Aging changes
(Changes in the elderly)
Last updated: Jun 05, 2020
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Summary
Aging is the time-related progressive functional decline that affects all organ systems. It is believed
to be caused by the accumulation of DNA damage, hormonal changes, and internally
programmed cellular changes. Effects of aging include stiffening of the arteries and calcification of
valves (cardiovascular system), osteoporosis and increased risk of fracture (musculoskeletal
system), decreased chest wall compliance and increased ventilation-perfusion mismatch
(respiratory system), susceptibility to recurrent infections and malignancies (immune system), and
decline in cognitive function and changes in sleep patterns (nervous system).
NOTES
FEEDBACK
Effects of aging
All cells are subject to the natural processes of aging. Aging is believed to be caused by the
accumulation of DNA damage, hormonal changes, and internally programmed cellular changes.
Aging affects all organ systems and leads to progressive functional decline.
Aging changes in the bones, muscles, and joints
• Increased bone resorption and osteoporosis, increased risk
of fracture (♀ > ♂)
o Postmenopausal osteoporosis: decreased estrogen levels → increased
bone resorption
o Senile osteoporosis (especially in individuals > 70
years): decreased osteoblast activity → decreased osteoid production
• Decreased lean body mass due to atrophy and loss of muscle
cells (sarcopenia)
• Degenerative changes in joints: stiffer and less flexible joints,
decreased synovial fluid and cartilage, calcification (e.g., in the shoulder),
height loss
Regular exercise and a diet rich in protein, vitamin D, creatine, and omega-3 fatty acids are
essential to ensure muscle growth and help prevent sarcopenia!
Aging changes in the skin
There is an increased incidence of:
• Noncancerous skin growths (e.g., keratoacanthomas, seborrheic keratosis)
• Cancerous growths such as basal cell cancer and squamous cell carcinoma
• Skin tags, warts, liver spots
• Hyperpigmented macules due to cutaneous deposition
of lipofuscin (typically in the face and dorsum of hand)
• Xerosis cutis and pruritus due to decreased lipid and sebum synthesis and
increased moisture loss
• Heatstroke due to decreased number of sweat glands
• Wrinkles due to:
o Decreased elastin synthesis → increased skin laxity and rigidity
o Decreased collagen synthesis → atrophy of
the dermis → wrinkle formation and decreased strength → increased risk
of skin damage (e.g., decubitus and bruises
)
o Increased crosslinking of elastin and collagen → skin stiffness and
decreased elastic recoil (elastosis)
[1]
o Decreased glycosaminoglycan (including hyaluronic acid) synthesis →
decreased dermal moisture retention → decreased dermal volume
o Decreased subdermal fat → skin sagging; risk of hypothermia
Aging changes in the nails and hair
• Nails
o Become more brittle and may become yellowed
o Toenails may become thicker
o Ingrown toenails and onychomycosis are more common
• Hair: graying, baldness (male pattern hair loss, female pattern hair loss)
Aging changes in the cardiovascular system
• Vascular sclerosis and stiffness→ increased systolic blood pressure
• Left ventricular hypertrophy and progressive stiffening with a 10%
increase in wall size
• Mitral and aortic valve thickening and calcification
• Marked decline in stress-induced and exercise-induced maximal heart
rate due to decreased response to the action of catecholamines
• Lipofuscin deposits in cardiac muscle
Aging changes in the respiratory system [2]
MAXIMIZE TABLETABLE QUIZ
Bodily changes Consequences
Weaker chest wall muscles • ↑ Chest • Increased
wall stiffness → o Alveolar-arterial
Calcification of costochondral junctions ↓ chest wall
gradient
compliance
Osteoporosis-induced kyphosis o V/Q mismatch
o Functional residual
Decreased elastin in • ↓ Elastic recoil →
capacity
pulmonary parenchyma ↑ lung compliance
o Residual volume
• Decreased
o PaO2
o Forced vital
capacity (FVC)
o Forced expiratory
volume after one second
(FEV1)
Bodily changes Consequences
• Unchanged: total lung
capacity (TLC; adjusted by
age)
o Exception:
Severe kyphosis can also
decrease TLC!
