Endocrinology Pt. 1 Flashcards
Short stature is defined as height that is ____ standard deviations below the mean
two
What is normal variant short stature?
What is pathologic short stature?
- What is normal variant short stature?
- Describes a child whose height is below the third percentile but is growing with a normal growth velocity
- What is pathologic short stature?
- Describes a child whose height is below the third percentile but is growing with a suboptimal growth velocity
Determining the target ___ ______ ______ may be helpful in distinguishing a patient with normal variant stature from pathologic
mid-parental height (MPH)
Most children, when they have completed their growth, are within ___ SDs, or __ inches of their MPH
+/-2SDs or 4 inches
What are key components of a history for short stature?
- Perinatal history
- Chronic diseases
- Chronic use of drugs
- Family history
- Social history
What perinatal history suggests hypopituitarism?
History of hypoglycemia, prolonged jaundice, cryptorchidism, or microphallus
What drugs can lead to short stature?
Steroids, or stimulants for ADHD that result in significant appetite suppression and poor weight gain
Why is social history critical in evaluation of short stature?
Because children who live in neglected or hostile environments may exhibit short stature because of psychosocial deprivation
What are normal ratios of upper-to-lower- body segment?
Birth = 1.7
3 years of age = 1.3
> 7 years of age = 1.0
What is used to calculate the upper-to-lower body segment ratio?
Lower segment: Pubic symphysis to heel
Upper segment: Total height minus lower segment
What are the two most common categories of normal variant short stature?
Familal short stature and constitutional delay with delayed puberty
What is familial short stature?
Height at least 2 SDs below the mean with a short MPH but with a normal bone age, a normal onset of puberty, and a minimum growth of 2 inches per year
What is consitutional short stature?
Height at least 2 SDs below the mean with a history of delayed puberty in either or both parents, a delayed bone age, and late onset puberty
What are the two categories of short stature?
Proportionate or disproportionate
What are causes of prenatal onset proportionate short stature?
- Environmental exposures (in utero exposure to tobacco and alcohol)
- Chromosome disorders (Down syndrome, Turner)
- Genetic syndromes
- Viral infection early in pregnancy
What are some causes of postnatal onset proportionate short stature?
- Malnutrition
- Psychosocial causes
- Organ system diseases, including GI diseases, cardiac disease, renal diseases, chronic lung diseases, and endocrinopathies
What is disproportionate short stature?
Short stature in patients who are very short-legged with an increased U/L ratio
What are two things to consider in disproportionate short stature?
Rickets: for patients with frontal bossing, bowed legs, low serum phosphorous level, and high serum alk phos
Skeletal dysplasia: for patients who are short with short limbs
What labs should be done in the evaluation of pathologic short stature?
CBC, ESR, T4, serum electrolytes, creatinine, bicarb, IGF-1
What radiographic studies are done in the evaluation of patients with pathologic short stature?
- Bone age: determination is very helpful to compare with chronologic age
- AP and lateral skull radiographs are necessary to assess the pituitary gland
If a person with short stature has bone age = chronologic age, what is the differential?
- Familal short stature
- Intrauterine growth retardation
- Turner syndrome
- Skeletal dysplasia
What endocrinopathies cause short stature?
- Growth hormone deficiency
- Hypothyroidism
- Hypercortisolism
- Turner syndrome
What are the clinical features of GH deficiency?
History of prolonged neonatal jaundice, hypoglycemia, cherubic facies, central obesity, microphallus, cryptorchidism, and midline defects may be present
What can cause GH deficiency?
Brain tumors, prior CNS irradiation, CNS vascular malformations, autoimmune diseases, trauma, congenital midline defects
Patients with GH deficiency have ______ bone age and must have an ____ to rule out a CNS lesion
delayed; MRI
IFG-1 levels are ____ in GH deficiency?
low
What is the management for GH deficiency?
Treatment includes daily subcutaneous injections of recombinant growth hormone until a bone age determination shows that the patient has reached nearly maximal growth potential
What lab findings are associated with hypothyroidism?
