ENDOCRINOLOGY BOARD REVIEW

September 24, 2010

Growth

Growth

After 18mos of age, growth curve should be followed closely Between 4y/o and adolescence, growth

below 4-5cm/yr should be assessed Percentiles should not be crossed

Pubertal growth spurt Girls early puberty Boys midpuberty

Growth Rate per Year

Age Inches Centimeters

Birth to 1 year 7 to 10 18 to 25

1 to 2 years 4 to 5 10 to 13

2 years to puberty 2 to 2.5 5 to 6

Pubertal growth spurt-girls

2.5 to 4.5 6 to 11

Pubertal growth spurt-boys

3 to 5 7 to 13

Question 1

Choose the correct statement comparing “familial or genetically determined short stature” and “constitutional delay of growth,” in regards to bone age.

A. Familial = delayed/ constitutional = advanced

B. Familial = equivalent/ constitutional = delayed

C. Familial = delayed/ constitutional = equivalent

D. Both are delayed

Constitutional delay of growth Variant of normal growth and pubertal

development Period of decreased linear growth within

first 3yrs of life Downward crossing of percentiles

Linear growth resumes at normal rate Along lower growth percentiles

Family history of “Late Bloomers”

Constitutional Growth Delay: Note deceleration followed by normal growth rate

Question 2

The physical findings depicted below corresponds to which tanner stage?

A. IB. IIC. IIID. IVE. V

Tanner Staging

Boys: Staged by genital development and pubic hair – starts at 9-14 Testis volume >= 4mL is pubertal

Mark of pubertal onset Girls: Staged by breast development and

pubic hair – starts at 10 ½ Stage II = breast buds

Mark of pubertal onset Stage IV = Areola elevated above breast

(secondary mound)

Hypothalamus and Pituitary

Hypothalamus

Neuroectodermal tissue

Inferior third ventricle

Pituitary stalk

Pituitary

Anterior Upgrowth of

ectodermal cells from Rathke’s pouch

Posterior Downgrowth of

neural tissue cells from the hypothalamus

Question 3

You are evaluating a patient in clinic and notice the abnormality pictured. Which of the following is most likely to be affected?

A. Growth hormone levels

B. Aldosterone levelsC. Catecholamine

levelsD. Insulin levels

Anterior Pituitary

Growth Hormone

Secretion GH-releasing factor

Inhibition Somatostatin

IGF-1, IGF-BP3

Anterior Pituitary

Growth Hormone Deficiency

Normal birth weight Normal growth pattern x

1 year “Kewpie” doll

appearance, “cherubic” Short, excess subq fat,

retarded body proportion changes and high-pitched voices

Diagnosed with stimulation test

Anterior Pituitary

ACTH

Secretion CRF from

hypothalamus

Inhibition Cortisol from

adrenals Prolonged steroid

use

Anterior Pituitary

Gonadotropins Secretion

GnRH Hypothalamus sends

pulses Increases during puberty

Inhibition Inhibin

FSH Aromatase (androgen to

estrogen) Spermatogenesis

LH Testosterone Androstenedione (estradiol)

Anterior Pituitary

TSH

Secretion TRH

Inhibition Thyroid Hormone

Actions Increases iodide

uptake, thyroglobulin synthesis and thyroid hormone

Anterior Pituitary

Prolactin Acts directly on target organ Initiation and maintenance of lactation Inhibited by dopamine from hypothalamus Hyperprolactinemia

Galactorrhea Pituitary adenomas Medication

Neuroleptics, antipsychotics, estrogens and anti-hypertensives

Question 4

You are on call in the PICU and following a very sick patient admitted with meningococcal meningitis. He has not had any urine output in the last 8 hours despite fluid administration. You order a BMP and his Na is 125. What is the most likely cause of the hyponatremia in this patient?

A. Diabetes insipidusB. Psychogenic polydipsiaC. Inappropriate fluid administrationD. SIADH

Posterior Pituitary

Hormones synthesized in hypothalamus and stored in posterior pituitary

Vasopressin AVP or ADH Released in response to increased osmotic

pressure in the blood Water balance

Increased reabsorption of water in collecting ducts of kidneys

Arteriolar vasoconstriction – HTN Increased thirst

Posterior Pituitary

Vasopressin Overproduction

Head trauma, brain tumors, encephalitis, pneumonia

SIADH HA, apathy, nausea, vomiting, impaired consciousness Decreased plasma osmolarity

Underproduction Central Diabetes Insipidus (DI)

Pituitary tumors, head trauma, infiltrative diseases, autoimmune or surgical

Increased plasma osmolarity

Posterior Pituitary

Vasopressin Resistant

Nephrogenic DI Tubules in kidney cannot respond Genetic or acquired (lithium)

