Endocrinology Flashcards
Short child, but normal growth velocity, predicted adult height = mid parental height. Bone Age = Chronological age
Familial Short Stature
Short Child, normal growth velocity, delayed entry into puberty, often positive family history, predicted adult height =mid parental height, Bone age < chronological age
Constitutional Growth and Maturation Delay
Two times in life where it is normal for a child to cross percentiles
During the first 2-3 years of life
During puberty
From 3-puberty there shouldn’t be any crossing of percentiles
Growth hormone deficiency S/Sx
Isolated. But can have many pituitary hormones affected. Poor growth velocity Delayed bone age Low IGF-1, IGF BP 3 Low response on 2 GH stimulation tests
Growth Chart of FTT
Weight before height
Growth Chart GH deficiency
Fall off the curve after 2 years
Length before weight. (Cherubs)
Growth Chart Constitutional Growth Delay
low centile, but follows curve.
Growth Chart of Glucocorticoid Excess
Increased weight
Male Puberty: when does peak growth occur
Tanner 4-5
Testicular size pre puberty
<2.5cm
Testicular size puberty
> 2.5cm
Female Puberty: peak growth
Tanner 3
Will grow 8cm after menarche
Order of Female Puberty
Thelarche
Pubic hair
Growth
Menarche
Normal Ages of Puberty Female
8-13
Normal Ages of Puberty Male
9-14
Klinefelter
Delayed Puberty
47 XXY, 1:600 males
Puberty at normal age (penile enlargement, pubic hair)
Disproportionately small firm testes, gynecomastia, infertility
Learning and behaviour problems
Turner syndrome Genetics
45X or mosaic 46XX (usually paternal origin)
Short stature if untreated (GH helps)
Gonadal failure 96% Infertility 99%
Turner S/Sx
Short stature
Congenital lymphedema
Horseshoe kidneys
Patella dislocation
Increased carrying angle of elbow (cubitus valgus)
Madelung deformity (chondrodysplasia of distal radial epiphysis)
Congenital hip dislocation
Scoliosis
Widespread nipples
Shield chest
Redundant nuchal skin (in utero cystic hygroma)
Low posterior hairline
Coarctation of aorta
Bicuspid aortic valve
Cardiac conduction abnormalities
Hypoplastic left heart syndrome and other left-sided heart abnormalities
Gonadal dysgenesis (infertility, primary amenorrhea)
Gonadoblastoma (increased risk if Y chromosome material is present)
Learning disabilities (nonverbal perceptual motor and visuospatial skills) (in 70%)
Developmental delay (in 10%)
Social awkwardness
Hypothyroidism (acquired in 15–30%)
Type 2 diabetes mellitus (insulin resistance)
Strabismus
Cataracts
Red-green color blindness (as in males)
Recurrent otitis media
Sensorineural hearing loss
Inflammatory bowel disease
Celiac disease (increased incidence)
Precocious Puberty Red Flags
Rapid Progression (BA advanced >2 years)
Predicted adult height <150cm or >2SD below Mid parental height
CNS S/Sx
Peripheral Precocious Puberty Symptoms
Differs from the normal order of development
Girls: Estrogen effects
Boys: testes are small and asymmetrical
What does this child have: isolated breast development usually at 6-24 months of age, < tanner 3, growth normal
Premature Thelarche (benign)
Pubic +/- axillary hard, body odour, acne, no thelarche, early DHEA secretion, growth normal. Bone age = height age
Premature Adrenarche
McCune Albright Diagnosis
Two or more of the following features are present:
Fibrous dysplasia
Café au lait macules, including characteristic jagged “coast of Maine” borders and tendency not to cross the midline
Hyperfunctioning endocrine disease
McCune Albright Endocrine problems
- Precocious puberty: The most common endocrinopathy is precocious puberty, which presents in girls (~85%) with recurrent estrogen-producing cysts leading to episodic breast development, growth acceleration, and vaginal bleeding. Precocious puberty in boys is much less common (~10–15%).
- Testicular abnormalities: Testicular abnormalities are seen in a majority (~85%) of boys.
- Hyperthyroidism: Hyperthyroidism occurs in approximately one-third of patients with McCune Albright syndrome.
- Growth Hormone Excess: Excess growth hormone secretion in approximately 10–15% of patients.
- Cushing’s Syndrome: In McCune–Albright syndrome, Cushing’s syndrome is a very rare feature that develops only in infancy.
Is McCune Albright GnRH dependent or independent
INDEPENDENT
Prevalence of T1DM
1:300
Criteria for diagnosis of diabetes
FPG > 7
RBG > 11.1
2hr OGTT >11.1
Neonatal Diabetes age of diagnosis
< 6months
Symptoms of Neonatal Diabetes
FTT
DKA at presentation
Treatment of Neonatal Diabetes
Sulfonylurea
Insulin
MODY Age of onset
<25
MODY patient characteristics
Lean, Asymptomatic
MODY Genetics
Autosomal Dominant
MODY: DKA?
Nope
MODY treatment
None
Sulfonylurea
T2DM age of onset
Puberty (rarely before 10)
T2DM Genetics
Obesity
Family History
Ethnic Predisposition
T2DM DKA?
Yes 5-20%
T2DM Treatment
Lifestyle
Metformin
Insulin
T1DM Age of onset
> 6 months
T1DM Genetic
Autoimmune
T1DM: DKA?
Yes! 15-67%
T1DM Treatment
Insulin
What percentage of children in DKA have cerebral edema
0.5-1%
Factors associated with development of cerebral edema
Bolus of insulin prior to infusion Early insulin administration (within first hour) Young children in DKA New onset diabetes Greater degree of acidosis Extracellular volume depletion
Management of Hyperglycemia
Total daily dose of insulin…then give 10-20% od TDD with rapid insulin
What is the insulin sensitivity factor
Amount that BG will drop for every unit of rapid insulin given
Target BG of 6-8
T2DM: Indication for insulin + metformin
significant metabolic decompensation
insulin may only temporary
Hormonal response to hypoglycemia
Decrease Insulin Increased Glucagon Increased Epi Increased cortisol and GH Symptoms Cognition
Critical Sample
Glucose Insulin C peptide BHB FFA GH Cortisol Lactate Extra plasma for specific tests. First urine void for ketones
Idiopathic Ketotic Hypoglycemia: what is it?
