Endocrinology Flashcards
Criteria for diagnosis of diabetes
- symptoms of diabetes AND RPG >=200mg/dL OR - FPG >=126mg/dL OR - Plasma glucose>200mg/dL during an OGTT OR - HgbA1c >=6.5%
HLA associated with T1DM
HLA DR, DQ
Antibody markers for T1DM
Anti-islet cell Ab, Anti-insulin Ab, anti-GAD65 Ab
B-cell mass % at onset of symptoms of T1DM
<10-20%
What are the different actions of insulin?
- Enhances tissue uptake of glucose, amino acids and lipids
- Enhances glycogen, protein and fat synthesis
- Inhibits glucose production (gluconeogenesis and glyconeolysis)
- Inhibits fat breakdown (lipolysis) and ketogenesis
“Counter-regulatory hormones”
- Cortisol
- Epinephrine
- Glucagon
- Growth Hormone
“Mild” DKA criteria
pH <15
“Moderate” DKA criteria
pH <10
“Severe” DKA criteria
pH <5
How do you calculate corrected Na+?
Corrected Na+ = measured Na+ + 0.016 (measured glucose-100)
“Pseudohyponatremia”
Cerebral edema IS/IS NOT related to DKA severity or duration or variations in usual fluid composition.
IS NOT
- Cerebral edema is related to high volume fluid delivery
_________ is the leading cause of morbidity and mortality in children with T1DM.
Cerebral edema
- Most common fatal complication of DKA
What did the Diabetes Control and Complications Trial 1993 (DCCT) show?
Reduced: retinopathy, nephropathy, neuropathy, neuropathy, macroangiopathic events, LDL
INCREASED WEIGHT GAIN
INCREASED HYPOGLYCEMIC EPISODES 3-FOLD, SO NOT RECOMMENDED FOR CHILDREN <13YRS
What is the Samogyi Phenomenon and how do you treat it?
Hypoglycemia leading to rebound hyperglycemia
Rx: decrease nighttime long-acting insulin
What is the Dawn Phenomenon, how do you treat it?
Counterregulatory early AM growth hormone
Rx: increase nighttime long-acting insulin
Which type of diabetes is associated with a higher genetic risk?
T2DM - ~100% monozygotic twins
~50% monozygotic twins in T1DM
A child is obese at 6yrs, what is the chance they will be obese as an adult.
25% chance
A child is obese at 12yrs, what is the chance they will be obese as an adult?
75% chance
Most common complication of obesity?
Psychological, low self-esteem
- Plasma glucose >600mg/dL
- Serum bicarbonate >15mmol/L
- No or small ketonuria
- Effective serum osmolarity >320 mOsm/L
- Profound dehydration
- Obese, minority children with T2DM, insulin-resistance
Hyperglycemic Hyperosmolar Syndrome
- High mortality rate
- Aggressive hydration, insulin later
- Complications: coma, seizures, renal failure, thrombosis, rhabdomyolysis, hyperthermia, pancreatitis, persistent hypernatremia
- Cerebral edema rare, replace urinary losses with 0.45% saline
Most endocrine etiologies of obesity are also associated with SHORT OR TALL stature
SHORT
- Mildly obese
- Really short
- H/o hypoglycemia…?seizures
- Micropenis
- Bone age delay
- Midline facial defect (CL, CP, single maxillary incisor)
- Optic nerve hypoplasia
Growth Hormone Deficiency (Hypopituitarism)
Single maxillary incisor
Hypopituitarism (GH deficiency)
- Floppy baby
- Almond-shaped eyes
- Mildly (or really) retarded
- Sucking problems…FTT early
- Then very obese later
- Hypoplastic penis/scrotum
- Small testicles and hands/feet
- Large appetite with foraging behaviors
Prader-Willi Syndrome
- Moderately obese
- Round face with short neck
- Delayed dental eruption, aplasia
- Short 4th metacarpals/metatarsals
- Extraskeletal calcification
- Variable hypocalcemia and hyperphosphatemia
- AD
Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy)
- Obesity
- Mental Deficiency
- Retinal dystrophy
- Polydactyly/Syndactyly/Brachydactyly
- Broad, short feet
- Abnormal kidneys
- Small penis/testes (hypogonadism)
- AR
Bardet-Biedl Syndrome
- Amenorrhea
- Hirsutism
- Obesity
- Hyperandrogenemia
- Premature Adrenarche
- Abnormal Abdominal Ultrasound
- LH elevation
PCOS
- Obesity later
- Hypotonia
- Brushfield spots
- Clinodactyly with simian crease
- Endocardial cushion defect
- Small penis and small testicles
Down Syndrome
- Mild obesity
- Growth deceleration
- Dry skin
- Constipation
- Hair loss
- Depressed/delayed relaxation phase of DTRs
- Weakness
Acquired Hypothyroidism
- Central obesity
- Round facies
- Thin extremities
- Easy bruisability
- Hypertension
- Osteoporosis
- Buffalo hump
Cushing Syndrome
Most common cause of cushing syndrome in children?