Oxytocin Released in response to nerve stimulation Contraction of the smooth muscle of the

uterus and myoepithelial cells lining the ducts of mammary glands

Thyroid

Thyroid

Location Neck Base of tongue Mediastinum

Hormones Thyroxine (T4) Tri-iodothyronine (T3) Need iodine for synthesis Transported by TBG,

albumin and transthyretin Free hormone is active

Thyroid

Goiter Hyper or hypo

Nodules 70-80% benign or cystic 1-1.5% of all childhood

cancers Neck irradiation, family

history of medullary carcinoma, rapid growth, fixation to adjacent structures, enlarged lymph nodes

Question 5

A mother brings in her teenage daughter for hyperactivity and emotional lability. ROS is positive for diarrhea, weight loss and heat intolerance. On physical exam you notice tachycardia and a slight prominence of the eyes. A laboratory evaluation would most likely reveal:A. TSH, freeT4, + TSH receptor antibodiesB. TSH, free T4, + antithyroperoxidase antibodiesC. TSH, free T4, + TSH receptor antibodiesD. TSH, free T4, + antithyroperoxidase antibodies

Thyroid

Hyperthyroid Soft and fleshy gland Tachycardia Weight loss Increased frequency of

bowel movements Heat intolerance Nervousness Widened pulse

pressure Tremor Fatigue

Warm, moist skin Fine, friable hair Separation of distal

margin of nail bed Restlessness Inability to sit still Emotional lability Short attention

span Excessive sweating

Thyroid

Hyperthyroidism Graves Disease

Stimulating antibody to TSH receptor

Exopthalmos Proptosis and lid lag

Large gland Warm on palpation

Bruit Labs

Increased T3 and T4 Decreased TSH

Thyroid

Congenital Hypothyroidism 1 in 4000 Cretinism

Broad nasal bridge Coarse facial features Mental retardation Short stature Puffy hands Protuberant tongue Delayed skeletal maturation

Treatment within 3-4 weeks

Newborn Screening

Thyroid

Hypothyroid Hypothalamic abnormalities Pituitary abnormalities Iodine deficiency Chronic lymphocytic thyroiditis Hashimoto thyroiditis

Anti-thyroid antibodies Thyroglobulin Thyroperoxidase

Positive FH Increased TSH, decreased T4

Thyroid

Hypothyroid symptoms Firm or bosselated gland Congenital vs Acquired Dry skin Constipation Hair loss Fatigue Cold intolerance Apathy Depressed or delayed relaxation

Acquired hypothyroidism: Note the sharp deceleration in growth before the onset of symptoms. Following initiation of therapy significant catch-up growth is seen.

Calcium and Phos Metabolism

PTH

Bone: Increases release of Ca and Phos

Intestine: Increased re-absorption of Ca and Phos

Kidney: Increases excretion of Phos Decreases excretion of Ca Stimulates Synthesis of Vit D3

Effects of PTH

Bone Intestine

Kidney Net Effect

Ca

Phos

Vitamin D

Bone Increases release of Ca Increases release Ph

Intestine Increases absorption of Ca Increases absorption of Ph

Kidney Improves reabsorption of Ca Increases reabsorption of Ph

Vitamin D

Bone Intestine

Kidney Net Effect

Ca

Phos

Calcitonin

Bone Inhibits reabsorption of Ca Inhibits reabsorption of Ph

Intestine (no specific effects)

Kidney Decreases reabsorption of Ca Decreases reabsorption of Ph

Net Effect of 3 Hormones

Ca Phos

Vit D

PTH

Calcitonin

Hyperparathyroidism

Results in hypercalcemia

Manifestation of multiple endocrine neoplasia I (MEN 1) Autosomal dominant Islet cell tumors Zollinger-Ellison syndrome Pituitary tumors

Symptoms:ParesthesiasIrritabilityMuscle CrampsTetanySeizures

Hypocalcemia

Question 6

A two day old infant experiences a prolonged seizure with respiratory arrest requiring intubation. BMP reveals hypocalcemia, and CXR demonstrates absent thymic shadow. Genetic testing is likely to reveal:

A. Trisomy 21B. Trisomy 18C. Deletion of 22q11.2D. Deletion of 15q13.3E. DF508 Mutation

Hypoparathyroidism

Idiopathic (Autoimmune) DiGeorge Syndrome

Dysmorphic features Cardiac defects Immune deficiency Thymic aplasia Low PTH Deletion of 22q11.2 May present with seizures secondary to

hypocalcemia

Ca low

P high

PTH low

Pseudohypoparathyroidism

PTH is elevated Unresponsiveness to PTH

(Bone/Kidney/Both) Albright hereditary osteodystrophy

Suspect in short child with hypocalcemia

Ca lowP highPTH high

Albright hereditary osteodystrophy

Vitamin D-Deficient Rickets

Vitamin D deficiency may result from Inadequate sunlight exposure Malabsorption Drugs that affect Vit D

