Endocrine Lecture Flashcards
What is the path of endocrine disorders?
🙣 Alteration in regulation of feedback system –
hyposecretion or hypersecretion of hormone
What factors cause hypo vs. hyper secretion of hormones?
🙢 Tumors
🙢 Trauma
🙢 Infections
🙢 Systemic or genetic disorders
🙢 Congenital disorders
🙣 Defect can originate at the pituitary-hypothalamic level, in organs, or elsewhere leading to unresponsiveness to endogenous hormones
🙣 Metabolic disorders – inborn errors causing disrupted
biochemical functioning
Endocrine pathologies may be assessed by considering
the following?
🙣 Growth disturbance / disorders
🙣 Abnormal pubertal / sexual development
🙣 Adrenal conditions
🙣 Thyroid conditions
🙣 Diabetes mellitus, types 1 and 2
🙣 Posterior pituitary gland dysfunction
What may be the first sign of an endocrine disorder?
🙣 Deviation from normal growth may be first sign of
endocrine disorder
Primary growth disorders?
🙣 Primary growth disorders – skeletal dysplasias,
chromosomal abnormalities, genetic short stature
Secondary growth disorders?
undernutrition, chronic disease, endocrine disorder, idiopathic delay
Factors Inhibiting Normal Growth?
🙣 Gastrointestinal disease
🙢 Celiac disease
🙢 Inflammatory bowel disease
🙢 Cystic fibrosis
🙣 Cardiovascular disease
🙢 Cyanotic heart disease
🙢 Congestive heart
failure
🙣 Renal disease
🙢 Uremia
🙢 Renal tubular acidosis
🙣 Hematologic disorders
🙢 Chronic anemia
🙣 Inborn errors of
metabolism
🙣 Pulmonary disease
🙣 Chronic infection
🙣 Anorexia nervosa
Growth Hormone (GH) Deficiency
🙣 Deficiency in the GH released by the pituitary
🙣 GH released in large bursts while sleeping
What do you see on physical exam in growth hormone deficiency?
dysmorphic features, midline defects, increased cranial pressure, thyroid, puberty, measures of body proportions, proportional short stature
What dx studies are used for growth hormone deficiency?
🙣 Diagnostic studies – evaluate for hypoglycemia, CBC, ESR, CMP, UA, growth hormone levels, TSH, free T4, bone age, celiac panel, stool studies, karyotype to rule out Turner syndrome in girls, Zn and Fe levels
What is constitutional growth delay?
🙢 History – normal length/weight at birth; slowed linear growth at 1-3 years; height at or just below 3rd percentile;
delayed puberty;
history of similar pattern in family
🙢 Physical examination – delayed bone age/normal growth
velocity for bone age, normal neurological exam
True or False constitutional growth delay is not a disease
True!
🙣 Delayed bone age with normal growth rate for bone age
What is growth excess?
🙣Tall for family; early puberty
🙣Must rule out:
🙢 Marfan syndrome
🙢 Klinefelter Syndrome
🙢 Overnutrition may cause advancing bone
age/early onset puberty
🙢 Excess adrenal androgens or gonadal steroids
Early precocious puberty?
🙣 Onset of pubertal signs prior to the normal age
(<8F,
<9M)
🙣 95% of girls will have signs of puberty at age 12 and
achieve menarche by age 14
🙣 85% of boys have increased testicular volume between 9 and 14 years
🙣 Premature adrenarche – early onset of pubic/axillary hair; not associated
with other features; usually idiopathic
increased risk of PCOS
Premature thelarche
isolated breast development without other signs
True precocious puberty – early onset of multiple features of puberty
bone age, LH, FSH, estradiol or testosterone; pelvic US in girls, testicular US in boys
Additional Diagnostic Studies - True precocious puberty:
🙢 Bone age
🙢 LH, FSH, estradiol or testosterone – with sensitive assay to detect early pubertal values (lower normal range).
🙢 If LH and FSH are high (in pubertal range: indication of central etiology) -
MRI to exclude CNS tumor.
