Adrenal Pathology and MEN Syndromes Flashcards
ACTH dependent Cushing syndrome =
ACTH independent Cushing syndrome =
ACTH dependent Cushing syndrome = secondary hyperadrenalism
ACTH independent Cushing syndrome = usually a primary hyperadrenal state
When would you see BL cortical hyperplasia of the adrenal glands?
ACTH dependent Cushing syndrome
What are 3 features of Primary aldosteronism (“Conn’s syndrome”)?
HTN
- refractory HTN
- adrenal mass and HTN
- HTN at a young age
- severe HTN (>160/100 mmHg)
Hypokalemia
Hypomagnesemia
What causes secondary aldosteronism?
Overactivation of the RAAS system
- diuretic use
- decreased renal perfusion
- arterial hypovolemia
- pregnancy
- renin-secreting tumors
Aldosterone-secreting adenoma are of what size?
Who do they affect?
What is a classic finding on histology?
There is a high incidence of what with these adenomas?
Often very small (< 2 cm)
Young patients: 30s-40s
Spironolactone bodies
High incidence of ischemic heart disease
What is a pituitary cause of Adrenogenital syndromes (“adrenal virilization”)?
What are 2 adrenal causes?
Pituitary: ACTH stimulation of androgens (Cushing disease)
Adrenal:
- Primary adrenal neoplasm (carcinoma > adenoma)
- Congenital adrenal hyperplasia (CAH)
What is the inheritance of CAH?
What is the underlying metabolic cause?
How does the hyperplasia occur?
AR
There is a deficiency of 21-hydroxylase, an enzyme responsible for steroidogenesis (inherited error of metabolism)
There is impaired feedback to the hypothalamus/pituitary, which causes the hyperplasia of the adrenals.
What causes Salt wasting syndrome?
What are some symptoms/presentations in men and women? (3)
What about in females only? (1)
What is the long-term consequence of adrenomedullary dysplasia?
21-hydroxylase deficieny leads to no mineralcorticoids and no cortisol.
Males and females:
Salt wasting -> hyponatremia
Hyperkalemia
Hypotension
Females:
Virilization (seen at birth)
Hypotension is the long-term consequence.
What causes Simple virilization syndrome (w/o salt wasting)?
What is a major symptom?
Partial 21-hydroxylase deficiency - some mineralocorticoids and small amount of cortisol, but not enough to prevent ACTH overproduction.
Virilization
What causes Non-classic/Late onset adrenal virilism?
What are 2 symptoms?
Partial 21-hydroxylase deficiency
Precocious puberty
Acne and hirsutism at the time of puberty
What marker is used to diagnose CAH?
What is done at birth to test for it?
Serum 17-hydroxyprogesterone
Heel stick of the baby
What is done for therapy for CAH? (2)
Glucocorticoids - it replenishes cortisol and provides a negative feedback for ACTH suppression (no further overstimulation of androgen production).
May give mineralocorticoids as needed.
What are potential causes of primary adrenal insufficiency? (2)
Secondary adrenal insufficiency? (2)
Primary
- loss of cortical cells
- defect in hormonogenesis
Secondary
- hypothalamic-pituitary disease
- HPA suppression by extra-adrenal steroid source
Primary acute adrenocortical insufficiency is an…
What causes it?
What is a concerning complication?
Adrenal crisis!
Rapid withdrawal of steroids
Massive adrenal hemorrhage (Waterhouse -Friderichsen syndrome)
Relative adrenal insufficiency causes a…
What are 3 changes seen?
Dramatic adrenal crisis!
Hypotension, hyponatremia and hyperkalemia
What adrenal cause might lead to sepsis?
Waterhouse Friderichsen syndrome - N. meningitidis infection
What symptoms would be seen in acute adrenal insufficiency? (6)
Hypotension (refractory to volume repletion) Abdominal pain Fever N/V Hyponatremia Hypoglycemia
What are symptoms of primary chronic adrenocortical insufficiency? (4)
Long duration of malaise, fatigue
Anorexia and weight loss
Joint pain
Hyperpigmentation of skin
How does hyperpigmentation occur as a result of elevated CRH?
CRH stimulates the production of POMC (pre-pro-hormone synthesized in the anterior pituitary) which is then cleaved to make ACTH and MSH.
Which disease is the same as Addison disease?
Primary chronic adrenocortical insufficiency
What was the most common cause of Addison’s disease at the time of its initial description?
What is the most common cause in developed countries now?
Tb
Autoimmune mediated
> 70% of all cases of primary hypoadrenalism in the western world =
Autoimmune adrenalitis - Autoimmune polyendocrine syndrome types 1 and 2
Autoimmune polyendocrine syndrome type 1 is caused by what?
What are the classic symptoms/findings? (6)
Mutation in AIRE gene
APECED
- adrenalitis
- parathyroiditis
- hypogonadism
- pernicious anemia
- mucocutaneous candidiasis (Ab’s against IL-17 and IL-22)
- ectodermal dystrophy
What are the 3 classic symptoms/findings in Autoimmune polyendocrine syndrome type 2?
Adrenalitis
Thyroiditis
T1DM
