Endocrinology 16, 35-40 Flashcards
1
Q
Testicular torsion
A
Sudden twisting of the spermatic cord within the scrotum
Urological emergency —> because of risk of ischemia and possible infarction of testis
2
Q
mechanism of testicular torsion
A
Intravaginal torsion,
Extravaginal torsion,
Long mesorchium
3
Q
irreversible damage occur after hour many hours of testicular torsion
A
6-12 hours
4
Q
testicular torsion most commonly affects patients of what age
A
Most commonly affects
* neonates (first 30 days of life) and
* pubertal boys (10-14 years)
5
Q
symptoms of testicular torsion (also in neonates)
A
- Abrupt onset of severe testicular pain,
- swollen testis,
- nausea/vomiting
- abnormal position of testis,
- absent cremasteric reflex
- negative Prehn sign (elevation of the scrotum relieves testicular pain —>
*positive in epididymitis
*negative in testicular torsion)
In neonates:
possible absent testis,
firm and painless scrotal mass
possible acute inflammation
(swollen, erythematous, tender scrotum)
6
Q
Prehn sign
A
(elevation of the scrotum relieves testicular pain —>
*positive in epididymitis
*negative in testicular torsion)
7
Q
diagnosis of testicular torsion
A
Diagnosis:
* duplex US of scrotum —> enlarged testis, twisting of spermatic cord, reduced or absent blood flow to/from testis
* heterogenous appearance of testicular parenchyma indicates testicular necrosis
8
Q
what indicates testicular necrosis
A
heterogenous appearance of testicular parenchyma indicates testicular necrosis
9
Q
treatment of testicular torsion
A
- Manual testicular detorsion: may be attempted prior to surgery for immediate pain relief but should not delay surgery
- Exploratory surgery:
*immediate reduction (untwisting) and orchidopexy (anchor testis to inner lining of scrotum ,
*orchiectomy if the testis is grossly necrotized
10
Q
sudden, severe, unilateral scrotal pain in a patient with abnormally positioned testis should be managed as —– until proven otherwise
A
testicular torsion until proven otherwise
11
Q
ovarian torsion
A
Sudden twisting of an ovary around the adnexal ligaments
Gynecological emergency —> because of risk of ischemia and ovarian necrosis
12
Q
ovarian torsion most commonly affect women of what age
A
Most commonly affects women of childbearing age
13
Q
symptoms of ovarian torsion
A
- Sudden-onset unilateral lower abdominal
- and/or pelvic colicky pain
- nausea/vomiting
- adnexal mass may be palpable
- adnexal tenderness
14
Q
diagnosis of ovarian torsion
A
- Urine or serum beta-HCG to rule out pregnancy
- Pelvic ultrasound with Doppler —>
*enlarged edematous ovary
*thickened Fallopian tube
*twisted vascular pedicle
15
Q
treatment of ovarian torsion
A
Exploratory surgery:
* adnexal detorsion with preservation of ovarian function and oophoropexy (anchor ovary) if patient is premenopausal
* salpingo-oophorectomy if the ovary is grossly necrotized or if patient is postmenopausal
16
Q
Cryptorchidism
A
Failure of one or both testicles to descend to their natural position in the scrotum *
Most common congenital anomaly of the genito-urinary tract
17
Q
Most common congenital anomaly of the genito-urinary tract
A
cryptorchidism
18
Q
symptoms of cryptorchidism
A
- Palpable (80%): testicles cannot be manually manipulated in the scrotum
- Non-palpable (20%): may be intraabdominal or absent
19
Q
variants of cryptorchidism
A
- inguinal testis (90%)
- intra-abdominal testis
- ascending testis (testicular retraction into scrotal pouch is possible however immediately retract and ascend into groin after manipulation)
20
Q
treatment of cryptorchidism
A
- Typically resolves without treatment via spontaneous descent
- Persistent cases require surgery, should be performed as soon as possible after 6 months of age —> Orchidopexy
21
Q
complications of cryptorchidism
A
- testicular cancer (risk is not eliminated by surgery)
- infertility (higher temperature of abdominal cavity is suboptimal for spermatogenesis)
- testicular torsion
- inguinal hernia
22
Q
Type 1 diabetes mellitus in children
A
Chronic hyperglycemia due to disturbance of insulin secretion and/or insulin effect —> leading to alterations in carbohydrate-, lipid- and protein metabolism
More than 85% of childhood DM are type 1
23
Q
percentage of T1DM in childhood
A
More than 85% of childhood DM are type 1
24
Q
incidence of T1DM
A
Incidence of T1DM in the pediatric age group is continuously increasing, mostly in children <5 years
25
Pathophysiology of T1DM
autoimmune destruction of beta cells in the pancreas —> absolute insulin deficiency
26
Is T1DM inherited or environmental?
