5. Robbins: Adrenal Glands Flashcards
(131 cards)
1
Q
Adrenal glands are made up of the [adrenal cortex] and the [adrenal medulla].
What are the zones of the adrenal cortex.
A
Capsule
- Zona glomerulosa => mineralcorticoids (aldosterone); SALTY
- Zona fasiculata => glucocorticoids (cortisol); SWEET
- Zona reticularis => sex steroids (estrogens and androgens); SEX
Medulla
GO FIND REX; MAKE GOOD SEX
2
Q
Adrenal glands are made up of the [adrenal cortex] and the [adrenal medulla].
What cells are in the adrenal medulla.
A
Chromaffin cells => catecholamines (mainly EPI)
3
Q
Syndromes of Adrenal Hyperfunction
A
- 1. Cushings Syndrome
- 2. Hyperaldosteronism
- 3. Adrenogenital or Virulizing Syndromes
4
Q
Vast majority of Cushings syndrome is due to what?
A
Iatrogenic Cushings Syndrome = exogenous glucocorticoid administration
5
Q
MCC of endogenous hypercorticolism?
A
ACTH-secreting pituitary adenomas (Cushings Disease)
6
Q
What are the causes of Hypercorticolism (Cushings Syndrome)?
A
-
Primary Hyperadrenalism (ACTH-independent)
- Adrenal adenoma
- Adrenal carcinoma
-
Secondary Hyperadrenalism (ACTH-dependent)
- ACTH pituitary adenoma
- Ectopic ACTH-secreting tumor
7
Q
What are ectopic ACTH-secreting tumors that cause Cushings syndrome?
A
- Small cell lung cancer *
- Pancreatic cancer
- Neural tumors
8
Q
Cushings Syndrome => hypercortisolism
What is the effect on the adrenal glands in ACTH-dependent causes of Cushings Syndrome (Cushings disease or ectopic ACTH-producing tumor)?
A
[Bilateral Cortical Hyperplasia]
9
Q
Bilateral atrophic adrenal glands would be expected in which variant of Cushing Syndrome?
A
“Iatrogenic” Cushing Syndrome = administration of exogenous glucocorticoids
10
Q
What are the serum levels of cortisol and ACTH like in adrenal adenomas/carcinomas?
A
- ↑↑↑ serum cortisol
- ↓↓↓ serum ACTH
11
Q
What are the serum levels of cortisol and ACTH like in ACTH-dependent causes of hypercortisolism?
A
- - ↑↑↑ serum cortisol
- - ↑↑↑ serum ACTH
12
Q
Morphological Changes in the Pituitary Gland in Hypercorticolism
A
- Pituitary change occur no matter the cause.
- 1. Crook hyaline change = high levels of endogenous or exogenous glucocorticoids cause the basophilic cytoplasm of ACTH-producing cells => homogenous and pale due to accumulation of intermediate keratin filaments in cytoplasm.
13
Q
Morphological Changes in the Adrenal Glands in Hypercortisolism
A
- Changes depend on cause;
- 1. Cortical atrophy
- 2. Diffuse hyperplasia
- 3. Macronodular or micronodular hyperplasia
- 4. Adenoma / carcinoma
14
Q
What causes bilateral cortical atrophy of the adrenal glands?
A
Exogenous glucocorticoids;
- Zona fasiculata and reticularis => atrophy because they are not stimulated
- Zona glomerulosa => NL thickness because does not respond to ACTH
15
Q
What is macronodular hyperplasia of the adrenal glands?
A
Adrenal glands are replaced with nodules (< 3 cm) with lipid-poor + lipid-rich cells; areas between nodules have micronodular hyperplasia
16
Q
What is micronodular hyperplasia of the adrenal glands?
A
1-3mm darkly pigmented (brown/black) micronodules made up of lipofuscin with atrophic intervening areas.
17
Q
Both benign and malignant adrenocortical adenomas are more common in which sex and age range?
A
Women in their 30s - 50s.
18
Q
What is a major morphological difference between adrenocortical adenomas and adrenocortical carcinomas?
A
- Adenomas: yellow, smaller (less than 30 gm), / thin- or well-developed capsules
- Carcinomas: MUCH large ( >300 gm), UNencapsulated masses
19
Q
How can we determine the cause of Cushings Disease?