Substrate deficient hypoglycemia Typical in children 1-5 Often small (<3rd centile height and weight) Usual history of recent viral illness Investigations normal
What is this: Dilute urine (<300m osmol) Increased serum osmolality (>300) Increased serum sodium Decreased body weight Dehydration
Diabetes Insipidus
Loss of vasopressin production (central) or action (nephrogenic)
What is this: Increased Urine osmolality Oliguria Hyponatremia Decreased serum osmolality Euvolemia or hypervolemia
SIADH:
inappropriate release or excess ADH activity
Etiologies: neurologic disease, response illness, drugs, hypothyroid, adrenal insufficiency. Nausea, surgery, pain, psychological stress
What is this: Increased urine output Hyponatremia Decreased serum osmolality Increased Urine sodium Increased Urine osmolality Increased Urine output Dehydration
Cerebral Salt Wasting
Micropenis term infant size
<2.5cm stretched
Clitoromegaly in term infant size
> 9mm
or breadth >6mm
Posterior Labial Fusion Definition
Anogenital ration >0.5 (distance from anus to posterior fourchette, divided by distance from anus to base of phallus)
Most common cause of female DSD
CAH!!
Virilizing maternal disease, maternal androgen use, ovotesticular DSDm XX testicular DSD, gonadal dysgenesis
Basic labs for 46XX DSD
17 OHP, serum lytes, glucose, ACTH, renin, testosterone, LH, FSH
46XY DSD work up
Testosterone, Dihydrotestosterone, LH, FSH, Mullerian Inhibiting Substance, Electrolytes, Glucose
Rare CAH in male with undervirilization: NOT ASSOCIATED WITH 17 OHP
Etiology of Congenital Hypothyroidism
Thyroid Dysgenesis (80%)
Dyshormonogenesis (10%)
Hypothalamic/pituitary (5%)
Transient (5%): intrauterine antithyroid meds, maternal blocking antibody, iodine deficiency.
What thyroid etiology is this:
Diffuse (or asymmetric) enlargement of thyroid gland
Increase TSH
Positive antibodies (thyroid peroxidase, anti thyroglobulin)
Hashimoto’s Thyroiditis
Hypothyroidism
Autoimmune disease: thyroid gland is gradually destroyed.
Some people eventually develop hypothyroidism with accompanying weight gain, feeling tired, constipation, depression, and general pains.
After many years the thyroid typically shrinks in size.
Potential complications include thyroid lymphoma
What Thyroid Etiology is this:
Thyrotropin Receptor Stimulating Antibody
Goiter in more than 95%
Eye disease not as common in children
Graves Disease
Third most common solid tumour in children and adolescents
Thyroid
What percent of paediatric Thyroid Nodules are malignant?
20%
What is the most common paediatric thyroid cancer?
Papillary
Graves disease treatmetn
First line: Methimazole
PTU: leading cause of hepatic failure…rare to use
Second Line: Radioactive iodine (can make eye disease worse)
Third Line: Surgery (<5 years, significant eye disease, very bulky disease)
Most common causes of primary adrenal insufficiency
CAH
Autoimmune destruction of adrenal cortex
Most common cause of secondary adrenal insufficiency
Glucocorticoid withdrawal.
Inheritance of CAH?
AR
What is Addison Disease?
AI mediated destruction of the adrenal cortex
S/Sx of Addison Disease
Weight loss Fatigue Hypotension Hyperpigmentation Hyponatremia Hyperkalemia Hypoglycemia Elevated Renin and ACTH LOW AM CORTISOL
Adrenal crisis: dosing of hydrocortisone for minor stress
2-3 x the replacement dose of hydrocortisone
Adrenal crisis: dosing of hydrocortisone for major stress
100mg/m2 IV/IM stat
then dose divided as q6-8
Symptoms of APS 1
AIRE gene mutation
CLASSIC TRIAD:
- mucocutaneous candidiasis (1st sign)
- Hypoparathyroidism (usually before puberty)
- Addison Disease (usually in adolescents)
Symptoms of APS 2
Polygenic
- AI Thyroid Disease
- Addison Disease
- T1DM
Etiology of Cushing Syndromes
Excess glucocorticoids Hypothalamic Pituitary Primary Adrenal ectopic ACTH Iatrogenic
What is Cushing DISEASE
Excess Pituitary ACTH production (pituitary adenoma)
Cushing Syndrome < 5 years…most likely etiology?
Adrenal Pathology…McCune Albright Disease
Cushing Syndrome > 5 years…most likely etiology?
Pituitary Disease
How to diagnose Cushing Syndrome?
24 hour urinary free cortisol to see if cortisol excess is present.
Early AM cortisol is not useful
Primary hormones affecting calcium metabolism
PTH
1, 25(OH)2 Vit D
Calcium and albumin relationship
For every change of 10 g/L of albumin, change in calcium by 0.2
How is calcium affected by alkalosis?
Lower it!
How much vitamin D should ALL infants get?
400 IU
Which infants should get 800IU daily of Vit D?
High risk Vit D Deficiency kids,
From Oct- April
North of 55th parallel
How much Vit D should pregnant and lactating women get?
2000IU
Definition of Osteroporosis
Decreased bone strength which leads to increased risk of fractures
What are clinical significant fractures?
2 or more long bone fractures by 10
3 or more long bone fractures by 19
1 or more vertebral compression fractures (loss >20% of vertebral body heigh at any age)
Secondary Osteoporosis Causes
Hypothyroidism
Chronic Illness
Physical inactivity
Vit D Deficiency
What is this:
Serum Osm >600 with a urine Osm <300
Diabetes Insipidus
Main Role of PTH
To maintain serum Calcium
Elevated PTH does what to calcium and Phosphate?
↑ Ca and ↓PO4 (kidney)
Decreased PTH does what to calcium and Phosphate?
↓ Ca and ↑ PO4 (kidney)
What is vitamin D’s main role?
absorb Ca and PO4
Increased 25 OHD does what to calcium and phosphate?
↑ Ca and ↑ PO4 (secondary ↓ PTH)
Decreased 25 OHD does what to calcium and phosphate?
↓ Ca - secondary↑ PTH - ↓PO4
Cause of hypocalcemia with LOW calcium and HIGH phosphate?
Hypo PTH
Cause of hypocalcemia with LOW calcium and LOW phosphate?
Hypovit D
Causes of Hypo parathyroidism
DiGeorge (aplasia or hypoplasia) Autoimmune parathyroiditis Infiltrative lesions Post surgical hypoparathyroidism Post radioactive iodine to thyroid gland PTH receptor defects
Causes of Vitamin D Deficiency
Reduced Intake or production Liver Increased catabolism Anti-seizure medications Renal Failure 1α-Hydroxylase Deficiency Hereditary 1,25(OH)2 D Resistance
What does the zona glomerulosa produce?
Aldosterone
What does the zona fasciculata produce?
Cortisol, androgens
What does the Zona reticular produce?
Cortisol and androgens
What does the medulla produce?
catecholamines
Glucorticoid function
glucose metabolism anti inflammatory immunologic ophthalmologic thyroid GFR
Mineralocoritcoid function?
RAS activation:
- Na retention
- K excretion
What is the pathophysiology of Addison Disease?
