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Adrenal gland pathology

Terms in this set (81)

Name all pathologies of Adrenal cortex:
-Hypercortisolism (Cushing syndrome)
-Adrenal insufficiency
-Acute adrenocortical insufficiency
-Chronic adrenocortical insufficiency (Addison disease)
Cushing syndrome is also called ________________ .

Cushing disease is also known as __________________.
Hypercortisolism

Primary hypthalamic-pituitary disease associated with hypersecretion of ACTH
Etiology of Cushing syndrome:
-Due to any disorder that produces elevation in glucocorticoid levels
<4 reasons>
1. administration of exogenous glucocorticoids (iatrogenic)
2. Primary hypothalamic-pituitary disease associated with hyper-secretion of ACTH
3. Secretion of ectopic ACTH by nonpituitary neoplasms
4. Primary adrenocortical neoplasms (adenoma, carcinoma), rarely cortical hyperplasia
What is the most COMMON cause for Cushing syndrome?
Administration of EXOGENOUS glucocorticoids (Iatrogenic)
Consequences of administration of exogenous glucocorticoids (e.g. Prednisone) :
-Leads to bilateral adrenal ATROPHY
-Cortisol low (adrenal atrophy), but glucocorticoids are HIGH due to exogenous administration
-ACTH is depressed
________________ accounts for 70% of cases of ENDOGENOUS Cushing syndrome.

________________ accounts for 15~20% of cases of ENDOGENOUS Cushing syndrome.
"Primary hypothalamic-pituitary disease associated with hypersecretion of ACTH" (pituitary cushing)

Primary adrenocortical neoplasia or hyperplasia (Adrenal cushing)
Who gets Pituitary Cushing syndrome (Cushing disease)?
-FEMALES > M (4:1)
-20~30 yo
Etiology of Cushing DISEASE (one associated with hypersecretion of ACTH by hypothalamus / pituitary) :
(problem at the level of hypothalamus & pituitary)

-COMMONLY due to ACTH-producing microadenoma (Adenoma so small that it doesn't have mass effects in the brain- no impinging)
-Rarely due to excessive ACTH release by hypothalamic CRH-producing tumor
Primary hypothalamic-pituitary disease associated with hypersecretion of ACTH is usually due to an ACTH-producing _______________.
Microadenoma
Consequence of Pituitary Cushing syndrome:
-Bilateral adrenal cortical HYPERPLASIA (due to elevated ACTH)
-Cortisol is elevated
-ACTH is elevated

(tumors in hypothalamus or anterior pituitary bombards adrenal cortex with ACTH)
Cushing syndrome due to exogenous vs. endogenous glucocorticoids :
<Exogenous >
-Bilateral adrenal atrophy
-Cortisol low
-ACTH depressed

<Endogenous >
-Bilateral adrenal cortical hyperplasia
-Cortisol elevated
-ACTH elevated
Etiology of Ectopic ACTH secretion by nonpituitary neoplasms:
-Commonly due to small cell carcinoma of LUNG
-carcinoid tumor or medullary carcinoma of THYROID

(e.g. some lung cancers can make ACTH on its own)
Consequence of Ectopic ACTH secretion by nonpituitary neoplasms:
-Bilateral cortical HYPERPLASIA
-ACTH is elevated
-Cortisol is elevated

(ACTH coming from lung or thyroid tumor drives the cortisol level UP)
Which type of Cushing syndrome is the RAREST?
Paraneoplastic Cushing syndrome
Consequence of Primary adrenocortical neoplasia or hyperplasia:
(Either a neoplasia or hyperplasia at the adrenal gland)
-Adenoma or carcinoma (>>> bilateral adrenal hyperplasia- rare)
-Cortisol is elevated
-ACTH is depressed

(whether it's adenoma/ carcinoma or hyperplasia, there's increased level of CORTISOL → produces negative feedback → ACTH depressed)
Cushing syndrome caused by administration of EXOGENOUS glucocorticoids is called _________________.

Cushing syndrome caused by primary hypothalamic-pituitary disease is called _________________.