Pathogenesis: multifactorial disease *
* Genetics (increased risk with affected relatives)
* Epigenetics
* Environment
* Precipitating factors
27
staging of T1DM
* Stage 1: normal blood sugar, 2+ islet autoantibodies (start of the disease)
* Stage 2: abnormal blood sugar, 2+ islet autoantibodies
* Stage 3: clinical features, 2+ islet autoantibodies
* Stage 4: long-standing T1DM
28
symptoms of T1DM children vs neonates
Hyperglycemia
* Children:
*polyuria
*enuresis (inability to control urination), *polydipsia
*polyphasic
*weight loss
*blurred vision
* Infants:
*vomiting
*dehydration
*toxicosis
*coma
29
diagnosis of T1DM
* investigation of blood glucose and ketones and/or urinary glucose and ketones
* Fasting blood glucose > 7 mmol/l + random blood glucose above 11,1 mmol/l TWICE
* In case of clear clinical symptoms, performing fasting oral glucose tolerance test is unnecessary and dangerous
30
In which case if performing fasting oral glucose tolerance test OGT unnecessary and dangerous
In case of clear clinical symptoms
31
Frequent misdiagnosis in T1DM
* Polyuria vs pollakisuria (increased urination frequency) —> urinary tract infection
* Kussmaul breathing —> lung or heart disease
* Liver capsule distension, acidosis —> acute abdominal catastrophe (eg appendicitis)
* Unconsciousness —> meningitis, encephalitis
32
treatment of T1DM
* insulin + diet + physical exercise
Insulin: aim is to mimic physiological secretion as well as possible by
* combining rapid + long acting insulin
* Continuous glucose monitoring + subcutaneous insulin pumps
33
monitoring of T1DM
HbA1c (glycated Hb) —> formation of sugar-Hb linkage indicates excessive sugar in
bloodstream,
measured to primarily determine 3-month average blood sugar level in diabetic patients
34
complications of T1DM
DKA,
retinopathy,
neuropathy
35
DKA precipitating factors
Precipitating factors: *
* Infections (50%): commonly gastroenteritis
* Omission of insulin: on purpose or by accident
* Puberty: recurrent DKA episode
36
DKA triad
hyperglycemia + acidosis + dehydration
37
fluid therapy in kids
first 10 kg : 100ml/kg
2nd 10 kg : 50 ml/kg
3rd 10 kg: 20ml/lkg
38
diagnosis of DKA
* Metabolic acidosis
*pH <7,3
*HCO3- <15 mmol/l
* Hyperglycemia (>11,1 mmol/l)
* Ketones in blood/urine
39
pH , HCO3, glucose level in DKA
* pH < 7,3
* HCO3- < 15 mmol/l
* glucose > 11mmol/l
40
symptoms of DKA
* frequent urination
* increased thirst
* dry mouth
* blurry vision
* sweet breath (ketones)
* nausea/vomiting
* abdominal pain
41
treatment of DKA
Treatment* :
A. ABCDE
B. Fluids
*Balanced crystalloids
*Calculate for 48h + add suspected fluid losses (5-10% depending on clinical situation)
*Administer slowly, unless patient is in shock —> fluid bolus: 10 ml/kg
*Complication of too fast fluid administration: cerebral edema
C. Insulin
*Fast-acting insulin IV (only switch to subcutaneous when patient has normal pH and is stabilized)
*0,05 U/kg/h
D. Insulin + glucose
*When glucose < 15 mmol/l —> change crystalloid solution to 5% glucose solution (10% is necessary if drop in glucose is too fast)
E. Electrolyte resuscitation
*Monitor K+ carefully for any decrease (insulin pushes K+ intracellularly) —> K+ < 5 mmol/l or
when child produce urine —> administer K+
*Monitor Na+ carefully (but have to calculate with corrected Na+ according to glucose levels) b.
