L23- Endocrine Pathology IV (adrenal) Flashcards
Primary Hyperaldosteronism = (1):
- (2) causes
- results in (3)
1- Conn’s syndrome
2- idiopathic, adenoma, carcinoma
3- Na retention (+ H2O in exchange for K+/H+) –> HTN, hypokalemia, metabolic alkalosis
Secondary hyperaldosteronism:
- (1) activity is increased in response to (2)
- (2) may result from (3)
1- RAAS
2:
i) dec effective blood volume
ii) dec renal blood flow
3:
i) liver cirrhosis, HF, nephrotic syndrome
ii) HTN
Hyperaldosteronemia:
- (1) are the initial results to indicate a screening test
- the screening test is then conducted with (2) results
1- HTN, hypokalemia, metabolic alkalosis (inc HCO3-)
2- inc aldosterone : renin (inc ARR / aldosterone renin ratio)
list the confirmatory tests for hyperaldosteronemia after intial screening tests
(many tests)
-Oral Na loading test
-FST = fludrocortisone suppression test: administer aldosterone like drug in order to cause low urinary / plasma aldosterone levels in normal people (positive if it remains elevated)
Hyperaldosteremia testing:
- (1) is the results or purpose of CT scan
- (2) describe the purpose adrenal venous sampling
1- Unilateral / Bilateral micro-/macro- adenoma OR bilateral hyperplasia
2- lateralizing the aldosterone source (R or L adrenal)
CAH:
- (1) definition
- (2) type of inheritance
- (3) is a specific change seen in cortisol deficiency
(congenital adrenal hyperplasia)
1- partial or total enzyme deficiency in synthesis of adrenal steroids
2- AR
3- inc ACTH secretion (hyperpigmentation) –> adrenal hyperplasia
list the main enzymes affected in CAH (deficiencies)
(congenital adrenal hyperplasia)
- 21-hydroxylase (90%)
- 11β-hydroxylase
- 17α-hydroxylase
21-hydroxylase deficiency clinical presentations (CAH)
1) simple virilizing (non-salt wasting)
2) Adrenal crisis / salt-wasting
3) late-onset CAH
describe the Simple Virilizing presentation of 21-hydroxylase deficiency (CAH)
(non-salt wasting, partial enzyme deficiency)
-generates sufficient mineralocorticoid to prevent salt-wasting ‘crisis’
Girls- ambiguous genitalia (= enlarged clitoris +/- labial fusion)
Boys- normal at birth –> penile enlargement, early pubic hair, rapid growth (height) when 4-5 yrs old
describe the Adrenal Crisis presentation of 21-hydroxylase deficiency (CAH)
(salt-wasting, severe enzyme deficiency)
-no aldosterone production => hyperkalemia, hyponatremia, hypotension (, metabolic acidosis)
-Females: virilization
describe the late-onset presentation of 21-hydroxylase deficiency (CAH)
- hirsutism
- infertility
21-hydroxylase deficiency Dx:
- (1) is found in blood (indicate timing)
- (2) is performed in borderline cases
- (3) is useful in measuring degradation products
1- high 17α-hydroxyprogesterone; morning sample
2- short synacthen test (administer ACTH-like drug for 15-30 mins, measure adrenal response –> should induce x2-5 hormone release in normal people)
3- urinary steroid profile
describe screening for 21-hydroxylase deficiency
1) Neonatal screening: measure 17α-hydroxyprogesterone in blood spot
2) Prenatal diagnosis:
- mutational analysis via chorionic villous sampling or amniocentesis
- mothers treated with dexamethasone
list the effects of 11β-hydroxylase deficiency
1) Androgen excess:
- Females: ambiguous genitalia (enlarged clitoris), virilization
- Males: precocious puberty (by age 5-6)
2) 11-deoxycorticosterone:
(some aldosterone / mineralocorticoid activity)
-mild HTN
-dec circulating angiotensin II
-varying degree of hypokalemia, alkalosis
list the effects of 17α-hydroxylase deficiency
Males- ambigous genitalia
Females: delayed puberty, absent secondary sex characteristics OR primary amenorrhea
-Excess mineralocorticoid –> varying degrees of HTN, hypokalemia (note- no elevated aldosterone b/c controlled by angiotensin II)
briefly describe the adrenal neoplasms
- benign Adenoma or malignant Carcinoma
- functional or non-functional
Functional:
- Zona Glomerulosa –> hyperaldosteronism
- Zona Fasiculata –> hypercortisolism (Cushing syndrome)
- Zona Reticulata –> virilizing (females) or feminizing (males)
Adrenal Adenoma:
- (benign/malignant)
- (2) route of diagnosis
- (3) indicates clinical significance
- (4) morphology
1- benign
2- incidental upon imaging (incidentalomas)
3- hormone production (functional adenoma)
4- small, yellow, very well differentiated
Adrenocortical Carcinoma:
- (1) describe prevalence
- (2) morphology
- (3) metastasis method
1- rare, sporadic, rare inherited (Li Fraumeni, Beckwith-Wiedemann)
2- large, hemorrhage, necrosis, anaplastic
3- (common) invades adrenal vein
Adrenal Medulla:
- (1) cells
- (2) are the most important diseases
1:
- chromaffin cells (neuroendocrine, neural crest cells)
- supporting / sustentacular cells
2:
- chromaffin cell neoplasm / pheochromocytoma
- neuronal neoplasm / neuroblastoma
describe the 10% rule
(Pheochromocytoma, everything below is ~10%)
- 10% extra-adrenal
- 10% malignant
- 10% bilateral
- 10% childhood
- 10% component of MEN2a/2b (multiple endocrine neoplasia)
- 10% not associated with HTN
**-10% inherited (old rule, now up to 25%)
describe the clinical features of pheochromocytoma
Episodic:
- HTN, HA
- anxiety, palpitations
- excess sweating (diaphoresis)
- cardiac arrhythmias
describe the Pheochromocytoma investigations
- Plasma Metaephrines testing (more sensitive)
- 24hr urinary catecholamines / metanephrines (during episode, more specific)
Imaging:
- MRI, CT scan
- MIBG = I(123)-metaiodobenzylguanidine scinigraphy (if MRI, CT fail, and biochemical testing is positive)
(1) is the most common childhood tumor, affecting (2). (3) is the most common product of (1), represented mostly by (4) in blood/urine. (5) is the main method of investigation.
1- neuroblastoma
2- mostly adrenal glands, occasionally SNS chain
3- dopamine
4- HVA, VMA (homovanillic acid, vanillylmandelic acid)
5- I(123)-metaiodobenzylguanidine scintigraphy: concentrate in >90% of tumors –> assesses spread of tumor and response to therapy