Cushing syndrome caused by secretion of Ectopic ACTH by Non-pituitary neoplasms

Cushing syndrome caused by primary adrenocortical neoplasms
Iatrogenic Cushing syndrome

Pituitary Cushing syndrome

Paraneoplastic Cushing syndrome

Adrenal Cushing syndrome
<Cushing syndrome>
-2 cases in which increase in Cortisol doesn't produce negative feedback on ACTH :
1. Primary hypothalamic-pituitary disease associated with hypersecretion of ACTH
2. Secretion of ectopic ACTH by nonpituitary neoplasm (e.g. lung cancer)

(ACTH constantly being replenished by the tumors)
When Ectopic ACTH is secreted by nonpituitary neoplasm,
-Cortisol is (elevated/ depressed)
-ACTH is (elevated/ depressed)

When there's the primary adrenocortical neoplasia/ hyperplasia,
-Cortisol is (elevated/ depressed)
-ACTH is (elevated/ depressed)
Elevated
Elevated

Elevated
Depressed
Clinical features of Cushing syndrome:
(Develops gradually and may be quite SUBTLE in early stages)
-Hypertension
-Weight gain
-Redistribution of adipose tissue (Truncal obesity, moon facies, buffalo hump)
-Decreased muscle mass & limb weakness
-Hyperglycemia, glucosuria, polydipsia
-Cutaneous striae
-Easy bruising
-Osteoporosis (↑ fracture)
-Hirsutism, menstrual abnormalities
-Mental disturbances
________________ disease cause Hyperglycemia.

________________ disease cause Hypoglycemia.
Cushing syndrome

Addison disease
What is the clinical presentation you see in this picture?

What disease is associated with this?
Cutaneous striae (stretch marks)

Cushing syndrome
Explain how Cushing syndrome results in hyperglycemia, glucosuria, and polydipsia:
-Hyperglycemia due to gluconeogenesis
-glucosuria due to inhibition of glucose uptake by cells → excreted
-Polydipsia because hyperglycemia depletes intracellular water → increased thirst
________________ disease cause Hypertension .

________________ disease cause Hypotension.
Cushing syndrome
& Pheochromocytoma

Addison disease
Why does muscle mass decrease and limbs become weak in Cushing syndrome?
Due to atrophy of MYOFIBERS.
Name 3 clinical manifestation of Cushing syndrome related to Redistribution of adipose tissue:
1. Truncal obesity
2. Moon facies
3. Buffalo hump
2 main Etiologies of Adrenal insufficiency:
-Primary adrenal disease (primary hypoadrenalism)
-Decreased stimulation of adrenals due to deficiency of ACTH at the level of pituitary (secondary hypoadrenalism)
Secondary hypoadrenalism :
Decreased stimulation of adrenals resulting from deficiency of ACTH
Addison disease is when adrenal insufficiency is caused by (primary/ secondary) hypoadrenalism and this becomes (acute/ chronic)
Primary ;
CHRONIC
(Adrenal crisis/ Addison disease/ both ) can be FATAL.
BOTH
When primary adrenal disease is ACUTE it's called __________________

When primary adrenal disease is CHRONIC it's called __________________
Adrenal crisis

Addison disease
Etiologies of ACUTE adrenocortical insufficiency:
-Waterhouse-Friderichsen syndrome (rare)
-Sudden withdrawal of long-term corticosteroid therapy (atrophic adrenal glands)
-STRESS (e.g. surgery) induced in patients with underlying chronic adrenal insufficiency (atrophic adrenal glands)
______________ disease cause weight GAIN

______________ disease cause weight LOSS
Cushing syndrome

Addison disease
Waterhouse-Friderichsen syndrome is caused by _______________.