A
Measure:
- 1. Serum ACTH
- Measure urinary steroid excretion after administration of dexamethasone.
20
Q
Results of dexamethasone suppresion test for a patient with Cushings Disease (pituitary microadenoma)?
A
- ACTH is elevated
-
Low dose dexamethasone test = ACTH not supressed
- No reduction in urinary excretion of 17-hydroxycorticosteroids
-
High dose dexamethasone test = ACTH suppressed
- Reduction in urinary excretion of 17-hydroxycorticosteroids
21
Q
Which cause of Cushing Syndrome will have elevated levels of ACTH which is completely insensitive to low or high doses of exogenous dexamethasone?
A
Ectopic ACTH-producing tumors
22
Q
Results of dexamethasone suppresion test for a patient with Cushing Syndrome caused by an adrenal tumor?
A
ACTH is low
- Low dose dexamethasone test = ACTH not supressed
- High dose dexamethasone test = ACTH not suppressed
*
23
Q
Hypercortisolism causes selective atrophy of fast-twitch myofibers resulting in what clinical manifestations?
A
- Decreased muscle mass
- Proximal limb weakness
24
Q
Results of dexamethasone suppresion test for a patient with Ectopic ACTH secretion?
A
ACTH is high
- Low dose dexamethasone test = ACTH not supressed
- High dose dexamethasone test = ACTH not suppressed
25
What does **aldosterone** do?
**Retain Na+** =\> **retain BV/BP.**
26
**Causes of _Primary_ Hyperaldosteronism**
How does it affect RAAS system?
1. **Primary Hyperaldosteronism:** ↑ aldosterone =\> supress RAAS (+)
1. _Bilateral Idiopathic hyperaldosteronism \*\*\* MC_
2. _Neoplasm_
* Aldosterone- secreting adenoma (Conn Syndrome)
* Adrenocorticocarcinoma
3. _Glucocorticordiod-remediable hyperaldosteronism_
27
**Causes of _Secondary_ Hyperaldosteronism**
Things that **(+) RAAS system** =\> **↑ plasma renin** =\> **↑ aldosterone**
1. Diuretic use
2. ↓ renal perfusion
3. Arterial hypovolemia and edema
4. Pregnancy (estrogen ↑ plasma renin)
5. Renin-secreting tumors
28
MC manifestation of **primary hyperaldosteronism** is \_\_\_\_\_\_\_\_\_\_.
**High BP**
29
**Primary Hyperaldosteronism** due to **Conn's syndrome** causes what:
1. **Adrenal mass (solitary aldosterone-secreting adenoma) + HTN**
2. **Severe** HTN (\>160/100 mmHg)
3. HTN at a **young age (30-40 YO)**
4. **Refractory** HTN
5. **Hypokalemia and hypomagnesia**
30
What is the _most common_ underlying cause of **primary hyperaldosteronism** and what is seen morhphologically in the adrenal glands?
- **Bilateral idiopathic hyperaldosteornism (IHA)**
- Characterized by **bilateral nodular hyperplasia** of adrenal glands
31
Germline and somatic mutations of which gene are present in **familial idiopathic hyperaldosteronism** and some **aldosterone-secreting adenomas?**
**KCNJ5** encoding a **K+ channel**
32
What is **glucocorticoid-remediable hyperaldosteronism?**
Rare cause of **primary _familial_ hyperaldosteronism** and due to:
* **[ACTH-responsive _CYP11B1_ gene promoter]** controlling **[_CYP11B2_ (gene encoding aldosterone synthase) on Chr 8]**
* ACTH =\> (+) production of _aldosterone synthase_ =\> ↑ aldosterone
33
In **glucocorticoid-remediable hyperaldosteronism** what is the function of ACTH?
ACTH =\> **(+) production of aldosterone synthase** =\> ↑ aldosterone
34
In **glucocorticoid-remediable hyperaldosteronism,** bc aldosterone production is controlled by ACTH, how can this production be suppressed?
Suppressible by **dexamethasone**
35
What can cause **decreased renal perfusion** =\> **2º Hyperaldosteronism?**
1. **Renal artery stenosis**
2. **Arteriolar nephrosclerosis**
↓↓↓ BF kidney =\> think entire body needs to ↑↑↑ BF =\> + RAAS, even though BP is fine.