🙢 If LH and FSH are low (in prepubertal range: indication of peripheral puberty) – initiated in ovaries, testicles, adrenal glands or pituitary gland.; Hypothalamic gonadotropin-releasing hormone (GnRH) stimulation test distinguishes central from peripheral puberty.
🙢 If etiology is peripheral puberty:
🙣 Pelvic ultrasonography of girls
🙣 Testicular ultrasonography of boys
🙣 Serum 17-OHP to rule out a severe form of CAH (congenital adrenal
If LH and FSH are high
in pubertal range: indication of central etiology)
If LH and FSH are low
(in prepubertal range: indication of peripheral puberty)
Hypothalamic gonadotropin-releasing hormone (GnRH) stimulation test distinguishes?
distinguishes central from peripheral puberty.
Early and Precocious Puberty
🙣 Accelerated linear growth, breast development, penile enlargement, pubic hair
🙣 Usually idiopathic in girls; 30% of boys have CNS tumors
Delayed Puberty
> 14 years in boys
Delayed Puberty
🙣 >14 years in boys;
> 13 years in girls with no clinical
features of puberty or lack of progression
🙣 Girls should progress to menarche _ years after
thelarche
5
🙣 Boys should attain Tanner stage 5 within 4.5 years
🙣 Most common cause is constitutional growth delay
What is the most common cause for delayed puberty?
constitutional growth delay
Delayed Puberty Etiology?
🙢
Constitutional Growth Delay – Primary Cause
delayed puberty etiology delayed bone age?
endocrine diseases
Delayed Puberty Etiology
🙣 Hypothalamic Pituitary Dysfun🙢ction (LH/FSH Deficiency)
🙢 Kallmann syndrome (anosmia and gonadotropin deficiency)
🙣 Gonadal Failure
Girls
🙢 Turner syndrome
🙢 Oophoritis
🙢 Galactosemia
🙢 Chemotherapy induced
Boys
🙢 Vanishing testes syndrome (in utero testicular torsion)
🙢 Chemotherapy or radiation
🙣 Adrenal gland steroids controlled by hypothalamic-
pituitary axis (HPA)
Corticotropin-releasing hormone (CRH) stimulates
production/secretion of ACTH by pituitary
🙣 ACTH regulates adrenal glucocorticoid (cortisol) and
androgen production
🙣 Adrenal gland also produces mineralocorticoid hormones (aldosterone) regulated by renin- angiotensin system
Cortisol
🙣 highest in the morning, low in the afternoon and
evening, and lowest at midnight.
Cortisol is secreted in response to?
🙣 secreted in response to hypoglycemia, hypotension,
pain, or other stressful events,
Cortisol?
🙣 has negative feedback on the synthesis and secretion
of CRH, vasopressin, and ACTH
Adrenal Insufficiency
🙣 Deficiency of hormones produced by adrenal cortex
🙣 Deficits of cortisol/aldosterone most detrimental
Primary adrenal insufficiency?
🙣 Primary adrenal insufficiency –
deficiency of both
1. mineralocorticoid
2. glucocorticoid
🙣 Secondary adrenal insufficiency?
deficiency only of
glucocorticoid
Physical exam for adrenal insufficiency?
🙣 Physical examination – dehydration, hypotension, excessive
pigmentation of skin/mucosa
DX tests for adrenal insufficiency?
🙣 Diagnostic studies – CMP (glucose), ABGs (metabolic acidosis), electrolytes (hyponatremia, hyperkalemia – aldosterone deficiency) , serum cortisol (>20 indicates sufficiency; <20 requires further evaluation) ), ACTH (elevated in primary adrenal insufficiency), 17-OHP, renin (elevated in aldosterone deficiency) and aldosterone levels (decreased in aldosterone deficiency)
Most common cause of preventable mental retardation?
congenital hypothyroidism
If hypothyroidism is untreated what happens?
irreversible brain damage, growth failure, deafness, neurological abnormalities
acquired hypothyroidism
Hashimoto’s thyroiditis – autoimmune disorder – most
common cause in children in the western world
🙣 Iodine deficiency – most common cause worldwide
What do you see on physical exam with hypothyroidism?