Exogenous steroids
“Primary”
At the end gland
“Secondary”
At the pituitary
“Tertiary”
At the hypothalamus
Anterior pituitary gland produces…
Portal system
Posterior pituitary gland produces…
ADH
Neural system
Triggers for ADH release
+ high osmolality –> ADH –>retain free water
- low osmolality –> ADH inhibition
If no ADH –> DIABETES INSIPIDUS and HYPERNATREMIA
If excess ADH –> SIADH and HYPONATREMIA
Rx for DI
Hydrate and give DDAVP
Rx for SIADH
Fluid restrict (1000mg/m2/day or less)
Decreased T4
Elevated TSH
PRIMARY HYPOTHYROIDISM
- Severe growth and developmental delay
- Prolonged jaundice
- Constipation
- Coarse features
- Umbilical hernia and large anterior fontanelle
CONGENITAL HYPOTHYROIDISM
- TSH > 25 after 24hrs is + screen
Abs in Hashimoto Thyroiditis
Anti thyroglobulin and Anti-TPO
Elevated TSH Low T4 Low Free T4 Low T3 Mild normocytic or microcytic anemia
Hypothyroidism
SUPPRESSED TSH
ELEVATED T4, Free T4, Total T3
Hyperthyroidism
Autoimmune markers in Graves Hyperthyroidism
+ TSH receptor Ab (TRAb)
+/- Anti TPO, Anti TG Abs
What percentage of solitary thyroid nodules are malignant?
20%
- Reassuring: cystic nodule, +TPO/TG Ab’s
- Non-reassuring: firm, rapid growth, +FH of medullary CA, h/o neck radiation
External genitalia is undifferentiated until…
9 weeks of age
Subnormal Testosterone or DHT
Insensitive to Testosterone
46XY DSD
Excess maternal androgens
Excess exogenous androgens
Excess adrenal androgens (CAH)
46XX DSD
Both ovary and testicle
Ovotestes 46XX, 46XY or mosaic
What is needed for external male genitalia
Testosterone/Dihydrotestosterone
- External female genitalia
- Internally male - no uterus, testicles present
- No pubic/axillary hair
- Breast tissue at puberty
- No menses
Complete AIS (XY DSD)
- Ambiguous genitalia
- Internally male-no uterus
- Some pubic hair
- Sex of rearing/gender - individualized
Partial AIS (Ambiguity Continuum)
Features of 5 Alpha Reductase Deficiency
- Cannot convert testosterone to highly active DHT
- Without DHT, external genitalia is not virulized
- At puberty, excessively high levels of testosterone can cause virilization
++ 17 OH Progesterone, Androstenedione, Testosterone, DHT
– 11 Deoxycortisol, Cortisol
21-Hydroxylase Deficiency
- Salt-wasting –> Na+ loss due to aldosterone deficiency
- Simple virilizing –> F ambiguous genitalia, M early adrenarche/puberty
- Non-classical –> presents in adolescence with hirsutism and menstrual irregularities
Most common form of CAH
21-Hydroxylase Deficiency
++ 11 Deoxycortisol, 11 Deoxycorticosterone DOC, 17 OH Progesterone, Androstenedione, Testosterone
– Aldosterone, Cortisol
11-B Hydroxylase Deficiency
- Virilization of females (excess androgens)
- *HTN IN LATER CHILDHOOD**
- If untreated (and non-lethal) –> advanced bone age, early adrenarche
Laboratory work-up for CAH
Pre +/- post ACTH stim
- 17 OH Progesterone –> 21 OH deficiency
- 11 Desoxycortisol/DOC (11 B OH deficiency)
- 17 OH Pregnenolone (3-B Hydroxysteroid)
- Renin/Aldosterone
- ACTH (should be very high)
- DHEA
Rx for Acute Salt Wasting-Adrenal Crisis (CAH)
- 10-20cc/kg NS bolus
- Hydrocortisone 25mg IM/IV, then 100mg/m2/day divided q6hrs
Rx chronic salt wasting and virilizing CAH
- Hydrocortisone 15mg/m2/day
- Fludro 0.1-0.2mg/day (SW only)
Follow-up for 17-OHP
Andro and renin levels q3 months
Primary adrenal insufficiency, mucocutaneous candidiasis, hypoparathyroidism
APS 1 (AIRE)
Primary adrenal insufficiency, DM1, Hashimoto
APS 2 (Schmidt)
- Adrenal cortex does not develop
- No virilization in F
- Normal male genital development
- Salt-losing crisis in neonatal period
Adrenal hypoplasia congenita
- Rx: fluid resuscitation, HC, then FC
- NR0B1 (DAX-1) gene
- Normal neurologic development initially, then loss of milestones, clumsiness
- Adrenal insufficiency
- X-linked
- BMT is only curative treatment
Adrenoleukodystrophy
- Near death experience - hypotension, hyponatremia, hyperkalemia, acidosis
- Weight loss
- Vomiting
- Hyperpigmentation (gums, creases of palms)
Signs of adrenal insufficiency
Causes of Cushing’s Syndrome
- Exogenous Steroids
- Cushing’s Disease (ACTH production)
