03: Childhood growth and problems; Endocrine Sx; Immunology of Endo Diseases Flashcards
Measuring children
length v height (spine compr)
sitting
head circumference
bone age: left wrist; measure potential
Tanner method: puberty
*serial measurement
* mid parental height
*
Puberty hormones
lh & fsh dormant
puberty: pulsatile releases esp during sleep
= gonad hormones
Most significant pubertal stages
*breast budding (B2)
* testicular enlargement (G2)
= puberty will progress onwards normally
Discuss the identification and management of hypothyroidism in the newborn.
AMBIGUOUS GENITALIA: exclude congenital adrenal hyperplasia !adrenal crisis first 2w of life
>multidisciplinary approach
> internal ogans, gonads (USS)
> karyotyping
CONGENITAL HYPOTHYROIDISM: d/t dyshormonogenic, athyreosis, hypoplastic, no thyroid/absent
*screening = heel prick, measure TSH
> thyroid hormone replacement
ACQUIRED HYPOTHYROID: common AuIm (hashimoto’s)
*lack of growth, and poor school performance
THYROID DEF: puffiness wt gain
Describe the clinical features of hypopituitarism in adults and children
chubbier and rounder, SHORT despite chubby etc.
> diet, exercise, psychological input
Discuss the pathological causes of short stature (including common short stature
syndromes).
UNDERNUTRITION; CHRONIC ILLNESS; IATROGENIC: steroid medication
PSYCHO-SOCIAL: home v care environments
HORMONAL:
GHdef.,
>GH replacement
THYROID DEF.: growth failure/obesity
>thyroid hormone replacement
SYNDROMES
TURNER SYNDROME: short, webbed short neck, weight carried neck, short limbs
PRADER-WILLI SYNDROME: short, obese, extreme floppiness
>GH treatment
NOONAN SYNDROME:
>GH treatment
ACHONDROPLASIA: skeletal dysplasia, short limbs, XR skeletal surveys
Discuss the effects of obesity on childhood growth.
girls: grow much faster, earlier
boys:
obese children = tall, concern if obese and not growing
State the common causes and principles of investigation of precocious and delayed
puberty.
*idiopathic in nature (girls), tumours (boys)
significant pubertal changes milestones, pituitary imaging
boys commonly affected by constitutional delay of growth
GONADAL DYSGENESIS: turner (girls), klinerfelter
CHRONIC DISEASE
IMPAIRED HPG axis
> GnRH agonist (girls before age of 8)
Non-Path causes of short stature
NON-PATH: familial constitutional: puberty delay vs peers, delayed bone age > short-term hormone boost small gestational age (SGA): >GH Tx
Precocious pseudopuberty
gonadotrophin independent
abdn sex steroid secretion
virilisaing/feminanising
OBESITY IN CHILDREN
BMI = plotted, skin folds, waist measurement
OBESE + SHORT = ABNORMAL
- hx
- ?syndrome, axis pathology, diabetes
- acanthosis nigricans (insulin resistance, t2DM, goitres flat pale features
Goitre
d/t genetic, iodince def., dyshormogenesis, malignancy, TSHoma
stridor (inspiratory wheeze)
> thyroidectomy !vocal cord function, hypothyroidism
Thyroid cancer types
MEDULLARY: c-cells; good prognosis
ANAPLASTIC: poor prognosis, uncontrolled dysreg growth
*FNAC
!lymph node, bone, lungs
> surgery
radio-iodine
Pathology of Parathyroid Glands
produce parathyroid hormone, which plays a key role in the regulation of calcium levels in the blood.
- ADENOMA = XS PTH secr.
- 2º to renal failure
- hypovitaminosis
- ectopic gland in chest (developmental)
- SESTAMIBI scan = metabolic active scanning
- USSS
> sx
Cushing’s Syndrome
xs glucocorticoids
: Weight gain, central obesity, moon facies, buffalo hump fat pad, easy bruising, thin skin, poor wound healing, purple abdominal striae, hirsutism, infertility, depression, irritability, opportunistic infections.