Anti adrenal cytoplasmic antibodies…destruction of the adrenal
May be part of APS 1 or 2
What is the pathophysiology of Adrenoleukodystrophy?
X linked
disorder of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body.
The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes.
Lab findings of Adrenoleukpdystrophy
High levels of VLCFA
Primary Adrenal Insufficiency Symptoms
Hypoglycemia Hypotension Hyperpigmentation Hyponatremia Hyperkalemia
Infants: sick quicker
Management of Adrenal Crisis
Salt: restore volume and Na Sugar: dextrose bolus Steroids: Hydrocortisone 100mg/m2 Support: BP, BW, Endo, PICU Search: for etiology
Management of chronic primary adrenal insufficiency
Hydrocortisone 10mg/m2 div TID
Fluorinef (if aldosterone deficient)
Monitor ACTH, renin, lytes, BP, growth
Stress Dosing
Secondary Adrenal Insufficiency Clues in the Neonate
Hypoglycemia
Lytes usually normal
Signs of associated deficiencies
(micropenis (gonadotropins), jaundice (thyroid), poor growth (GH), mid face hypoplasia and visual impairment)
Secondary Adrenal Insufficiency Signs/Symptoms
Hypoglycemia
Hypotension
NO MINERALOCORTICOID SYMPTOMS
Secondary Adrenal Insufficiency Treatment
Hydrocortisone
DO NOT NEED FLORINEF
STRESS DOSING
CAH Labs
Lytes, glucose, gas
17 OHP, androgens, cortisol, renin, aldosterone
ACTH stimulation test
CAH Management
Hydrocortisone, +/- florinef, +/- NaCl
Cushing Syndrome Investigations
24 hour urinary free cortisol (elevated)
Dexamethasone Suppression Test (NORMAL would be a cortisol < 50 at 8am. would be high in Cushing)
Cushing Syndrome Treatments
Transphenoidal Surgery
Inhibitor of adrenal steroid genesis (metyrapone, ketoconazole)
Adrenalectomy
Adrenal Tumours Age group
< 10 years
What % of adrenal tumours are bilateral?
2-10%
What % of adrenal tumours have endocrine function?
> 90%
Catecholamine secreting tumor
Pheochromocytoma
Where do most Pheochromocytomas occur?
90% in adrenal medulla
What % of Pheochromocytomas are bilateral?
> 20%
Associated syndromes of Pheochromocytoma
NF Von Hippel-Lindau MEN-2A, MEN-2B Tuberous Sclerosis Sturge Weber Ataxia Telangiectasia
Management of Pheochromocytoma
Surgery is high risk Pre-op alpha and B adrenergic blockade fluid transabdominal exploration prolonged follow up screen relatives
Muellerian Ducts are the precursors to what structures?
Fallopian tubes
Uterus
Upper 1/3 of the vagina
Wolffian Ducts are the precursors to what structures?
Vas Deferens
Epididymis
Seminal Vesicles`
Default for an embryo is to develop into what sex?
Female
If you can palpate gonads, the child is what karyotype?
XY
Always palpating testis! Ovaries are not palpable
Absent SRY
Phenotypically Normal Female. Only discover on karyotype
Will have ovaries
5 alpha reductase deficiency phenotype
Can’t convert testosterone to DHT
External structures will not develop normally
Testis normal
No muellerian structures
Complete AIS phenotype
Will develop testis
Cannot do any actions of testosterone or DHT
No migration of testis.
Muellerian structures regress because MIS expressed.
No external Male genitalia due to lack of DHT
Mutation in MIS phenotype
Will develop as male, but muellerian structures will not regress
Pan hypopit
micropenis
Newborn with ambiguous genitalia.
On US, no goons in the inguinal canal. Gonads are in the abdomen. Uterus also seen. What is it?
CAH
CAH accounts for what percentage of all DSDs?
40-50%
Incidence of CAH
1:15 000
Non classic CAH S/Sx
No ambiguous genitalia Premature pubarche Accelerated bone age hirsutism menstrual irregularity infertility acne
Inheritance of CAH
AR
First investigation in primary amenorrhea
Pregnancy Test
THEN
LH/FSH, prolactin, TSH
Definition of secondary amenorrhea
Menstruation stops for >3 cycles after menarche
Incidence of Turner Syndrome
1:2500
Turner Syndrome Features
Shield chest wide spaced nipples lymphedema in the infant growth failure pectus excavatum epicanthal folds blue sclera ptosis low hair line low set ears small mandible short stature scoliosis Short 4th metacarpal
Most common cause of delayed puberty
Constitutional Delay
What is functional suppression?
Seen in ED
Seen in situations of excess stress
Chronic Disease (IBD, Celiac)
What is the athletic Triad
Low energy/Disordered eating
Amenorrhea (functional suppression of HPG axis)
Osteopenia/osteoporosis
Treatment of athletic triad
Increased calorie consumption
Three categories of delayed puberty
Hypergonadotropic hypogonadism
Permanent hypogonadotropic hypogonadism
Functional hypogonadotropic hypogonadism
Primary Gonadal Failure: Boys and girls
1) Kilnefelter’s syndrome-males
2) Turner syndrome- females
Hypergonadotropic hypogonadism Labs
Elevated LSH/FSH
Low levels of testosterone and estradiol
No pubertal development
Karyotype of Klinefelter’s
47 XXY
or XY/XXY mosaicism
Phenotype of Klinefelter’s
Penile growth and pubic hair can be normal Small Testes (<6mL) Tall stature Gynecomastia Behavioural problems
Permanent hypogonadotropic hypogonadism Labs
Low LH/FSH
No pubertal development
Low sex hormones
Inheritance of Kallman’s Syndrome
X linked
Pathophysiology of Kallman’s Syndrome
GnRH deficiency and Anosmia
What conditions are Functional hypogonadotropic hypogonadism
Athletic Triad
Easting disorders
Excessive Stress
Chronic Disease
What is the incidence of congenital heart disease in Turners?
30-45%
What are the most common CHD in Turners?
