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Lectures > Pediatric endocrine disorders > Flashcards

Pediatric endocrine disorders Flashcards

1
Q

Normal and abnormal growth

A

Normal growth - mediated by multiple growth factors and nutrition

  • in utero –> insulin and other growth factors are most important; growth hormone is less important
  • postnatally –> growth hormone becomes the predominant growth factor

Abnormal growth - any deviation from the standard normal curve –> too short or too tall

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2
Q

Causes of tall stature

A
  • obesity
  • precocious puberty
  • growth hormone excess –> gigantism/acromegaly depending on whether or not the epiphyses have fused
  • hyperthyroidism
  • genetic (tall parents)
  • klinefelter syndrome
  • marfan syndrome/homocysteinuria –> suspect if arm span is taller than the height
  • overgrowth syndromes
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3
Q

Overgrowth syndromes

A

Beckwith-wiedeman - 11p15

  • macroglossia
  • hypoglycemia
  • macrosomia (excessive birth weight)
  • abdominal wall defects
  • ear creases
  • neoplasms

Sotos syndrome - NSD1 gene

  • cerebral gigantism (large head)
  • grow quickly in childhood but normal adult height

Weaver’s syndrome

  • fetal and childhood overgrowth
  • dysmorphic facies
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4
Q

When is evaluation for short stature needed?

A
  • child is crossing percentiles –> this is normal early in life, but after the age of 4, a child who is growing at the 75th percentile should continue to do so; would be concerning if they all of a sudden started growing at the 25th
  • child is below 3rd percentile
  • child is outside of genetic expectations
  • child/family are having concerns
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5
Q

Diagnostic considerations for short stature - systemic and genetic diseases

A

Systemic disease

  • GI/nutrition - inflammatory bowel, celiac, malnutrition
  • renal - chronic renal insufficiency, RTA
  • resp - CF or severe asthma
  • cardiac - cyanotic disease of CHF
  • ENT - obstructive sleep apnea

Genetic disease

  • skeletal dysplasia –> achondrodysplasia/hypochondroplasia
  • multiple syndromes/genetic diseases
  • mucopolysaccharidoses
  • inborn errors of metabolism
  • Turner syndrome
  • genetic (short parents)
  • idiopathic short stature/SHOX deficiency
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6
Q

Diagnostic considerations for short stature - Prader willi syndrome

A

Association with deletion or uniparental disomy of chromosome 15q-

  • occurs in 1/15,000 births
  • at birth –> hypotonic, poor feeders, have failure to thrive, delayed motor skills, decreased muscle mass
  • age 3-4 –> develop hyperphagia and become very obese
  • developmental delay, behavioral problems
  • hypogonadism/delayed puberty
  • usually develop short stature
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7
Q

Diagnostic considerations for short stature

  • constitutional delay of growth and devt
  • small for gestational age
  • psychological deprivation
A

Constitutional delay of growth and development – late bloomers

Small for Gestational age (SGA) - Birth weight and/or length at least 2 SD below mean for gestational age

  • –> of the 3 % of babies born SGA, about 10 % do not show catch up growth by age 2 - 3 years
  • –> these children are GH resistant and will grow in response to higher than typical doses of GH
  • –> may be related to variations in the IGF-1/IGF-1 receptor haplotypes
  • –> SGA children have insulin resistance and are at increased risk for Type 2 diabetes and obesity

Psychosocial deprivation – children with extensive chronic stress/neglected don’t grow as well – removal from environment stimulates normal growth

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8
Q

Diagnostic considerations for short stature - endocrine disease

A
  • hypothyroidism
  • cushing syndrome/adrenal insufficiency
  • growth hormone deficiency
  • growth hormone resistance –> laron dwarfism
  • turner syndrome
  • hypoparathyroidism
  • Rickets
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9
Q

Diagnostic considerations for short stature - SHOX mutation

A

The SHOX (short stature homeobox containing) gene encodes isoforms of a homeodomain transcription factor important in human limb development

  • SHOX “haploinsufficiency” has been implicated in 3 human growth disorders = turner syndrome, idiopathic short stature, and leri-weill dyschondrosteosis (heterozygous shox mutation)
  • langer mesomelic dysplasia = homozygous form of shox mutation
  • SHOX mutations were found in 2-15% of children with idiopathic short stature
  • important to identify kids with short stature due to SHOX deficiency because they respond to treatment with GH
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10
Q

Pediatric growth hormone deficiency

  • clinical features
  • causes
  • diagnosis
A

Clinical features
- normal size at birth, growth failure after 6 months, excessive adiposity, +/- hypoglycemia