—> administer Na+ if too low
42
fluid bolus type and amount in DKA
Balanced crystalloids
*Calculate for 48h + add suspected fluid losses (5-10% depending on clinical situation)
*Administer slowly, unless patient is in shock —> fluid bolus: **10 ml/kg **
43
insulin dosage and when to switch from IV to subcutaneous ?
only switch to subcutaneous when patient has normal pH and is stabilized)
**0,05 U/kg/h**
44
Type of insulin used in DKA
Fast-acting insulin IV
(only switch to subcutaneous when patient has normal pH and is stabilized)
45
when to switch crystalloid solution to 5% glucose solution
in DKA treatment
When glucose < 15 mmol/l —> change crystalloid solution to 5% glucose solution (10% is necessary if drop in glucose is too fast)
46
insulin effect on potassium
(insulin pushes K+ intracellularly)
K+ < 5 mmol/l
or
when child produce urine —> administer K+
47
Mild, moderate, severe dehydration percentage
mild 3-5%
moderate 6-10%
severe >10%
48
Congenital adrenal hyperplasia (CAH)
Group of autosomal recessive defects in the enzymes that are responsible for cortisol/aldosterone/ androgen (rarely) synthesis
* All subtypes are characterized by
*low levels of cortisol
*+ high levels of ACTH
*+ adrenal hyperplasia
49
pathophysiology of CAH
* low levels of cortisol —> lack of negative feedback to the pituitary —> increased ACTH
—> adrenal hyperplasia + increased synthesis of adrenal precursor steroids
50
subtypes of CAH
21β-hydroxylase defect (95%)
11β-hydroxylase defect (5%)
17α-hydroxylase defect (rare)
51
General clinical features of CAH
General:
* hypoglycemia (cortisol production is not sufficient to maintain glucose levels)
* adrenal crisis
* failure to thrive
* hyperpigmentation (↑melanocyte-stimulating hormone: cleaved from ACTH precursor)
52
21β-hydroxylase defect clinical features
* Hypotension (↓aldosterone + DOC) ‣
* XX —> female pseudohermaphroditism (clitoromegaly or male external genitalia), precocious puberty, virilization, irregular menstrual cycles, infertility
* XY —> normal male external genitalia at birth, precocious puberty
53
11β-hydroxylase defect clinical features
* Hypertension (↑DOC)
* XX —> female pseudohermaphroditism (clitoromegaly or male external genitalia), precocious puberty, virilization, irregular menstrual cycles, infertility
* XY —> normal male external genitalia at birth, precocious puberty
54
17α-hydroxylase defect (rare) clinical features
* Hypertension (↑DOC)
* XX —> normal female external genitalia at birth, delayed puberty, sexual infantilism (ovaries cannot produce estrogen)
* XY —> male pseudohermaphroditism (female external genitalia), delayed puberty, sexual infantilism
55
treatment aim in CAH
Treatment: aim is to
* replace deficient hormones and
* reduce excess androgen production
56
Treatment which is indicated in all subtypes of CAH
Glucocorticoid replacement therapy is indicated in all forms of CAH
(hydrocortisone in pediatrics)
57
treatment of 21β-hydroxylase defect
1. Glucocorticoid replacement therapy (hydrocortisone in peds)
2. fludrocortisone (aldosterone substitution)
3. salt supplements
58
treatment of 11β-hydroxylase defect
1. Glucocorticoid replacement therapy ( hydrocortisone in pediatrics)
2. spironolactone (block mineralocorticoid receptor)
3. reduced salt intake
59
treatment of 17α-hydroxylase defect
1. Glucocorticoid replacement therapy (hydrocortisone in pediatrics)
2. spironolactone (block mineralocorticoid receptor)
3. estrogen replacement therapy (XX)
4. reduced salt intake
60
Disease of the thyroid gland
* Hypothyroidism
*Congenital hypothyroidism
* Hyperthyroidism
*Neonatal hyperthyroidism
*Graves disease
61
Congenital hypothyroidism etiology
* Primary (more common):
*ectopic thyroid gland (60%)
*thyroid aplasia/hypoplasia (30%)
*defects in thyroxin synthesis