1- Bicuspid AV
2- Coarctation of the aorta
3- Partial Anomalous Pulmonary Venous return
Prolonged QT
Screening in girls with Turners
1) Hypertension screening annually
2) Sensioneural and conductive hearing loss
3) Vision screening: hyperopia and strabismus
4) Increased risk of hypothyroidism and celiac disease
Treatment of Turner’s
1) Estrogen to induce secondary sexual characteristics and to achieve maximum bone density
2) Progestin to induce menstruation
3) Growth hormone once there is evidence of growth failure
4) Harvesting gonadal tissue for potential future use for fertility
Neurological Symptoms of Hypocalcemia
Chvostek sign Trousseau Sign Muscle Cramping Tetany Paresthesias Carpopedal Spasms Laryngospasms Seizures
Hypocalcemia investigation
PTH
Critical Sample for hypocalemia
Ionized Calcium Phosphate Mg Alk Phos Vit D Urine Calcium LFTs Bun Cr
PTH Roles in calcium metabolism
Stimulates kidneys and bones to reabsorb calcium
increased the synthesis of 1, 25 OHD …increases calcium gut absorption
Where is calcium absorbed
duodenum and jejunum
Hypocalcemia Signs and Symptoms
Common in newborns 12-72 hours
HYPERREFLEXIA (Chvostek sign, trousseau sign)
Hypocalcemia + Dysmorphic Features
Di George
Albright hereditary osteodystrophy
Rickets
Causes of Hypocalcemia
- Low PTH (low secretion or resistance)
- Vitamin D problem
Drugs TLS Rhabdomyolysis Hypo/hypermagnesmia Critical Illness
Stimulus for PTH release
Low Calcium
High PTH
Low 1, 25 vit D
1, 25(OH) Vit D is regulated by
25 hydroxylase (liver) 1 alpha hydroxylase (kidney)...requires PTH
PTH function
Increases Calcium (bone resorption, renal absorption, activating vitamin D)
Increases Renal Wasting of Phosphate
Activation of 1, 25 (OH) vit D
Low calcium, low PTH…whats the issue?
HYPOPARATHYROIDISM
PTH should be high in low calcium
Labs in Hypoparathyroidism
Low Ca High Phos Low PTH Normal or High Alk phos Increased Urine Ca Decreased 1, 25 vit D
Acquired causes of HypoPTH
Post surgery
Radiation
Chronic anemia leading to iron deposition secondary to transfusions
APS 1 (AI Hypo PTH, Addison Disease, Chronic Mucocutaneous Candidiasis)
Infiltrative Disease (excessive copper deposition, sarcoid, neoplasm, amyloidosis)
Maternal HyperPTH
Hypo/Hypermagnesia
Treatment for Hypo PTH
Calcium
1, 25 Hydroxy vitamin D (calcitriol)
What is this:
PTH is high in the setting of hypocalcemia in a child with dysmorphic features
Pseudohypoparathyroidism
Appropriate PTH response to low calcium…but it doesn’t correct it.
S/Sx Pseudohypoparathyroidism
S/Sx Hypocalcemia
Short Stature
Abnormal Bones
Fetal Death
What is Albright hereditary osteodystrophy (AHO)?
Genetic cause of pseudohypoparathyroidism
Short stature, obesity, short metacarpals/metatarsals, short neck, hyperpigmentation
PTH is released appropriately, but there is no response to it (this is a receptor function and downstream signalling problem)
Suspect this condition in a short child who presents with hypocalcemia and a family history with similar features
PTH is extremely elevated
Signs and Symptoms of Hypercalcemia
painful bones demineralization renal stones constipation abdominal pain/N/V ileus lethargy weakness depression (in longstanding hypercalcemia) mild cognitive impairment CVS: short QT interval, bradycardia, HTN
What would you expect to see of these labs in hyper calcemia? Ca: PTH: Phos: Vit D: Alk Phos: Urine calcium
Ca: High
PTH: Low
Phos: High or normal
Vit D: low or N
Alk Phos: low or N
Urine calcium: Increased (want to pee out the extra)
Causes of Hypercalcemia
Hyperparathyroidism
Excessive calcium/vitamin D intake
Immobilization
VIP-oma
Renal failure
Other: Williams sx, cancer, low phosphate, drugs, other endocrinopathies
(hyperthyroidism, adrenal insufficiency, pheochormocytoma)
Primary Hyper PTH
Primary hyperparathyroidism: PTH secretion is normal or high in the presence of high calcium
Causes of Hyper PTH
Neonatal
- Neonatal severe primary hyperparathyroidism (CasR gene loss of function)
- Transient (secondary to maternal hypoparathyroidism or with pseudohypoparathyroidism)
Older children:
Adenoma
Hyperplasia
Cancer (rare)
Familial hypocalciuric hypercalcemia
What is Secondary Hyperparathyroidism
High/normal PTH in context of low Ca
Neonatal severe primary hyperparathyroidism: S/Sx and Treatment
Usually present in the first 6 mos of life with FTT, hypertonia and dehydration secondary to
polyuria
Extremely high levels of PTH and calcium
If one 1 allele affected -> benign familial hypocalciuric hypercalcemia
Urine calcium/creatinine ratio of <0.01 = consistent with this diagnosis
Tx: total parathyroidectomy
Transient neonatal hyperparathyroidism
Can occur in infants born to mothers with hypoparathyroidism or with pseudohypoparathyroidism
Cause = chronic intrauterine hypocalcemia leading to hyperplasia of the fetal parathyroid glands
Usually affects the bones and resolution expected between 4-7 mos of age
Causes of Hyper PTH in Children
Parathyroid adenoma (benign) Gland hyperplasia
Renal/neck U/S and PET scan to identify the adenoma location
Can have hyperparathyroidism as part of a genetic syndrome/association (MEN1, which
presents with PPP tumors, (Parathyroid, Pituitary and Pancreas)
Treatment of Hyper PTH
Surgery generally the best option for children
If no surgery -> bisphosphonates and calcimimetics (bridge to surgery -> suppress the production of PTH)
Complications = vocal cord paralysis and permanent hypoparathyroidism
What is Hungry Bone Syndrome
Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia
Exacerbated by suppressed PTH levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover.
High PTH leads to leeching of calcium from bones. Once high PTH is corrected, calcium is deposited in demineralized bones rapidly, leading to severe hypocalcemia
What is MEN 1
MEN1 (PPP!!) -> pituitary, parathyroid gland, pancreas
Parathyroid gland hyperplasia, pituitary tumours, insulinomas, gastrinomas
MEN gene suppressor tumour production
Tx: total parathyroidectomy (and bilateral cervical thymectomy – big risk for ectopic parathyroid glands
and thymic cancer syndrome with MEN1)
What is MEN 2
MEN 2a
Parathyroid adenomas + medullary thyroid cancer, pheo
Less common in MEN2a
What is Hyperparathyroidism jaw-tumour syndrome
Characterized by parathyroid adenomas and fibroosseous jaw tumours
High risk for parathyroid cancer and adenoma
Associated with Wilms tumours and polycystic kidney disease
What is FAMILIAL HYPOCALCIURIC
HYPERPARATHYROIDISM
Autosomal dominant condition
Caused by mutations that lead to inactivation of the calcium sensing receptor (CASR) gene
-> don’t sense calcium levels properly
Hypercalcemia
Hypocalciuria (PTH inappropriately high or normal in context of hypercalcemia)
Normal or elevated PTH
Normal renal function
Normal phenotype (no dysmorphic features)
Diagnosis of familial hypocalciuric hyperparathyroidism
Dx: 24 hour calcium/creatinine clearance, then if < 0.020 -> test for mutations in the CaSR gene
Serum calcium and creatinine drawn while hypercalcemia present and at the same time as urine calcium and creatinine is collected to allow calculation of calcium clearance
Generally do not need treatment
Causes of Secondary HyperPTH
Appropriate elevation of PTH in the setting of a low calcium
Causes: Low calcium intake Any problem with the vitamin D pathway Malabsorption of calcium Kidney disease
Symptoms of Hypothyroidism
Decreased energy Depression Cold intolerance Constipation periods are longer and heavier.
