Endocrinology Flashcards
In T1DM
Which is the most common antibody seen in a young child?
Which is the most common antibody seen in an older child?
Insulin autoantibody in younger children
Glutamic acid decarboxylase (GEA) antibody in older children
How does Diazoxide work?
Diazoxide opens ATP-dependent potassium channels on pancreatic beta cells in the presence of ATP and Mg2+, resulting in hyperpolarization of the cell and inhibition of insulin release
Adrenal hypoplasia affects mainly boys and is due to abnormalities in which gene?
DAX1 gene
_________ antibodies (TPOABs) and ________ antibodies demonstrable in 90% children with lymphocytic thyroiditis and in many with Graves
Thyroid antiperoxidase antibodies (TPOABs) and antithyroglobulin antibodies
Hashimotos thyroiditis/lymphocytic thyroiditis is associated with which AI disorders?
Type 1 polyglandular syndrome:
(2 of the triad of hypoparathyroidism, Addisons Disease and mucocutaneous candidiasis -> HAM disease)
and
Type 2 APS (Schmidt syndrome)
Addison’s, T1DM and Thyroiditis
TPO antibodies are found in __% with T1DM
20%
Children with _____, ____ and ____ syndromes are at increased risk for AI thyroid disease
Children with Down, Turners and Klinefelters syndromes are at increased risk for AI thyroid disease
Which medication can commonly cause hypothyroidism?
Amiodarone- it consists of 27% iodine by weight
Pharyngeal arches are made of ________
Pharyngeal cleft are made of____
Ectoderm or mesoderm or endoderm
Arches - mesoderm
Cleft - ectoderm
1st pharyngeal arch typically forms structures important for ______
Chewing!
Thyroglobulin is synthesised by _______ cells and secreted into the _________
Synthesised in the follicular cell and secreted into the colloid
Iodine is pumped into the colloid through the ______ channel
Pendrin
In the colloid Iodide is oxidased to Iodine by ______
Thyroperoxidase
Helps make T3 and T4
T_ is more active and has a half life of ____
T3 - half life of 1-2 days
T_ is the predominant secreted hormone and T_ is more active
T4 predominant, but T3 most active
Very brief TSH surg on day __
D0-1 of life (40 weeks gestation)
Complications from neonatal Graves is _______
Craniosynostosis
What has the fastest treatment for neonatal hyoerthyroidism?
Lugol’s Iodine
Pendrin syndrome is an autosomal recessive disorder associated with ______
Pendrin channel is the deficit
Mild to moderate hypothyroidism, goitre, sensorineural hearing loss
Delayed TSH surge (in congenital hypothyroidism) can be seen in _______.
TSH suppression can also be seen with ______
Monozygotic twins
Dopamine and other ionotropes can also suppress TSH
What would be the diagnostic test for consumptive hypothyroidism?
Elevated reverse T3
Naemangiomas can produce Type 3 deiodinase whcih facilitates the conversion of T4 -> reverse T3
Which syndrome….?
Severely increased TSH results in the alphasubinit activating LH receptor as well as the TSH recepor.
Very high TSH from the hypothyroidism, increases the LH and results in polycystic ovaries
Van Wyk Grumbach syndrome
An IGSF1 (a loss of function) mutation results in ____
Isolated central hypothyroidism - X linked Recessive
Other features may be delayed onset puberty, late onset macroorchidism, variable prolactinaemia
What are some features used to score thyroid storm?
Temperature, CNS effects, GI dysfunction, Cardiac dysfunction (tachycardia, congestive heart failure, atrial fibrillation)
Male , with developmental delay, congenital hypotonia, and general muscle weakness.
TFT’s show slightly raised T3 and normal TSH…. what is the syndrome?
Allan-Herndon-Dudley Syndrome (MCT8 channel defect)
Xlinked condition, Abnormality in channel for thyroid hormone in neurons
What is the most common long term complication of cranial irradiation?
Growth hormone deficiency
What are factors that decrease GH secretion?
Obesity, psychosocial deprivation, excess glucocorticoids, carbohydrates
GH deficiency leads to abnormally slow ______
Other features?
Growth velocity and often have increased adiposity.
