes
>> Turner syndrome
>> Noonan syndrome
>> Prader-Willi syndrome - Chronic renal failure
- Idiopathic short stature
What is the definition of short stature?
Height <3rd centile
What are the possible causes of tall stature?
- *Nonpathological**
- Constitutional growth spurt
- Familial tall stature
Pathological
- Genetic causes
>> Homocystinuria
>> Klinefelter syndrome
>> Marfan syndrome
>> Sotos syndrome
:: Excessive growth physical growth in the first 2-3 years of life
:: Associated with:
~ Macrocephaly
~ Protrusive forehead
~ Hypertelorism
~ Awkward gait
~ Unusual aggressiveness or irrtability
>> Beckwith-Wiedemann syndrome
:: Macrosomia
:: Macroglossa
:: Midline abdominal wall defects (omphalocele, umbilical hernia etc.)
:: Neonatal hypoglycemia
- Endocrine causes
>> Hyperthyroidism
>> Hypophyseal gigantism
>> Precocious puberty