Weakened baroreceptor/chemoreceptor • Poor ventilatory • Hypoxia
response response to ↓
• Hypercapnia
O2 and ↑
CO2 levels
Weakened respiratory muscles • ↓ Cough reflex • ↑ Susceptibility
to aspiration and infection
Weakened immune system • ↑ Susceptibility to infection
Aging changes in the genitourinary system
• Kidneys
o Decreased glomerular filtration rate (GFR), diffuse sclerosis of glomeruli
o Decreased renal mass and replacement of parenchyma by fat and fibrosis,
predominantly in the renal cortex → decreased maximal concentrating
ability
o Decreased number of nephrons
o Decreased acid load excretion
• Urinary and sexual
o Increased urinary frequency and urgency
o Increased risk of urinary tract infection
o Decrease in libido (typically more pronounced in women than men)
o Women
§ Postmenopausal estrogen deficiency leading to:
§ Vaginal atrophy, dryness, and irritation
§ Increased risk of yeast infections and other UTIs
§ Possibly dyspareunia
§ Decreased tone of pubic muscles → prolapse of vagina, uterus,
or bladder
o Men
§ Testicular atrophy
§ Enlarged prostate gland
§ Slowed urination, erection, and ejaculation
§ Increased refractory period
Aging changes in the immune system
• Impaired immune response and regulation of inflammation predispose
individuals to recurrent infection, impaired wound healing, malignancy, and
autoimmune disease.
• Decreased antibody and cell-mediated immune responses to a new antigen
o A decline in the counts of most subsets of B cells and T cells (exception:
memory T-cell and memory B-cell counts increase)
o Decreased affinity of antibodies for new antigens
§ Decrease in the variety of B-cell receptors for antigens
§ Increase in the proportion of monoclonal cell lines
§ Impaired affinity maturation and impaired V(D)J recombination
• Total immunoglobulin level remains the same.
• Macrophage and neutrophil counts do not decrease but they are less
effective in their functions (e.g., phagocytosis).
• Increased number of NK cells, PGE2, and increased autoantibody production
Among the elderly, a decreased immune response leads to an increased need for
booster vaccinations.
Aging changes in the endocrine system
• Decreasing hormones
o Calcitonin, growth hormone, renin, aldosterone, melatonin (loss of
normal circadian rhythms)
o Estrogen and prolactin in women (e.g., contributes to breast atrophy)
o Testosterone gradually decreases in men.
• Increasing hormones: FSH, LH, norepinephrine, parathyroid
hormone (contributes to osteoporosis)
Aging changes in the nervous system
• Presbycusis: progressive high-frequency hearing loss due to loss
of hair cells at the base of the cochlea
• Presbyopia: impaired accommodation (near object focusing) due to
decreased elasticity of the lens; decreased ciliary muscle strength
• Decreased sense of smell and taste
• Reduced ability to detect vibration, touch, temperature, and pressure
changes (increased risk of pressure ulcers, hypothermia, and burns)
• Decreased cerebral blood flow and brain volume
• Fluid intelligence declines, whereas crystallized intelligence increases
• Altered sleep patterns: early morning awakening, later sleep
onset, decreased REM, and decreased slow-wave sleep
• After the 6th decade of life
o Decline in executive function, working memory, processing speed, and
attention span
o In most cases, no clinically significant impairment in social and occupational
functioning
o Increased suicide risk in case of physical and mental illnesses (particularly
depression), functional impairment, and stressful life events (e.g., loss of a
partner)
References:[3][4][5][6][7][8][9]
Osteoporosis
Last updated: Apr 17, 2020
QBANK SESSION
CLINICAL SCIENCES
LEARNED
Summary
Osteoporosis is a skeletal condition in which the loss of bone mineral density leads to decreased
bone strength and an increased susceptibility to fractures. The disease typically
affects postmenopausal women and the elderly, as an abrupt decrease in estrogen and age-
related processes play a key role in the development of osteoporosis. Further risk factors include
inactivity, smoking, and alcohol consumption. Osteoporosis usually remains asymptomatic until
the first occurence of fragility fractures (following minor trauma), particularly of the vertebrae. After
repeated vertebral fractures, patients may also develop thoracic hyperkyphosis and lose height.
