Adrenal Pathology Flashcards
What gross reactive changes would be expected in the case of iatrogenic Cushing syndrome from corticosteroid use?
Bilateral adrenal atrophy
What gross reactive changes would be expected in the case of ACTH dependent Cushing syndrome?
Bilateral cortical hyperplasia
Describe the further diagnostic workup of Cushing’s syndrome in the setting of low ACTH
In confirmed hypercortisolism with low ACTH levels, you know it is ACTH-independent aka adrenal Cushing’s
Next step is CT/MRI of abdomen to determine whether there is an adrenal adenoma/carcinoma OR bilateral adrenal hyperplasia
Presentation of primary hyperaldosteronism (Conn’s syndrome)
Typically presents as severe refractory HTN at a young age, confirmed by presence of adrenal mass
Also see hypokalemia and hypomagnesemia
What are some things that can cause secondary hyperaldosteronism?
Diuretic use Decreased renal perfusion Arterial hypovolemia Pregnancy Renin-secreting tumors
[all are things that increase RAAS activity]
Size, age of onset, characteristic histologic feature, and major complication associated with aldosterone-secreting adenoma
May be very small (<2cm)
Young patients (age 30-40)
Histologically may see spironolactone bodies (exist in pts previously treated with this drug)
High incidence of ischemic heart disease!
How do you determine (based on lab workup) whether pt has primary or secondary hyperaldosterone activity?
Check plasma renin activity! — if it is high in the setting of high aldosterone, it is most likely secondary hyperaldosteronism
Pituitary vs. adrenal adrenogenital syndromes
Pituitary: ACTH stimulation of androgens (Cushing disease)
Adrenal: primary adrenal neoplasm (adneoma or carcinoma), congenital adrenal hyperplasia (CAH)
Inheritance pattern of congenital adrenal hyperplasia
Inherited error of metabolism — autosomal recessive!
Congenital Adrenal Hyperplasia (CAH) involves a defective enzyme responsible for steroidogenesis resulting in impaired feedback to the hypothalamus/pituitary, with resultant hyperplasia. 90-95% of CAH cases are caused by a deficiency in what enzyme?
21-hydroxylase
Describe syndrome caused by 21-hydroxylase deficiency
Salt wasting syndrome — complete lack of 21-hydroxylase results in NO mineralocorticoids and NO cortisol
Presents in males and females with hyponatremia, hyperkalemia, and hypotension. Females also show virilization at birth
Long term consequence of adrenomedullary dysplasia (i.e, in the setting of CAH)
Hypotension
Describe pt presentation in the case of a partial lack of of 21-hydroxylase
Some mineralocorticoids and some amount of cortisol, but not enough to prevent ACTH overproduction, so virilization still occurs
Most commonly presents with precocious puberty, and acne and hirsutism at the time of puberty
How is CAH diagnosed?
2 options:
Direct measurement of serum 17-hydroxyprogesterone
ACTH-stimulation test (normally would see response in glucocorticoid production with minimal effect on androgen production; in CAH the opposite occurs)
Tx options for CAH
Glucocorticoids! — replenishes cortisol AND provides negative feedback for ACTH suppression (no further overstimulation of androgen production)
Can give mineralocorticoids as necessary
Primary vs. secondary adrenocortical insufficiency
Primary: loss of cortical cells or defect in hormonogenesis
Secondary: hypothalamic-pituitary disease or HPA suppression by extra-adrenal steroid source
Major causes of primary acute adrenocortical insufficiency
Relative adrenal insufficiency (adrenal crisis)
Rapid withdrawal of steroids
Massive adrenal hemorrhage (waterhouse friderichsen syndrome)
Pathophysiology of exogenous steroid withdrawal
Steroid administration results in suppression of ACTH production by the pituitary through negative feedback
If prolonged, adrenal hypofunction or even atrophy can result
Rapid withdrawal of exogenous steroids results in adrenal insufficiency
Causes of adrenal hemorrhage
Sepsis (Waterhouse Friderichsen syndrome — usually d/t Neisseria meningiditis)
Neonatal period
Trauma
Postsurgical pts
Coagulopathy
Signs/symptoms important in recognizing ACUTE adrenal insufficiency
Hypotension (refractory to volume repletion)
Abdominal pain
Fever
N/V
Hyponatremia
Hypoglycemia
Signs/symptoms of CHRONIC adrenocortical insufficiency
Long duration of malaise, fatigue
Anorexia and weight loss
Joint pain
Hyperpigmentation of skin
What is Addison’s disease and what is the most common cause?
