Endocrine Lecture

Question 1

What is the path of endocrine disorders?

Answer 1

🙣 Alteration in regulation of feedback system –
hyposecretion or hypersecretion of hormone

Question 2

What factors cause hypo vs. hyper secretion of hormones?

Answer 2

🙢 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

Question 3

Endocrine pathologies may be assessed by considering
the following?

Answer 3

🙣 Growth disturbance / disorders
🙣 Abnormal pubertal / sexual development
🙣 Adrenal conditions
🙣 Thyroid conditions
🙣 Diabetes mellitus, types 1 and 2
🙣 Posterior pituitary gland dysfunction

Question 4

What may be the first sign of an endocrine disorder?

Answer 4

🙣 Deviation from normal growth may be first sign of
endocrine disorder

Question 5

Primary growth disorders?

Answer 5

🙣 Primary growth disorders – skeletal dysplasias,
chromosomal abnormalities, genetic short stature

Question 6

Secondary growth disorders?

Answer 6

undernutrition, chronic disease, endocrine disorder, idiopathic delay

Question 7

Factors Inhibiting Normal Growth?

Answer 7

🙣 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

Question 8

Growth Hormone (GH) Deficiency

Answer 8

🙣 Deficiency in the GH released by the pituitary

🙣 GH released in large bursts while sleeping

Question 9

What do you see on physical exam in growth hormone deficiency?

Answer 9

dysmorphic features, midline defects, increased cranial pressure, thyroid, puberty, measures of body proportions, proportional short stature

Question 10

What dx studies are used for growth hormone deficiency?

Answer 10

🙣 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

Question 11

What is constitutional growth delay?

Answer 11

🙢 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

Question 12

True or False constitutional growth delay is not a disease

Answer 12

True!
🙣 Delayed bone age with normal growth rate for bone age

Question 13

What is growth excess?

Answer 13

🙣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

Question 14

Early precocious puberty?

Answer 14

🙣 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

Question 15

🙣 Premature adrenarche – early onset of pubic/axillary hair; not associated
with other features; usually idiopathic

Answer 15

increased risk of PCOS

Question 16

Premature thelarche

Answer 16

isolated breast development without other signs

Question 17

True precocious puberty – early onset of multiple features of puberty

Answer 17

bone age, LH, FSH, estradiol or testosterone; pelvic US in girls, testicular US in boys

Question 18

Additional Diagnostic Studies - True precocious puberty:

Answer 18

🙢 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

Question 19

If LH and FSH are high

Answer 19

in pubertal range: indication of central etiology)

Question 20

If LH and FSH are low

Answer 20

(in prepubertal range: indication of peripheral puberty)

Question 21

Hypothalamic gonadotropin-releasing hormone (GnRH) stimulation test distinguishes?

Answer 21

distinguishes central from peripheral puberty.

Question 22

Early and Precocious Puberty

Answer 22

🙣 Accelerated linear growth, breast development, penile enlargement, pubic hair
🙣 Usually idiopathic in girls; 30% of boys have CNS tumors

Question 23

Delayed Puberty

Answer 23

> 14 years in boys

Question 24

Delayed Puberty

Answer 24

🙣 >14 years in boys;

> 13 years in girls with no clinical
features of puberty or lack of progression

Question 25

🙣 Girls should progress to menarche _ years after thelarche

Answer 25

5

Question 26

🙣 Boys should attain Tanner stage 5 within 4.5 years 🙣 Most common cause is constitutional growth delay

Question 27

What is the most common cause for delayed puberty?

Answer 27

constitutional growth delay

Question 28

Delayed Puberty Etiology? 🙢

Answer 28

Constitutional Growth Delay – Primary Cause

Question 29

delayed puberty etiology delayed bone age?

Answer 29

endocrine diseases

Question 30

Delayed Puberty Etiology

Answer 30

🙣 Hypothalamic Pituitary Dysfun🙢ction (LH/FSH Deficiency)

Question 31

🙢 Kallmann syndrome (anosmia and gonadotropin deficiency)

Answer 31

Question 32

🙣 Gonadal Failure

Answer 32

Girls 🙢 Turner syndrome 🙢 Oophoritis 🙢 Galactosemia 🙢 Chemotherapy induced Boys 🙢 Vanishing testes syndrome (in utero testicular torsion) 🙢 Chemotherapy or radiation

Question 33

🙣 Adrenal gland steroids controlled by hypothalamic- pituitary axis (HPA)

Question 34

Corticotropin-releasing hormone (CRH) stimulates

Answer 34

production/secretion of ACTH by pituitary

Question 35

🙣 ACTH regulates adrenal glucocorticoid (cortisol) and androgen production

Question 36

🙣 Adrenal gland also produces mineralocorticoid hormones (aldosterone) regulated by renin- angiotensin system

Question 37

Cortisol

Answer 37

🙣 highest in the morning, low in the afternoon and evening, and lowest at midnight.

