Endocrine disorders Flashcards
Case
A 3740-g infant is delivered vaginally after an uncomplicated 38-
week gestation. Health-care providers have immediate difficulty
in determining whether the infant is a boy or girl.
The baby is born to a 27 year old primigravid, with no known comorbidities.
There is note of regular prenatal-check-up. Patient
was born with fair cry and fair activity. Patient has fair suck, but
not in respiratory distress
Physical examination
Asleep, comfortable, not in distress
HR 177, RR 55, sat 92% BP 60/40
Weight 3.7kg Length: 48 cm HC: 35
Anicteric sclerae, pink conjunctivae, no facial dysmorphisms
Equal chest expansion, clear breath sounds, no adventitious lung
sounds
Adynamic precordium, distinct heart sounds, no murmurs
Globular, NABS, no palpable masses
Patent anus, with small scrotal sacs that resemble enlarged labia
and no palpable testes with either a microphallus and
hypospadias or an enlarged clitoris. No vaginal opening is
apparent.
Complete digits, fair pulses, with CRT 5 secs
CBC
Hgb 155, Hct 0.51, WBC 15.0, Neuts 0.65, Lym 0.22, Plt 350
MCV 75, MCH 20, MCHC 25, RDW 19
Electrolytes
Na 131, K 5.2, Cl 88, glucose 110 mg/dL
ABG
pH 7.44, pCO2 45, pO2 94, HCO3 31, sats 99%
17OHP elevated
Karyotype: Standard XX chromosome on pair 23
Congenital Adrenal Hyperplasia
Autosomal recessive disorder of adrenal steroid production with
an enzymatic deficiency (usually 21-hydroxylase) causing
inadequate production of cortisol, excessive production of
androgenic intermediary metabolites, and virilization
Microphallus
*Phallic size is the most important physical exam as it can determine sex (Pediatr Rev)
-Will not present with toxic looking infant, but cannot be totally ruled out.
Virilization
*Ambiguous genitalia
-Will not present
with toxic looking infant, but cannot be totally ruled out.
Neonatal sepsis
*Due to hypotension and poor perfusion
-Ambiguous genitalia is not
present. But concomitant illness has to be ruled out
Inborn error of
metabolism
*Presence of hypotonia, with toxic looking infant
-Ambiguous genitalia is not
present. But concomitant illness has to be ruled out
True hermaphroditism
(Sex chromosome DSD, ovotestis,
mixed gonadal dysgenesis)
-Ambiguous
genitalia Will not present
with toxic looking infant,
but cannot be totally ruled out.
CBC+/- blood cultures to rule out sepsis
Electrolytes and fingerstick glucose
ABG check for acidosis for IEM
Newborn screen, confirmatory 17OHP
Karyotype as emergency
Abdominal ultrasound to check for gonads
Management
Fluid resuscitation – fluid maintenance – replace salt loss
Maintain normoglycemia
Hydrocortisone supplementation (think fludrocortisone
supplementation)
General Pediatrics
Chronic therapy with oral hydrocortisone and fludrocortisone
Address dose adjustment during acute stress
Growth monitoring, immunization, etc.
CH 576-580: ADRENAL DISORDERS
Adrenal gland
1) Cortex – steroid synthesis
a. Glomerulosa – aldosterone (Na retention, K secretion)
b. Fasciculata – cortisol
c. Reticularis – sex steroids (androgen, DHEA)
2) Inner medulla – catecholamines (dopamine, E, NE)
What is CAH?
CONGENITAL ADRENAL HYPERPLASIA (CAH)
Etiopatho
- Autosomal recessive disorder of cortisol synthesis
leading to inc secretion of ACTH (corticotropin) causing
adrenal hyperplasia and overproduction of metabolites
- Deficiency of 21-hydroxylase (90%)
o Causes excess substrates shunted towards
synthesis of sex hormones
o Adrenal insufficiency + ambiguous genitalia
(F infants)
o Lack of 21hydroxylase à no cortisol and
aldosterone à shunting of substrates
towards testosterone/estradiol production
o Common in PH (1:10,000)
What are the clinical manifestations of CAH?
CM
1. Progressive wt loss, anorexia, vomiting, dehydration
2. Weakness, hypotension
3. May appear at 2wks of age
4. Shock, arrythmia, death
What are the types of CAH?
Salt-losing, classic form
Simple Virilizing, classic form
Non-classic form
What is the salt-losing, classic form?
-70% of patients with classic 21-hydoxylase deficiency
-wt loss, anorexia, nausea, vomiting, weakness, salt craving
-hypoglucemia, hyponatremia, hyperkalemia, metabolic acidosis
-symptoms appear at 10-14 days of age
-signs of virilization
What is simple virilizing, classic form?
