Endocrinology - PowerPoint Presentation

Slide1

Endocrinology

Pediatric Board Review

Graeme Frank, MD

May 14

th

, 2011Slide2

CalciumSlide3

An otherwise healthy 6-week infant presents with a generalized seizure. She is exclusively breast fed. The child is somewhat sleepy with a non focal examination.

Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1The most likely diagnosis is:

PseudohypoparathyroidismHypoparathyroidismVitamin D deficiencyAlbright’s hereditary osteodystrophy

10Slide4

Actions of PTH

1.

2.

Ca PO

4

NET EFFECT

25 OH Vit D

1,25 (OH)

2

Vit D

1

 hydroxylase

3.

GutSlide5

This same 6-week infant with hypoparathyroidism

(Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1) What is an important diagnostic consideration (i.e. what is the underling disorder causing the hypoparathyroidism)?

DiGeorge syndrome – thymic aplasia, congenital heart disease, immune deficiency Slide6

Biochemical changes in rickets

Ca PO4 Bone Urine

N

Minimal

changes

Stage 1

N

Rickets

Aminoaciduria

Phosphaturia

Glycosuria

Bicarbonaturia

Stage 2Slide7

Initial

Ca:

PO4:Alk Phos: 9.7

3.1

2514

2 ½ weeks

9.8

3.5

2185

4 months

10.5

6.5

518Slide8

Which is consistent with vitamin D

deficiency rickets?

Normal Normal LowLow Low LowLow High High

Low Normal Normal

Normal Low High

Calcium

Phos

Alk Phos

10Slide9

Choose correct answer

Vitamin D deficiency ricketsRenal osteodystrophy (renal rickets)

BothNeither1. Increased phosphate level2. Increased PTH level3. Increased creatinine level

B

C

BSlide10

THYROIDSlide11

Baby A, born on 5/27/10. Newborn screening tests, performed on 5/29/10 revealed:

Normal rangeTSH 37 µIU/ml < 20T4 10.1 µg/dl 9-19

Which statement is most accurate:Baby A has congenital hypothyroidism warranting urgent therapyBaby A will develop mental retardation if untreated

Baby A likely does not have any thyroid abnormality

Baby A has an altered hypothalamic set-point for T4

10Slide12
Slide13

Venipuncture:

(1/25/10)

Normal rangeTSH 488 IU/ml (0.3-5.5)T4 1.2 g/dl

(4.5-12.5)

You are contacted by your state Neonatal Thyroid Screening Program. Baby X was born on 1/4/10. His newborn screening tests, performed on 1/6/10 revealed:

Initial filter paper

Normal range

TSH >200



IU/ml

< 20

T4 2.1 

g/dl

9-19 Slide14

Congenital hypothyroidism

Thyroid dysgenesis/agenesisPrevalence 1 in 4,000 [Whites 1 in 2,000; Blacks 1 in 32,000]2:1 female to male ratio

Clinical features include:hypotonia, enlarged posterior fontanelle, umbilical hernia, indirect hyperbilirubinemiaLaboratory findings: Very high TSH and low T4Therapy: Thyroxine – keep TSH in normal rangeSlide15
Slide16

6 month female with

congenital hypothyroidism

..following 4 months therapySlide17

A baby with gastroschisis has the following TFTs on day 5 of life:

T4 2.1 μg/dL (4.5-12.5) TSH 2.3 μIU/mL (0.3-5.0)

The most likely diagnosis is:Hypothyroidism due to thyroid dysgenesis Central hypothyroidism

TBG deficiency

Hypothyroidism from excess iodine exposure

Normal thyroid function (as the TSH is normal)

10Slide18

Central hypothyroidism - rare

TBG deficiency

1:2800vs.Slide19

Thyroxine (T4)

Major product secreted by the thyroid Circulates bound

to thyroid binding proteins - thyroid binding globulin (TBG)Only a tiny fraction (< 0.1%) is free and diffuses into tissuesWhen we measure T4, we measure the T4 that is bound to proteinThe level of T4 is therefore largely dependent on the

amount of TBG

Changes in T4

may reflect

TBG variation

rather than underlying pathologySlide20

TBG

deficiency

Central hypothyroidismFree T4 Low Normal

TBG level Normal Low

T3RU Low HighSlide21

Thyroid function in a 17 year old:

