Pathology of the adrenals

Question 1

Embryogensis of the adrenals

Answer 1

• Medulla is derived from neuroectoderm
• Cortex is derived from mesoderm
• Cortex tumors are yellow
• Medullary tumors are grey (look like brain tissue)

Question 2

Anatomy of the adrenal

Answer 2

• In a normal adrenal, the medulla is confined to the head and body only, and does not extend into the tail
• Zones (from superficial to deep) of the cortex: GFR
• Glomerulosa: secretes aldo (not dependent on pituitary) in response to activation of RAS
• Fasciculata: secretes GCCs (dependent on ACTH)
• Reticularis: secretes androgens (dependent on ACTH)
• Adrenal medulla secretes epi/NE

Question 3

Enzymatic defects of the adrenals

Answer 3

• Congenital defects in cortisol synthesizing enzymes lead to low cortisol, compensating high ACTH and thus hypertrophy of adrenals (cortex)
• Most common is C-21-hydroxylase deficiency, which may be partial (more common) or severe
• Since cortisol production is limited, there is increased production of other hormones, namely 17-ketosteroids which cause virilization (increased male characteristics)
• Sx are variable (based on age and sex), but often seen in newborn
• Newborn females have intrauterine masculinization resulting in pseudohermaphroditism (gonads normal)
• Newborn males show macrogenitosomia
• May have decreased aldo production which can lead to hyponatremia and hypotension

Question 4

Acute hemorrhagic destruction of adrenals (Waterhouse-friderichsen syndrome)

Answer 4

• Caused by GN sepsis (usually meningococcemia), or burns/hypovolemic shock
• Onset is acute w/ febrile illness followed by circulatory collapse and death
• Present w/ cutaneous ecchymoses as a result of DIC
• Adrenals are enlarged/distorted w/ massive hemorrhage
• Must replace cortisol and pressers as well as Rx underlying cause/DIC (pts are adrenal insufficient)

Question 5

Addison’s disease

Answer 5

• Leads to chronic adrenal insufficiency, may be primary (adrenal destruction) or secondary (hypothalamic/pituitary lesions)
• In 1o addisons there is hyper pigmentation, vitiligo (irregular white patches), electrolyte disturbance (met acidosis, hyperkalemia, hyponatremia) and hypotension
• In 2o addisons there is no hyper pigmentation and no electrolyte disturbances (RAS axis intact since nothing wrong w/ adrenals)

Question 6

Etiologies of primary addison’s

Answer 6

• Autoimmune (75-90%): both sporadic and familial cases, when it occurs w/ hashimoto thyroiditis the condition is Schmidt syndrome
• Infections: TB
• Metastatic CA: usually from lung/breast
• Amyloidosis

Question 7

Myelolipoma and adenoma of adrenal cortex

Answer 7

• Myelolipoma: incidental finding on CT scan or autopsy, are benign mesenchymal tumors of cortex and are ASx
• Adenomas of cortex: usually circumscribed and encapsulated, they must be differentiated from nodules
• Adenomas may be functional and cause a variety of Sxs

Question 8

Primary aldosteronism (Conn syndrome)

Answer 8

• Most of these cortical adenomas are small and yellow
• Micro: solid nests of large, clear, lipid-laden cells which resemble zona fasciculata and sometimes glomerulosa
• Pts have hypokalemia, alkalosis, hypertension, polyuria and polydipsia (all due to excess aldo)

Question 9

Cushing’s syndrome

Answer 9

• Due to excessive GCC release, causes obesity, HTN, striae, amenorrhea/impotence, osteoporosis, hirsutism, red (plethoric) complexion, acne, mental disturbances
• Adenomas are yellow w/ sometime brown mottling, encapsulated (<30g)
• The uninvolved cortex and the contralateral cortex are atrophied due to negative feedback decreasing ACTH
• Clinically most cases are due to exogenous GCCs, can also be due to pituitary adenoma or ectopic ACTH secretion

Question 10

Carcinoma of the adrenal cortex

Answer 10

• Are usually large (200-300g), bulky, yellow and often completely replace the gland
• There may be necrosis and hemorrhage
• Micro: mitoses and vascular invasion, cells are pleomorphic and hyperchromatic
• Most carcinomas are functional, they may produce: aldosteronism, cushing’s syndrome, adrenal virilism, feminism
• These are associated w/ p53 abnormalities and may be seen in pts who also have colon CA and/or pancreatic CA

Question 11

Neuroblastoma

Answer 11

• Most common extra cranial solid tumor in infancy/childhood
• Peak incidence in first 5 yrs of life, tumor is often bilateral and usually in adrenal medulla
• Highly aggressive and malignant, may produce catecholamines
• Amplification of cMyc and poor prognosis
• Micro: closely packed small blue undifferentiated round cells w/ scant cytoplasm and central zone of neurofibrils
• May differentiate into ganglioneuroblastoma or ganglioneuroma
• More likely to calcify than wilms tumor

Question 12

Pheochromocytoma

Answer 12

• Mostly found in adults, causes paroxysmal HTN and hyperglycemia due to catecholamine production/release
• Usually benign and unilateral
• 10% tumor: 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial, 10% in children
• Associated w/ MENII syndromes (IIA/Sipple: pheo + medullary thyroid CA + hyperparathyroid, IIB: pheo + medullary thyroid CA + neurofibromas)
• Pheos are positive for chromaffin rxn (tumor turns brown-black when incubated w/ potassium dichromate)
• Capsular/vascular invasion may occur, malignancy is Dx based on metastases