Primary chronic adrenocortical insufficiency
Most common cause used to be tuberculosis, but in developed countries has now shifted to autoimmune etiology
What condition comprises >70% of all cases of primary hypoadrenalism in the western world?
Autoimmune adrenalitis
Gene mutation and clinical features of autoimmune polyendocrine syndrome type 1
Mutation in AIRE gene
Adrenalitis Parathyroiditis Hypogonadism Pernicious anemia Mucocutaneous candidiasis Ectodermal dystrophy
Manifestations of autoimmune polyendocrine syndrome type 2
Adrenalitis
Thyroiditis
Type 1 diabetes mellitus
Presentation of adrenocortical insufficiency
Lack of corticosteroids —> vague malaise, N/V, hypoglycemia, and refractory hypotension
Lack of mineralocorticoids —> hyperkalemia and hyponatremia
Diagnosis of adrenocortical insufficiency
Random cortisol test
ACTH-stimulation test
T/F: the adrenal glands are a common point of metastasis for many types of carcinoma
True
Difference in presentation of adrenal cortical adenomas vs. adrenal cortical carcinomas
Adenomas = incidental on radiography; functional
Carcinoma = incidental on radiography; functional; ALSO show compression/invasion of adjacent structures and are virilizing
The adrenal medulla is comprised of _____ cells deriving from the neural crest and is responsible for ________ secretion under sympathetic control
Chromaffin
Catecholamine (epi/norepi)
Presentation of pheochromocytoma
Pts can present with profound hypertension resulting from catecholamine secretion from the tumor
25% are familial
What is the 10% rule of pheochromocytoma?
10% are extra-adrenal (paraganglioma — zellballen!)
10% are bilateral
10% are in kids
10% are malignant (can only tell by metastasis)
10% are not associated with HTN
Chronic or paroxysmal hypertension is present in >90% of cases of pheochromocytoma. What is the classic triad that also characterizes pheochromocytoma?
Headache
Palpitations
Diaphoresis
Acute vs. chronic complications of pheochromocytoma
Acute = related to catecholamine surges
Chronic = cardiomyopathy
How to diagnose a pheochromocytoma
Urine and plasma metanephrines
Benign tumor affecting the adrenals that is made up of fat and bone marrow that varies in size and can present with hemorrhage
Myelolipoma
Positive functional assays for adrenal incidentalomas
Dexamethasone suppression test for hypercortisolism
Pheochromocytoma
[also show CT enhancement characteristics]
MEN type 1 is caused by a germline mutation in the MEN1 tumor suppressor gene (codes for menin). What are the clinical manifestations of this syndrome?
Primary hyperparathyroidism
Pancreatic endocrine tumors
Pituitary adenomas (lactotroph, somatotroph)
[3 P’s]
note, you can also see duodenal gastrinomas
Mutation and clinical manifestations of MEN type 2A
Germline gain of function mutation in RET proto-oncogene
Clinically:
Pheochromocytoma
Medullary thyroid carcinoma
Parathyroid hyperplasia
Mutation and clinical manifestations of MEN type 2B
Germline gain of function mutation in RET proto-oncogene (specific point mutation)
Clinically:
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal neuromas
Mutation associated with familial medullary thyroid carcinoma
Germline gain of function mutation in RET protooncogene (specific mutations)
Marfan syndrome may be a clue for what type of MEN syndrome?
MEN2B
Describe the pineal gland
Comprised of photoreceptor-containing neural tissue
Responsible for melatonin secretion
Tumors associated with pineal gland
Germ cell tumors
Pineocytoma
Pineoblastoma