Normal rangeTSH: 3.7 µIU/ml 0.3-5.5T4: 13.4 µg/dl 4.5-12

Which of the following medication could explain the thyroid function abnormalityINH

Retinoid acid

Ciprofloxacin

Ortho Tri-Cylen

Doxycycline

10Slide22

Conditions that cause alterations in TBG

Increased TBG

Decreased TBGInfancy Familial deficiencyEstrogen Androgenic steroid treatment - OC Pill Glucocorticoids (large dose) - pregnancy Nephrotic syndromeFamilial excess AcromegalyHepatitisTamoxifen treatmentSlide23

A 12-yr female has diffuse enlargement of the thyroid. She is asymptomatic. Her disorder is most likely associated with which of the following pathological processes

Infectious

InflammatoryAutoimmuneToxic (drug)Neoplastic

10Slide24

Normal thyroid

Hashimoto thyroiditisSlide25

DC

16 year 7 month

Growth failure x 1 1/2 years

Labs

:

TSH:

1008

µIU/ ml (0.3-5.0)

T4:

<1.0

µg/dl (4-12)

Antithyro Ab.

232 U/ml (0-1)A-perox Ab. 592 IU/ml (<0.3)Prolactin: 29 ng/ml (2-18)Cholesterol: 406 mg/dl (100-170)Slide26

DC

Start of thyroxineSlide27

Background

: Autoimmune destruction of the thyroid Family history in 30-40% Lymphocytic infiltration

Clinical: Growth failure, constipation, goiter, dry skin, weight gain, slow recoil of DTR

Laboratory

:

High TSH

Anti-thyroglobulin and anti-peroxidase antibodies

Therapy

:

Thyroxine

Hashimoto thyroiditisSlide28

15 year old female with a history of easy fatigability.

Found to have an elevated pulse rate at recent MD visit Thyroid function: Normal rangeTSH < 0.1



IU/ml

0.3-5.5

T4 14.8 

g/dl

4.5-12

T3 580 ng/dl

90-190Slide29

Restlessness,

poor attention spanEye changes

Goiter

Tachycardia, wide pulse

pressure

Increased GFR

- polyuria

Diarrhea

Menstrual

abnormalities

MyopathySlide30

Antithyroid medication

(Methimazole or Propylthiouracil [PTU]) Pros : 25% remission rate every 2 years

Cons: Drug induced side effects - skin rashes, agranulocytosis, lupus-like reactionRadioactive iodine (131I) Pros : Easy. Essentially free of side effects

Cons: Long term hypothyroidism

Surgery

 Blockers if markedly hyperthyroid

Therapy for Graves disease

:Slide31

Sexual differentiationSlide32

Ambiguous genitalia is found in a newborn. The baby is noted to be hyperpigmented. Ultrasound demonstrates the presence of a uterus. The most useful test to aid in the diagnosis of this medical condition is:

Testosterone

17-hydroxyprogesteroneSerum sodium and potassiumDHEASDHEAS/androstenedione ratio

10Slide33

Cholesterol

Pregnenolone

Progesterone DOCACorticosterone

ALDOSTERONE

17 (OH) pregnenolone

DHEA

17 (OH) progesterone

Androstenedione

Compound S

CORTISOL

TESTOSTERONE

Desmolase

3-

-HSD

3-

-HSD

3-

-HSD

17-OH

17-OH

21-OH

21-OH

11-OH 11-OHSlide34

If she has salt wasting congenital adrenal hyperplasia, which abnormalities are likely to develop. True or False for each

Increased serum potassiumDecreased serum sodium

Decreased bicarbonateDecreased plasma cortisolIncreased plasma renin activityT

T

T

T

TSlide35

A 1-year male infant has non palpable testes.

Of the following, the most appropriate next step would be:

Re-examination in 18 monthsRefer the patient for an exploratory laparotomyBegin therapy with LHRHMeasure the plasma testosterone after stimulation with HCGBegin therapy with testosterone enanthate, 50 mg IM monthly for 3 months.