Physical Exam Findings of Hypothyroidism
Goiter Dry hair/skin Enlarged thyroid gland Poor relaxation phase of reflexes (delayed reflexes) Cool extremities Narrow pulse pressure Over weight
What is Hashitoxicosis?
*** Autoimmune Hypothyroidism may in fact present with symptoms of hyperthyroidism (clinical or subclinical)
Secondary to a massive release of stored thyroid hormone
How do you differentiate Hashitoxicosis from Graves Disease?
Differentiating features from those of Graves disease (autoimmune hyperthyroidism):
absence of eye findings on exam (proptosis)
negative thyrotropin receptor-stimulating immunoglobulins.
Most sensitive test for hypothyroidism
TSH
Lab findings for primary Hypothyroidism
High TSH, low T4 = primary hypothyroidism
Most likely cause for acquired hypothyroidism
Hashimotos (AI thyroiditis)
Who is at increased risk of Hashimotos?
Increased risk with Down Syndrome, Turner Syndrome, Noonan syndrome, Celiac disease,
T1DM, alopecia areata
~70% = genetic predisposition
Other causes of Hypothyroidism
Meds (especially those with iodides, or anti-epileptics)
Others: lithium, amiodarone, interferon alfa, hormone replacements
Craniospinal radiation
post Graves tx (radioactive iodine or thyroidectomy)
Nephropathic cystinosis
Langerhans cell histiocytosis
Hypothalamic or pituitary dysfunction (central hypothyroidism)
Environmental factors (that are considered triggers); infections, excess iodine consumption, stress, smoking
Clinical Presentation of Hypothyroidism/Hashimotos
Most of the time -> asymptomatic at presentation
~70% of patients will present with an asymptomatic goiter (often the first manifestation) -> non
tender, rubbery consistency
Children will often have growth failure at presentation as T4 is needed for linear growth
Moderate or severe hypothyroidism presents with non-specific symptoms: poor school
performance, slowing growth velocity (usually another early manifestation that usually goes
unnoticed), decreased energy, constipation
Weight gain (usually as a result of excess fluid not actual obesity)
Tibia myxedema
Cold intolerance
Increased need for sleep
Bradycardia
Muscle weakness
Delayed osseous maturation (delayed bone age)
Delayed or precocious puberty (precocious: +++TSH binding to FSH receptors)
Galactorrhea -> increased TRH stimulating prolactin production
Menometrorrhagia
Headaches and visions problems -> enlargement of the pituitary gland, sometimes with
enlargement of the suprasellar fossa after chronic primary hypothyroidism (secondary to
thyrotroph hyperplasia)
Investigations for Hypothyroidism/Hashimotos
serum free T4
TSH
Anti-thyroglobulin antibodies
Anti-peroxidase antibodies
Should an US be done in the work up of hypothyroidism?
No
Treatment of Hypothyroidism
Levothyroxine
Dosed weight based, increases with age
Monitor dosing by following the free T4 and TSH every 4-6 months until growth is complete
AND 6 weeks after any dosage change
Diet: high fiber food, soy products or soy-containing formula and some medications (iron,
calcium) can affect absorption
Any intestinal malabsorption (ie. celiac, IBD), may require higher doses
Which of the following is a cause of acquired hypothyroidism:
Sick Euthyroid Syndrome
Medications
Iodine Deficiency
All of them
What is Sick Euthyroid
Defined as a changes in TSH and free T4 during a time of acute or chronic illness in an otherwise
healthy child without a history of thyroid disease
TSH levels can also be low in children with severe illnesses secondary to dysfunction of the HPA axis
Thought to be due to an alteration in the deiodinase enzyme activity
What are the lab findings in sick euthyroid
First change is generally a decline in T3, followed by T4 (free T4) and TSH
Generally, the lower the T4, the worse the clinical outcome
Does not need to be treated
The TSH will recover first and often be above the upper limit of normal for a period of time, followed
by normalization of the free T4 and T3, then normalization of the TSH
What is the most common cause of hypothyroidism world wide?
Iodine Deficiency
List 3 meds that can cause hypothyroidism
Thionamides used to treat hyperthyroidism (methimazole, carbimazole, propylthiouracil)
Side effects =
- liver failure (propylthiouracil) – not recommended in kids
- Hypotension
Lithium – generally does not require treatment
Amiodarone – contains 2 iodine molecules
Lab findings on Subclinical Hypothyroidism
High TSH, normal T4
What is the outcome for subclinical hypothyroidism
An elevated TSH in the context of a normal T4 (“compensated”)
Outcome -> most children go back to a euthyroid state with only a minority continuing on to
develop hypothyroidism
Increased risks = goiter, antithyroid antibodies, increasing TSH levels over time
In someone with subclinical hypothyroidism, who would you treat?
Treatment:
TSH < 10: repeat and screen for antibodies, repeat is often normal
TSH 10-20: repeat level x 1 then treat
TSH >20: treat with thyroxine
Consider treatment for children with a large goiter, associated conditions such as T1DM, high TSH
levels, or symptoms of hypothyroidism
Low TSH Low T4 is what kind of hypothyroidism
Central
High TSH, low T4 is what kind of hypothyroidism
Primary
Causes of Central Hypothyroidism
Hypopituitarism (genetic or secondary to hypothalamic or pituitary tumours)
- Craniopharyngiomas
- Pituitary adenomas
- Rathke cleft cysts
- Empty sella syndrome
- Surgery or irradiation
- Meningiomas
Trauma
Genetic
Autoimmune
- Lymphocytic hypophysitis
- Polyglandular autoimmune syndrome
Infiltrative
- Sarcoidosis
- LCH
Infections
-TB
Most common congenital endo disorder
Hypothyroidism
What is the most common cause of congenital hypo thyroid.
Most cases (~85%) are due to thyroid gland dysgenesis
- Abnormal development of the thyroid gland leading to agenesis, thyroid hypoplasia or an ectopic
thyroid gland
Usually sporadic or idiopathic, most of the time there is no genetic link
~10-15% of cases = dyshormonogenesis
- the thyroid doesn’t make hormones effectively -> decreased production secondary to defects in the enzymes and ion transporters
autosomal recessive condition
Signs and Symptoms of congenital hypothyroidism
Most are normal at birth!!!