36
What can cause **arteriolar hypovolemia and edema =\> 2º hyperaldosteronism?**
1. **CHF**
2. **Cirrhosis**
3. **Nephrotic Syndrome**
37
How does activity of the **RAAS** and levels of **renin** differ between **primary** and **secondary hyperaldosteronism?**
- **Primary**= suppression of RAAS and ↓ renin
- **Secondary** = activation of RAAS and ↑↑↑ renin
38
Morphology of **Bilateral Idiopathic Hyperplasia**
**Diffuse** and **focal hyperplasia** of cells in **zona granulosa**
**- Wedge shaped:** extend from [periphery =\> center].
39
**Gross Morphology** of **Alderone-producing Adenomas** (Conns Syndrome)
* **Well-cicumscribed**, **solitary**, **small** (\<2 cm) and buried within the gland (**not visibly enlarged)**
* **Bright yellow** and resemble **lipid-laden fasciculata cells** (more than glomerulosa)
* More often on **L** adrenal gland.
40
What is a characteristic histological feature of **aldosterone-secreting adenomas**?
**Spironolactone bodies=\>** _Eosinophilic_, _laminated cytoplasmic inclusions_
41
Patients with **aldosterone-secreting adenoma** have a HIGH incidence of \_\_\_\_\_\_\_\_\_\_
**Ischemic Heart Disease**
42
Pt presents with **HTN**: we want to **evaluate for hyperaldosteronism.**
How do we diagnose?
**1. Stop taking meds t**hat affect plasma renin and aldosterone.
**2. Measure plasma renin and aldosterone.**
* ↑↑↑ ratios of plasma aldosterone: renin activity (↑ ALD; ↓ renin) =\> 1º Hyperaldosteronism
* =\> If +: confirm with a [aldosterone supression test]
* ↑↑↑ plasma aldosterone AND renin (↑ ALD; ↑ renin) =\> 2º Hyperaldosteronism
43
Tx for _primary hyperaldosteronism_ caused by an **adenoma** vs. **bilateral hyperplasia?**
* - **Adenomas** =\> surgically resect
* **- Bilateral hyperplasia** =\> Aldosterone ANT (Spironolactone)
44
Causes of **Adrenogenital Syndromes (Adrenal Virulization)**
**_Pituitary causes:_**
* ACTH stimulation of androgens (Cushings disease)
**_Adrenal gland causes:_**
* Primary adrenal neoplasms (adenoma or carinoma)
* Congenital adrenal hyperplasia (CAH)
45
What is the most common cause of _adrenal virulization_ due to a _primary adrenal neoplasm?_
**Carcinoma**
46
**Androgen-secreting adrenal carcinomas** often secrete what other hormone?
**Cortisol** and are known as "**mixed syndromes"**
47
What is **CAH (Congenital Adrenal Hyperplasia)?**
* Group of **AR** **inherited errors of metabolism** that cause a _deficiency/total lack_ of _enzymes_ involved in _making cortical steroids,_ particulary cortisol.
1. Steroid precursors build-up behind the defective step =\>
2. Channeled into other pathways =\>
3. ↓ production of gluco/mineralcorticoids & ↑ production of androgens =\> **virulization**.
4. Impaired feedback to hypothalamus/pituitary =\> **hyperplasia**.
48
What enzyme is most commonly deficient in **CAH (congenital adrenal hyperplasia)?**
**21-hydroxylase** **(dt mutation in CYP21A2)**
## Footnote
* Thus, only thing adrenal gland can produce are the _sex steroids_. _↓ of cortisol_ means that the pituitary continues to _produce ACTH, resulting in ↑ sex steroids_. This **cycle** is responsible for the virilization seen in this syndrome.
* 17-hydroxyprogesterone (17-OHP) will spike however.
49
**21-hydroxylase deficiency** can cause what syndromes?
Most common\*\*\*?