10Slide36

History

9 day old male infant

1 day history of decrease feeding, vomiting and lethargy. ExaminationIll appearing infant with poor respiratory effortVital signs: T 99



F HR 100/min BP 61/40 RR 24/min

Resp: Subcostal retractions but clear to auscultation

Cardiac: Regular rate and rhythm. Normal S1 and S2

Abdomen: Soft, non distended. Non tender. No HSM

Neuro: Lethargic. No focal deficit

Genitalia: Normal male. Bilateral descended testesSlide37

Laboratory data:

WBC 16.7

Hb 16.4

Hct 49

Plt 537 K

Na 121

K 9.3

Cl 83

CO

2

6.7

Glucose 163

BUN/Creat 33/0.2

CSF:

Chemistry: Protein 74 Glucose 82

Microscopy: WBC 6 RBC 100Slide38

Emergency therapy

Fluid resuscitation:20 ml/kg Normal saline

Glucocorticoid2 mg/kg Solucortef IV Monitor EKGSlide39

Modes of presentation

ClassicalSimple virilizingVirilizing with salt loss

“Non classical” / Late onsetSlide40

Therapy and evaluation of therapy

Glucocorticoid (Hydrocortisone)Monitor growth, 17-OHP, urinary pregnanetriolFluorocortisol (Florinef 0.1 – 0.45 mg/day)

Blood pressure, plasma renin activity (PRA)Supplemental saltUntil introduction of infant foodSlide41

History

15 year female presents with primary amenorrhea

Breast development began at 10 yearsExaminationHeight: 5 ft 7 in Weight 130 lb

Tanner 5 breast development

Scant pubic hair

What is your diagnosis?Slide42

XY Genotype

Testosterone

Estradiol

Androgen

Receptor

Estrogen

Receptor

Aromatase

Complete androgen insensitivitySlide43

15 yr female presents with primary amenorrhea.

Breast development began at 10 yTanner 5 breasts, scant pubic hairWhich of the following clinical features is the most likely to give you the correct diagnosis

Blood pressure in all 4 extremitiesCareful fundoscopic examinationRectal examination

Measurement of blood pressure with postural change

Cubitus valgus and shield shaped chest

10Slide44

TESTIS

Leydig

cellsSertolicellsGonadal Primordia

Testosterone

Wolfian ducts

DHT

Normal male

ext. genitalia

Epidymus

Vas deferens

Seminal vesicles

Female

OVARY

No SRY

No AMH

No testosterone

Mullerian

ducts

Wolfian duct

regression

Normal female

external genitalia

Fallopian tubes

UterusUpper vagina

No AMH

Mullerian duct

regression

nor DHTSlide45

Gonadal Primordia

Y

ChromosomeTESTIS

SRY

Leydig

cells

Sertoli

cells

Testosterone

AMH

Mullerian duct

regression

Wolfian ducts

DHT

Epidymus

Vas deferens

Seminal vesicles

Normal male

ext. genitalia

No AMH

No testosterone

Mullerian

ducts

Wolfian duct

regression

Normal female

external genitalia

Fallopian tubes

Uterus

Upper vagina

nor DHTSlide46

Gonadal Primordia

Y

ChromosomeTESTIS

SRY

Leydig

cells

Sertoli

cells

Testosterone

AMH

Mullerian duct

regression

Wolfian ducts

DHT

Epidymus

Vas deferens

Seminal vesicles

Normal male

ext. genitalia

No AMH

No testosterone

Mullerian

ducts

Wolfian duct

regression

Normal female

external genitalia

Fallopian tubes

Uterus

Upper vagina

nor DHTSlide47

Early PubertySlide48

The earliest sign of puberty in a male is:

Enlargement of the penis

Enlargement of the testesGrowth accelerationPubic hair growthAxillary hair growth

5Slide49

2 year old girl with breast development. No growth acceleration. No bone age advancement

No detectable estradiol, LH or FSHThe most likely diagnosis is:

Ingestion of her mother’s OCPsPrecocious pubertyPremature adrenarchePremature thelarcheMcCune Albright Syndrome

10Slide50

Benign Premature Thelarche

Isolated breast development80% before age 2 Rarely after age 4Not associated with other signs of puberty

(growth acceleration, advancement of bone age)Children go on to normal timing of puberty and normal fertilityBenign processRoutine follow-up Slide51

5 year female with 6 months of pubic hair growth. Very fine axillary hair as well as adult odor to sweat.