Osteoporosis is diagnosed through a bone density test (dual-energy X-ray absorptiometry),
while fractures are usually confirmed through conventional x-ray. Management of osteoporosis
includes prophylactic measures and medical therapy. The prophylaxis consists mainly of adequate
intake of calcium and vitamin D and regular physical activity with strengthening exercises. Both
help to maintain or even increase bone mass and improve balance, thereby reducing the risk of
falling. Medical therapy is indicated in cases of severely reduced bone density or
osteoporotic fractures. The most commonly used drugs are bisphosphonates, which inhibit bone
resorption and can significantly decrease the risk of fractures. There are several other possible
medical therapies (e.g., teriparatide, raloxifene), which may be indicated in special cases (e.g.,
severe osteoporosis, breast cancer prophylaxis required) or if patients have contraindications
to bisphosphonates.
NOTES
FEEDBACK
Definition
• Osteoporosis: insufficient bone strength with increased susceptibility
to fractures
• Osteopenia: decreased bone strength but less severe than osteoporosis
NOTES
FEEDBACK
Epidemiology
• Sex: ♀ > ♂ (∼ 4:1)
• Age of onset: 50–70 years
• Demographics: higher incidence in individuals of Asian, Hispanic and
northern European ancestry than in black populations
References:[1]
Epidemiological data refers to the US, unless otherwise specified.
NOTES
FEEDBACK
Etiology
• Primary osteoporosis (most common form)
o Type I (postmenopausal osteoporosis): postmenopausal women
§ Estrogen stimulates osteoblasts and inhibits osteoclasts. The
decreased estrogen levels following menopause lead to increased
bone resorption.
o Type II (senile osteoporosis): gradual loss of bone mass as patients age
(especially > 70 years)
• Secondary osteoporosis
o Drug-induced/iatrogenic: especially after systemic long-term therapy
with corticosteroids (e.g., in patients with autoimmune disease)
§ Other: Long-term therapy with anticonvulsants, L-
thyroxine, anticoagulants,proton-pump inhibitors, aromatase inhibitors
o Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism,
hyperparathyroidism, renal disease
o Multiple myeloma
o Immobilization
o Alcohol abuse
• Risk factors
o Cigarette smoking
o Family history of osteoporosis
o Malabsorption, malnutrition (e.g., a vegan diet low in calcium and vitamin
D)
o Low body weight
References:[1][2][3][4][5]
NOTES
FEEDBACK
Clinical features
• Mostly asymptomatic
• Pathological fractures: spontaneous fracture following mild physical
exertion or minor trauma (e.g., lifting something, bending over, or
sneezing/coughing)
o Localizations: vertebral (most common) > femoral neck
> distal radius (Colles) fracture (Colles fracture), fractures of the long
bones (e.g., humerus)
o Vertebral compression (crush) fractures are commonly asymptomatic, but
may cause acute back pain and possible point tenderness without
neurological symptoms
o Long-term findings after repeated vertebral compression fractures
§ → Decreased height (loss of 2–3 cm with each fracture)
§ → Thoracic hyperkyphosis → stooped posture with a “dowager's hump”
References:[1][6][7]
NOTES
FEEDBACK
Diagnostics
• DXA (dual-energy X-ray absorptiometry)
o Calculates bone mineral density (BMD) in g/cm2
o Indications
§ General recommendation for women ≥ 65 years and men ≥ 70 years