(This is because of the partial trans placental crossing of maternal T4, which makes up about 1/3 of the normal
level for newborns)
Usually normal birth weight and length, but can have macrocephaly secondary to myxedema of the
brain
Other symptoms can present at 2-4 weeks including:
Large fontanelles
Prolonged physiologic jaundice
Feeding difficulties secondary to lethargy, choking, poor appetites
Hypothermia
Edema of the face, eyelids, extremities and genitals
Coarse facial features
Late findings: macroglossia, poor suck, developmental delay, umbilical hernia, increasing lethargy,
increasing failure to thrive
By 3-6 mos, the clinical manifestations are all present
Lab work for congenital Hypo thyroids
Newborn screen: TSH +/- T4 after day 2 -> elevated TSH, low/normal T4 (TSH after the first week should be less than 10 mIU/L)
Primary TSH method detects congenital hypothyroidism secondary to dysgenesis or dyshomonogenesis but misses central hypothyroidism
Central hypothyroidism may be missed if only use TSH for screening (better with a T4/TSH approach)
T4 test will detect overt CH, central hypothyroidism, hypothyroxinemia in sick/premature babies, and
hyperthyroxemina but will miss compensatory hypothyroidism (with normal T4 but elevated TSH)
and transient hyperthyrotropinemia (iodine defiency)
Need to confirm the positive screen with a repeat TSH, T4 and diagnostic scan (uptake scan, can confirm dysplasia)
If no uptake -> U/S to see if the thyroid is actually there
Dyshormonogenesis -> enlarged gland with increased uptake
Screen positive for Hypothyroidism …next step?
TREAT. Do not delay for repeat testing.
What is premature thelarche
- benign condition
- seen in females, usually before the age of 2.
- isolated breast development, with no other
signs of puberty.
Growth is not accelerated, and bone age is normal.
Extensive investigation is not recommended.
If seen in <2 years of age, there is generally regression of breast tissue.
If >2 years, regression is not as common. Girls >2 years of age should be monitored, as they could progress to
central PP.
What is premature adrenarche
- early maturation, or exaggerated response to
physiologic maturation of adrenal gland. - presents as pubarche (pubic hair) with no
other signs of puberty. - Bone age is normal.
DHEAS can be mildly elevated.
Extensive investigation is not needed as long as there
are no other signs of puberty or signs of
virilization.
Children should be monitored as they can progress to central PP
Three causes of peripheral precocious puberty
Peripheral PP is gonadotropin independent. The HPG
axis is not active. Here the sex steroids are either:
Androgens that are coming from the adrenal gland
(testosterone can be converted to estrogen by
aromatase)
Sex steroids are from the gonads, but are not being
driven by LH/FSH. Instead, the hormone production
is stimulated by bHCG secreting tumors, activating
mutations of LH receptor, or gonadal tumors that are
independently secreting sex hormones
Exogenous hormones (ingestion of OCP, tea tree oil, etc)
What is the normal age of puberty for a girl?
Normal puberty begins between 7 and 13
years in girls
Normal puberty does not start until age 8 in
Caucasian girls, but may start as early as 7 in
black and hispanic girls.
What is normal age of puberty for males?
between 9 and 14 in boys
Order of puberty in females
Breast budding, pubic hair, growth spurt,
menarche
Girls growth 5-7cm after menarche.
Pubic hair development will precede breast
budding in 10-15% of girls.
Order of puberty in males
Testicular growth, pubic hair, penile growth,
growth spurt
Testes >4 mL
What is a worrisome feature that would make you suspicious of true precocious puberty?
A growth spurt associated with symptoms of puberty is
worrisome for true precocious puberty.
GH secretion increases during puberty in response to sex steroids.
Approximately half of pubertal growth spurt is due to sex hormone effects on epiphyseal growth and half due to GH.
What must you look for on physical exam for a ?precocious puberty
Visual field testing, tanner staging by inspection
and palpation, skin inspection for café au lait
spots, and inspection of her limbs/MSK
What causes of precocious puberty have cafe au last spots?
Café au lait spots are seen in both Neurofibromatosis and McCune Albright syndrome.
Fibrous dysplasia of bone is seen in McCune Albright, an important syndrome to rule out in PP.
What is the McCune Albright syndrome triad?
café au lait spots
gonadotropin independent precocious puberty
fibrodysplasia
How does McCune Albright present?
In girls, the PP often presents as vaginal bleeding followed by breast budding, without pubic hair.
In boys, it can be bilateral (or unilateral) testicular enlargement with penile enlargement, scrotal rugae, and body odor.
Investigations for premature adrenarche
A bone age
Benign premature adrenarche and benign premature thelarche do not cause significant advancement in bone age.
Central or peripheral precocious puberty
would result in advancement of the bone age.
DHEAS is the main androgen secreted by the adrenal glands. A mild increase above normal is expected in benign premature adrenarche.
Head imaging is indicated to investigate central PP.
GnRH stimulation test is the gold standard to assess function and activity of the HPG axis….only if true signs and symptoms of PP.
Pelvic and gonadal US is useful to investigate for ovarian cysts.
How does a GnRH stimulation test work for differentiating central versus peripheral precocious puberty?
If it’s peripheral, the LH doesn’t rise. Because the only way you have LH surge/rise, is if you’ve had GnRH priming (by many many pulses) before
So if you are central, you have these pulses going, and you will respond
Therefore a positive GnRH stimulation test indicates central precocious puberty, a negative stimulation indicates peripheral (gonadotropin independent) PP.
What is the triad of PCOS?
Polycystic ovarian syndrome is characterized by the triad of oligo-ovulation or anovulation (menorrhea), clinical or biochemical hyperandrogenism, and ovarian cysts.
The pathophysiology of PCOS is not completely understood. It is associated with obesity, insulin resistance, and puts women at increased risk of metabolic syndrome and type II diabetes.
What is the treatment of PCOS?
Treatment is with hormonal contraception to regulate menstruation and oppose androgen action, and insulin sensitizing agents such as metformin.
What are the complications of PCOS?
Main complications of PCOS are metabolic syndrome, type II diabetes (patients must be screened for this), endometrial cancer (secondary to periods of anovulation), and fertility issues.
When do boys typically develop pubic hair
Pubarche characteristically follows, with most boys attaining Tanner 3 pubic hair ~1-1.5 y after onset of puberty.
The growth spurt occurs during genital
stages 3 and 4, during which time spermarche occurs.
The onset of facial hair and voice change, occur during genital stage 4.
What are some good clues in males for central PP?
Growth spurt and testicular growth.
What are clues for peripheral PP in males?