No breast development, no growth spurtThe most likely diagnosis is:

Precocious pubertyBenign premature adrenarcheNon-classical congenital adrenal hyperplasiaAdrenal tumorPinealoma

10Slide52

Benign Premature Adrenarche

Production of adrenal androgens before true pubertal development beginsPresents as isolated pubic hair in mid childhoodNo growth acceleration

No testicular enlargement in boysIf normal growth rate, routine follow-upIf accelerated growth and/or bone age advancement, screen for CAHVirilizing tumor (adrenal/gonadal)Slide53

Choose correct answer

Premature theralchePremature adrenarche

BothNeither1. Growth acceleration2. Normal adolescent sexual development3. Onset of gonadal function usually in 3-4 years

D

C

BSlide54

You suspect a 16 year female has Turner syndrome. The most definitive diagnostic test is

Buccal smear

Chromosome analysisMeasuring her FSH and LHDetermining her bone ageDetermining her testosterone level

5Slide55

5 year old girl with pubic hair and rapid growth. She has no breast development

Possible sources of androgens:

LiverAdrenalOvaryPituitaryPinealT

F

F

F

TSlide56

5 year old girl with pubic hair and rapid growth. She has no breast development

Which of the following should be considered

Answer T or F for each:Central precocious pubertyCongenital adrenal hyperplasiaMcCune Albright syndromeBenign premature adrenarcheAdrenal tumor

F

T

T

F

FSlide57

When does puberty occur?

Classic teaching8 -13 in girls (menarche ~ 2 years after onset of puberty)9 -14 in boys

Case:Breast development: 6 yearsMother had menarche: 9.5 yearsSlide58

Why

Reactivation of hypothalamic –pituitary –gonadal axisSlide59

Gonadatropin dependent (central) precocious puberty

Clock turns on earlyIdiopathic > 95 % girls

~ 50 % boysHypothalamic hamartoma (Gelastic seizures)NF (optic glioma)Head traumaNeurosurgeryAnoxic injuryHydrocephalusSlide60

Treatment

WhyPsychosocialHeightWhatGnRH agonistSlide61

Gonadotropin independent precocious pubertySlide62

7 year male presents with 6 month history of pubic and axillary hair growth as well as adult body odor.

Mother thinks he is growing faster than his peers

No exposure to androgensPM&SH – nil of note

Mother had menarche at 12 yr

Father had normal timing of his puberty

Medications – noneSlide63

Height 50

th

percentile (last height at 25th)Weight 40th percentile

No café au lait macules

No goiter

Heart and lungs: normal

Abdomen: Firm hepatomegaly with irregular border

Prepubertal

Asymmetric

Pubertal

Adrenal source

Enlarged testicle Precocious pubertySlide64

Height 50

th

percentile (last height at 25th)Weight 40th percentile

No café au lait macules

No goiter

Heart and lungs: normal

Abdomen: Firm hepatomegaly with irregular border

Genitalia:

Pubic hair - Tanner 2

Scrotal thinning

Testes 5 ml bilaterally (pubertal >3 ml)

Rest unremarkableSlide65

7 year male with signs of puberty

Pubertal Central precocious

puberty

Gonadotropins

LH

G

Leydig cell

LABS

:

Testosterone 48 ng/dl (<10)

FSH <0.1 mIU/mL

LH <0.1 mIU/mL

TSH 1.0

μ

IU/mL

T4 8.9

μ

g/dLSlide66

Precocious puberty in the male

Gonadotropins

Prepubertal PubertalGonadotropin independent Central precocious

precocious puberty puberty

HCG

LH

*

McCune Albright

syndrome

G

G

*

Familial male

Precocious puberty

(testotoxicosis)

1. Gonadotropin independent PP

2. Polyostotic Fibrous Dysplasia

3. Café au lait macules

Leydig cellSlide67

Final diagnosis

: Gonadotropin independent precocious

puberty secondary to an βHCG secreting hepatoblastomaSlide68

5 year old with breast development

and growth acceleration

- Estradiol 62 pg/ml (<10) FSH <0.1 mIU/mL LH <0.1 mIU/mLGonadotropin independent

precocious pubertySlide69

McCune Albright syndrome:

Café au lait macules

Gonadotropin independentprecocious pubertyPolyostotic fibrous dysplasiaSlide70

Growth disorders anddelayed pubertySlide71

Delayed puberty

Hypogonadism

Hypergonadotropic

Hypogonadism (

↑FSH, LH)

Primary gonadal failure

- Chromosomal

- iatrogenic (cancer therapy)

- autoimmune oophoritis

- galactosemia

- test. biosynthetic defect

Hypogonadotropic

Hypogonadism (



FSH, LH)

ConstitutionaldelayCentral Hypogonadism- Isolate gonad. def. - MPHD- Kallmann (anosmia)- Functional Slide72

A 15 yr boy has short stature and delayed puberty. He is now in early puberty (Tanner 2). His parents are of average stature. His height and weight are just below 3rd percentile.