This syndrome is associated with which adrenal disease?
massive sepsis due to Neisseria meningitidis

Acute Adrenocortical insufficiency
In patients with Atrophic adrenal glands, the glands cannot ________________.
produce adequate amounts of glucocorticoids
Addison disease is also referred to as _________________.
Chronic adrenocortical insufficiency
4 common Etiologies of Addison disease:
-Autoimmune adrenalitis
-Infections
-Acquired immune deficiency syndrome (AIDS)
-Metastatic cancers

→→all cause destruction of adrenal cortex
________________ is when there's a progressive destruction of adrenal cortex.
Addison disease
What is the most COMMON cause of primary adrenal insufficiency?
Autoimmune adrenalitis
(autoimmune destruction of steroid-producing cells in adrenal cortex)
Infection by which organisms commonly destroy adrenal cortex and cause Addison disease?
-Tuberculosis (most common)
-Fungi: Histoplasmosis + coccidiomycosis
When Addison disease is caused by Metastatic neoplasms, most cases are metastasized from WHERE?
Lungs + Breast
What causes Addison disease in AIDS patients?
-Cytomegalovirus infection
-Mycobacterium infection
-Kaposi sarcoma
Clinical features of Addison disease:
-90% of adrenal cortex must be destroyed before clinical manifestations appear
-Progressive weakness + fatigue
-Vomiting, weight loss, diarrhea
-Hyperpigmentation of skin + mucous membranes (esp. Nipples, areolae, perineum)
-STRESS (infections, trauma, surgical procedures) may precipitate acute adrenal CRISIS → (intractable vomiting, abdominal pain, hypotension, coma, vascular collapse, and death)
Before any other findings, what is one of the EARLIEST clinical findings you'll see in Addison disease?
Bronzing of the skin
___________% of adrenal cortex must be destroyed before clinical signs start appearing.
90%
Addison disease patients get hyperpigmentation of skin b/c increased level of __________________ stimulate ________________.
ACTH ;
melanocytes

(when low level of Cortisol signals pituitary to make more ACTH, melanocytes can also be stimulated)
Where are the common regions of hyperpigmentation in Addison disease patients?
-Nipples
-Areolae
-Perineum

(Areas where it's not sun-exposed on daily basis)
Lab features of Addison disease:
-Hyperkalemia
-Hyponatremia
-Hypotension
-Hypoglycemia
In Addison disease:
-(hypokalemia/ Hyperkalemia)
-(Hypoglycemia/ hyperglycemia)
-(Hypotension/ Hypertension)
-(Hyponatremia/ Hypernatremia)
Hyperkalemia
Hypoglycemia
Hypotension
Hyponatremia
In Addison disease, the decreased _______________ results in K+ (retention/ loss) and Na+ (retention / loss)
Aldosterone
Retention ;
Loss

(loss of sodium ions → leads to water loss too → hypotension)
Explain why Addison disease can result in hypoglycemia:
There's no glucocorticoids to signal the LIVER to break down glycogen and promote gluconeogenesis → impaired gluconeogenesis → low glucose
Pheochromocytoma is a (benign/ malignant) tumor
BENIGN
(except the 10% which are malignant)
Pheochromocytoma is a neoplasm of _______________, composed of ______________ cells, which are derived from _______________.
Adrenal MEDULLA

Chromaffin cells
Neural crest
Pheochromocytoma causes sudden, sustained ________________
Hypertension ***

(b/c the body is being bombarded with catecholamines)
________________ causes sudden, sustained HYPERTENSION
Pheochromocytoma
Pheochromocytoma synthesize and release _______________.
Catecholamines (epinephrine, norepinephrine) + other peptide hormones
***"Rule of 10's" in Pheochromocytoma:
1. 10% arise in extra-adrenal site (carotid body)
2. 10% are bilateral
3. 10% are malignant
4. 10% are NOT associated with hypertension
"25% Rule" in Pheochromocytoma:
25% harbor a germ-line mutation and arise in associated with familial syndrome

(The other 75% are isolated findings, no family predilection)
When the Pheochromocytoma arise in Extra-adrenal site (carotid body), it's called __________________.
Paraganglioma
10% of pheochromocytoma that are MALIGNANT are usually in those tumors arising in ________________.
Extra-adrenal sites
25% of pheochromocytoma arise from ___________________.