* **1. Classic salt-wasting syndrome** (complete lack)
* **2. Simple virilizing syndrome** (partial lack)
* **3. Non-classic/late-onset adrenal virilism** (partial lack) \*\*\*\*
50
**_Salt-Wasting Syndrome_**
* Enzyme activity
* Levels of glucocorticoids/mineralcorticoids/androgens
* Symptoms and M/W
**_Salt-Wasting Syndrome_**
* **Complete lack** of 21-hydroxylase
* **No** mineralcorticoids and glucocortiods (cortisol); **↑ androgens**
* _Symptoms in M/W_
* No mineralcorticoids:
* 1. **Salt-wasting (=\> hyponatremia), hyperkalemia (↑ K+)**
* 2. Acidosis, **Hypotension** =\> seize, CV defects, death
* In F =\> virulization is present at birth.
51
How does the presentation of **salt wasting syndrome** differ in males vs. females at birth?
**- Females present EARLIER:** d/t easily recognizable virilization at birth
- **Males** dx **5-15 days after birth** due to some salt-losing crisis
52
Patients w/ **_severe_ salt-wasting 21-hydroxylase deficiency** what can happen?
**↓ cortisol** & **adrenomedullary dysplasia** (developmental defects of medulla) =\>
* ↓ catecholamine secretion =\>
* **HYPOtension & circulatory collapse**
53
**Simple Virilizing Adrenogenital Syndrome (**_without salt wasting_)
* Enzyme activity
* Levels of glucocorticoids/mineralcorticoids/androgens
* Symptoms and M/W
* Partial lack of 21-hydroxylase
* **Some mineralcorticoids** and **small cortisol,** but _not enough to prevent ACTH overproduction_; ↑ androgens (testosterone)
* Genital ambiguity (virilization) at a _later age._
54
Most common form = **Nonclassic/late-onset adrenal virilism**
* Enzyme activity
* Levels of glucocorticoids/mineralcorticoids/androgens
* Symptoms and M/W
* **Partial** lack of 21-hydroxylase
* Some gluco/mineral; increase androgens
* Symptoms in M/W
* Virtually **asymptomatic**
* **Mild manifestations** (_Precocious puberty,_ _acne_ and _hirsutism_ @ puberty)
55
**Morphological Change** in **_all_** cases of Congenital Adrenal Hyperplasia (CAH)
**BILATERAL hyperplastic**; some times ↑↑↑ 10-15x normal weights
56
57
Pt's with **CAH** are **treated** with what?
1. **Exogenous glucocorticoids:** replenishes levels AND ↓ ACTH levels via negative feedback
2. **Mineralocorticoid supplementation** given in salt-wasting variants
58
2 ways of diagnosis of **CAH**
1. ↑↑↑ **Serum 17-hydroxyprogesterone**
2. **ACTH-stimulation test:** no ↑ in glucorticoids/cortisol, but ↑ in 17-OHP.
59
In what case is **Serum 17-hydroxyprogesterone** the highest? Lowest?
* Highest = classic congenital adrenal hyperplasia
60
What is mandated thoughout the US and EXTREMELY important for diagnosing bbs with CAH, who were not ID'd through family history?
**Heel stick test**
61
What is **Adrenocortical Insufficiency?**
Decrease in the ability of the adrenal cortex (**hypofunction**) to produce steroids, especially cortisol. Can be primary or secondary causes,.
62
**Amyloidosis**, **sarcoidosis**, and **hemochromatosis** may all lead to what type of adrenal dysfunction?
**Primary adrenocortical insufficiency**
63
**_Primary_ Adrenocortical Insufficiency**
1. **Loss of adrenal cortical tissue (or steroid producing cells)**
2. **Problem making hormones**
64
**_Secondary_ Adrenocortical Insufficiency**
1. Hypothalamic - pituitary disease
2. Exogenous steroids suppress HPA axis
65
**Primary _acute_ adrenocortical insufficiency** occurs in what clinical settings?
Causes adrenal crisis in:
1. - Pt with **chronic adrenocortical insufficiency,** who encounter stress that causes rapid ↑ in steroid production, but adrenals cant.
2. - In patients **on exogenous steroids**, where acute stress causes **rapid withdrawl of steroids** or **failure to ↑ dose** & atrophied adrenals can't respond well.
