Endocrinology Flashcards
Hypoglycemia in neonates
very common 1st 3 days of life (metabolic needs outstrip E stores)
serum level <55 mg/dL +symptoms= abnormal
DDx of hypoglycemia- causative illness
shock
heart failure
liver dysfunction
DDx of hypoglycemia- intoxications
alcohol
drug effects
ackee fruit
DDx of hypoglycemia- inadequate substrate
SGA
ketotic hypoglycemia
maple syrup urine dz
DDx of hypoglycemia
hyperinsulinism including factitious (Munchausen by proxy)
DDx of hypoglycemia counter-regulatory hormone deficiency & metabolic d/or inhibiting normal response
gluconeogenesis glycogenolysis fatty acid oxidation organic acid metabolic d/o galactosemia
Adrenal basics
hypothalamus makes CRH
CRH stimulates pituitary
pituitary makes ACTH
ACTH stimulates adrenal cortisol & androgen production
Adrenal aldosterone production is related to?
renin & angiotensin, not really ACTH
Congenital adrenal hyperplasia (CAH)
caused by absence of adequate adrenal function
adrenals may be congenitally hypertrophic from excess pituitary stimulus
may be obvious at birth d/t ambiguous genitalia at birth (excess steroid precursors converted to excess androgens)
salt-losing congenital adrenal hyperplasia
infants- manifests as mineralocorticoid deficiency, usu. w/o virilization
hyponatremia & hyperkalemia by age 5 to 7 days
MCC of salt losing CAH
21-hydroxylase deficiency
salt-losing CAH presentation
vomiting
dehydration
acidosis
often mistaken for hypertrophic pyloric stenosis
in HPS, hypochloremia & low to normal K+ is present
Tx of salt-losing CAH
oral glucocorticoids & mineralcorticoids
Addison dz (primary adrenal insufficiency)
autoimmune destruction of adrenal cortex
glucocorticoid & mineralcorticoid deficiencies
Addison dz presentation
hyperpigmentation salt craving postural hypotension fasting hypoglycemia episodes of shock w/ severe illness
Tx of Addison dz
oral glucocorticoids & mineralcorticoids
What is secreted in response to low calcium
PTH
what raises serum calcium & depresses phosphate?
PTH
low PTH, low calcium, high phosphate confirms what?
a problem w/ PTH production= hypoparathyroidism
hypoparathyroidism often results from?
DiGeorge syndrome
what is necessary for PTH production?
magnesium
neonatal tetany may result from?
dietary hyperphosphatemia in a newborn fed cow’s milk
rickets results from what type of deficiency?
Vitamin D
not from hypoparathyroidism
vitamin D (after hydroxylation twice) enhances what?
calcium absorption & bone deposition
panhypopituitarism
typically d/t trauma or shock
tx of panhypopituitarism
growth hormone replacement (esp. in CH)
thyroxine replacement
glucocorticoid replacement
diabetes insipidus (free water loss, hypernatremia)-tx w/ desmopressin
attention to sex hormone replacement depending on age & gender
Diabetes Mellitus
defined as fasting blood sugar >126 mg/dL
-or-
2-hr postprandial blood sugar over 200
sporadic hyperglycemia is common in children when?
during illness
screening test for DM (diagnostic in adults)
glycated hemoglobin (HgbA1C)
Type I DM
insulin deficiency
autoimmune destruction of pancreatic B cells
What is the MC endocrine problem in CH?
Type I DM
1/300-500 under 18 yo
What is the 1st finding in Type I DM?
postprandial hyperglycemia
Type I DM has higher rates in what population?
whites
People are prone to________________with more complete insulin deficiency
ketosis
Clinical presentation of Type I DM
polyuria (may manifest as enuresis)
polydipsia
polyphagia (often w/ paradoxical wt loss)
dehydration/ketosis- abdominal pain, vomiting, worsening mental status/fatigue, breath & sweat ketosis
Labs for Type I DM
glucose level
electrolytes & kidney function
UA- glycosuria, ketones, low pH
lab surveys for auto-antibodies & insulin-like growth factor depend on preferences of local endocrinologists
diabetic ketoacidosis
inability to maintain anabolic state
increased glucose levels
increased glucose levels in diabetic ketoacidosis causes what
renal osmotic fluid losses
loss of intravascular fluid volume
loss of total body Na+, K+: reported Na+ artefactually low w/ high glucose
ketosis by lipolysis
acidosis worsened by both ketonemia, lactic acid/ dehydration
What is unusual in diabetic ketoacidosis & confirmation of its source should be determined
fever
Diabetic ketoacidosis tx
restoration of intravascular fluids
restoration of anabolic state
how does restoration of intravascular fluids help in diabetic ketoacidosis
often helps reduce acidosis & glucose levels; excessive IV fluid repletion can cause cerebral edema & be fatal; electrolyte restoration; acid shift will alter K+ levels
how does restoration of anabolic state help in diabetic ketoacidosis
exogenous insulin restored euglycemia & halts ketone production
what often follows the original dx of Type I DM
“honeymoon” period- original DKA set off by acute illness while capacity for insulin production is low but not insufficient for well periods
long term tx goals of type I diabetes
insulin regimen
diet
exercise
complications to avoid in chronic mgnt of type I diabetes
renal failure visual impairment cardiovascular dz iatrogenic hypoglycemia ketosis during dehydrating circumstances
type II DM
insulin resistance- hyperinsulinemia, reduced sensitivity to insulin
DKA presentation less common
gradual onset of sx’s
growing more common in younger pts (correlates w/ obesity)
type II DM is common in what populations?