§ In younger individuals if additional risk factors are present (e.g.,
prolonged glucocorticoid use, low BMI (< 21 kg/m2) or weight < 127 lb,
alcohol use, smoker, amenorrhea)
o Results: T-score
§ Osteoporosis: T-score ≤ -2.5 SD
§ Osteopenia: T-score of -1 to -2.5 SD
• Plain radiography
o If osteoporosis is diagnosed: radiographic assessment of the whole skeletal
system is recommended, particularly if a fracture is already suspected or
height loss has occurred
o Increased radiolucency is detectable in cortical bones once 30–50% of
bone mineral has been lost
o Osteoporosis can be diagnosed if vertebral compression fractures are
present
§ Commonly an incidental finding because such fractures are typically
asymptomatic
• Clinical chemistry: usually normal (see Laboratory evaluation of bone
disease), but some markers may be used for assessing risk of fracture
o Urine: ↑ cross-links (e.g., deoxypyridinoline), markers of bone turnover
o Blood tests
§ Primary osteoporosis:
§ Alkaline phosphatase possibly elevated
§ Other parameters normal (e.g., serum calcium, phosphate)
§ Secondary osteoporosis: abnormal results depending on underlying
disease (e.g., hypercalcemia in hyperparathyroidism)
• Pathology:
o Thin, disconnected trabecular structures
o Attenuated, pitted cortical bone
o Increased osteoclast number and activity
Osteoporosis is diagnosed if T-score ≤ -2.5 SD and/or a fragility fracture is present.
References:[1][8][9][10]
NOTES
FEEDBACK
Differential diagnoses
• Osteomalacia
• Hyperparathyroidism
• Metastases
• Multiple myeloma
• Intraosseous hemangioma
References:[1]
The differential diagnoses listed here are not exhaustive.
NOTES
FEEDBACK
Treatment
Lifestyle measures
• Diet
o Avoid alcohol and nicotine
o Sufficient intake of calcium
and vitamin D
• Physical activity with strength and balance training
• Avoid or minimize glucocorticoids
Medical therapy
• Indication
o History of fragility fractures
o T-scores ≤ -2.5
o T-score between -1 and -2.5 with severely increased risk of fracture
• Drugs
o 1st-line treatment: bisphosphonates (alendronate,
risedronate); inhibit osteoclasts and therefore bone resorption
o Alternative treatment options: in the case of
contraindications/unresponsiveness to bisphosphonates or certain risk
factors
§ Teriparatide (parathyroid hormone analog): alternative for severe
osteoporosis (T-score ≤ -3.5) or for patients with contraindications
to bisphosphonates
§ Raloxifene (selective estrogen receptor modulator, SERM) for patients
with contraindications to bisphosphonates or those who also
require breast cancer prophylaxis (but increases the risk
of thromboembolism)
§ Denosumab (monoclonal antibody against RANKL)
: for patients with impaired renal function, or no success
with bisphosphonates
o Consider hormonal therapy
§ Estrogens: for women with intolerance to 1st- or 2nd-line treatment options
or with persistent menopausal symptoms
§ Usually in combination with progestin
§ Contraindications: breast cancer, coronary heart disease, deep vein
thrombosis
§ Testosterone: for men with hypogonadism
Bisphosphonates should be taken in the morning and evening at least 30 minutes before meals to
prevent bisphosphonates from forming complexes with calcium. To prevent esophagitis, they
should also be taken with plenty of water and an upright position should be maintained for at
least 30 minutes following intake!