Phenytoin, phenobarb Signs/Symptoms

Poor linear growth Delayed walking Muscle weakness Bone pain Hypotonia Anorexia

Ca NL/lowP lowPTH highAlkP high

Vitamin D-Deficient Rickets

Others

Vitamin D-Resistant Rickets Resistance to Vit D, even when high

amounts used Findings in first months of life

Pseudovitamin D-Deficiency Rickets AKA 1 -a hydroxylase deficiency or Vit-D

dependent rickets type I Findings appear in early infancy Autosomal recessive

Adrenals

Adrenal Gland

Cortex Glucocorticoids Mineralocorticoids Androgens

Medulla Epinephrine Norepinephrine

Adrenal Glands

Cushing Excessive glucocorticoids

Endogenous or exogenous steroid exposure

Causes Adrenal tumors Pituitary adenomas (Cushing disease) Ectopic ACTH production

Adrenal Gland

Features of Cushings Rounded facies Plethora Central obesity Impaired linear growth Fatigue Hypertension Buffalo hump Muscle weakness and muscle wasting Skin is thin and easily bruised Osteopenia/osteoporosis

Adrenal Gland

Cushings Labs Elevated 24-hour

urine free cortisol excretion

Elevated salivary cortisol

Delineating the cause High- and low-

dose dexamethasone suppression tests

Adrenal Gland

Addison’s Disease Insufficiency

Glucocorticoid Mineralocorticoid

Causes Autoimmune destruction Tuberculosis Autoimmune polyendocrine syndromes Adrenoleukodystrophy, Wolman disease, hereditary

unresponsiveness to ACTH, Allgrove syndrome, and congenital adrenal hypoplasia

Massive adrenal hemorrhage can occur with meningitis or traumatic births

Adrenal Gland

Addison’s Weight loss Wasting of

subcutaneous tissue

Hyperpigmentation Weak Confused Decreased

circulating plasma volume

Adrenal Gland

Addison Labs

Hyponatremia Hyperkalemia

Less pronounced disease in ACTH deficiency

If untreated Weaken Vascular collapse

Question 7

A 3-week-old female infant is brought to the ER for vomiting, decreased oral intake and lethargy of 3 days’ duration. Because the infant had not regained her birthweight at the 2-week visit, the mother was instructed to wake her every 2 hours to breastfeed. On PE, the infant’s temp is 98.6F, HR 190, BP 60/30. She appears thin and lethargic and has a poor suck. Her anterior fontanelle and eyes appear sunken, and her CR is 3 secs. You note an enlarged clitoris and partial labial fusion. Assessment of serum electrolytes in this infant is MOST likely to reveal

A. HyperchloremiaB. HyperglycemiaC. HypernatremiaD. HypokalemiaE. Hyponatremia

Adrenal Gland

CAH Autosomal recessive Symptoms reflect specific defect

21-hydroxylase deficiency Most common Decreased glucocorticoid

Hypoglycemia Decreased mineralocorticoid (severe forms)

Salt-wasting Hyperkalemia/hyponatremia

Elevated 17-hydroxyprogesterone Excess androgens

Masculinization Shock and death if untreated

Adrenal Gland

Other forms of CAH Less severe 21-hydroxylase deficiency

May present later Premature pubarche, rapid growth, skeletal

maturation

11β-hydroxylase

17α-hydroxylase Delayed puberty Undervirilization of males

Adrenal Gland - Medulla

Pheochromocytoma Rare Catecholamine-secreting tumor

Norepinephrine, Epinephrine, Dopamine (rarely) Symptoms

HA, diaphoresis, palpitaions, tremor, nausea, weakness, anxiety, weight loss

Hypertension (episodic), AMS, arrhythmia Syndromes

MEN 2A, 2B, NF, VHL Diagnosis

Plasma metanephrines, 24-hour urine catecholamines and metanephrine

Sexual Differentiation

Sexual Differentiation

SRY gene Short arm of Y chromosome Promotes differentiation of Sertoli cells Mutations lead to male to female sex

reversal Ambiguous genitalia

“the baby” Endocrine, urology, psychologist or social

worker Palpate for gonads

Sexual Differentiation

Ambiguous Genitalia CAH

No palpable gonads 17-hydroxyprogesterone

Leydig cell hypoplasia, inborn errors of testosterone synthesis, androgen insensitivity Palpable gonads LH, FSH, testosterone,

dihydrotestosterone Complete androgen

insensitivity Externally female Uterus absent Labial or inguinal gonads

Sexual Differentiation

Persistent mullerian duct syndrome Persistance of structures

in normal 46,XY male Cryptorchidism or

testicular ectopia Defect in anti-mullerian

hormone Agenesis of the phallus

Developmental

Question 8

You are examining a 2-week-old male infant for the first time and note an undescended right testicle. His mother asks when is the optimal time to correct this problem.