HY, DM, impaired glucose tolerance
> Transabdominal Laparoscopic Adrenalectomy
Conn’s Syndrome
xs aldosterone
Increased Na reabsorption by distal tubule and collecting duct of the nephron & Increased K/H excretion
Increased ECF volume
Hypertension +/- Hypokalemia
phaeochromocytoma
xs Catecholamines
*tumour
Tachycardia, palpitations, pallor, tremor, headache & sweating / Hypertensions, Orthostatic hypotension, Pallor, Retinopathy, Fever & Tremor
- urine metanephrines
- MIBG scans
Neuroendocrine Tumours
gut endocrine cells (origin)
MEN1
- insulinoma = hypo
- gastrinoma = peptic ulcers
- glucagonoma = DM
FUNCTIONAL: SEROTONIN & CHROMOGRANIN SECRETION
- asymp
- intestinal obstruction/bleeding
*urinary 5-HIAA serum chromogranin
Describe common organ specific and non-organ specific autoimmune disease.
organ-specific Vs non-organ specific
TSH R = hyper/hypo insulin R = hyperglc/hypoglc myasthenia gravis (ACh R)
NON-SPEC
haemolytic anaemia = TBC ag (multiple)
Illustrate the multifactorial aetiology of autoimmune disease.
Antigens that induce tolerance are called tolerogens, or tolerogenic antigens = self-tolerance = failure = AuIm disease
*T and B cells bearing these self-reactive
molecules must be either eliminated or downregulated so that the immune
system is made specifically tolerant to self-antigens.
CENTRAL TOLERANCE: THYMUS, eliminating T cells high affinity to self-ag, BM site regulating b cell tolerance
PERIPHERAL TOLERANCE:
- removal/apoptosis of identified mature self-reactive lymphocytes
- Treg suppress activation of self-reactive lymphocytes
- sequestration of self-ag from immune system (immune privelege sites)
•CNS, testes and eyes, and thus cannot engage
antigen receptors - induction of peripheral tolerance is antigen
recognition without co-stimulation or “second signals. - WIDELY VARIABLE GENETIC FACTORS: HLA associations
- infections (Coxsackie B/mumps for DM1)
- drugs
- UV radiation
Describe the immuno-pathological mechanisms involved in causation of
autoimmune disease.
- inapt access of self-ag
- ⇧local expression of co-stimulatory molecules
- dysregulated presentation of self-molecules to immune system
- inflamm. = ⇧proteolytic enzymes = non-sepcific breakdown = cryptic epitope creation presented to responsive T cells
- self-ag altered by viruses, FR, ionising radiation
Illustrate the roles of cell mediated and humoral immune mechanisms in
autoimmune thyroid disease (as an illustration of all autoimmune endocrine
disorders).
SELF-REACTIVE T CELLS require COSTIMULATION FROM DENDRITIC CELLS to induce autoimm. but if COSTIMULATION is deficient in resting APC = peripheral tolerance via anergy (via SEQUESTRATION)
APC activated by MICROBES = expression of costimators = activating self-toleranct immune cells
Define and classify autoimmune polyendocrine syndromes
group of clinical conditions characterized by functional
impairment of multiple endocrine glands due to loss of immune tolerance.
alopecia, vitiligo, celiac disease, and autoimmune gastritis with vitamin B12 deficiency that affect nonendocrine organs.
- genetic factor + env.
- eventually leads to organ failure
- early infancy to old age
APS-1: auim regulator gene mutations *chronic mucocutaneous candidiasis *hypoparathyroidism *addison's disease \+enamel hypoplasia
APS-2: commoner than APS-1 *DM1, AuIm Thyroid, Addison's Disease *F>M *young adulthood (later than APS-1 onset) \+celiac, alopecia, vitiligo etc.
IPEX: inherited.
*DM1 early
* enteropathy with intractable diarrheal and malabsorption
* Dermatitis that may be eczematiform, ichthyosiform, or psoriasiform.
*earlier dev than APS1
IgE (eosinophillia)
kidney disease
Illustrate the importance of endocrine autoantibodies as primary pathogenic agents or as secondary non-pathogenic markers of disease.
Mediate pathogenesis of AuIm disease as well as providing speciifc phenotypic info for screening/dx
Hashimoto Thyroiditis
common cause of acquired hypothyroid, F>M
inital: transient thyrotox. + enlargement
AuIm nature