References:[1][11][12][5]
NOTES
FEEDBACK
Puberty
Last updated: May 17, 2018
QBANK SESSION
CLINICAL SCIENCES
LEARNED
Summary
Puberty refers to the phase of development between childhood and adulthood in which complete
functional maturation of the reproductive glands and external genitalia occurs. The other
processes that characterize this transitional phase are the development of secondary sex
characteristics, growth spurts, and psychosocial changes. The stages of development during
puberty are classified according to the Tanner stages. Although there is considerable variation
between individuals, on average puberty begins at the age of 11 in girls and 13 in boys. Puberty
that begins abnormally early is referred to as precocious puberty and can be due to a peripheral
cause (peripheral precocious puberty) or a central cause involving the hypothalamo-
hypophyseal axis (central precocious puberty, or CPP). At the other end of the disease spectrum,
puberty may be delayed or absent. This delay can be constitutional, secondary to underlying
conditions, or due to hypogonadism.
NOTES
FEEDBACK
Normal puberty
• Definition: phase of development between childhood and complete,
functional maturation of the reproductive glands and external genitalia
(adulthood)
• Phases of pubertal changes
o Gonadarche: activation of reproductive glands by
the pituitary hormones FSH and LH
o Adrenarche: activation of adrenal androgen production
o Thelarche: onset of breast development
o Pubarche: onset of pubic hair growth
o Menarche: onset of menstrual bleeding
§ Anovulatory cycle: The menstrual cycle may be irregular in adolescents
during the first few months/years after menarche. This is not
pathological.
o For further details, see physical changes during puberty below.
• Physiology: unknown initial trigger → ↑ activators and/or ↓
inhibitors of GnRH secretion → ↑ GnRH pulsing
→ ↑ FSH and ↑ LH levels
• Influential factors
o General health (nutritional state, body weight)
o Genetics
o Social environment (e.g., family stress)
• Girls
o Normal age of onset: 8–13 years
o Normal order of changes: adrenarche → gonadarche → thelarche (age of
onset 8–11 years)
→ growth spurt (age of onset 11.5–16.5 years) → pubarche (mean age of
onset 12 years)→ menarche (age of onset 10–16 years
; mean age: 13 years)
• Boys
o Normal age of onset: 9–14 years
o Normal order of changes: adrenarche → gonadarche (age of onset 9–14
years)
→ pubarche (mean age of onset 13.5 years)→ growth spurt (mean age of
onset 13.5 years) → androgenic hair growth
The first visible sign of puberty in males is testicular enlargement, while in females it
is breast development.
References:[1][2][3][4][5]
NOTES
FEEDBACK
Physical changes during puberty
Tanner stages
• Sexual maturity ratings (SMR) to assess the development of secondary sexual
characteristics (e.g., pubic hair, breast and genital development)
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Development of pubic hair (boys and girls)
Ph1 Usually no pubic hair, vellus hair possible
Ph2 Sparse, lightly pigmented hair (straight or curled) on the labia/base of the penis
Ph3 Dark, coarse, curly hair spreading over the pubic symphysis
Ph4 Adult pubic hair that does not extend to the inner thighs
Ph5 Adult pubic hair that extends to the inner thighs with horizontal upper border
Ph6 Further growth of pubic hair along linea alba in the direction of the umbilicus (in 80% of men and
10% of women)
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Breast development (girls)
B1 Prepubertal appearance and size; occasional elevation of the nipple
Breast development (girls)
B2 Enlarged mammary glands form a breast bud; slight increase in areolar diameter, nipple protrusion
B3 Further enlargement of mammary glands; breast bud extends beyond the areolar diameter
B4 Nipple and areola form a secondary mound which projects above the breast tissue
B5 Adult breast; areola with projection of papilla only
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Genital development (boys)
G1 Prepubertal appearance and size of the testes, scrotum, and penis
G2 Testicular volume of 4 mL; larger scrotum; no penile enlargement; scrotal skin changes darkens in
color and texture
G3 Continued enlargement of the testes and scrotum; longer penis
G4 Testicular volume of 12 mL; scrotum growth; longer and wider penis
G5 Testes, scrotum, and penis attain adult appearance and proportions
Other morphological changes during puberty
• Breast changes (boys):
o Occur approximately within 18 months of pubertal onset in males; usually
during Tanner stage 3
o Lasts for ∼ 6–18 months
o Gynecomastia is diagnosed in a pubertal male when the palpable
subareolar gland and ductal tissue is ≥ 2 cm.
o See pubertal gynecomastia.