- Adrenal Adenoma/Carcinoma
- Ectopic ACTH production
Headache
HTN
Palpitations
Sweating
Pheochromocytoma
- urinary catecholamines, urinary metanephrines, MRI of adrenals, MIBG scan
- Rx; alpha-adrenergic blockade, surgical resection
Differential for hyperinsulinemia in neonates
- IDM
- Malposition of UA catheter
- Beta-cell dysfunction (Hyperinsulinism)
- Perinatal stress/hypoxia
- BWS
Differential for hypoglycemia in neonates
- Prematurity
- Hyperinsulinism
- Hypopituitarism
Hypoglycemia at random times with respect to food
Hyperinsulinism
Hypoglycemia and no/trace ketones after an event
Insulin or FA oxidation defect
Hypoglycemia and midline defects or nystagmus
Pituitary (GH/cortisol)
Hypoglycemia after overnight fast
Pituitary (GH/cortisol) or FA oxidation defect
PTH net effect
Increase serum calcium
Decrease serum phosphorus
Vitamin D net effect
Increases absorption of both calcium and phosphorus
AND feedback inhibitor for PTH
3 mechanisms by which PTH increases calcium
- Increased bone resorption
- Increased calcium resorption from kidney
- Increasing vitamin D –> increased gut absorption
What are signs of hypocalcemia
- Tetany
- Chvostek (7th nerve)
- Trousseau (BP cuff)
- Irritability
- Cardiac defects
- Palatal defects
- Broad nose, long fingers
- T-cell dysfunction (DiGeorge) - infections
DiGeorge/Velocardiofacial Syndrome
- 22q11 deletion
– Ca
++PO4
–PTH
Hypoparathyroidism
– Ca
++PO4
++PTH
Pseudohypoparathyroidism
–Ca
–PO4
++AP
Rickets
- Bowing of legs
- Widening, cupping and fraying of distal metaphyses
- X-linked (still affects females)
- LOW SERUM PHOS
- HIGH URINE PHOS
- NORMAL SERUM CALCIUM
- High AP
- NORMAL VIT D
Hypophosphatemic Rickets = genetic rickets
Rx: Rocaltrol and Phosphorus
++PTH
++Ca
–PO4
Hyperparathyroidism-Parathyroid Adenoma
Can be part of MEN I, II
–iPTH
++Ca
–PO4
++PTHrP
Elevated PTHrP (secreted by tumor)
–PTH
++Ca
++PO4
Hypervitaminosis D
This syndrome is associated with hypercalcemia and a cocktail personality
Williams Syndrome
Rx for hypercalcemia
Hydration Furosemide Glucocorticoids Calcitonin Bisphosphonates
Growth Velocity first 3 years of life
Rule of 24 (year x GV = 24) 1st year - 24cm/year 2nd year - 12cm/year 3rd year - 8cm/year Puberty peak is 10cm/year boys, 8cm/year girls
Most common cause of short stature
Constitutional delay
- “late bloomer”
- normal labs
- delayed bone age
- otherwise healthy
Side effects of GH
- Head-shoulders-knees & hips
- pseudotumor cerebri
- scoliosis (association or causation)
- SCFE
- Associated with thyroid and cortisol deficiencies
- Increased risk of colon CA
- Small at birth
- Limb assymetry
- Triangular head
- Cryptorchidism
- No catch-up growth
Russell-Silver Syndrome
Tanner stage at which menarche occurs
Tanner stage 4
Thelarche
Breast development
- first sign of puberty in 90%
- age 8-13* (controversy)
- Eight is great, 13 is too late
Adrenarche/Pubarche
Pubic hair
- follows thelarche shortly
- age 9-13
Growth Spurt
Tanner 2-3 = peak growth
Menarche commencement
~ 2 years after the start of puberty
- avg age is 12.4 years
Order of pubertal development
T-A-G-Me = thelarche, adrenarche, growth spurt, menarche
First sign of puberty in males
Phallic enlargement
Puberty progression in males
T-H-P-G-A
Testicular enlargement - Hair - Penile enlargement - Growth spurt (III-IV) - Axillary/Facial hair
9 is fine, 14 is draw the line
Precocious puberty
Development of secondary sexual characteristics:
- before 8yrs in F
- before 9yrs in M
Central or peripheral/pseudo precocious
Most common cause of central precocious puberty in girls
95% idiopathic
Most common cause of central precocious puberty in boys
Majority are not idiopathic
Cafe-au-lait
Fibrous Dysplasia
Precocious Puberty
McCune Albright Syndrome
- G-protein abnl
- Girls>Boys
- Other endocrine systems also involved
Rx Central Precocious Puberty
GnRH agonists - Leuprolide or Histrelin
- down-regulates receptors on pituitary gland
Delayed puberty
No secondary sexual development by age 13 in girls, 14 in boys
Nonendocrine vs. Endocrine
Anosmia and delayed puberty
Kallmann Syndrome