Black & Latino
risk factors for type II DM
FH
ethnicity
overweight
PCOS
contributing societal factors of type II diabetes
overweight fast foods soft drinks school lunches sedentary lifestyles- TV, computers, video games falling PE requirements
diagnosing type II DM
random glucose concentration >200mg/dL
fasting plasma glucose >126 mg/dL
glucose tolerance testing- 2 hr plasma glucose >200 mg/dL
glycated Hgb (HgbA1C)
co-morbidities with type II DM
dyslipidemia
HTN
obesity
tx of overweight & type II DM
tx focuses on glucose control & wt loss
limited data to support changes in lifestyle, diet, exercise, metformin
metformin
reduces hepatic glucose production
increases sensitivity to insulin
reduces intestinal glucose absorption
the thyroid develops from the_______&________ pharyngeal pouches starting in the_______week of gestation
3rd & 4th
4th week
at which week does the thyroid migrate & the thyroglossal duct degenerates
7th week
where is T4 converted to T3
in the tissue
what is more physiologically active? T4 (thyroxine) or T3 (triiodothyronine)
T3
most T3/T4 is bound to what?
thyroid binding globulin (TBG): <1% free
physiologic activity of thyroid hormone primarily depends on….
free T4
TSH surge can cause a false + in_____________when screened for hypothyroidism
neonates
some things that may cause total T4 to be abnormal while FT4 is normal
if TBG levels are abnormal
certain drugs bind TBG (anticonvulsants)
pregnancy/estrogen can stimulate TBG
fetal hypothyroidism may result in absence of
distal femoral epiphysis
thyroid imaging can show
ectopic thyroid (lingual thyroid) or athyreosis
T4
primarily bound to thyroxine-binding globulin, but also binds w/ lesser affinity to other proteins
free unbound T4 is active, enters cells & converted to T3
primary hypothyroidism
d/t defective or absent thyroid
secondary hypothyroidism
d/t defective TSH synthesis or action (hypothalamic or pituitary hypothyroidism)
congenital
dz developed in utero
acquired
onset usually >6 mo of age
low FT4 diagnoses
hypothyroidism
high TSH diagnoses
primary hypothyroidism
low FT4, low/normal TSH suggests
central pituitary hypothyroidism
mildly high TSH that is incompletely glycosylated can result in
hypothalamic hypothyroidism d/t lack of TRH and therefore has decreased biological activity
congenital hypothyroidism basics
1 in 3500/4000 newborns
girls affected twice as often as boys
most cases are sporadic- only 10-15% are inherited defects
primary congenital hypothyroidism
90% d/t thyroid dysgenesis: athyreosis, ectopia, or hypoplasia
toxoplasmosis
Down syndrome
defective hormonogenesis d/t enzyme defects
secondary congenital hypothyroidism
TSH or TSH-receptor defects
transplacental maternal TSH-receptor blocking antibodies (secondary to maternal autoimmune thyroiditis), causing transient fetal hypothyroidism
maternal iodine deficiency
congenital hypothyroidism during the 1st 2 wks of life
large fontanelles
hypothermia
poor feeding
prolonged jaundice
congenital hypothyroidism beyond 1 month of age
darkened, mottled skin
labored breathing
diminished stool frequency
lethargy
congenital hypothyroidism after 3 months
umbilical hernia infrequent, hard stools dry skin w/ carotenemia macroglossia generalized swelling (myxedema)
acquired hypothyroidism 6 mo-3 yrs
deceleration of linear growth
umbilical hernia
dry skin w/ carotenemia
macroglossia, hoarse cry
acquired hypothyroidism during CH
delayed eruption of teeth, shedding of primary teeth
m. weakness, pseudohypertrophy
infrequent, hard stools
precocious sexual development: breast development or enlarged testes w/o sexual hair
generalized swelling (myxedema)
causes of acquired hypothyroidism
drug-induced hypothyroidism via meds- in breastmilk, lithium, propylthiouracil (PTU), methimazole endemic goiter (iodine deficiency) Hashimoto's thyroiditis (autoimmune) irradiation excision
Hashimoto’s thyroiditis
aka chronic lymphocytic, chronic autoimmune thyroiditis
insidious onset
firm, freely moveable, painless goiter (occasional sensation of tracheal compression)
hoarseness, dysphagia
T4, FT4 usually nml (may be elevated-hashitoxicosis, early- or depressed- late)
TPOAb & TGAb usually present, thought titers often low
what is the MCC of goiter & acquired hypothyroidism
hashimoto’s thyroiditis
what may decrease the size of a goiter, but is not needed in euthyroid pt’s
L-thyroxine
hypothyroidism is the end result of what
autoimmune thyroiditis, usually in 2nd/
acute suppurative thyroiditis
infection via patent thyroglossal duct
deQuervain’s (subacute) thyroiditis
caused by mumps, EBV, influenza, echovirus, coxsackievirus, adenovirus
acquired autoimmune-mediated infantile hypothyroidism
other rare thyroiditis
hypothyroidism complications
untreated hypothyroidism results in impaired intellect- can be severe & irreversible in infants w/ congenital dz
typically reversible in CH>3 yrs who develop acquired dz
what is the MC result of untreated acquired hypothyroidism in CH?