• Growth spurts
o Vary between the sexes (occurs two years earlier in girls); lasts for ∼ 2 years
o Includes ↑ growth in trunk and limbs
o Assessed using growth velocity charts
• Bone growth
o Accelerated during puberty
o Order of growth: ↑ length → ↑ width → ↑ mineral content
→ ↑ density
• Body weight and composition
o Boys: ↓ body fat (early puberty) → ↑ lean body mass (later puberty)
o Girls: gradual ↑ body fat
o Affected by nutritional status
• Skin changes: pubertal hormonal fluctuation → ↑ sebum secretion
and excessive sweating → acne vulgaris, hyperhidrosis, and hair problems
(e.g., seborrheic dermatitis)
• Myopia: due to axial growth of the eye
• Other physical changes associated with menarche:
o Anemia: ♀ > ♂
o Irregular menses (usually related to anovulatory cycle)
References:[3][6]
NOTES
FEEDBACK
Stages of adolescence
Adolescence is the period of physical and psychological development from the onset of puberty to
adulthood (age of majority).
Adolescence is associated with an increased risk of mortality and morbidity due to an increase
in risk-taking behavior.
• Mortality: motor vehicle accidents, suicide, homicide
• Morbidity: sexually transmitted infections
, eating disorders, depression
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Stage of adolescence Onset Features
Early 10–14 years • Self-esteem and body issues
Stage of adolescence Onset Features
Middle 15–16 years • Development of an independent identity
• Mood swings
• Narcissistic within relationships
Late ≥ 17 years • Less egoistic
• Develops closer relationships with individuals
• Idealistic thoughts
• Awareness of the future
NOTES
FEEDBACK
Precocious puberty
• Definition: the appearance of secondary sexual characteristics before the
age of 8 years in girls and 9 years in boys
• Classification
o Central precocious puberty (gonadotropin-dependent precocious puberty,
true precocious puberty)
o Peripheral precocious puberty gonadotropin-independent precocious
puberty, peripheral pseudopuberty, peripheral precocity)
o Isosexual: premature development of secondary sexual
characteristics appropriate for gender (can be complete or incomplete, as
described above)
o Heterosexual: masculinization of girls or feminization of boys
§ Boys: McCune-Albright syndrome, estrogen-secreting leydig cell tumor
§ Girls: congenital adrenal hyperplasia
• Clinical features
o Precocious puberty may manifest with either development of all the
secondary sexual features or occasionally as isolated
premature thelarche, adrenarche, or menarche.
o Accelerated growth and early skeletal maturity
o Central precocious puberty (CPP): Premature sexual development typically
follows the normal pattern of puberty, except that it is early.
o Peripheral precocious puberty: may not follow the normal developmental
pattern; may exhibit possible features of underlying
condition (e.g., café-au-lait spots in neurofibromatosis, testicular mass
in Leydig cell tumor)
Central precocious puberty
• Definition: precocious puberty with elevated GnRH levels
• Etiology
o Idiopathic or constitutional (most cases)
o CNS lesions
o Pituitary gonadotropin-secreting tumors (rare)
o Systemic conditions: tuberous sclerosis, neurofibromatosis
o Obesity-related precocious sexual development due to increased levels
of leptin in obesity
• Pathophysiology: premature activation of the hypothalamo-hypophyseal
axis → abnormally early initiation of pubertal changes → early development
of secondary sexual characteristics and gonadarche
• Diagnosis
o Laboratory tests
§ Basal LH and FSH: increased
§ GnRH stimulation test (gold standard): Gonadotropin (LH und FSH)
levels increase after intravenous administration of GnRH.