- Increased TSH
- Low T4
- Positive antithyroid peroxidase antibodies
What suppresses sex steroids in the prepubescent state?
Sensitive negative feedback at the level of the hypothalamus
Puberty begins when there is a reduction in ______ _______ resulting in activation of the _______
Hypothalamic inhibition; HPGA (hypothalamic-pituitary-gonadal axis)
Onset of female puberty is between __ and __ years of age
7 and 13
________ is the onset of breast development
Thelarche
What is the first sign of puberty in girls?
Breast buds (adrenarche in 15% of girls)
Menstruation begins at __ - __ years of age
9-15
What are the roles of FSH and LH in menstruation?
FSH stimulates the ovaries to produce ovarian follicles, which in turn produce estrogen
LH is responsible for the positive feedback in the middle of the menstrual cycle resulting in the release of egg
Male puberty onset is between __ and __ years of age
9 and 14
What is the first sign of male puberty?
Testicular enlargement
What are the roles of FSH and LH in male puberty?
FSH: Stimulates the seminiferous tubules in the testes to produce sperm
LH: stimulates the testicular Leydig cells to produce androgens, which in turn are responsible for penile enlargement and the growth of axillary, facial, and pubic hair
_______ _______ children develop secondary sexual characteristics earlier than do most children
African American
What is precocious puberty in girls vs boys?
Girls: Presence of breast development or pubic hair before 7 years of age or menarche before 9 years of age
Boys: Any pubertal changes before 9 years of age
When is premature thelarche most likely to occur?
Within the first 2 years of life
What causes premature thelarche?
Transient activation of the HPGA, resulting in transient ovarian follicular stimulation and a release of low levels of estrogen
When is treatment indicated for premature thelarche?
If there is also pubic hair development or a rapid growth spurt
Premature adrenarche is more common in ___ than ____
girls > boys
When does premature adrenarche clasically present? What is the treatment?
After 5 years of age, with the onset of pubic hair growth, axillary growth and apocrine odor
No treatment is indicated
What is isosexual precocious puberty/Central precocious puberty (CPP)?
The early onset of gonadotropin mediated puberty is a normal state, except that the hypothalamus has been activated earlier than usual
What is the difference in etiology of CPP in girls and boys?
Girls: most cases are idiopathic
Boys: Tends to be organic, and all cases need evaluation with an MRI of the head
What CNS abnormalities can cause isosexual precocious puberty?
- Hydrocephalus
- CNS infections
- Cerebral palsy
- Benign hypothalamic hamartomas
- Malignant tumors (astrocytomas and gliomas)
- Severe head trauma
What is the GnRH stimulation test in CPP?
Ideal test to demonstrate premature activation of the hypothalamus
By injecting GnRH into patient, the LH response (and FSH) can be used to assess activation of the HPGA; patients with CPP have a dramatic increase in LH secretion
What is the outcome of the GnRH stimulation test in peripheral precocious puberty (PPP)?
These patients would be expected to have a flat response on injection of synthetic GnRH
What is peripheral precocious puberty (PPP)?
Precocious puberty that is independent of the HPGA (caused by the peripheral production of male or female sex steroids and not FSH or LH)
How do boys present with PPP? How do girls present?
Boys: Present with either feminization or with premature onset of pubic hair (no testicular enlargement because no FSH increase)
Girls: Present with virilization or breast development
What are some causes of PPP?
In general, include exposure to exogenous steroids, gonadal tumors, adrenal tumors, and nonclassic congenital adrenal hyperplasia
What causes of PPP in males can result in testicular enlargement (3)?
- McCune Albright syndrome: bony changes, skin findings (cafe-au-lait) and endocrinopathies
- Testotoxicosis: Testes enlarge bilaterally independent of the HPGA
- ß-HCG secreting tumors: Found in the chest, pineal gland, gonad, or liver (hepatoblastoma); ß-HCG cross reacts with LH and can bind LH receptors
How do you evaluate PPP in males and females?
