Sunday, November 5, 2017

Steroid Hormone synthesis pathway (Clinical aspect)

Hello Awesomites :D

I was reviewing the corticosteroid synthesis pathway and its applied.
Let us begin. :))
Adrenal gland consist of two parts :-
1. MEDULLA
2.CORTEX
Adrenal dysfunction includes hyperfunction / hypofunction of medulla and cortex.
1. MEDULLA

A) HYPERFUNCTION - pheochromocytoma
                                        -Neuroblastoma
2.CORTEX

A)HYPERFUNCTION -Conn's disease
                                      -Cushing's syndrome (Primary tumors)
                                                                          (excess ACTH -pituitary hypersecretion,ECTOPIC)
B)HYPOFUNCTION -ACTH deficiency (Iatrogenic , pituitary insufficiency)

C)CONGENITAL ADRENAL HYPERPLASIA (from partial enzyme deficiencies due to mutation in genes)

Clinical features of CAH :-

1.DUE TO DECREASED ALDOSTERONE :-
-Sodium wasting (hyponatremia+dehydration+shock)
 (early presentation)
-increased potassium
-acidosis
2.DUE TO DECREASED CORTISOL:-
-Hypoglycemia
-increased ACTH
3.DUE TO INCREASED TESTOSTERONE :-
In female , virlization.
In male, No symptom, increased size and pigmentation of penis.

Q. What is the difference between 21-hydroxylase deficiency and 11beta hydroxylase deficiency ?
Ans. In 21-hydroxylase deficiency, hypotension occurs due to salt wasting.
Accumulation of 11-deoxycorticosterone as a result of 11 beta hydroxylase deficiency leads to "HYPERTENSION".

Q.Most common form of CAH is due to mutation or deletion of which gene?
Ans. CYP21A resulting in 21-HYDROXYLASE DEFICIENCY .

Q.Which Enzyme deficiency showing virlization in females?
Ans. -21 hydroxylase
        -3beta HSD
       -11 Beta hydroxylase.

Q. Two hypertensive form of CAH.
Ans. 11beta hydroxylase and 17hydroxylase deficiency.

Other points :
- Females with 17-hydroxylase deficiency appear phenotypically female at birth but do not develop breasts and mensturate in adolescent because of INADEQUATE ESTRADIOL PRODUCTION(17 hydroPregnenolone is also a precursor of estrogen). They may present with hypertension.
-CAH is a type of enzyme deficiency. So it can be partial or complete .There is a severity spectrum.
More severe form shows salt wasting.
Milder form shows "NON CLASSICAL TYPE of CAH".

Diagnosis:-

  • 17hydropregnenolone with or without ACTH test
  • CYP21A2 panel,sequencing,deletion
  • Carrier screening test (Preconception test)
  • Karyotyping ( In case of ambiguity of sex)
  • Hormones and electrolytes
Treatment:-
  • Counsel the parents.
  • Protect from Adrenal insufficiency ( Give mineralocorticoid and glucocorticoid)
  • Avoid salt wasting crisis during illness,stress,etc. ( Increase dose of glucocorticoid,Give IV fluids and sodium and dextrose)
  • Surgery ,sex assignment.
(Note :- There are two more variants of CAH 1. Lipoid CAH 
2.POR deficiency ( P450 oxidoreductase enzyme deficiency) - also involved in both sterol and steroid synthesis pathway).


Study hard.
-Upasana Y. :)

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