Question 38

Cortisol is secreted in response to?

Answer 38

🙣 secreted in response to hypoglycemia, hypotension, pain, or other stressful events,

Question 39

Cortisol?

Answer 39

🙣 has negative feedback on the synthesis and secretion of CRH, vasopressin, and ACTH

Question 40

Adrenal Insufficiency

Answer 40

🙣 Deficiency of hormones produced by adrenal cortex 🙣 Deficits of cortisol/aldosterone most detrimental

Question 41

Primary adrenal insufficiency?

Answer 41

🙣 Primary adrenal insufficiency – deficiency of both 1. mineralocorticoid 2. glucocorticoid

Question 42

🙣 Secondary adrenal insufficiency?

Answer 42

deficiency only of glucocorticoid

Question 43

Physical exam for adrenal insufficiency?

Answer 43

🙣 Physical examination – dehydration, hypotension, excessive pigmentation of skin/mucosa

Question 44

DX tests for adrenal insufficiency?

Answer 44

🙣 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)

Question 45

Most common cause of preventable mental retardation?

Answer 45

congenital hypothyroidism

Question 46

If hypothyroidism is untreated what happens?

Answer 46

irreversible brain damage, growth failure, deafness, neurological abnormalities

Question 47

acquired hypothyroidism

Answer 47

Hashimoto’s thyroiditis – autoimmune disorder – most common cause in children in the western world 🙣 Iodine deficiency – most common cause worldwide

Question 48

What do you see on physical exam with hypothyroidism?

Answer 48

🙣 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.

Question 49

What do you see in older children with hypothyroidism?

Answer 49

🙣 Delayed/subnormal growth velocity 🙣 Goiter 🙣 Weight gain 🙣 Delayed DTRs 🙣 Dry skin 🙣 Poor dentition

Question 50

🙣 Down Syndrome children are at higher risk for hypothyroidism:, test at 6m,12m, and then annually

Question 51

🙣 If on thyroid replacement, recheck TSH, free T4 4-6 wks. after dosage change

Question 52

🙣 Hypothyroidism – replacement with levothyroxine with frequent monitoring/more often in children <3 years

Question 53

Age 🙣 0-3 months 🙣 3-6 months 🙣 6-12 months 🙣 1-5 years 🙣 6-12 years 🙣 >12 years

Answer 53

🙣 10-15 🙣 8-10 🙣 6-8 🙣 5-6 🙣 4-5 🙣 2-3

Question 54

Hyperthyroidism

Answer 54

🙣 Overproduction of thyroid hormone or excessive thyroid replacement 🙣 Graves’ disease (autoimmune disease) – most common

Question 55

Hyperthyroidism 🙢 History

Answer 55

🙣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

Question 56

Inborn Errors of Metabolism

Answer 56

🙣Assessment of any critically ill neonate, infant, child

Question 57

Disorders of Carbohydrate Metabolism

Answer 57

Inability to metabolize 🙢 Monosaccharides – glucose, galactose, fructose 🙢 Polysaccharide – glycogen 🙣 Aberrant glycogen synthesis/disorder of gluconeogenesis 🙣 Glycogen Storage Diseases 🙣 Galactosemia

Question 58

🙣Galactosemia

Answer 58

🙢 Disorder of galactose metabolism 🙢 Dietary galactose principle carbohydrate in human milk, non-soy formulas

Question 59

🙣 Diagnostic studies – newborn screen, urine reducing substances after feeding; GALT activity in RBCs deficient; galt-1-P levels elevated

Answer 59

Galactosemia

Question 60

Urea Cycle Disorders

Answer 60

🙣 Defect in any enzyme of urea cycle – hyperammonemia; inability to detoxify waste nitrogen 🙣 Ammonia is end product – toxic to CNS

Question 61

Urea Cycle Disorders

Answer 61

🙣 Clinical findings – hyperammonemia begins after protein ingestion – 🙣 Clinical findings – hyperammonemia begins after protein ingestion – ammonia level= >100

Question 62

urea cycle disorders

Answer 62

🙢 Acute care to establish source of glucose/rapidly decrease ammonia levels 🙢 Chronic care – reduce protein consumption 🙢 Vulnerable to metabolic decompensation, mental retardation, death

Question 63

Amino Acid Metabolism Disorders: Aminoacidopathies and Organic Acidurias and Acidemias

Answer 63

🙣 Most common: PKU, maple syrup urine disease

Question 64

Organic Acidur🙢ias and Acidemias 🙣Phenylketonuria (PKU)

Answer 64

🙢 Deficiency of phenylalanine hydroxylase

Question 65

PKU management

Answer 65

🙣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

Question 66

🙣Homocytinuria

Answer 66

🙢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

Question 67

🙣 Clinical findings – does not usually present in children; screen those at risk

Answer 67

dyslipidemia