Boys: Check serum FSH, LH, testosterone, and ß-HCG
Girls: Check serum FSH, LH, and estradiol levels
GnRH stimulation test may be warranted in addition for both sexes
Delayed puberty in boys means no testicular enlargement by ____ years of age
14
Delayed puberty in girls means no breast tissue by ____ years of age or no menarche by ___ years of age
13;14
What two categories of disorders lead to delayed puberty?
Hypogonadotropic hypogonadism
Hypergonadotropic hypogonadism
What is the difference between Hypogonadotropic hypogonadism and Hypergonadotropic hypogonadism?
- Hypogonadotropic hypogonadism: Inactivity of the hypothalamus and pituitary gland; patients have low FSH, low LH, and in turn, low testosterone and low estradiol
- Hypergonadotropic hypogonadism: End organ function (gonadal failure) leading to high FSH and high LH levels with low testosterone or low estradiol levels
What are some causes of hypogonadotropic hypogonadism?
- Constitutional delay of puberty (more common in boys than girls)
- Chronic diseases
- Hypopituitarism
- Primary hypothyroidism
- Prolactinoma
- Genetic syndromes
What genetic syndromes can cause hypogonadotropic hypogonadism?
- Kallman syndrome: Isolated gonadotropin deficiency associated with anosmia
- Prader-Willi syndrome
- Lawrence-Moon-Biedl syndrome
What chromosomal disorders can cause hypergonadotropic hypogonadism?
In boys: Klinefelter syndrome (XXY)
In girls: Turner syndrome (XO) or gonadal dysgenesis
How is delayed puberty evaluated?
CBC, ESR, T4, testosterone or estradiol, FSH, LH, prolactin level, and bone age are necessary
During the first __ weeks of gestation, the gonadal tissue remains undifferentiated
7 weeks
Male sexual differentiation is initiated by the ____ gene located on the short arm of the Y chromosome
SRY
What is secreted by the fetal testes after differentiation?
Testosterone and anti-mullerian hormone (AMH)
What are the functions of testosterone and anti-mullerian hormone in male development?
- Testosterone (from Leydig cells) stimulates the development of the Wolffian ducts (epididymis, vas deferens, and seminal vesicles)
- Anti-Mullerian hormone (Sertoli cells) inhibits the development of Mullerian structures
What is the purpose of DHT (dihydrotestosterone) in male sexual differentiation?
- Penile enlargement
- Scrotal fusion
- Masculinization of external genitalia
What can cause ambiguous genitalia in an undervirilized male (pseudohermaprhodite)?
- Inborn error in testosterone synthesis
- Gonadal intersex (conditions in which the internal structures are a combo of both male and female structures)
- Partial androgen insensitivity
What two rare conditions make up gonadal intersex?
- Mixed gonadal dysgenesis (MGD): Karyotype with a 45, XO/46 mosaicism
- True hermaphroditism: Ambiguous genitalia with both ovarian and testicular gonadal tissue; karyotype is usually 46, XX, but can also be 46, XY
What can cause female pseudohermarphroditism? What is the most common cause?
- CAH caused by 21-hydroxylase deficiency is most common
- Virilizing drug used by mother during pregnancy
- Virilizing tumor in mother during pregnancy
When evaluating a patient with ambiguous genitalia, Increased blood pressure suggests ___ with _______ deficiency; decreased blood pressure suggests ______ ______
- Increased BP: CAH with 11ß-OH deficiency
- Decreased BP: Adrenal insufficiency
What are the laboratory studies for male and female pseudohermaphrodites?
Male: DHT and testosterone levels; if serum testosterone is low, further evaluation for error in androgen synthesis is indicated
Female: Serume electrolytes, testosterone level, and further studies to look for evidence of CAH
What is the management of pseudohermaphroditism?
Focus is on gender assignment as soon as possible with input from a pediatric urologist on surgical options
What is produced by the adrenal cortex?