🙣 Congenital hypothyroidism usually detected in NB screening
🙣 NB PE may appear normal
🙣 Prolonged jaundice
🙣 Constipation
🙣 Umbilical hernia
🙣 Large fontanelles
🙣 Macroglossia
🙣 Decreased muscle tone
🙣 Poor feeder
🙣 Poor peripheral circulation
🙣 Cool, cyanotic skin in extremities.
What do you see in older children with hypothyroidism?
🙣 Delayed/subnormal growth velocity
🙣 Goiter
🙣 Weight gain
🙣 Delayed DTRs
🙣 Dry skin
🙣 Poor dentition
🙣 Down Syndrome children are at higher risk for
hypothyroidism:, test at 6m,12m, and then annually
🙣 If on thyroid replacement, recheck TSH, free T4 4-6
wks. after dosage change
🙣 Hypothyroidism – replacement with levothyroxine with frequent monitoring/more often in children <3 years
Age
🙣 0-3 months
🙣 3-6 months
🙣 6-12 months
🙣 1-5 years
🙣 6-12 years
🙣 >12 years
🙣 10-15
🙣 8-10
🙣 6-8
🙣 5-6
🙣 4-5
🙣 2-3
Hyperthyroidism
🙣 Overproduction of thyroid hormone or excessive
thyroid replacement
🙣 Graves’ disease (autoimmune disease) – most common
Hyperthyroidism
🙢
History
🙣increased appetite with weight loss,
🙣fatigue
🙣muscle weakness
🙣emotional lability,
🙣poor concentration,
🙣poor sleep
🙣palpitations
🙣goiter
🙣thyroid bruit
🙣tachycardia
🙣wide pulse pressure
🙣Underweight
🙣exophthalmos
🙣warm/moist skin
🙣tremor
🙣hyperreflexia
Inborn Errors of
Metabolism
🙣Assessment of any critically ill neonate, infant, child
Disorders of Carbohydrate
Metabolism
Inability to metabolize
🙢 Monosaccharides – glucose, galactose, fructose
🙢 Polysaccharide – glycogen
🙣 Aberrant glycogen synthesis/disorder of
gluconeogenesis
🙣 Glycogen Storage Diseases
🙣 Galactosemia
🙣Galactosemia
🙢 Disorder of galactose metabolism
🙢 Dietary galactose principle carbohydrate in human milk, non-soy formulas
🙣 Diagnostic studies – newborn screen, urine reducing substances after feeding; GALT activity in RBCs deficient; galt-1-P levels elevated
Galactosemia
Urea Cycle Disorders
🙣 Defect in any enzyme of urea cycle –
hyperammonemia; inability to detoxify waste nitrogen
🙣 Ammonia is end product – toxic to CNS
Urea Cycle Disorders
🙣 Clinical findings – hyperammonemia begins after
protein ingestion –
🙣 Clinical findings – hyperammonemia begins after
protein ingestion –
ammonia level= >100
urea cycle disorders
🙢 Acute care to establish source of glucose/rapidly decrease ammonia levels
🙢 Chronic care – reduce protein consumption
🙢 Vulnerable to metabolic decompensation, mental retardation, death
Amino Acid Metabolism Disorders: Aminoacidopathies and
Organic Acidurias and Acidemias
🙣 Most common: PKU, maple syrup urine disease
Organic Acidur🙢ias and Acidemias
🙣Phenylketonuria (PKU)
🙢 Deficiency of phenylalanine hydroxylase
PKU management
🙣Management
🙢 Limiting dietary intake of phenylalanine
🙢 Goal of serum phenylalanine – 120-360 mmol/L
🙢 Modified formula
🙢 Limited phenylalanine for life
🙢 Strict control in pregnant females with PKU
🙢 Referral to dietician
🙣Homocytinuria
🙢Cystathionine synthase deficiency
🙣 Management/complications
🙣 Vitamin B6 for some children
🙣 Frequent monitoring of homocystine/methionine
🙣 High risk for metabolic stroke
🙣 Untreated – ocular lens dislocation, progressive mental retardation, thromboembolic events, convulsions
🙣 Clinical findings – does not usually present in children;
screen those at risk
dyslipidemia
