Steriod Hormone Metabolism

Question 1

3-Beta-hydroxysteriod Dehydrogenase Deficiency

Answer 1

Cause:Deficiency in the HSD3B2 enzyme
Result: Inability to convert Pregnenolone to progesterone, as well as DHEA to Androstenedione (so, no aldosterone, cortisol and active sex hormones [androgen & estrogen])
Sx:
- no aldosterone > inc Na+ excretion (hyponatremia), retention of K+ (hyperkalemia) & hypotension.
- No Cortisol > hypoglycaemia, hyponatremia and hyperkalemia (due to mineralocortocoid activity)
-No Sex hormones: all patients with female genitalia
Tx: Supplemented corticosteroids to activate -ve feedback system

Question 2

17-alpha-Hydroxylase (CYP17) Deficiency

Answer 2

Cause: Deficiency in CYP17 enzyme
Result: Inability to synthesize active sex hormones AND cortisol, leads to an increased production of Aldosterone
Sx: Increased Aldosterone produces hypertension and hypernatremia. All patients present with female genitalia.

Question 3

Classic 21-alpha-Hydroxylase (CYP21) Deficiency

Answer 3

Cause: Complete deletion of the CYP21 gene
Result: Inability to synthesize Cortisol AND Aldosterone - presents in utero as a result of a complete deletion of the CYP21 gene
Sx: Hyponatremia, Hyperkalemia, Hypoglycemia, -Increased ACTH > high Androgens > female newborns will present with ambiguous genitalia. -Male babies will fail to thrive and will present with vomiting and diahrrea > circulatory collapse
- In less severe cases, only the isoform in the Cortisol pathway is affected, allowing normal Aldosterone production and NO salt losing crisis.
Tx: Oral corticosteroids to initiate negative feedback mechansim, lowering ACTH secretion
Keywords: Commonest form of Congenital Adrenal Hyperplasia

Question 4

Late onset 21-alpha-Hydroxylase (CYP21) Deficiency

Answer 4

Cause: Partial deficiency in CYP21 activity
Result: Deficiency in the synthesis of cortisol & aldosterone (but milder than classic)
Sx: Later in life at puberty. Precocious puberty as well as virilization, hirutism and irregular menses in females
Tx:
Dx:
Keywords:

Question 5

11-Beta-Hydroxylase (CYP11B1) Deficiency

Answer 5

Cause: 11-Beta-Hydroxylase (CYP11B1) Deficiency
Result: No cortisol oraldosterone + build up of deoxy-corticosterone, which has mileralocorticoid properties
Sx: Later in life at puberty. Precocious puberty as well as virilization, hirutism and irregular menses in females, but Inc deoxycorticosterone levels lead to hypertension, hypernatremia bc of the mineralocorticoid activity
Tx: Oral corticosteroids to combat androgenital syndrome

Question 6

Cushing’s Syndrome

Answer 6

Cause: Hyper-production of glucocorticoids due to hyperactivity of adrenal glands bc of: XS ACTH, ectopic tumor producing ACTH, tumor of adrenal glands or anterior pituitary
Result: XS cortisol
Sx:
- Hyperglycemia, muscle wasting and atrophy, hypertension, hypokalemia, hypernatremia.
- Moon face, buffalo hump, premature ischemic heart disease
Keywords: More common in women than men

Question 7

Addison’s Disease

Answer 7

Cause: Hypoactivity of adrenals due to autoimmune attack
Result: Lack of corticosteroids secretion: no aldosterone, no cortisol
Sx:
- No Aldosterone > Dec Na +, Inc K+, hypotension.
- No cortisol > hypoglycemia, Dec Na+
- Addisonian Crisis: extreme drop in blood sugar & BP
- First symptoms: fever, lethargy, anorexia, rapid weight loss, abdominal pain, pigmentation of the skin & hypotensive collapse.
- Later: Postural hypotension, nausea, vomiting, & dehydration
- Skin Rashes bc of ACTH XS > melanocytes stim
Tx: Intravenous saline for hyponatremia & hydrocortisone for rashes
Dx: Asaying ACTH: cortisol ratio or checking for adrenal antibodies

Question 8

Chronic Adrenal failure

Answer 8

Sx: Weight loss> anorexia, weakness, general malaise, fever, depression, impotence, and amenorrhea

Question 9

Acute Adrenal Failure

Answer 9

Sx: Presents with hypovolaemic shock and sever hypoglycaemia; can worsen if untreated