List 3 examples:
Familial syndrome
(25% harbor a germ line mutation)

-MEN-2A and 2B
-Neurofibromatosis type 1
-Von Hippel-Lindau disease
Clinical features of Pheochromocytoma:
-Abrupt or sudden elevation in BP
-Tachycardia, palpitations, headache
-Sweating, tremor
-Chest pain, nausea, vomiting
-Sudden release of catecholamines may precipitate congestive heart failure, pulmonary edema, and myocardial infarction
What serious complications can be result from Pheochromocytoma ?
-Congestive heart failure
-Pulmonary edema
-Myocardial infarction
Lab features of Pheochromocytoma:
Increased URINARY catecholamines
1) Vanillylmandelic acid
2) epinephrine
3) norepinephrine
If a patient is suspected of Pheochromocytoma, physician is going to order which lab test?
Urinary catecholamines
(Vanillylmandelic acid, catecholamines)
Multiple endocrine neoplasia syndromes are characterized by __________________ (3).
-Hyperplasia
-Adenoma
-Carcinoma
of multiple endocrine organs
_______________ is the only cause of HYPERTENSION that can be cured very quickly.
Pheochromocytoma

(tumor that cause hypertension but can simply be treated by surgical excision)
Multiple endocrine neoplasia syndromes occur at (younger/ older) age than sporadic tumors.

Multiple endocrine neoplasia syndromes are (more/less) aggressive and have (higher /lower) recurrence rate than sporadic tumors.
younger

More ; Higher
Multiple endocrine neoplasia syndromes:
-1) Hyperplasia 2) adenoma 3) Carcinoma of multiple endocrine organs
-arise in MULTIPLE endocrine organs either synchronously or metachronously (but will eventually have all 3 AT THE SAME TIME)
-Often MULTIFOCAL, even in ONE organ
-usually preceded by asymptomatic stage of endocrine hyperplasia
-More AGGRESSIVE and higher recurrence rate than sporadic tumors.
When Multiple endocrine neoplasia syndromes involve HYPERPLASIA, it's usually preceded by _______________
ASYMPTOMATIC stage
MEN Type 1 :
-Parathyroid (primary hyperparathyroidism)
-Pancreas (leading cause of death)
-Pituitary (prolactin-secreting adenoma)

(PPP)
MEN type 1 tumor in ________________ gland is the leading cause of DEATH.
Pancreas

(tumors in pancreas often functional - elaborate hormones)
MEN Type 2A:
-thyroid (medullary carcinoma)
-Adrenal medulla (pheochromocytoma)
-Parathyroid (primary hyperparathyroidism)

(TAPa)
About 50% of patients with MEN Type 2A will have _______________.
Pheochromocytoma
Primary hyperparathyroidism is found in MEN Type (1/ 2A/ 2B)
Type 1 + Type 2A
Etiology of MEN Type 1, 2A, 2B:
Autosomal dominant inheritance
MEN Type 2B:
-Thyroid (medullary carcinoma)
-Adrenal medulla (pheochromocytoma)
-Extraendocrine manifestations (mucosal ganglioneuroma, marfanoid habitus)

(TAEx)
How to treat Men type 2A and 2B:
-Prophylactic thyroidectomy
to prevent carcinoma
-Get evaluated for RET protooncogene.
(all patients with MEN 2A and 2B carry RET protooncogene mutation)

(Whether patients have medullary carcinoma or not, they must have thyroid gland taken out, b/c medullary carcinoma can KILL them.)
ALL patients with MEN2A and 2B carry _____________ mutation
RET(rearranged during transfection) protooncongene mutation
Compare the medullary carcinoma of thyroid in MEN type 2A vs. MEN type 2B:
One caused by MEN TYPE 2B is MORE AGGRESSIVE than in MEN2A.
2 Extra-endocrine manifestations of MEN type 2B:
-Mucosal ganglioneuromas - nerve cell tumors on mucosa (esp. mouth)
-Marfanoid habitus - long, tall extremities
What is the clinical significance of MEN Type 2B?
MEDULLARY CARCINOMA of thyroid

(if thyroid glands are not prophylactically taken out, they can die of this)
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