Endocrine Pathology: Adrenal Gland

Question 1

Adrenal Cortex Hyperfunction

1. AKA
2. symptoms are caused by

Answer 1

1. Cushing’s syndrome

2. chronic excess of cortisol (glucocorticoids)

Question 2

Adrenal Cortex Hyperfunction

1. Caused by? (4) Give examples

Answer 2

1. exogenous sources of glucocorticoid therapy used over a long period of time (most common)
2. pituitary or hypothalamic sources with hypersecretion of ACTH (basophilic adenoma, endogenous sources more common in young women)
3. Ectopic production of ACTH by nonendocrine tumor (small cell carcinoma of the lung, endoogenous source more common in middle age men)
4. Primary pathology of adrenal cortex causing excess secretion of cortisol independent of ACTH (rare compared to the other causes)

Question 3

Adrenal Hyperfunction

1. What does exogenous cortisol do to adrenal cortex?
2. What does an ACTH producing pituitary adenoma do to the adrenal cortex?
3. What does an ectopic source of ACTH do to adrenal cortex?

Answer 3

1. cortical atrophy
2. bilateral diffuse or nodular hyperplasia of the cortex
3. cortical hyperplasia

Question 4

Adrenal Hyperplasia

1. What can occur besides growth?
2. Histo look
3. Gross look of an adenoma
4. Gross look of a carcinoma
5. Histo look of adrenal carcinoma

Answer 4

1. pigmentation due to lipofusion
2. loses holes that are lipid producing cells
3. yellow mass (due to cholesterol), rest of adrenal gland is OK and may be functioning;
4. large, hemorrhagic, looks infiltrative
5. marked anaplasia

Question 5

Adrenal Hyperplasia: Clinical manifestations

1. What happens to glucocorticoids?
2. Other symptoms

Answer 5

1. increased glucocorticoids (w/ or w/o increased ACTH depends on pathogenesis)
2. central obesity, moon faces, plethora (hypervolemia), loss of muscle mass, weakness, fatigability, acne, hirsutism, menstrual abnormality, hyperglycemia (diabetes), hypertension, osteoporosis, skin striae, easy bruisability, poor wound healing, psychosis

Question 6

Primary Hyperaldosteronism

1. Define
2. Etiology (2)
3. Who gets the second one?

Answer 6

1. condition characterized by excess secretion of cortical aldosterone independent of renin-angiotensin system
2. Bilateral idiopathic cortical hyperplasia (60%);
   Conn’s syndrome- solitary adenoma of the cortex (35-40%); females>males; 30-40 y/o

Question 7

Primary Hyperaldosteronism: Clinical Manifestations

1. What happens to aldosterone and renin?
2. What happens to serum sodium and extracellular fluid volume?
3. What happens to serum potassium?
4. other symptoms

Answer 7

1. increased aldosterone, decreased renin
2. increased serum sodium, increased extracellular fluid volume
3. decreased serum potassium
4. HTN, weakness, parathesias, visual disturbances

Question 8

Secondary Hyperaldosteronism

1. What happens to aldosterone and renin?
2. Why?

Answer 8

1. both are increased

2. renal ischemia –> renin release –> aldosterone release

Question 9

Androgenital Syndromes

1. Define
2. Etiologies (2)

Answer 9

1. conditions characterized by structural or biochemical abnormalities of the adrenal cortex which leads to a disorder of sexual differentiation
2. Adrenal cortical carcinoma/adenoma secreting excess androgen
3. defect of enzyme involved in synthesis of cortical steroids; different syndromes develop based on which enzyme is deficient; usually autosomal recessive

Question 10

21 hydroxylase deficiency

1. What is it a type of?
2. What does the enzyme usually do?
3. What happens when it is missing?
4. When does it present in females?
5. When does it present in males?
6. What happens to actual cortical glands?

Answer 10

1. adrenogenital syndrome
2. converts progesterone to deoxycortisone (which is later converted into cortisone)
3. deficiency of aldosterone and salt wasting, decreased production of cortisol;
   shift in steroidogenesis in favor of increased androgen production
4. at birth due to ambiguous genitalia
5. harder to tell, a few days after birth when baby becomes dehyrdated
6. bilateral cortical hyperplasia due to increased ACTH

Question 11

21 hydroxylase deficiency/ Androgen secreting adenoma: Clinical Manifestations (2)

Answer 11

1. Virilism

2. Salt loss- depending on enzyme deficiency

Question 12

Adrenal Cortex Hypofunction: Primary Acute Adrenocortical Insufficiency

1. Define
2. Usually caused by?
3. 2 Other causes

Answer 12

1. sudden significant loss of corticosteroids necessary to maintain normal metabolic homeostasis or inability to respond immediately with enough corticosteroids to meet metabolic demand
2. physicians w/ rapid withdrawal of steroids when a pt’s adrenals have been suppressed by long term steroid therapy
3. Destruction of the adrenal gland (Waterhouse-Friderichsen syndrome)
4. insufficient levels of steroids to meet a crisis or stress in a pt with chronic cortical insufficiency