decreased linear growth
untreated acquired hypothyroidism in CH can also be assoc. w/
hypercholesterolemia slowed school performance slipped capital femoral epiphysis chronic constipation most are reversible w/ tx
Levothyroxine (L-thyroxine)
must be individualized d/t individual differences in absorption & metabolism
over tx w/ L-thyroxine can result in
early closure of cranial bones
L-thyroxine should not be given at the same time as what?
soy or iron-enriched formula
supplemental iron or Ca2+
fiber supplements
these impair absorption
Monitoring L-thyroxine
careful monitoring of TSH/FT4 until values normalize
after 3 yrs of age, annual monitoring of TSH (primary hypo) & FT4 (secondary or central) is adequate
hypothyroidism screening
if TSH is elevated a confirmatory serum test is required
start tx ASAP while waiting on confirmatory tests
prior to neonatal screening pts w/ hypothyroidism presented w/
neurologic impairment protrusion of tongue thick dark hair mottling umbilical hernia widened fontanelles consistent w/ delayed bone maturation
screening for hypothyroidism in healthy children
monitor ht & growth velocity annually
should be at least 5 cm/yr for CH ages 4 to onset of puberty
hyperthyroidism
overactive thyroid
95% of CH cases are d/t Graves dz
-autoimmune, Ab-mediated stimulation of thyroid
-thyroid stimulating immunoglobulins (TSI) directed against TSH receptors
can manifest as thyrotoxicosis
graves dz
autoimmune d/o occurs in 1/5000 CH -most commonly seen in adolescents -only 2% present before age 10 5x's more common in females than males FH is common can occur in conjunction w/ other endocrine d/o can be cyclic w/ spontaneous remissions & exacerbations
Clinical presentation of Graves dz
- difficulty concentrating & sleeping, nervousness, fatigue
- facial flushing, sweating, heat intolerance
- tremors, palpitations
- wt loss despite increase in appetite
- diarrhea
- proximal m. weakness
- palpitations, tachycardia, systolic HTN w/ wide pulse pressure, overactive precordium
- goiter (diffusely enlarged, soft), proptosis
- menstrual irregularities
Graves dz lab findings
elevated T4 & FT4, TSH low
I-123 uptake elevated, not suppressed w/ T3
TGAb & TSI often found in 95%
bone findings in Graves dz
advanced skeletal maturation
premature closure of cranial sutures
osteoporosis w/ longstanding hyperthyroidism
tx of hyperthyroidism
B-blockers- large doses of propranolol can decrease conversion of T4 to T3
Iodide for acute mngt- blocks the effect of TSH on thyroid, reduces iodine trapping, reduces vascularity, inhibits release of hormone
Thioamides for treating hyperthyroidism
reduce hormone production, may take 2-3 wks for a response
-propylthiouracil (PTU)
-methimazole (MMI)
both cross placenta, but PTU preferred during pregnancy
both present in breastmilk, but concentrations so low that they are not a CI
PTU
blocks peripheral conversion of T4 to T3
MMI
longer half life
carbimazole converts to MMI
Side effects of PTU & MMI
pruritic papular/urticarial rash hair loss joint pain/stiffness nausea, HA transient granulocytopenia rarely, agranulocytosis occurs requiring discontinuation of drug
radioiodine ablation
oral I-131 concentrates in thyroid
cure rate 90%
for people who have sig SE from meds or who do not achieve remission w/ drug therapy
perm. hypothyroidism occurs in 40-80%
avoided in young CH since risk of thyroid CA after radiation greates in children <5 yrs
surgical thyroidectomy (subtotal or total)
for those who fail medical therapy, have significant SE, have large (>80g) goiters, or severe opthalmopathy
cure rate 90%
Potential complications of surgical thyroidectomy
hypoparathyroidism
recurrent laryngeal n. damage
permanent hypothyroidism
neonatal hyperthyroidism
newborns of affected mothers are at risk for thyrotoxicosis b/c TSIs cross the placenta
-duration after birth depends on 1/2 life of maternal Abs, ranging from wks to months
neonatal hyperthyroidism can present w/
arrhythmias
heart failure
exopthalmos
long term sequelae of neonatal hyperthyroidism
craniosynostosis
cognitive defects
rebound hypothyroidism
tx of neonatal hyperthyroidism includes
iodide followed by PTU or MMI
- reserpine/propranolol may be needed for arrhythmias
- transection of thyroid isthmus may be considered if there is RDS d/t tracheal compression
Diabetic ketoacidosis is defined as
Arterial pH less than 7.5
Bicarbonate less than 15
Ketonemia/ketonuria