Small testes with secondary sex characteristics
What are causes of central PP?
CNS tumors, trauma, CNS infection,
hydrocephalus, CNS radiation, chemotherapy, and
idiopathic are all causes of central PP
(gonadotropin dependent).
What are causes of peripheral PP?
Peripheral (gonadotropin independent) PP can be
caused by gonadal tumors, McCune Albright
Syndrome, Familial Testotoxicosis (activating
mutation of the LH receptor), CAH, Adrenal
tumors, HCG producing tumors (germ cell tumors,
hepatoma), and primary hypothyroidism.
What is Familial Testotoxicosis?
- gonadotropin independent (peripheral) PP
- Caused by an activating mutation in the LH receptor gene.
- autosomal dominant manner.
- generally presents between 2 and 4 years
of age.
Patients have accelerated growth, early development of secondary sexual characteristics.
Patients have increased levels of androgens
(testosterone) with low levels of LH and a
negative GnRH stimulation test.
Can primary hypothyroidism cause PP
High levels of TSH can cause increase in FSH and
also potentially cross react with gonadotropin
receptors, leading to breast development in girls
and testicular enlargement in males. An increase
in somatic growth is not seen.
How do you calculate mid parental height?
Midparental height is calculated as follows:
Boys = maternal height in cm + 13 cm +
Paternal height in cm / 2
Girls = maternal height in cm + paternal height
in cm -13cm / 2
Conversion from inches to cm is: Inches x 2.54
= cm
When does growth occur with respect to tanner staging of a boy and girl?
Half of pubertal growth spurt is due to sex hormone
effects on epiphyseal growth and half due to GH.
Females peak in their growth spurt ~tanner stage 3, males at tanner stage 3-4, which tends to be ~2 years later in males
Females peak growth velocity is 8.25 cm/year,
males is 9.5cm/year. The combo of longer period of prepubertal growth + greater growth velocity explains the greater height in males.
Females grow an average of 5-7 cm after menarche.
Females achieve 99% completion of growth at bone age 15, males at bone age 17. Years of growing left can be estimated by doing a bone age.
Is PP more common in males or females?
Precocious puberty is 5-10x more common in females than males.
What is the most common cause of PP in females?
Idiopathic central PP accounts for 90% of PP in females, but only 50% in males.
Work up of male with PP?
Bone age, GnRH stimulation test, bHCG, MRI,
TSH
If mass found on MRI in kid with PP…what investigations should be done?
CRH/ACTH: AM cortisol, ACTH stimulation test
GH: following growth, GH stimulation test if
decreased growth velocity, or hypoglycemia
Prolactin: Prolactin level
ADH: electrolytes, monitor for polyuria/polydipsia
TRH/TSH: TSH and fT4 level
When is gynecomastia normal?
It is seen in up to 90% of newborn males, secondary to maternal estrogens and bHCG.
Neonatal physiologic gynecomastia resolves in the neonatal period.
A second spike is seen
during puberty, when up to 50-70% of pubertal males will develop gynecomastia. 90% will self resolve in 1-3 years.
Best treatment for central PP?
Treating with a long acting GnRH agonist
(lupron) takes away the pulsatile rhythm, and thus inhibits
gonadotropin secretion, arresting puberty. Most patients
have regression of secondary sexual characteristics.
Removal of the hamartoma will decrease any abnormal
GnRH secretion, however it will not arrest puberty. The
HPG axis has already been primed and has entered a
pubertal state.
What side effects are associated with PP?
Decreased final adult height
Early drug experimentation and onset of
sexual activity
Psychological distress
Mild sleep disturbance
Xray for Rickets findings
thickened growth plate
frayed metaphyseal edge
Cupping
Osteopenia
Widening of metaphysis
What is Rickets?
Inadequate mineralization of the growth plate cartilage and osteoid despite growth -> thickened growth plate with an increased circumference which increased bone width
Overall softening of the bones, making them easier to bend with little force
Most common cause: vitamin D deficiency
What investigations do you need to complete the work-up for suspected rickets?
Calcium, Phos, Mg
CBC, LBC
25-hydroxyvitamin D
1,25-hydroxyvitamin D
Alk Phos
Urine Ca/Cr ratio
Parathyroid hormone (PTH)
Expected Lab results in Rickets for the following:
Calcium Phosphorus Alk Phos PTH 25-hydroxyvitamin D 1,25-dihydroxyvitamin D BUN/Cr Electrolytes Urine Sample
vCalcium: low (can be normal in early and/or mild disease. The elevated PTH will act to
keep calcium normal intially)
Phosphorus: low
Alk Phos: high
PTH: high
25-hydroxyvitamin D (low)
1,25-dihydroxyvitamin D (low or normal (normal in early disease, will become low as 25
vitamin D stores are used up))
BUN/Cr: normal
Electrolytes: normal
Urine Sample: can be helpful for determining a urinary excretion of calcium and can
demonstrate the presence of glycosuria or protein which would be suspicious for Fanconi
syndrome.
What do you test to look at patients via D status
25-hydroxyvitamin D is the major circulating form and storage form of vitamin D and is the gold standard for determining a patient’s vitamin D status, as there is little
regulation of that step in the pathway.
Treatment for Vit D Deficient Rickets
There are 2 ways to treat:
- a significantly large amount of vitamin D (300,000-600,000 IU) PO or IM as multiple doses over 1 day.
(This is the ideal treatment for a patient who may not comply with a daily dose)
Daily (high) dose of vitamin D (2000-5000 IU per day) over a period of 4-6 weeks.
Continue supplementation after acute treatment - stand-alone supplement or part of a multivitamin.
What are the recommendations for Vit D intake for children and adolescents?
Breastfed children: 400 IU/day, older children: 600IU/day
If living in region of poor vit D Increase from 600 IU/day to 800 IU/day
Why does rickets of prematurity happen?
Inadequate calcium and phosphorus to meet growth requirements, leading to demineralization of bones and pathologic fractures
80% of maternal calcium and phosphate is transferred in the third trimester, thus born prematurely misses this key time
Supplemented breastmilk infant formula generally do not have enough calcium and phosphorus for premature babies – need additional supplementation
Additional risk factors = cholestatic jaundice, prolonged NICU admission, prolonged use of TPN, medications (diuretics, steroids) and soy formula, multip
Best marker for Rickets Recovery?
ALP. Marker of bone turnover
How do you differentiate between the two types of Vitamin D dependent Rickets?
You can differentiate the 2 types of VDDR by looking at the 1,25 hydroxyvitamin D!