The MOST appropriate time at which to recommend surgical repair for this infant if spontaneous descent has not occurred is

A. 4 monthsB. 12 monthsC. 24 monthsD. 36 monthsE. 48 months

Cryptorchidism

Migration Kidneys to scrotum 3% of male infants Treatment

6-12 months Orchiopexy

Increased risk for malignancy Surgical intervention

does not alter risk

Precocious Puberty

Precocious Puberty

Girls <8

Boys <9

Central Gonadotropin-dependent

Activation of HPG axis FSH, LH

Hypothalamic hamartomas Gelastic seizures

Intracranial neoplasms

Precocious Puberty

Gonadotropin-independent Increased gonadal steroids No HPG axis involvement McCune-Albright syndrome

Café-au-lait Polyostotic fibrous dysplasia Precocious puberty

Gonadal or adrenal neoplasms Rare

Familial male-limited precocious puberty

Question 9

During the hospital discharge examination of a term female neonate, you palpate a 1-cm mass beneath her right nipple. There is no erythema at the site and no discharge from either nipple. The mass is nontender and freely mobile. The genitalia appear mildly swollen but are otherwise normal.

Of the following, the MOST appropriate treatment is

A. Excisional biopsyB. Fine-needle aspiration of the massC. IM gonadotropin-releasing hormoneD. Oral cephalexinE. Reassurance of the parents

Premature Thelarche

Breast tissue development Uni or bilateral May regress or persist

Diagnosis of exclusion No other signs of pubertal

development Exogenous estrogen

1-2y Self-limited Normal in neonates

Premature Pubarche

Pubic hair <8y in girls; <9.5y boys

Axillary hair, body odor, acne

Due to Premature adrenal

pubertal maturation PCOS

Late onset CAH Tumor - rare

Delayed Puberty

Delayed Puberty

Constitutional Delay Normal variant

Central Kallmann Syndrome

Hypothalamic hypogonadism Acquired

Trauma, neoplasm, infiltrative disorders, hyperprolactinemia, chronic illness - anorexia, CF, sickle cell

Gonadal Turner, Klinefelter Trauma, chemotherapy, radiation

Delayed Puberty

Other Androgen insensitivity

Inguinal or labial mass Primary amenorrhea

17-hydroxylase deficiency Cannot produce sex steroids

Turner Syndrome

XO Short stature Gonadal failure

Streak ovaries Other

Cubitus valgus, shieldlike chest, webbed neck

Cardiac Renal

Mosaic

Klinefelter Syndrome

47, XXY

Small, firm testes

Gynecomastia

Neurobehavioral difficulties

You will get more diabetes than you ever dream of on Purple team!

Diabetes

Hypoglycemia

Hypoglycemia

Signs and symptoms ANS, Epinephrine, CNS

glucopenia Fasting vs. Stress vs.

Iatrogenic

Hyperinsulinism Most common cause in

neonates Mutations of enzymes,

iatrogenic, adenoma Beckwith-Wiedemann

Macrosomia, macroglossia, omphalocele, hemihypertrophy and embryonal tumor

Hypoglycemia

Ketotic hypoglycemia Common cause of childhood hypoglycemia 18 months to 5 years Resolves by 8 to 9 years

Other Hypopituitarism, GSD, disorders of

gluconeogenesis

Obesity

Question 10

You care for a 17-year-old boy who is overweight. He has gained 44 lb (20 kg) in the last year, especially in his abdominal area. On examination today, his blood pressure is 158/90 mm Hg using a large, appropriately sized cuff. His mother has a similar body habitus and is being treated for type 2 DM. Of the following, the MOST likely abnormalities to expect in this patient if his presentation continues into adulthood is

A. High triglycerides and low HDLB. Hypoglycemia from insulin sensitivityC. Low concentrations of C-reactive protein in the bloodD. Low fibrinogen concentration with bleeding diathesesE. Low triglycerides and low LDL

Obesity

Look for causes of secondary obesity Endocrine Genetic CNS

Metabolic Syndrome Obesity Insulin resistance Dyslipidemia HTN Increased risk of developing Type 2 DM and

CV disease Look for PCOS

Hyperandrogenism, irregular menses, chronic anovulation