Other features - Hypoglycaemia and small penis in babies
Where is IGF-1 produced?
The liver
IGF-1 reduced in malnutrition and increased with obesity
How does hypothyroidism impact growth?
- Reduced chondrocyte division at epiphyseal plate
- Marked GH and markedly reduced IGF-1 secretion
How do you calculate midparental height for a boy?
(Dad’s height + mother’s height +13cm)/2
Range +/- 8cm
Height velocity in boys peaks at?
~13-14 years (7-12cm/year)
Girls 11-12 yr
Best screening test for growth is?
Height velocity - it is above 25th centile, there is not growth failure - hormone levels should be okay
How do you do formal GH testing?
A normal IGF-1 makes GH deficiency unlikely
But typically you do a stimulation test with - Arginine (protein), Clonidine (sleepy), insulin, and glucagon
Short stature, craniofacial and body asymmetry, low birthweight, microcephaly, triangular facies, 5th finger clinodactyly, congenital cardiac defects
Russell-Silver Syndrome
__% with Turner syndrome will have short stature as their only feature
50%
SHOX gene is found on which genes?
Is found on the X and Y gene; it is expressed in chondrocytes and abnormality leads to reduced growth
Having a missing chromosome i.e. Turners syndrome - reduced growth
Kleinfelters - XXY - increased growth
Common side effects of GH treatment?
- T2DM
- Benign intracranial hypertension
- In PWS -> worsens OSA (must have PSG prior
- SUFE
- Scoliosis
- Malignancy
Which medication is used to suppress excess glucocorticoid production?
Ketoconazole - inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase
Antimullerian hormone is secreted by _______
Testosterone is secreted by _______
AMH secreted by Sertoli cells
Leydig cells secrete testosterone
SRY codes for release of _______ which triggers the male reproductive system
Release of testis determining factor
Mesonephric (wolfian) duct gives arise to _____ reproductive system
Paramesonephric duct (Mullerian) gives rise to ______ reproductive system
Wolfian - male (epididymus, vas deferens, seminal vesicle)
Mullerian - female (uterus, fallopian tube and upper vagina)
In males, ________ causes the mullerian duct degenerates into appendix testes.
This happens in week _
The mullerian inhibiting hormone.
Testosterone needed for Wolfian duct to progress into vas deferens
This happens in week 7
What is the role of Dihydrotestosterone?
Masculinises the male genitalia
Phenotypical differentiation of external genitalia happen at week ___
After week 12
In females, the gubernaculum becomes __________ and ________
The superior portion - ovarian ligament - anchoring the ovaries
The inferior portion - round ligament - connecting the uterus to labia majora
In males,
- LH stimulates leydig cells to produce ____
- FSH stimulates sertoli cells to produce ____
Leydig cells -> testosterone
Sertoli cells -> Sperm
Tanner scale?
Male:
I: prepubertal
II: Soft pubic hair, slight enlargement of testes
III: Pubic hair becomes coarse, penis and testes enlarges
IV: Penis begins to widen
Female: I: prepubertal II: Soft pubic hair, some breast buds III: Coarse pubic hair, breast mounds IV: Pubic hair spreads
What is the order?
Menarche, thelarche, adrenarche?
1) Thelarche
- increased oestrogen -> breast development
2) Adrenarche
- Assoc with increased androgens
3) Menarche
- Increased oestrogens -> menses
- ~2.5yr after thelarche
Which gene is associated with Denys-Drash?
WT gene
Why does descended gonads mean male?
Because, testes descend and ovaries don’t.
Testicular tissue produces testosterone, which has paracrine effects to allow the testes to descend. This indicates the presence of SRY gene.
How do you differentiate Frasier syndrome and Denys-Drash?
Both are caused by mutations of WT1 gene and present with DSD and proteinuria.
Denys-Drash syndrome: renal failure with mesangial sclerosis, assoc. with bilateral Wilm’s tumour and gonadoblastoma
Frasier syndrome: FSGS, mutation in intron 9 and gonadoblastoma. NOT assoc with Wilm’s tumour
Which enzyme deficits in CAH are going to be associated with undervirilisation in males?