-30% of patients with classic 21-hydroxylase deficiency
Signs of virilization:
*female infants: ambiguous genitalia/masculinized external genitalia (clitoral enlargement, labial fusion, urogenital sinus)
*Male infants: appear normal at birth. postnatal signs of androgen excess include rapid somatic growth, accelerated skeletal maturation, stunting, pubic and axillary hair, acne, deep voice, enlarged penis, scrotum and prostate but prepubertal testes
What is the nonclassic form?
-attenuated, late onset form of adrenal hyperplasia
-may be asymptomatic, or may have precocious adrenarche, hirsutism, acne, menstrual irregularity, infertility
How is CAH diagnosed?
Dx
1. Inc serum 17-OHP – most reliable to establish 21-
hydroxylase deficiency
2. Low serum cortisol
3. Elev ACTH, renin
4. Low aldosterone (inappropriate for renin level)
5. Hypoglycemia, hyponatremia, hyperkalemia
6. NBS and confirmatory tests (17-OHP, serum Na, K, RBS)
APPROACH to infant with GENITAL AMBIGUITY
APPROACH to infant with GENITAL AMBIGUITY
- PE – note where urethral opening lies and check fusion
of anterior portion of labioscrotal folds
- If vaginal opening open but clitoris enlarged – late exposure to androgens
- Fully formed scrotum, normal and small penis (microphallus) – normal exposure to androgen during
9-13 wks AOG
- GOAL: identify life threatening disorders (CAH)
- 46XY (Swyer syndrome) – small phallus that does not
increase in size after androgen therapy à usually
raised as female, some revert to male gender
1. First step: determine whether
- virilization of female
- underdevt of male
2. UTZ to check for organs
3. Karyotype determination
4. Usually CAH in females – determine level of 17OH and
androstenedione; Harder in males
How is CAH managed?
Mgt
1. Correct shock and dehydration
- 1st hr: D5%NSS 20 ml/kg
- Maintenance IVF: correct e’ abN
2. Replace deficient hormones
a. CS – inhibit excessive production of androgens and prevent progressive virilization
o Hydrocortisone initially 100 mg/m2 IV then
100 mg/m2 in the next 25h, then 15-
20mg/m2/d in 3 divided doses
o Double/triple doses during periods of stress
(surgery, infection)
o Continued indefinitely in classic 21- hydroxylase deficiency
o Monitor growth and hormonal levels
o At or near completion of linear growth (puberty): Prednisone/Prednisolone,
Dexamethasone
b. Fludrocortisone 100 mcg/tab 0.05-0.10 mg/m2– mineralocorticoid replacement
3. NaCl supplementation 1g/tab OD – for salt-losing ds
- 1g NaCl = 17 mEq Na
4. Surgery – for ambiguous genitalia
Surgical restoration:
- gonads and internal organs discordant to gender
decide to be removed
- dysgenetic gonads with Y material remove to prevent
gonadoblastomas or dysgerminoma
- reconstructive surgery usually at 2 years old
5. Psychological support
What is Addison disease?
Patho
- Acquired primary adrenal insufficiency
- Early: isolated cortisol deficiency
- Late: all adrenocortical fxn lost
Etiology
- MC: autoimmune destruction of adrenal glands,
usually sparing the medulla
- Infection (MC: meningococcemia (Waterhouse- Friderichsen syndrome)
- Drugs (ketoconazole, mitotane, etomidate)
- Hemorrhage from child abuse/anticoagulant use
What are the clinical manifestations of Addison disease?
CM
1. Muscular weakness, malaise, anorexia, nausea,
vomiting, weight loss, orthostatic hypotension, salt
craving
2. Inc skin pigmentation (skin creases, mucosa, scars)
3. Acute decompensation (adrenal crisis) during minor
infectious illness
Diagnostics of Addison
Blood:
*low serum Na, increased K
*hypoglycemia, ketosis, acidosis
*high ACTH with low or inappropriately normal cortisol and aldosterone
*most definitive test: measurement of serum levels of cortisol before and after administration of ACTH (cortisol is low and does not increase normally after ACTH administration)
urine electrolytes:
*elevated urinary excretion of Na and Cl-
*low urinary excretion of K
Management of Addison
For acute Adrenal Insufficiency:
*D5 0.9 NSS IV: to correct hypoglycemia, hypovolemia, hyponatremia
*Hydrocortisone succinate:
-IV bolus then divided doses every 6 hours for 1st 24 hours (50mg/m2 IV bolus then 25-100 mg/m2/day as IV infusion or in divided doses every 6 hours), or
*As much as 10mg for infants, 25mg for toddlers, 50mg for older children and 100mg for adolescents administered as bolus, and similar amount in divided doses every 6 hours for the first 24 hours
Chronic replacement therapy:
*Hydrocortisone 10mg/m2/day in 3 divided doses, or equivalent doses if prednisone twice daily
*Fludrocortisone if with aldosterone indufficiency
*Monitor ACTH levels
*Prevention of adrenal crisis:
Increase in hydrocortisone dose 2-3 fold during stress (infection/surgery(
*Advise parents to visit ER if with persistent vomiting and unable to tolerate oral hydrocortisone
What are the clinical manifestations of pheochromocytoma?