* Secondary:
*cerebral mid-line defects
*pituitary aplasia/hypoplasia,
*perinatal stress
* Transient neonatal hypothyroidism: *temporary deficiency of thyroid hormones after birth, typically in first few months, later baby recovers
62
Primary types of congenital hypothyroidism
ectopic thyroid gland (60%)
thyroid aplasia/ hypoplasia (30%)
defects in thyroxin synthesis
63
secondary types of congenital hypothyroidism
* Secondary:
*cerebral mid-line defects
*pituitary aplasia/hypoplasia,
*perinatal stress
64
Transient neonatal hypothyroidism
rare type of congenital hypothyroidism
*temporary deficiency of thyroid hormones after birth, typically in first few months, later baby recovers
* From:
*maternal autoimmune thyroiditis
*maternal drug use (thyreostatics, amiodarone)
*maternal iodine deficiency
*preterm baby (immature hypothalamic-pituitary axis)
65
symptoms of congenital hypothyroidism
* Usually little to no symptoms are present at birth as maternal T4 can cross placenta -->
symptoms can develop over weeks-months if screening is not performed
* Sleepiness
* poor feeding
* severe or prolonged jaundice
* constipation
* large fontanelles
* hernias ‣ (umbilical hernia)
* macroglossia
* abdominal distension
* hypotonia, hypothermia, failure to thrive
66
can T4 pass through placenta?
* Usually little to no symptoms of hypothyroidsm are present at birth as **maternal T4 can cross placenta** -->
symptoms can develop over weeks-months if screening is not performed
67
complication of congenital hypothyroidism
cretinism —> from untreated hypothyroidism that leads to impaired development of the brain and skeleton —> skeletal abnormalities + permanent intellectual disabilities
68
screening of congenital hypothyroidsim
measure TSH from dried blood samples taken in the postnatal 48-72 h —> increased
levels are indicative of congenital hypothyroidism
69
treatment of congenital hypothyroidism
lifelong hormone replacement might be necessary
70
Neonatal hyperthyroidism risk in mother with graves disease
Occurs in approx 5% of babies born to mothers with Graves’ disease —> **transplacental passage of maternal TSH receptor antibodies**
71
symptoms of neonatal hyperthyroidism
* May arise directly after birth or delayed up to 10 days later as a result of transplacental maternal antithyroid medication (keeps levels low in baby as well)
* Irritability
* restlessness
* tachycardia
* diaphoresis
* hyperplasia
* poor weight gain
* diffuse goiter (can cause tracheal compression)
* microcephaly (due to craniosynostosis: premature fusion of cranial sutures)
72
how long for symptoms of neonatal hyperthyroidism to show and why
May arise
* directly after birth or
* delayed up to 10 days later as a result of transplacental maternal antithyroid medication (keeps levels low in baby as well)
73
treatment of neonatal hyperthyroidism
* resolves within 1-3 months (transient)
* Infants with symptoms —>
*methamizol (inhibit peroxidase —> decrease thyroid hormone synthesis) and
*propanolol (decrease heart rate, blood pressure)
74
complications of neonatal hyperthyroidism
untreated hyperthyroidism can lead to
cardiac failure + intellectual disability
75
most common cause of hyperthyroidism in children
graves disease
76
symptoms of graves disease
* Heat intolerance, excessive sweating (increased basic metabolic rate)
* weight loss, frequent bowel movements,
* glucose intolerance
* Pretibial myxedema (glycosaminoglycan deposition, non-pitting edema)
* thyroid acropachy (nail clubbing)
* hypertension
* Graves ophthalmology (exophthalmos, edema of the periorbital tissue
* goiter
* Tachycardia, increased blood pressure,
* tremor
* Oligo/amenorrhea, infertility, gynecomastia
* Anxiety, insomnia, hyperreflexia
* Young children often show growth spurt
77
treatment of graves disease
