weight gain Flashcards
differentials for weight gain
Obesity
Cushings Disease
Prader-Willi Syndrome
Hypothalamic obesity
What is the etiology of weight gain?
Etiology:
- Dysregulated control system of appetite and satiety
(hypothalamus and negative feedback loop):
o Leptin – satiety hormone
o Ghrelin – hunger hormone
o Glucose, insulin, CRH, POMC, neuropeptide
Pathophysiology of obesity?
Pathophysio
- Multifactorial
- Interaction of genetics, environment
- Energy imbalance: energy in exceeds energy used
resulting to high energy stored.
o For every 100 cal excess/d = additional
10lbs/d
- Imbalance of caloric intake and energy expenditure
- Endocrine causes (hypothyroidism, GC excess, GH
deficiency, craniopharyngioma, chromosomal defect)
What are the clinical manifestations of obesity?
CM
1. BMI >95th percentile for age (gender specific) or +2SD
(or >30 kg/m2 at 19 yrs) based on WHO/CDC growth
charts
2. Inc Waist circumference
3. Acanthosis nigricans, striae – consider DM
4. Metabolic syndrome – central obesity, HTN, glu
intolerance, hyperlipidemia
5. Irregular/missed menses – r/o PCOS
6. Snoring – consider OSA
7. Social anxiety
Diagnostics
Dx
1. FBS, insulin, HbA1c
2. Lipid profile (cholesterol, TG, HDL, LDL)
3. LFT (ALT/AST, GGT)
4. Liver UTZ, ovary and uterus – r/o NAFLD, PCOS
5. Hormonal assays – TSH, T4, LH, FSH, cortisol
6. Chromosomal analysis
7. CT scan/MRI – r/o craniopharyngioma, adrenal tumor
8. Others – 25-OH VitD, sleep study, uric acid, fasting
serum insulin
What are the complications of obesity?
- Stroke, idiopathic intracranial HTN, cataracts, CAD,
DM, dyslipidemia, HTN, pulmo ds, liver ds, GB ds, gyne
abN, osteoarthritis, tibia vara, gout, urinary stress
incontinence, gout, cancer, depression, poor self
esteem, OSA - Dyslipidemia:
o Low HDL: M <40 mg/dL, F <50 mg/dL
o High LDL: >110 mg/dL
o High TG: >150 mg/dLP
Prevention
Prevention
1. Screening overweight children
2. Promotion of BF, access to fruits and veg, walkable
communities, 60min/d activity, encourage sports
What is the etiology?
CH 577: CUSHING DISEASE
Etiology
- Result of abnormally high blood levels of cortisol or
other glucocorticoids
- MC cause: prolonged exogenous administration of GC
- >6yo: endogenous Cushing syndrome MC cause =
ACTH secreting pituitary tumor (Cushing disease)
- <6yo: MC cause = adrenal cause
What is the pathophysiology?
Pathophy
- CRH released by hypothalamus –> ACTH produced by
pituitary gland –> adrenal gland secrete cortisol
- Cortisol – primary stress hormone. Promotes
glycogenolysis and gluconeogenesis, regulate
metabolism, reduce inflammation, assist with memory
formulation, control salt and water balance and BP
What are the clinical manifestations of Cushing disease?
CM
1. Rounded face, prominent cheeks, moon facies
2. Buffalo hump, generalized obesity
3. Abnormal masculinization
4. Impaired growth
5. HTN
6. Susceptibility to infection
7. Purplish striae on hips, abdomen, thigh
8. Delayed puberty
9. Emotional lability
10. Weakness, headache
11. Hyperglycemia –>DM
12. Osteoporosis
What are the diagnostics?
Dx
1. Cortisol – serum: loss of circadian rhythm of cortisol (N
diurnal pattern= serum cortisol highest at 8am and
decrease to <50% by midnight)
- Midnight cortisol level >4.4 mcg/dl = Cushing
syndrome
a. Salivary – screening test for OPD. Reflect
the unbound, biologically active serum
cortisol
b. Elevated Urinary cortisol
2. Single-dose dexamethasone suppression test –
Dexamethasone 25-30 mcg/kg (max 2mg) given at
11pm then determine plasma cortisol level at 8am
- N: dexamethasone provides negative feedback to the
pituitary (N = < 5 mcg/dl)
- Cushing: persistently high cortisol levels despite dexa
(> 5 mcg/dl)
3. 2-step dexamethasone suppression test –
Dexamethasone low dose (30 mcg/kg/d q6) and high
dose (120 mcg/kg/d q6) are administered on
consecutive days
- to determine whether Cushing is caused by:
a. Pituitary adenoma: high dose
dexamethasone suppresses cortisol levels
b. Ectopic ACTH-secreting tumor or cortisolsecreting
adrenal tumor – cortisol levels
remain elevated despite low and high dose
dexamethasone
4. CT scan/MRI – detect adrenal tumors, pituitary
adenomas
5. Bilateral petrosal sinus sampling – localize small
pituitary adenomas not visible on MRI
What is the management?
Mgt
1. Transsphenoidal pituitary microsurgery – tx of choice
2. Adrenalectomy – for pituitary adenoma unresponsive
to tx, aldosterone-producing adenoma and ectopic
ACTH-secreting metastatic tumor
3. Ketoconazole, metyrapone, aminoglutethimide,
etomidate – inhibitors of adrenal steroidogenesis.
Medical tx as adjunctive tx after unsuccessful pituitary
surgery, or preoperatively to normalize circulating
control
4. Supportive – CS replacement tx
What is Prader-Willi Syndrome?
CH 47: PRADER-WILLI SYNDROME
- Complex genetic condition
Etiology
- Loss of function of genes in a region of chromosome 15
o Deleted paternal gene, inactive maternal
gene
o Uniparental disomy: 2 copies of chr15 are
maternal copies
- associated with advanced maternal age
- embryo starts off as trisomy 15 then loss of paternal
chromosome
- elevated ghrelin à satiety defect, relative
hypoinsulinemia
what are the clinical manifestations of Prader Willi?
- infant: hypotonia of prenatal onset, postnatal growth
delay, feeding difficulties (cannot consume enough
calories to maintain weight, NGT feeding), FTT - 1st 4 yrs: muscle tone improves with voracious appetite
- Obesity
- Hyperphagia
- Moderate MR, developmental disability
- Short stature, small hands and feet
- Hypogonadotrophic Hypogonadism
- Fascies with narrow bifrontal diameter, almond eyes,
full cheeks, triangular mouth - Fair skin and light-colored hair
What are the diagnostics?
Dx
- clinical dx
1. Genetic testing – recommended for NBs with
pronounced hypotonia