All of the following are likely EXCEPT:

A bone age of 12 ½ yearsGrowth hormone deficiencyAdult height in the normal rangeAcceleration of growth and sexual maturation over the next 2 years.History of normal length and weight at birth

10Slide73

A 15 yr male has delayed puberty. He also has headaches, diplopia and increased urination. His height is < 3

rd percentile. Which of the following is the most likely diagnosis?

Diabetes mellitusPinealomaCerebellar tumorCraniopharyngiomaPituitary adenoma

10Slide74

A 14 yr male has tender gynecomastia (3 cm in diameter bilaterally). He is in early to mid puberty. In most cases the best management for this gynecomastia is:

Treatment with an anti-estrogen (e.g. Tamoxifen)

Treatment with an aromatase inhibitorTreatment with a dopamine agonist (bromocryptine)SurgeryReassurance

10Slide75

DiabetesSlide76

A 12 year female patient presents with a 4 week history of polyuria, polydipsia, and marked weight loss.

She is noted to have deep, sighing respiration. Glucose is 498 mg/dL, pH is 7.06. Her electrolytes show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9.The MOST important initial management is:

insulin drip 0.1 u/kg/hr½ NS with 40 meq K at 2x maintenanceBicarb 1 meq/kg slowly over 1 hour

20 ml/kg normal saline bolus IV

10Slide77

GTT in a 16 year obese female:

Time Glucose (mg/dL) -0- 109 -120- 188 Which of the following statements are correct?

This patient has:Type 2 diabetesImpaired glucose tolerance but normal fasting glucose

Normal glucose tolerance

Both impaired fasting glucose and impaired glucose tolerance

10Slide78

Fasting

2 hr post load

< 100

< 140

Normal

≥ 100

≥ 140

< 126

< 200

Pre-diabetes

≥ 126

≥ 200

Diabetes

Definition of diabetesSlide79

This obese patient with IFG and IGT is at risk for the development of all the following EXCEPT

Type 2 diabetes

DyslipidemiaHypertensionSlipped capital femoral epiphysisHashimoto thyroiditis

Metabolic syndrome

10Slide80

A 13 year male has new onset type 1 diabetes mellitus. Therapy for this child may include all of the following EXCEPT:

Glargine (Lantus) and Lipro insulin (Humalog)

Detemir (Levemir) and Aspart insulin (Novolog)Metformin Analog insulin administered via an insulin pump

10Slide81

MiscellaneousSlide82

Side effects of corticosteroids include all of the following except

hypertension

hypoglycemiadecrease bone mineralizationmyopathycataracts

10Slide83

What is the most likely diagnosis in this newborn infant?

Mother has SLE

Anasarca from cardiac failureSystemic allergic reaction Congenital nephrotic syndromeTurner syndrome

10Slide84

5 year old male with short stature

Turner syndrome

VATER syndromeAlbright’s hereditary osteodystrophyNoonan syndromeGoldenhar syndrome

10Slide85

A moderately obese adolescent female has irregular periods, hirsutism and acne.

Of the following, which is the most likely diagnosis?

Cushing syndromePolycystic ovarian syndromeVirilizing adrenal tumorNon-classical CAHHyperprolactinemia

10Slide86

Choose correct answer

Diabetes mellitusDiabetes insipidus

BothNeither1. Osmolality of serum > 300 Osm/L2. Osmolality of urine > 500 mOsm/L3. Hypernatremia

2 Na + BUN/2.8 + Gluc/18Slide87

Choose correct answer

Diabetes mellitusDiabetes insipidus

BothNeither1. Osmolality of serum > 300 Osm/L2. Osmolality of urine > 500 mOsm/L3. Hypernatremia

C

A

B

2 Na + BUN/2.8 + Gluc/18