Causes

  • isolated - idiopathic/genetic
  • multiple pituitary hormone deficiency –> genetic, traumatic delivery, midline defects
  • CNS tumors
  • CNS trauma
  • irradiation
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11
Q

Pediatric growth hormone deficiency

  • diagnosis
  • treatment
A

Diagnosis
- gold standard = lack of appropriate peak GH after provocative stimuli –> hypoglycemia, arginine, L-dopa, clonidine

Treatment - GH at 0.3 mg/kg/week given subQ 6 days/week until height velocity <2cm/year or bone age = 15 in girls/17 in boys

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12
Q

Adult growth hormone deficiency

A
  • diagnosed by GH stim test
  • GHD adults have increased osteoporosis, hypercholesterolemia, poor lean body mass, greater cardiac risk and poorer quality of life
  • problems reverse with therapy
  • therapy may increase risk of cancer and diabetes
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13
Q

Short stature interventions

A
  • treat underlying cause of short stature
  • growth hormone treats a number of conditions but is very expensive
  • options to slow puberty so that there is longer time for linear growth
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14
Q

Differential diagnosis of short stature

A

Dysmorphic appearance

  • abnormal karyotype –> turners or trisomy 21
  • normal karyotype –> consider other genetic causes

normal appearance

  • weight > height –> GH deficiency, hypothyroidism, cushings
  • weight = height –> idiopathic short stature, familial short stature, constitutional growth delay
  • height > weight –> consider malnutrition states or excess energy expenditure
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15
Q

Normal puberty

A

Girls

  • onset (breast bud) age 8-13
  • menarche within 5 years from breast bud development

Boys
- onset (testicular enlargement) age 9-14

Recent studies have shown that early signs of puberty (breast budding in girls ages 6-8) are common and usually non-pathologic, especially in african american girls

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16
Q

Pubertal evaluation

A

Lab evaluation

  • increase in 89 AM LH, FSH, estradiol/testosterone
  • GnRH stimulation testing –> can differentiate central from peripheral precocious puberty

Bone age evaluation –> children with precocious puberty will have accelerate bone development

17
Q

Differential diagnosis for delayed puberty in a girl

A
  • Turners syndrome
  • Primary gonadal failure
  • Pituitary dysfunction
  • hypothalamus - anorexia, Kallman’s syndrome (no pulses of GnRH)
  • androgen insensitivity syndrome –> genotypic male but androgen receptor mutation prevents action of testosterone, so phenotypically female
  • constitutional delay –> late bloomer
18
Q

Differential diagnosis for delayed puberty in a boy

A
  • constitutional delay –> more common in boys
  • primary gonadal failure
  • –> Kleinfelter syndrome
  • –> XY gonadal dysgenesis
  • –> cryptochidism/anorchism
  • pituitary lesion
  • hypothalamus - Kallman’s syndrome –> people with kallman also can’t smell, so this might be a clue as to this etiology
19
Q

Treatment of delayed puberty

A
  • treat underlying problem
  • begin low dose estrogen in girls, then increase dose and begin cycling with added progestin
  • begin low dose testosterone in boys, increase dose over time to adult dosing
20
Q

Precocious puberty - terminology

A

True precocious puberty - gonadotropin dependent

  • breasts and pubic hair in girls
  • testicular enlargement and pubic hair in boys

Premature thelarche - breasts only, before age 8

Premature adrenarche - pubic hair only, before age 8

21
Q

Initial evaluation of precocious puberty

A
  • history and physical
  • get bone age to determine how aggressive the process is –> if they have a lot of estrogen/testosterone, their bones will look much older than their age
  • determine if gonadotropin-dependent vs. gonadotropin independent –> if you have a high estrogen level but low FSH/LH, we know the estrogen is coming from somewhere else in the body
  • differentiate by 8 AM labs or GnRH stim test
22
Q

Causes of central precocious puberty

A
  • 10x more common in females
  • for females - idiopathic 85-95% of time
  • for males - tumor risk = 20%
  • CNS lesions - trauma, hypothalamic hamartoma, cranial irradiation, craniopharyngioma, meningitis
  • peripheral precocious puberty can push pituitary into starting central precocious puberty –> if the pituitary sees estrogen coming from anywhere, it will think its ok to start secreting GnRH
23
Q

