179b/180b/183b - Adrenal Pathology, Adrenal Medulla, Adrenal Cortex Flashcards
What 3 things regulate aldosterone secretion?
- RAAS
- Hyperkalemia
- ACTH
ACTH stimulates desmolase, the 1st step in aldosterone synth; however, not a primary regulater of aldosterone synthesis
Where do parasympathetic paragangliomas usually arise?
Parasympathetic nerves in the head, neck, and upper mediastinum
“Head and Neck paragangliomas”
Which pharmacologic agent can be used to block glucocorticoid receptors?
Mifepristone
(progesterone receptor/glucocorticoid receptor antagonist)
11-beta-hydroxylase is required to synthesize aldosterone
Why don’t people with 11-beta-hydroxylase deficiency have low blood pressure?
Deoxycorticosterone can activate aldosterone receptors, leading to water and Na+ reabsorption -> hypertension
Deoxycorticosterone is the substrate of 11-beta-hydroxylase in aldosterone synthesis
Which enzyme converts norepinephrine to Epinephrine?
Where is this enzyme found?
Phenylethanolamine N-methyl transferase
ONLY in the adrenal medulla
=> no other organ can secrete epinephrine
Which tumors most commonly metastasize to the adrenal gland? (2)
Renal cancer
Lung cancer
Which genetic syndromes are associated with pheochromocytoma? (3)
- MEN 2
- Von Hippel-Lindau
- NFM-1
A. Zona Fasiculata
- Mifepristone is also a glucocorticoid receptor antagonist
- Cortisol is produced in the zona fasiculata
What tumors are associated with Von Hippel Lindau? (6)
- CNS Hemangioblastoma
- Pancreatic cyts
- Pheochromocytomas
- Retinal angioma
- Renal cysts
- Renal cell carcinomas
The Hippo might need CPPRRR
What tumors are common to MEN-2A and MEN-2B?
How can they be differentiated?
-
Both = medullary tumors
- Medullary thyroid carcinoma
- Pheochromocytoma
- Caused by activating mutation in the RET proto-oncogene
-
MEN-2A
- Parathyroid hyperplasia
- Less severe than MEN-2B
-
MEN-2B
- Marfanoid appearance (Thin face, big lips, tongue nodules)
- Mucosal neuroma
What is the effect on insulin and glucagon secretion of:
- alpha-adrenergic receptor activation:
- beta-adrenergic receptor activation:
- alpha-adrenergic receptor activation: Inhibits secretion
- beta-adrenergic receptor activation: Stimulates secretion
What is the most common adrenal tumor?
Adrenal cortial adenoma
(Benign)
Describe the gross and histological findings of an adrenal cortical adenoma
Like the normal adrenal gland
- Gross: Yellow-ish
- Histological No necrosis, hemorrhage, or mitosis
What cells are ganglioneuromas derived from?
Neural crest cells
- Ganglion cells
- Schwannian stroma
What is the most common caue of isolated hypoaldosteronism?
Hyporeninemic hypoaldosteronism
(Type IV renal tubular acidosis)
What is the name for a catecholamine-producing tumro in the…
Adrenal medulla?
Outside of the adrenal medulla?
- Adrenal medulla: pheochromocytoma
- Produces epinephrine
- Outside of the adrenal medulla: paraganglioma
- Produces norepinephrine
What is the embryonic origin of the adrenal medulla?
Neural crest cells
Describe the characteristics of NFM-1 (5)
- Neurofibroma
- Café-au-lait spots
- Iris harmatoma
- Axillary and inguinal freckling
- Pheochromocytoma in ~2%
What genetic mutation is associated with MEN-2?
How is it inherited?
Germline point mutation in the RET proto-oncogene
Autosomal dominant
Are sympathetic or parasypathetic paragangliomas more likely to be symptomatic?
Sympathetic
Describe the pathological findings of an adrenal cortical carcinoma
- Hemorrhage and necrosis
- Larger; >6.5cm, >100gm
- Invades surrounding tissue
Basically, if it looks abnormal its a carcinoma
What kind of cells are found in the paraganglia of the adrenal gland
Neuroendocrine cells that stain with chromaffin staining
(Similar to adrenal medulla cells)
What genetic mutation ins associated with Von Hippel-Lindau?
How is it inherited?