- Mineralcorticoids (aldosterone)
- Glucocorticoids (cortisol)
- Androgens (DHEA)
What causes primary adrenal insufficiency? How do patients present?
Causes: destruction of the adrenal cortex or enzyme deficiency
Presentation: Signs and symptoms of cortisol deficiency (anorexia, weakness, hyponatremia, hypotension, and increased pigmentation over healed scars), and aldosterone deficiency (failure to thrive, salt craving, hyponatremia, and hyperkalemia)
What causes secondary adrenal insufficiency?
Any process that interferes with the release of cortisol-releasing hormone from the hypothalamus or ACTH from the pituitary
In contrast to primary adrenal insufficiency, serum _______ may be normal in secondary adrenal insufficiency because there is no ________ deficiency
potassium; aldosterone
What is the most common cause of secondary adrenal insufficiency?
Iatrogenic (long term dosage of glucocorticoids)
What is CAH? What is the inheritance pattern?
CAH is an autosomal recessive congenital enzyme deficiency in the adrenal cortex; most common cause of ambiguous genitalia when no gonads are palpable
What are the three main types of CAH?
- 21-hydroxylase deficiency (90% of cases)
- 11-ß hydroxylase deficiency
- 3ß-hydroxysteroid dehydrogenase deficiency
What are the three different subtypes of 21-hydroxylase deficiency?
- Classic salt-wasting CAH: both mineralcorticoid and glucocorticoid pathways are affected (cortisol and aldosterone deficiency)
- Simple virilizing CAH: Only the glucocorticoid pathway is affected
- Nonclassic CAH: Late onset with very mild cortisol deficiency and no mineralcorticoid involvement
How do patients with 11ß-hydroxylase deficiency differ from patients with 21-hydroxylase deficiency?
Present similarly except that they (11ß-hydroxylase) are hypertensive and hypokalemic
Patients with 21-hydroxylase deficiency have increased __________________ levels
Patients with 11ß-hydroxylase deficiency have incerased levels of ___________
Patients with 3ß-hydroxysteroid dehydrogenase deficiency have increased levels of __________ and ________
- 21-hydroxylase: increased 17-hydroxyprogesterone levels
- 11ß-hydroxylase: Increased 11-deoxycortisol levels (compound S)
- 3ß-hydroxysteroid dehydrogenase: DHEA and 17-hydroxypregnenolone
What is the management for CAH?
- Cortisone is administered at a dose that sufficiently suppresses ACTH production so that androgen production decreases (but not enought to interfere with proper growth)
- Mineralocorticoid replacement (flucortisol) may be given at a dosage that normalizes plasma renin activity (PRA)
What is Addison’s disease?
Adrenal insufficiency resulting from autoimmune destruction of the adrenal cortex by lymphocytic infiltration
How is acquired adrenal insufficiency evaluated?
ACTH stimulation test is the test of choice and measures adrenal cortisol reserve by comparing the baseline cortisol level with the cortisol level 1 hour after ACTH injection (would see blunted response; normally the cortisol level doubles)
What is the management of acquired adrenal insufficiency (Adrenal crisis)?
- Prompt treatment requires IV fluids with 5% dextrose in normal saline (to correct hypotension and hyponatremia, and to prevent hypoglycemia)
- Parenteral steroids are given until the patient is stablized
What are the clinical features of glucocorticoid excess?
Poor growth with delayed bone age, central obesity, moon facies, nuchal fat pad, easy bruisability, purplish striae, htn, and glucose intolerance
What are the three major causes of hypercortisolism?
- Iatrogenic (the most common cause)
- Cushing Syndrome (excessive glucocorticoid production by benign or malignant adrenal tumors)
- Cushing disease (Excessive ACTH production by a pituitary tumor such as a microadenoma)
How is glucocorticoid excess diagnosed?
- Elevated free cortisol in 24 hour urine collection
- Absence of expected cortisol suppression seen in an overnight dexamethasone suppression test
What is the second most common chronic disease of childhood?
Diabetes mellitus