CM
1. HTN – sustained > paroxysmal
2. Headache, palpitations, abdominal pain, dizziness,
pallor, vomiting, sweating, convulsions
3. Asx’c in between HTN
4. Polyuria, polydipsia, growth failure
5. Severe: precordial pain radiating into arms, pulmonary
edema, cardiomegaly, hepatomegaly
What are the diagnostics for pheochromocytoma?
Catecholamine levels
-elevated blood or urinary levels of catecholamines (eg. dopamine, norepinephrine, epinephrine) and metabolites (normetanephrine, metanephrine)
-predominant cathecholamine excreted in urine among children is norepinephrine
-best sensitivity and specificity: measurement of plasma metanephrine
-urinary excretion VMA is increased but no longer routinely used due to false-positive results from consumption of vanilla-containing food
Imaging
-CT, MRI - to localize tumor
-85% of tumors are found in adrenal glands, 95% are within the abdomen and pelvis
What is the management?
Mgt
1. Surgical removal of tumor
2. Pre-operative a & b-adrenergic blockade and fluid
loading
3. Transabdominal exploration of all usual sites because
tumors are often multiple
Differentials?
Cushing syndrome
Disorders of gonads and puberty
BOYS
-Complete sexual maturity is
usually achieved by 17-18yo
-Sequence of pubertal
events: testicular
enlargement, adrenarche,
continued testicular and
penile enlargement, peak
height velocity with peak
weight velocity
-gynecomastia (60%) at SMR
2-4
-ejaculation at SMR3
-voice change at SMR 3-4
-fertility established at SMR 4
GIRLS
-sequence of pubertal events:
thelarche, adrenarche, peak
height velocity, continued
breast and hair development,
menarche, completion of
puberty
-ave duration of completion
of puberty is 4 yrs
-menarche (90%) during SMR
4
-Filipino girls ave age of
menarche 13.3 yrs and cycles
may be anovulatory for 2 yrs
after menarche
-full fertility usually achieved
within 2 yrs of menarche (ave
age 14-15yo)
give the SMR stages in females
PUBIC HAIR
1-preadolescent
2-sparse, lightly pigmented, straight, medial border of labia
3-darker, beginning to curl, increased amount
4-coarse, curly, abundant, but less than in adult
5-adult feminine triangle, spread to medial surface of thighs
BREASTS
1-preadolescent
2-breast and papilla elevated as small mound; diameter of areola increased
3-breast and areola enlarged, no contour separation
4-areola and papilla form secondary mound
5-mature, nipple projects, areola part of general breast contour
Give the SMR stages in males
PUBIC HAIR
1- none
2-scanty, long, slightly pigmented
3-darker, starting to curl, small amount
4-resembles adult type, but less quantity; coarse, curly
5-adult distribution, spread to medial surface of thighs
PENIS
1-preadolescent
2-minimal change/enlargement
3-lengthens
4-larger, glans and breadth increase in size
5-adult size
TESTES
1-preadolescent
2-enlarged scrotum, pink, texture altered
3-larger
4-larger, scrotum dark
5-adult size
DISORDERS OF GONADS
Patho
-internal and ext genitalia formed at 6-13 wks AOG
-fetal gonad and external genitalia – bipotential (can develop into
male and female phenotype)
-presence of SRY –> differentiates into a testes –> Leydig cells
secrete testosterone –> converted to DHT –> causes enlargement,
rotation and fusion of the labioscrotal folds into scrotum –> forms penis
-female phenotype develops unless specific male influences alter
development
-total absence of androgens –> female
Genetic causes of hypertrophic hypogonadism
Noonan syndrome
Klinefelter syndrome
Turner syndrome
What is Noonan syndrome?
NOONAN SYNDROME
Affectation: males and females
Karyotype: Normal
Clinical:
short stature, webbing of the neck, low hairline, pectus carinatum/excavatum, right-sided CHD (mainly valvular, pulmonic stenosis), cardiomypathy, cubitus valgus, hypertelorism, downward slanted palpebral fissures, ptosis, micrognathia
Subnormal IQ, high frequency sensorineural hearing loss
cryptochordism, small testes, delayed puberty
Management: Human GH
What is Klinefelter Syndrome?
KLINEFELTER
affects males
Karyotype: 47 XXY
48 XXXY, 48 XXYY, 49 XXXYY
*diagnosis rarely made before puberty due to paucity of signs and symptoms in childhood
*behavioral or psychiatric disorders *anxious, immature, or excessively shy), learning disabilities, verbal cognitive defects, deficits in executive function
*tall, slim, long legs disproportionate to the arms
*small testes and phallus, cryptochordism, low testosterone, delayed puberty, gynecomastia, sparse facial hair, azoospermia, infertility
*increased incidence of metabolic syndrome, breast cancer, leukemia, lymphoma
Management: replacement therapy with testosterone preparation