* Antithyroid medications: 1st line **Methamizole **
* Symptom control: **beta-blockers **(atenolol, propanolol )
* Radioactive iodine ablation:
*potential first line treatment in patients >10 years or
*second line if relapse after long-term therapy
* Surgery (near-total thyroidectomy): in children < 5 years who do not improve with antithyroid drugs or if have large goiters
78
Hypocalcemia etiology
* Vitamin deficiency
* diabetes
* acute renal failure
* prematurity
* birth asphyxia (oxygen deprivation around birth/delivery)
* DiGeorge syndrome
79
clinical features of hypocalcemia
usually
* asymptomatic
* neuromuscular excitability (spasms)
* seizures
* tetanus
80
treatment of hypocalcemia
asymptomatic infants initiating feeding is usually enough, if not: Ca substitution
81
Hypercalcemia etiology
* idiopathic infantile hypercalcemia
* hyperparathyroidism
* Williams syndrome,
* hypercalcemia of malignancy
* vitamin D intoxication
* familial hypocalciuric hypercalcemia
* sarcoidosis
* renal failure
* Addison’s disease
* iatrogenic (eg thiazide diuretics)
82
clinical features of hypercalcemia
* anorexia
* nausea/vomiting
* failure to thrive
* constipation
* abdominal pain
* polyuria
* polydipsia
* apathy
* drowsiness
* depression
83
treatment of hypercalcemia
treat underlying condition
84
Hypoparathyroidism etiology
* failure in parathyroid development (agenesis/dysgenesis) eg in DiGeorge sy
* radiotherapy,
* surgery (post-thyroidectomy)
* magnesium deficiency (failure in PTH secretion)
* pseudohypoparathyroidism (PHP) (end-organ resistance to the actions of PTH)
85
PTH effect
PTH —> bone resorption —>
release calcium + phosphate into blood,
BUT increased phosphate excretion by kidneys
86
lab value of hypoparathyroidism
low plasma calcium
high plasma phosphate
low serum PTH
87
Hyperparathyroidism is it common in children ?
UNCOMMON
88
Etiology of hyperparathyroidism
* parathyroid adenoma
* MEN1
* MEN2
* secondary hyperparathyroidism (rickets, chronic renal failure)
* transient neonatal hyperparathyroidism (maternal hypoparathyroidism)
89
lab values in hyperparathyroidism
high serum PTH
high plasma calcium
low plasma phosphate
90
Rickets
Disorder of impaired mineralization of cartilaginous growth plates due to vitamin D deficiency
Only occur in children (growth plates have not fused yet) (adult version is osteomalacia)
91
osteomalacia vs rickets
rickets only occur in children (growth plates have not fused yet) =Disorder of impaired mineralization of cartilaginous growth plate
(adult version is osteomalacia)
92
etiology of rickets
Vitamin D-deficiency since breast milk has low amounts (need supplementation)
93
pathophysiology of rickets
↓vitamin D —> hypocalcemia —> defective cartilaginous growth plate mineralization
Hypocalcemia —>↑PTH levels —>↓phosphate levels —> also impair mineralization
94
clinical features on rickets
* Bone deformities:
*Bending of primarily the long bones
*Distension of the bone-cartilage junctions *Rachitic rosary: bead-like distension of the bone-cartilage junctions of the ribs *
*Marfan sign: distension of the epiphyseal plate of the distal tibial with widening and
cupping of the metaphysis gives the impression of a double medial malleolus on inspection and palpation of the ankle
*Craniotabes: softening of the skull *
*Genu varum *
* Increased risk of fracture
* Harrison groove: depression of the thoracic outlet due to muscle pulling along costal insertion of the diaphragm
* Late closing of fontanelles, impaired growth
95
diagnosis of rickets
Lab:
↓calcium,↓phosphate,
↑PTH, ↑ALP
Imaging: bone deformities typical for Rickets
Bone biopsy: impaired bone mineralization
96
treatment of rickets
vitamin D (indicated in all infants who are exclusively breastfed)
97
Growth disorders what to consider?