Question 13

Waterhouse-Friderichsin Syndrome

1. What is the underlying cause?
2. What happens?
3. What is the usual cause?

Answer 13

1. Septicemia, usually meningococci
2. Hypotension, shock, DIC —> massive bilateral adrenal hemorrhage and destruction
3. Neisseria meningitis

Question 14

Primary Chronic Adrenal Cortical Insufficiency: Addison’s Disease

1. Define
2. Etiologies (4)
3. Pathology

Answer 14

1. chronic destruction of the adrenal cortex leading to hypofunction (90%) destroyed
2. Autoimmune adrenalitis (70%; Autoimmune polyendocrine (APS) type 1; APS type 2; isolated autoimmune adrenalitis (polygenic)
3. TB
4. AIDS
5. Metastatic Cancer, especially lung, stomach, and breast
6. Varies with etiology

Question 15

Primary Chronic Adrenal Cortical Insufficiency: Addison’s Disease

1. What happens to cortisol? ACTH? what happens to 17-ketosteroids and 17-hydroxycorticoids in urine?
2. What happens to sodium? chloride? HCO?, glucose? serum potassium?
3. Other symptoms
4. Why does the skin become hyperpigmented?

Answer 15

1. decreased cortisol, may have increased ACTH; 17-keto/17-hydroxy in urine decrease
2. decrease in Na, Cl, HCO3, and glucose, increase serum Potassium
3. hyperpigmentation of skin, hypotension, weakness, fatigability, anorexia
4. MSH is released along with ACTH, used as a precursor for melanocytes

Question 16

Secondary Adrenocortical Insufficiency

1. Define
2. Etiology (2)

Answer 16

1. hypoadrenalism caused by a reduction in ACTH levels

2. Prolonged steroid therapy (most common); multiple causes including pituitary or hypothalamic destruction

Question 17

Secondary Adrenocortical Insufficiency: Clinical Manifestations

1. What happens to ACTH? cortisol? androgens? mineralocorticoids?
2. What happens when exogenous ACTH is given? What does this tell you?
3. Is there hyperpigmentation? why?

Answer 17

1. decreased ACTH, cortisol, and androgens; normal mineralocorticoids
2. cortisol rises; tells you that this is secondary (does not occur in primary)
3. no; melanotropic hormone is low along with low levels of ACTH (they are released together)

Question 18

Pheochromocytoma

1. Define
2. Where do they occur?
3. Malignant or benign? How do you tell?
4. Are most sporadic or related to a disorder? What disorders?

Answer 18

1. neoplasm arising from neuroendocrine cells (chromaffin cells) in the paraganglion system (adrenal medulla/extra-adrenal paraganglion system)
2. 85-90% arise in adrenal medulla
3. could be either or; tell by malignancy
4. most are sporadic, 25% occur due to MEN syndrome or familial paragangliomas 1,3, and 4 (mutations in succinate dehydrogenase complex enzymes)

Question 19

Pheochromocytoma: Clinical Manifestations

1. Symptoms (5)
2. What causes symptoms?
3. How is it diagnosed?
4. What familial syndromes is it found in?

Answer 19

1. HTN (sustained or in paroxysms), headache, sweating, anxiety, tremor
2. release of catecholamines which can precipitate an AMI, CHF< ventricular fibrillation, CVA
3. chemical diagnosis; evaluation of urinary catecholamine metabolites including metanephrine (from epi) and vanillymandelic acid (VMA, from NE)
4. MEN type II or IIA, MEN type III or IIB, von Hippel-Lindau, von Recklinghausen, Sturge-Weber, SDH syndromes

Question 20

Neuroblastoma

1. Define
2. Gross look; where does it arise?
3. Micro look
4. Who gets it?
5. How does it present?

Answer 20

1. neoplasm which arises in the adrenal medulla or extra-adrenal paraganglion tissue
2. large bulky tumors; 25% in adrenal glands, others in paravertebral regions of the posterior mediastinum and abdomen
3. small, primitive appearing cells w/ dark nuclei in sheets or Homer-Wright rosettes
4. one of the most common childhood neoplasms; 90% occur before 5 y/o
5. large abdominal mass in a child younger than 2 years w/ a fever; older child presents with metastases

Question 21

Multiple Endocrine Neoplasia Syndromes

1. Define
2. What do you get in MEN 1?
3. MEN IIa?
4. MEN IIb?
5. Mutant gene locus in MEN I
6. Mutant gene locus in MEN II

Answer 21

1. MENs are inherited conditions (autosomal dominant) which are characterized by multiple endocrine neoplasms
2. parathyroid, pancreas, pituitary, adrenal and thyroid lesions
3. medullary thyroid carcinoma, pheochromocytoma
4. medullary thyroid carcinoma, pheochromocytoma, mucocutaneous ganglioneuromas
5. MEN I (tumor suppressor gene)
6. RET (proto-oncogene)