Causes of peripheral/gonadotropin-independent precocious puberty - girls

A
  • exogenous sex steroids –> OCPs, estrogen creams
  • ovarian cyst
  • gonadal hypersecretion = McCune-albright syndrome –> triad of gonadal hypersecretion, polyostotic fibrous dysplasia, and cafe-au-lait spots
  • –> can have other endocrinopathies
  • –> caused by Gs-protein mutation that causes gene to be constitutively turned on
  • ovarian or adrenal tumor
  • ectopic estrogen secreting tumor
  • hypothyroidism (severe) –> TSH subunit is the same as FSH, so appears to ovaries as FSH in high concentrations, and triggers ovarian secretion of estrogen
  • –> does not spontaneously reverse when hypothyroidism is treated and TSH goes down
  • –> girls only
  • non-classic CAH
24
Q

Causes of peripheral/gonadotropin-independent precocious puberty - boys

A
  • non-classical CAH
  • testicular hypersecretion –> familial male precocious puberty = mutation in LH receptor so it is stuck in “on” position
  • exogenous steroids –> testosterone gel/cream
  • testicular or adrenal tumor
  • McCune albright syndrome
  • ectopic tumor - androgen or hCG secreting (hepatoblastoma)
25
Q

Treatment for precocious puberty - factors to consider

A

Factors to consider in treatment

  • treat underlying pathology, if any
  • preservation of adult height outcome (get height prediction from bone age) –> most of these kids have accelerated bone age, so even though they look tall now they will probably stop growing sooner than they should
  • appropriate timing of menarche
  • important to consider the burden and expense of therapy
26
Q

Treatment of gonadotropin dependent precocious puberty

A

GnRH agonists

  • leuprolide depot –> given as IM shot monthly or every 3 months
  • histrelin –> implants last 1 year

You need gnrh to pulse in order to stimulate pituitary hormones, so if you just overwhelm it by giving a steady stream it will stop activating the pituitary from secreting LH/FSH

27
Q

Treatment of gonadotropin independent/peripheral precocious puberty

A
  • aromatase inhibitors –> testolactone, anastrazole, letrozole
  • steroid pathway blockers –> ketoconazole
  • androgen receptor blockers –> spironolactone
  • estrogen receptor blockers –> tamoxifen
28
Q

Premature thelarche

A
  • idiopathic –> usually benign and self limited; seen in 1-3% of toddler girls
  • ovarian cyst/hypersecretion –> may be episodic or progressive
  • exogenous estrogens –> got into mom’s OCPs

differentiate from true precocious puberty by looking at growth pattern, bone age and other signs

29
Q

Premature adrenarche

A
  • idiopathic –> often does not lead to central precocious puberty
  • non-classical CAH –> milder form of CAH, may lead to central precocious puberty, hirsutism, severe acne, altered fertility
  • adrenal/gonadal tumor –> rare, usually progressive process

Differentiate from true precocious puberty by looking at growth pattern, bone age and other signs

30
Q

Disorders of sexual development

A

Congenital Adrenal Hyperplasia - most common = virilization of female infant + under virilization of male infants

Ovotesticular DSD - both ovarian and testicular tissue in gonads, “true hermaphroditism”
Androgen Insensitivity Syndrome- complete and partial – 46XY phenotypic female
- complete will look totally female
- partial may have some tissues that respond to testosterone so may be some virilization

5 alpha reductase deficiency – may present with ambiguous genitalia, won’t have peripheral conversion of testosterone to DHT which is what is necessary to virilize the male genitalia  often develop enough testosterone during puberty to have normal testicular development so should be raised as male

31
Q

Pediatric presentations of other endocrinopathies

A

Adrenal = CAH

Thyroid = congenital hypothyroidism

Calcium = DiGeorge syndrome

32
Q

CAH

A

Caused by a mutation in one of P450 enzymes in cholesterol to steroid pathway
- 21-hydroxylase deficiency is most common form, occurs ~ 1:10,000 births
- common cause of ambiguous genitalia
- Causes salt-wasting due to hypoaldosteronism as well as virilization
- 46 XX females appear virilized,
but 46 XY males have a typical
phenotype and can have an adrenal crisis if not identified - this is why the newborn screen is so important!

33
Q

Congenital hypothyroidism

A
  • occurs 1/4000 births, on newborn screen in every state
  • since thyroid horomne participates in CNS myelinization, hypothyroidism during the first three years of life causes permanent loss of IQ points
  • hallmark of hypothyroidism in children is growth failure
34
Q

DiGeorge syndrome

A
  • cardiac abnormalities
  • abnormal facies
  • thymic aplasia –> results in infections
  • clef palate
  • hypoparathyroidism/hypocalcemia
  • deletion on chrom 22

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