According to
* sex
* Consider ethnic background
* genetics (parents heights)
98
Growth disorders diagnosis
Growth curve changes 2+ percentiles in one year (+/- 2 SD)
* Measuring of body length laying down if under 2 yrs, of body height standing up if above 2 yrs
* Bone age (biological age): compare to data base of normal bone development at certain ages
99
Calculation of mid-parental height (MPH)* :
Boys MPH = (fathers height + mothers height)/2 + 6,5 cm
Girls MPH = (fathers height + mothers height)/2 - 6,5 cm
100
Calculation of target height channel
* helps determine whether child is growing according to family’s genetic background
*
Boys = (fathers height + mothers height)/2 + 13 cm
Girls = (fathers height + mothers height)/2 - 13 cm
101
Disproportionate growth:
limbs or trunk is shorter/taller than rest of body’s proportions would suggest
either short trunk OR short extremeties
102
short stature etiologies
* nonpathological :
*Familial short stature
*Constitutional growth delay:delay in pulsatile hypothalamic GnRh release, temporary
* Endocrine :
*Hypothyroidism: impaired skeletal development due to iodine deficiency, intellectual disability
*GH deficiencies: impaired bone + muscle development
*Glucocorticoid excess (eg medications): accelerated bone resorption
inhibited chondrogenesis
cushingoid features (central obesity, moon facies, skin modifications, HTN)
*Type 1 DM: malabsorption + malnutrition
* Genetic : Laron sy, turner, down sy, williams, cystic fibrosis
* Psychosocial :
*Maternal substance use (eg alcohol): intrauterine growth retardation, low birth weight ‣
*Psychosocial short stature: emotional deprivation or stress —> malnutrition + low GH levels ‣
*Psychiatric conditions (eg anorexia):
103
genetic etiologies of short stature
* Laron sy: GH receptor mutation —> tissue insensitivity to GH;
*microcephaly
*prominent forehead
*saddle nose
*delayed puberty
*small genitalia
* Turner sy (XO monosomy): skeletal abnormalities, gonadal dysgenesis, cardiovascular defects
* Down sy:
*craniofacial dysmorphia
*skeletal abnormalities
*developmental delay, obesity
* Williams sy:
*cognitive impairments
Elfin-like facies
cardiovascular abnormalities
* Cystic fibrosis: malnutrition, failure to thrive, chronic infections
104
diagnosis of short stature
1) malnutrition
2) 2) hypothyroidism
3) 3) bone dysplasia
4) 4) delayed puberty
5) 5) GH shortage
105
treatment of short stature
treat underlying disorder if possible *
* Discontinuation of growth-inhibiting medications
* If delayed puberty —> sex hormones
* GH supplementation
106
short stature
Endocrine etiology
*Hypothyroidism:
impaired skeletal development due to iodine deficiency,
intellectual disability
*GH deficiencies:
impaired bone + muscle development
*Glucocorticoid excess (eg medications): accelerated bone resorption
inhibited chondrogenesis
cushingoid features
(central obesity, moon facies, skin modifications, HTN)
*Type 1 DM: malabsorption + malnutrition
107
tall stature etiologies
* Non pathological: familial tall stature
* endocrine:
*Hyperparathyroidism
*obesity
*Pituitary gigantism (GH excess):
*McCune-Albright sy
*Precocious puberty
* Genetic:
*Fragile X syndrome
*Weaver sy
*Sotos sy
*Simpson-Golabi-Behmel sy
*Marfan syndrome
*Klinefelter syndrome
*Beckwith-Wiederman syndrome:
*Triple X syndrome
*Homocysteinuria
*Proteus syndrome:
108
endocrine etiologies of tall stature
* Hyperthyroidism: palpitations, weight loss, heat intolerance, anxiety, menstrual irregularities, tachycardia, tremor