17 alpha , sTAR , 3Beta-HSD (partially)
Which enzyme deficit in CAH is going to cause hypertension?
CYP11B1
In CAH 21 hydroxylase deficiency - you get a build up of?
17-hydroxyprogresterone
Neonatal diabetes is caused by which mutation?
Glucokinase
Which insulin is used in the insulin pump?
Aspart, Lispro (Rapid acting)
What is the effect of GLP-1 on glucose metabolism?
Glucagon-like peptide receptor:
- Increase insulin secretion (but less likely to have hypoglycaemia)
- Stimulate glucose-dependent insulin release iselt cells (also slow gastric emptying, inhibit glucagon release and reduce food intake)
Name 4 conditions that can reduce the red blood cell survival and falsely decrease HbA1C values?
Blood loss Haemolytic anaemia Splenomegaly End stage renal disease Pregnancy
Name 4 condition that can decrease red cell turnover and can falsely increase values of HbA1C?
Iron def anaemia
Uraemia
Raised triglycerides or bilirubin
Chronic alcohol, opioids and salicylate
Which type of MODY is least likely to have diabetic complications?
MODY 2
Often incidental finding of mild hyperglycaemia and rarely associated with complications - glucokinase
Which hormone is most sensitive to radiation?
Growth hormone
GH > Gonadotrophins (LH) > ACTH > TSH
Cortisol elevated with an intermediate (5 to 20) or normal/high ACTH:
Is this ACTH Dependent or
ACTH independent?
ACTH Dependent
(this includes Cushing’s disease)
You may also see hyperpigmentation
What is the reason for hypertension in 11 beta hydroxylase deficiency?
11 deoxycortisol
Which 2 congenital adrenal hyperplasia cause hypertension?
11 beta hydroxylase
17 alpha hydroxylase
Ledig cells are stimulated by which hormone?
Luteneising hormone
but early in pregnancy (first trimester) - bHCG is responsible
(beta HCG and LH have similar structure)
StAR mutation leads to….
Lipoid CAH -> lipid accumulation in adrenocortical cells
(Severe glucocorticoid and mineralocorticoid deficiency)
Presents as female in both XX or XY
Somatic (or mosaic) mutation in GNAS1 leads to
McCune Albright syndrome
What disorder of sexual development does McCune Albright leads to ?
Precocious puberty (gonadotropin-independent)
What is the inheritance pattern of complete androgen insensitivity syndrome?
X-Linked recessive inheritance
Mutation in androgen receptor gene
What is the second most common type of CAH and what is the most common presentation?
11-beta hydroxylase
Hypertension and virilisation
Why do you get hypertension in 11-beta hydroxylase deficiency?
11-Deoxycortisol has mineralorticoid effect
In a male, Tanner stage 2 correlates to:
Testicular enlargement and some very mild pubic hair development
Pubic hair is more related to Tanner stage __
3 (but does start at stage 2)
How do you differentiate peripheral precocious puberty vs benign adrenarche
Precocious puberty has both adrenarche and thelarche
Side effects of PTU?
Severe hepatotoxicity, agranulocytosis, hepatitis, vasculitis
How is sublingual ectopic thyroid gland diagnosed?
Technetium scan
Radio-131-iodine scan - used for ablation
Hypophosphatemic rickets and Dent’s, which is more common in boy vs girl?
Dent disease: More likely in boys because X linked recessive
X linked hypophosphatemia is equal in both (X linked dominance)
How is the Vit D best stored in the body?
D3 (25, hydroxylase)
1,25 is used up very fast
Which cell in the pancreas produces glucagon?
Alpha cells
Short long bones, madelung deformity, muscle hypertrophy, genu valgum, increased carrying angle…
Which syndrome?
Leri-Weill Dyschondosteosis
Difference between constitutional delay vs poor spinal growth (in a child that has had radiation)
In constitutional delay there is a delayed bone age
What common endocrinological anomaly does Vincristine cause?
SIADH - hyponatraemic hypervolaemic (or euovlaemic)
Which cells produce AMH?
Sertoli cells
testosterone made by Leydig cells
How does OCP help with PCOS?
Androgens cause SHBG to fall