What is Vitamin D Dependent Rickets type 1
Deficiency in 1-alpha hydroxylase -> can’t convert 25-hydroxyvitamin D into 1,25 hydroxyvitamin D
normally present during the first 2 years of life with the classic features of rickets
Important differences:
1,25 hydroxyvitamin D level is low as PTH will be high and should activate 1-alpha hydroxylase to convert it
Do not respond to conventional treatment of vitamin D deficient rickets
NEED TO TREAT WITH CALCITRIOL
What is Vitamin D Dependent Rickets type 2
Early onset (within a few months of birth) of hypocalcemia and severe rickets
Hypocalcemia is due to decreased intestinal resorption as this depends on the VD receptor
Hypotonia and muscle weakness
Severe dental caries
Alopecia (approx. 50-70% of pts, associated with a more severe form)
Difference from VDDR-1: extremely high 1-25 Vitamin D as it’s a receptor problem, so the feedback loop senses persistently low vitamin D and attempts to make more!
Treatment of Vitamin D Depentdent rickets 2
Extremely high doses of vitamin D (in an attempt to overcome the resistance
Alopecia sadly does not get better
Russel Silver Physical Characteristics
IUGR
Characteristic facies (normal head circumference, blue
sclerae, small triangular facies, a high forehead that tapers to a small jaw, micrognathia, prominent nasal bridge, and down-turning corners of the mouth)
Growth asymmetry,
Growth retardation.
Birth weight is generally <2SD of the mean, with normal head size
Babies are at risk for hypoglycemia.
Approximately 50% of children will have cognitive
impairment.
What is Madelung Deformity?
Madelung deformity is a deformity of the
wrist that is characterized as radial and palmar
angulations of the distal aspect of the radius.
The distal radius stops growing early. The ulna
keeps growing, dislocates, and forms a bump.
It is seen in Leri-Weill mesomelic dwarfism
(dyschondrosteosis), which is caused by a
mutation in the SHOX gene, and also in Turner
Syndrome.
How do you define constitutional growth delay?
1) slowing growth velocity during the first 2 years after birth, typically with both weight and height
crossing growth percentiles downward;
2) a normal or near-normal growth velocity, with height below but parallel to the 5th percentile during
prepubertal years;
3) delayed BA and pubertal maturation;
4) adult height usually within the normal range and within genetic potential
For what conditions is GH indicated for?
- Growth hormone deficiency documented by 2 GH stimulation tests
- Turner Syndrome
- SHOX (short homeobox gene) deficiency
- Selected syndromic causes of short stature (on a case by case basis)
- Growth retardation secondary to chronic renal failure and RTA.
Which of the following cancer treatments can
affect future growth?
Cranial radiation
Spinal radiation
Corticosteroids
Resection of brain tumor
All of them!!
Cranial radiation can affect the production of pituitary hormones in the future. Deficiencies in growth hormone and TSH will lead to decreased growth and short stature. If the neck is included in the radiation field, there is a risk of thyroid cancer and also primary hypothyroidism. Thyroid hormone is required for growth.
Spinal radiation can cause damage to growth plates in the vertebrae and decreased growth of the spine. As growth of the extremities in the case of normal, this causes disproportionate short stature. With a decreased Upper:lower segment ratio. Arm span would be greater than height.
High dose corticosteroids can decrease growth velocity.
Cranial surgery, depending on the site, can cause deficiencies in the pituitary hormones mentioned above.
What does the hypothalamus release?
The hypothalamus produces and releases releasing and inhibiting hormones (GHRH, GnRH, TRH, and CRH), that act on the anterior pituitary.
What does the anterior pituitary release?
The anterior pituitary makes and releases hormones (growth hormone (GH), leutinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH))
that act on target organs.
What does the posterior pituitary release?
Antidiuretic hormone (ADH) and oxytocin are the 2 hormones produced by neurosecretion in the hypothalamic nuclei and released from the posterior pituitary.
What are counter regulatory hormones?
Growth hormone, glucagon, epinephrine, and cortisol are termed “counter regulatory hormones”.
Blood glucose concentrations are normally kept in
a tight range by the action of these hormones and insulin.
Insulin is an anabolic hormone that shifts glucose into cells and stimulates glycogen synthesis.
The counter regulatory hormones are released in
response to low serum glucose levels, and also during the stress response.
They act in concert to increase serum glucose levels by glycogenolysis, gluconeogenesis, and mobilizing amino acid and fat stores to contribute to gluconeogenesis.
Growth hormone specifically acts to inhibit glucose
uptake by muscles, and to activate lipolysis, thereby providing glycerol for gluconeogenesis and fatty acids for ketogenesis. Children with growth hormone deficiency are therefore at risk for hypoglycemia.
How do you accurately assess a GH level
Growth hormone is secreted in a pulsatile pattern in response to GHRH
random GH level may not be detectable, and therefore is not useful.
To establish a definitive diagnosis of GH deficiency, one
must demonstrate sub normal GH levels during a GH stimulation test on two separate occasions.
What is central DI?
Central DI is caused by decreased production of ADH by the posterior pituitary.
What is peripheral/nephrogenic DI?
Nephrogenic DI is caused by a failure of ADH/receptor interaction in the kidney.
What are the risks associated with GH?
pseudotumor cerebri, slipped capital femoral epiphysis, gynecomastia, and worsening of scoliosis.
What Tanner stage is this:
testicular volume less than 1.5 ml; small penis
1 (prepubertal)
What tanner stage is this?
testicular volume between 1.6 and 6 ml
2
What tanner stage is this?
Skin on scrotum thins, reddens and enlarges; penis length unchanged (9–11
2
What tanner stage is this?
testicular volume between 6 and 12 ml
3
What tanner stage is this?
scrotum enlarges further; penis begins to lengthen
3
What tanner stage is this?
testicular volume between 12 and 20 ml
4
What tanner stage is this?
scrotum enlarges further and darkens; penis increases in length
4
What tanner stage is this?
testicular volume greater than 20 ml
5
What tanner stage is this?
adult scrotum and penis (14+)
5
What tanner stage is this? (breasts)
no glandular tissue: areola follows the skin contours of the chest
1
What tanner stage is this?
breast bud forms, with small area of surrounding glandular tissue; areola begins to widen
2
What tanner stage is this?
breast begins to become more elevated, and extends beyond the borders of the areola, which continues to widen but remains in contour with surrounding breast
3
What tanner stage is this?
increased breast sizing and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast
4
What tanner stage is this?
breast reaches final adult size; areola returns to contour of the surrounding breast, with a projecting central papilla.
5
What tanner stage is this?
no pubic hair
1
What tanner stage is this?
small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females)
2
What tanner stage is this?
Hair becomes more coarse and curly, and begins to extend laterally
3
What tanner stage is this?
adult-like hair quality, extending across pubis but sparing medial thighs
4
What tanner stage is this?
hair extends to medial surface of the thighs
5
What tanner does peak growth happen for males?
4-5
What tanner stage will peak growth happen for females?
3