Mutated vHL gene (tumor suppressor)
Autosomal dominant
What are the layers of the adrenal cortex?
What do they secrete?
- Zona Glomerulosa secretes mineralocoricoids (aldosterone)
- Zona Fasciculata secretes glucocorticoids (cortisol)
- Zona Reticularis secretes androgens (testosterone)
What are the 2 main types of medullary tumors?
-
Pheochromocytoma
- Tumor in the adrenal medulla
-
Paraganglioma
- Tumor in the extra adrenal sympathetic and parasympathetic ganglia
Both tumors arise from chromaffin cells
What cells are neuroblastomas derived from?
Neural crest cells
(Same as ganglioneuroma, but neuroblastoma has characteristic round blue cells and occurs in children)
Is cortical hyperplasia typically unilateral or bilateral?
Bilateral
Which pharmacologic agents can be used to block mineralcorticoid receptors? (2)
Spironolactone
Eplerenone
How do we measure catecholamine levels?
Look for metabolites (metanephrines) in the urine
Cannot directly measure serum levels
What cells are pheochromocytomas derived from?
Chromaffin cells of the adrenal medulla
How does black licorice affect blood pressure
Licorice will increase blood pressure
- Contains glycyrrhizinic acid, which blocks 11-beta-hydroxysteroid dehydrogenase II
- Normally, 11-beta-hydroxysteroid dehydrogenase inactivates cortisol to cortisone
- Inhibition -> more coritosl -> activates aldosterone receptors
- -> Hypertension
What is the defining gross feature of diffuse cortical hyperplasia?
Diffuse, symmetric enlargement of the cortex
(Ex: Congenital adrenal hyperplasia)
What does the adrenal medulla produce?
Catecholamines
- Inside of the medulla = epinephrine
- Contains the enzyme needed to convert NE to Epi
- Extra-adrenal tissue = norepinephrine
Which image shows adrenal cortical carcinoma?
Which shows adenoma?
What are “zellballen”?
What adrenal tumor are they associated with?
Nests of large tumor cells
Pheochromocytoma
Are neuroblastomas benign or malignant?
Malignant
(Small round blue cells)
Which medullary tumor carries the highest risk of malignancy?
Paraganglioma
A patinet is scheduled to have a pheochromocytoma removed in 2 weeks.
What should you give them before the surgery?
- FIRST give alpha blocker (phenoxybenzamine) for 1 week
- Lower BP
- Expand blood volume - Increase Na+, fluid intake
- THEN give beta blocker (propanolol)
Goal is to prevent hemodynamic collapse when the tumor is removed
What are the classic histological findings of neuroblastoma? (2)
Small round blue cells
Homer-Wright Rosettes
Which is the active form: cortisol or cortisone?
Which enzyme converts one to the other?
Cortisol is active
11-beta-hydroxysteroid dehydrogenase
- Type I: activates cortisone to cortisol
- Liver, lung, omental fat
- Type II: inactivates cortisol to cortisone
Where do sympathetic gangliomas usually arise?
- Chromaffin cells of the paraganglia
- Sympathetic chains of the chest
What is the effect of Epinephrine/NE on blood glucose?
Epinephrine and NE -> increased blood glucose
Stimulates gluconeogenesis, glycogenolysis
Which population is associated with neuroblastoma?
Children
Are ganglioneuromas benign or malignant?
Benign
(Also, not hormonally active)
Which pharmacologic agents can be used to block steroidogenesis? (2)
Ketoconazole (blocks demolase, 17,20 lyase, 17-alpha-hydroxylase
Metyrapone (blocks 11-beta-hydroxylase)
What clinical signs/symptoms (altogether) would increase your suspicion for pheochromocytoma or paraganglioma? (5)
- Headaches
- Palpitations
- Diaphoresis
- HTN
- Abdominal pain
Which hormone will be elevated in a patinet with an extra-adrenal pheochromocytoma?
Norepinephrine
Extra-renal pheo = paraganglioma
Which mutation is associated with paraganglioma genetic syndromes?
What is its normal function?
Succinate Dehydrogenase (SDH)
- Component of the mitochondrial electron transport chain complex 2
- Catalyzes the oxidation of succinate -> fumarate in the Krebs cycle
How does cortisol impact red blood cell production?
Cortisol is necessary for RBC production
(but also suppresses all aspects of the immune system)