* Obesity: high BMI, early onset of puberty, slightly advance bone age ‣
* Pituitary gigantism (GH excess):
*before growth plate is closed —> gigantism,
*after growth plate is closed —> acromegaly,
tumor mass symptoms (headache, visual disturbance),
elevated IGF1 level,
oral glucose tolerance test (tumor won’t show negative feedback on GH secretion)
* McCune-Albright sy: mutation in G-protein activating gene —> causing
*peripheral precocious puberty
*+ ovarian follicular cysts
*+ café-au-lait spots
*+ polyostatic fibrous dysplasia in bones
* Precocious puberty: early puberty, abnormal LH + FSH + estradiol + testosterone + betaHCG
109
McCune-Albright sy
mutation in G-protein activating gene —> causing TALL STATURE
*peripheral precocious puberty
*+ ovarian follicular cysts
*+ café-au-lait spots
*+ polyostatic fibrous dysplasia in bones
110
tall stature genetic etiologies
* Fragile X syndrome: long narrow face, protruding ears, hypotonia, macroorchidism, intellectual disability
* Weaver sy:
*macrocephaly
broad forehead
large ears
hypertelorism
hypotonia
wide philtrum
* Sotos sy:
*dolichocephaly
*macrocephaly
*prominent forehead
*hypertelorism
*learning disability
* Simpson-Golabi-Behmel sy:
*coarse facial features
*macrostomia
*macroglossia
*risk of neoplasm
*often normal mental development
* Marfan syndrome: hyperextensible joints, long limbs,
*cardiac + ophthalmological abnormalities ‣
* Klinefelter syndrome: **disproportionally long limbs**, poorly developed secondary sex
characteristics, mild learning difficulties
* Beckwith-Wiederman syndrome: macrosomia, hemihypertrophy, macroglossia, neoplasm risk
* Triple X syndrome: clinodactyly, wide neck, under-develop ovaries + breasts, CoA ‣
* Homocysteinuria: marfan phenotype, learning difficulties, predisposition to thromboembolism
* Proteus syndrome: macrocephaly, epidermal nevi, vascular malformations, large hands + feet
111
treatment of tall stature
treat underlying disorder if possible *
* If puberty has not started yet —> induce puberty (sex hormones* closes epiphyseal plate)
* If puberty has started —> epiphysiodesis (surgical ablation of epiphysis to stop bone from growing)
112
short term and long term effect of increasing androgens for growth spurt
*↑[androgen] in childhood —>
fast growing spurt (testo promotes growth)
but long-term it might cause short stature (testo closes epiphyseal plate)
113
Physiological changes during puberty:
* Tanner stages
*Breast development (girls)
*Genital development (boys)
*Pubic hair development (boys and girls) ‣
* Bone growth: growth spurt
* Bodyweight and composition: boys decrease fat content, girl increase fat content
* Dermatological changes: acne vulgaris,
hyperhidrosis
114
Physiological first signs of puberty:
* Girls —>
*breast development (thelarche) at
8-12yrs
*menstrual bleeding (menarche) at 10,5-14,5yrs
* Boys —>
*testicular volume approx 4 ml at 9-14 yrs
115
tanner stages
116
Disorders of early pubertal growth and sexual maturation
* Precocious puberty: appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys
*central
*peripheral
117
girls vs boy how common is precocious puberty
10x more common in girls than boys
118
define precocious puberty
appearance of secondary sexual characteristics
before the age of 8 years in girls *
and 9 years in boys
119
classification of precocious puberty
* Central (“true”) precocious puberty —> gonadotropin-dependent
* Peripheral precocious puberty —> gonadotropin-independent
* Benign pubertal variants:
*precocious thelarche (breast development)