§ Sex hormones
§ ♂: ↑ serum testosterone
§ ♀: ↑ serum estradiol
o Imaging
§ Brain MRI/CT with contrast
§ X-ray of the left hand
• Therapy
o GnRH agonist (e.g., leuprolide, buserelin), with close monitoring of
therapy
o Manage underlying cause
Peripheral precocious puberty
• Definition: precocious puberty without elevated GnRH levels
• Etiology
o ↑ Androgen production, e.g.:
§ Ovarian cyst (most common cause)
§ Congenital adrenal hyperplasia
§ Virilizing ovarian and adrenocortical tumors
§ Leydig-cell tumor
o ↑ Estrogen production, e.g.:
§ HCG-secreting germ cell tumors (e.g., granulosa cell tumor)
§ Rarely: adrenal gland tumors that produce estrogen
§ McCune-Albright syndrome
o ↑ β-HCG production: e.g., hepatoblastoma
o Primary hypothyroidism
o Obesity-related precocious sexual development due to
compensatory hyperinsulinemia (caused by increased insulin
resistance in obesity)
• Diagnosis
o Imaging: ultrasound of the pelvis, testicles, and abdomen
o Laboratory tests
§ ↑ Estrogen/testosterone (depending on the tumor), ↓ FSH, ↓ LH
§ Tests to detect primary underlying causes: e.g., TSH, FT3, β-HCG,
CT/MRI
• Therapy
o Precocious puberty caused by excessive hormonal production from
a tumor in the body: surgical removal
o Precocious puberty caused by CAH: cortisol replacement (see “Treatment”
under congenital adrenal hyperplasia)
o Ovarian cysts: No intervention is necessary, as spontaneous resolution
of ovarian cysts is common.
Central precocious puberty has a central cause (e.g., hypothalamic lesions) and
high GnRH levels; precocious pseudopuberty has a peripheral cause (e.g., germ cell tumors),
without elevated GnRH levels!
Benign pubertal variants
• Benign premature thelarche
o Other secondary sexual characteristics are absent, but linear growth is
normal
o May also be present in toddlers and neonates
• Premature adrenarche
o Onset of pubarche and/or axillary hair < 8 years in girls and < 9 years in
boys
o Most common in African-American and Hispanic populations, patients
with obesity, and patients with insulin resistance
• Benign prepubertal vaginal bleeding
o No other secondary sexual characteristics present
o Trauma, infection and sexual abuse need to be excluded!
Obesity-related precocious sexual development
• Obesity is associated with early pubertal development
• Summary of pathomechanism: Obesity causes
compensatory hyperinsulinemia (due to increased insulin resistance) and
higher levels of leptin, which both lead to earlier development of sexual
characteristics.
References:[1][2][7][8][9][10][11]
NOTES
FEEDBACK
Delayed onset of puberty
• Definition: absent or incomplete development of secondary sex
characteristics by the age of 14 in boys or 13 in girls
• Etiology
1. Constitutional growth delay (most common cause of delayed puberty)
§ Definition: a temporary delay in growth and onset of puberty that is not
caused by any pathological process
§ Etiology: may be inherited as an autosomal dominant, recessive, or X-
linked trait
§ Diagnosis: X-ray showing a bone age that is less than the individual's
chronological age
§ Treatment: No treatment is needed, as catch-up growth eventually
occurs and the individual reaches a normal adult height.
2. Malnutrition and other chronic diseases (such as inflammatory bowel
disease, hypothyroidism, or psychosocial deprivation)
3. Hypogonadism
• Diagnosis
o Monitoring over time
o History: delayed (not interrupted!) growth, nutritional habits, medication,
positive family history of delayed onset of puberty
o X-ray of the hand
§ Allows association between skeletal maturation and chronological age
§ Shows delayed bone age
o Basal LH and FSH
o In the case of primary amenorrhea → also measure TSH and prolactin
• Therapy
o Treatment of the underlying disease
o Watchful waiting: careful serial growth measurements at frequent
intervals ∼ every 6 months
o When pubertal delay is severe: gonadal steroids
