Adrenal Flashcards
Layers of the cortex of the adrenal gland?
G: Zona glomerulosa -Aldosterone F: Zona Fasciculata -Cortisol R: Zone Reticularis -Sex Steroids
Medulla=catecholamines
Endogenous Hypercortisolism
- Paraneoplastic cushing syndrome
-secretion of ectopic acth; mostly by small cell carcinoma of the lung
10% of cases of endogenous cushing syndrome - Primary Adrenal Neoplasms including adenoma carcinoma and rarely hyperplasia
-15-20% of cases of endogenous cushing syndrome
How does Pituitary cushings adrenal cushing paraneoplastic cushings iatrogenic cushings affect the adrenal gland?
Pituitary cushings: adrenal hyperplasia
adrenal cushing: tumor (adenoma or carcinoma) or hyperplasia (diffuse or nodular)
paraneoplastic cushing: adrenal hyperplasia
iatrogenic cushing: adrenal atrophy
Hyperaldosteronism
Primary and secondary causes
- Primary (independent of renin angiotensin system)
- Bilateral idiopathic hyperaldosteronism
- Adrenocortical Neoplasm
- Familial hyperaldosteronism - Secondary (activation of renin angiotensin system)
- Decreased renal artery profusion
- Arterial hypovolemia and edema
- Pregnancy
Hyperaldosteronism clinical manifestations
Hypertension with long term cardiovascular compromise (MI and stroke)
Hypokalemia cuasing neuromuscular manifestation like weakness, paresthesias, visual disturbances and occasionally tetany
Adrenogenital syndromes
Etiology
Primary/Secondary
conditions characterized by structural or biochemical abnormalities of the adrenal cortex which which leads to a disorder of sexual differentiation(adrenal virilism)
Etiology
Primary: adrenocortical neoplasms (usually virilizing carcinoma) or congenital adrenal hyperplasia
Secondary: Pituitary causes (excess secretion of ACTH leading to increased production of adrenal androgens, may be associated with features of cushing syndrome
Congenital Adrenal Hyperplasia
Autosomal recessive
-Defect in the enzyme involved in adrenal steroid biosynthesis, particularly cortisol
- decreased cortisol–increased ATCH
- Adrenal hyperplasia–increased precursor steroids
- increase in synthesis of androgens
- some enzyme defects also impair aldosterone biosynthesis–salt loss
- 21 hydroxylase deficiency is most common CAH defect
Acute adrenal insufficiency in the setting of sepsis (waterhouse-friderichsen syndrome)
- septicemia, usually meninogocci
- hypotension, shock, DIC
- massive bilateral adrenal hemorrhage and destruction
Addison’s Disease
Clinical manifestations
chronic destruction of the adrenal cortex with multiple etiologies leading to hypofunction (usually occurs when 90% of cortex destroyed)
Clinical
Initial progressive weakness and easy fatigability
Gastrointestinal disturbances like anorexia, nausea, vomiting, weight loss and diarrhea
-decreased mineralocorticoids leads to loss of sodium, hyperkalemia, volume depletion and hypotension
-hypoglycemia may occur due to glucocorticoid deficiency
-stress like infection, trauma may precipitate an acute adrenal crisis
Autoimmune adrenalitis
Gross and Histo
Gross: very small glands
cortices markedly thin
Micro
- diffuse atrophy of all cortical zones
- lymphoplasmacytic infiltrate
- medulla is unaffected
Are cushing syndrome and hyperaldosteronism most commonly caused by adenomas or carcinomas?
adenomas
Are virilization neoplasms most commonly caused by adenomas or carcinomas?
carcinomas
Adenomas of the adrenal gland
Gross
Histo
Gross
most are nonfunctional
1-2 cm diameter
yellow to yellow brown cut surface
Histo
Cytoplasm ranges from eosinophilic to vacuolated depending on lipid content
-not much mitotic activity seen
-minor degree of nuclear pleomorphism
Adrenal carcinoma
Rare neoplasm
any age
rare causes include Li-fraumeni sydnrome and Beckwith Wiedemann syndrome
Gross
-large poorly demarcated invasive lesions
cut surface with areas of hemorrhage and necrosis
tendency to invade the adrenal vein, vena cava and lymphatics with regional and distant metastasis
-median survival about 2 years
Histology:
- may be composed of well differentiated cells or bizarre pleomorphic cells
- invasion and metastasis are the most reliable indicators !
Adrenal medulla
Derivation
Cells
Secrete
neural crest derivation
chromaffin cells and their supporting sustentacular cells
-secrete catecholamines
-similar collections of cells distributed throughout the body in the extra adrenal paraganglion system
Pheochromocytoma
neoplasm arising from neuroendocrine cells (chromaffin cells) in the paraganglion system (adrenal medulla/etra-adrenal paraganglion system)
-give rise to surgically correctable form of hypertension
10% rule 10% extra adrenal 10% bilateral 10% malignant 25% being associated with germline mutation
- RET gene (MEN2 and 3)
- NF1
- VHL
- genes SDHB, SDHC, SDHD
Pheochromocytoma Gross and Histology
Gross:
small circumscribed to large hemorrhagic masses
grey tan, focally, congested cut surface
Histology:
ZELLBALLEN!!!!!
nests composed of chromaffin cells surrounded by supporting/sustentacular cells
-rich vascular network
-metastasis is required for definitive diagnosis of malignancy
Clinical features of pheochromocytoma
hypertension-sustained or paroxysms
- headache, sweating, anxiety, tremor
- symptoms caused by release of catecholamines which can precipitate an AMI, CHF, ventricular fibrillation, CVA
- chemical diagnosis****-urinary catecholamine metabolites
1. METANEPHRINE
2. VANILLYLMANDELIC ACID (VMA)
Neurobastoma
Definition: a neoplasm which arises in the adrenal medulla or extra adrenal paraganglion tissue
- one of the most common childhood neoplasms; 90% occur before age 5
- large abdominal mass in child
- younger than 2 years with fever
- older child presents with metastases
Gross
- large bulky tumors
- 25% in adrenal glands
- others arise in the paravertebral regions of the posterior mediastinum and abdomen
Histo:
small, primitive appearing cells with dark nuclei, sheets or rosettes
MEN1
Autosomal dominant 11q13 tumor suppressor gene 3P's 1. Parathyroid 2. Pancreas 3. Pituitary
Most common: primary hyperthyroidism (hyperplasia or adenoma)
Leading cause of death: endocrine tumors of the pancreas-functional tumors metastasize
Pituitary -most commonly has prolactin secreting macroadenomas
MEN2A
Autosomal Dominant Ret protooncogene (10q11.2)
- Thyroid-medullary carcinoma -in virtually all untreated cases in first 2 decades, may b multiple (Calcitonin)
- Adrenal medulla-Pheochromocytoma in 50% of patients though only 10% are malignant (Catecholamines)
- Parathyroid-10-20% have hyperparthyroid (Calcium)
MEN 2B
Spectrum of thyroid and adrenal medullary changes similar to 2A with the following differences:
- Mucosal ganglioneuromatosis and marfanoid habitus are characteristic
- NO parathyroid
-RET mutation-prophylactic thyroidectomy to prevent development of medullary carcinomas