*premature adrenarche (pubic hair development)
*precocious menarche (menstruation)
120
Central precocious puberty: etiology
elevated GnRh levels
Etiology:
1. idiopathic (most common)
2. CNS lesions
3. obesity-related
4. neurofibromatosis
121
central precocious puberty pathophysiology
early activation of hypothalamo-hypophyseal axis —>
abnormally early initiation of pubertal changes —>
early development of secondary sexual characteristics
122
clinical features of precocious puberty
follows normal pattern of puberty, except that its early
123
diagnosis of precocious puberty
* Serum LH + FSH: increase
* GnRH stimulation test: gonadotropin levels should increase
* Brain MRI/CT: to rule out CNS lesion
124
treatment of precocious puberty
GnRH agonist
125
Peripheral precocious puberty:
without GnRH, due to peripheral synthesis of OR
exogenous exposure to sex hormones
126
Peripheral precocious puberty: etiology
Etiology:
* ↑androgen production
*(congenital adrenal hyperplasia
*ovarian tumors
*adrenocortical tumors)
* ↑estrogen production
*McCune-Albright sy
*HCG-secreting germ cell tumors)
* ↑β-hCG production
*dysgerminoma
*malignant embryonal cell carcinoma
*choriocarcinoma)
* primary hypothyroidism
* exogenous steroid use
* obesity-related
127
clinical features of Peripheral precocious puberty:
may not follow normal pattern of puberty, and exhibit other features of
underlying conditions (eg café-au-lait spots in McCune-Albright sy)
128
diagnosis of Peripheral precocious puberty:
* Serum LH + FSH: decrease *
* GnRH stimulation test: gonadotropin levels does NOT increase *
* Serum testosterone/estradiol: increased (depending on tumor) *
* Specific tests:
*TSH, T3
*corticotropin stimulation test
*US of ovaries/testis/abdomen
129
treatment of Peripheral precocious puberty:
* Tumor —> surgery
* CAH —> cortisol and enzyme replacement
* Ovarian cysts —> no intervention, spontaneous resolution is common
130
Disorders of delayed pubertal growth and sexual maturation
Absent or incomplete development of secondary sex characteristics by
age of 14 years in boys and
13 years in girls
131
etiology of delayed pubertal growth and sexual maturation
* **Physiological**: constitutional delay of puberty
* **Pathological:**
* Hypergonadotropic hypogonadism:
-Primary gonadal insufficiency:
*Klinefelter sy
*Turner sy
*androgen insensitivity sy
-Secondary gonadal insufficiency: *chemotherapy,
*pelvic irradiation,
*infections
*trauma/ surgery
*autoimmune disorders
* Hypogonadotropic hypogonadism:
*CNS lesion, Kallmann sy, Prader-Willi sy, Gaucher disease
* Malnutrition
132
Primary gonadal insufficiency:
Hypergonadotropic hypogonadism
* Klinefelter sy
* Turner sy
* androgen insensitivity sy
133
Secondary gonadal insufficiency:
Hypergonadotropic hypogonadism
* chemotherapy
* pelvic irradiation
* infections
* trauma/surgery
* autoimmune disorders
134
Hypogonadotropic hypogonadism:
CNS lesion
Kallmann sy
Prader-Willi sy
Gaucher disease
135
clinical features of delayed puberty
depends on underlying condition
136
diagnosis of delayed puberty
* Medical history
* Serum LH + FSH + testosterone/estradiol:
*Low/normal with low testosterone/estradiol —>
-constitutional growth delay
-isolated GnRH deficiency
-functional hypogonadotropic hypogonadism
-or hypothalamic-pituitary disorders
*Elevated —> primary hypogonadism
Specific tests:
*prolactin level,
*IGF-1 level,
*TSH, T3
*karyotyping
*CBC
*MRI/CT
*abdominal US
137
treatment of delayed puberty
treat underlying condition *
* Hormonal therapy: testosterone or estradiol