3. - **Massive adrenal hemorrhage,** occurring in _newborns_ after long/difficult delivery; pt's on _anticoagulant therapy who develop DIC_; and in _Waterhouse-Friderichsen Syndrome_
66
If patient is taking e**xogenous corticosteroid**s, what happens to adrenals?
**Atrophy**
67
What is **Waterhouse-Friderichsen Syndrome** characterized by?
1. **Bacterial infection** (often due to Neisseria meningidits) =\> **sepsis** (rapidly progressing hypotension =\> shock) =\>
2. **DIC** + **purpuric rash**=\>
3. **Massive bilateral adrenal hemorrhagic necrosis** and **primary acute adrenocortical insufficiency**
4. =\> adrenals become **"sacs of clotted blood"**
68
Which 5 bacterial species may be associated with **Waterhouse-Friderichsen Syndrome?**
1. **- N. meningitidis**
2. - H. influenzae
3. - Pseudomonas
4. - Pneumococci
5. - Staphylococci
69
**Histological examination** of the **adrenals** in **Waterhouse-Friderichsen syndrome** show hemorrhage that starts where and then travels how?
Starts within **medulla** near thin-walled venous sinusoids =\> peripherally into **cortex**, often leaving islands of recognizable cortical cells
70
What are 6 signs/sx's that should raise suspicion of **acute adrenal insufficiency?**
1. **- HYPO**tension (refractory to volume repletion)
2. - **HYPO**natremia/ **_hyper_**kalemia
3. - **HYPO**glycemia
4. - Abdominal pain
5. - Fever, N/V
71
90% of all cases of **primary _chronic_ adrenocortical insufficiency (Addison's Disease)** can be attributed to one of what 4 disorders?
1. **- Autoimmune adrenalitis**
2. - Tuberculosis
3. - AIDS
4. - Metastatic cancers
72
Most common cause of **primary _chronic_ adrenocortical insufficiency** in _developed_ countries?
**Autoimmune adrenalitis** (APS1 or APS2)
73
Most common cause o*f* **primary _chronic_ adrenocortical insufficiency** _worldwide_?
**Tuberculosis** ---\> Autoimmune
74
Primary _Chronic_ Adrenocortical Insufficiency (Addison’s Disease) **Symptoms**
1. **Joint pain**
2. **No appetite (weight loss)**
3. **Malaise** / **fatigue**
4. **Hyperpigmentation** (due to ACTH → **αMSH**)
75
**_Autoimmune polyendocrine syndrome type 1 (APS1)_**
* Mutations:
* Affects what organs:
* Causes:
Mutation in the **AIRE on Chr 21q22** that affects the [adrenals, parathyroid, gonad and blood] causing
1. Adrenalitis
2. Parathyroiditis
3. **Hypo**gonadism
4. Pernicious anemia
76
What is **APECED?**
Autoimmune PolyEndocrinopathy, **Candidiasis** and **Ectodermal Dystrophy** (APECED):
When **ASP1** + **mucocutaneous candidiasis** (Ab against IL-17/22) and **ectodermal dystropgy**
77
What is **Ectodermal dystrophy**?
Abnormalities of **skin**, **dental enamel,** and **nails**
78
**Autoantibodies against** which _2 cytokines_ seen in autoimmune polyendocrinopathy syndrome type 1 (APS1) _are the reason for chronic mucocuntaneous infections?_
**IL-17** and **IL-22**
79
When does **autoimmune polyendocrine syndrome type 2 (APS2)** usually develop and what are the characteristic findings?
- **Early adulthood**
- [**Adrenal insufficiency (adrenalitis**) + **AI thyroiditis _OR_ Type 1 DM**]
80
Which 3 infectious agents may cause **primary _chronic_ adrenocortical insufficiency**?
1. **TB** used to be most common cause
2. **Histoplasma capsulatum**
3. **Coccidioides immitis**
81
**AIDS** patients are at ↑ risk for developing **adrenal insufficiency** from what?
- **CMV** and **Mycobacterium avium-intracellulare**
- **Noninfectious** (**Kaposi** Sarcoma)
82
**Metastatic neoplasms** that affect the adrenals and causing **adrenocortical insufficiency** most often arise from which 2 sites; what are some other sites which may be implicated?
- **Lungs** and **breast** **cancer** = most common
- May also be from [GI cancers, malignant melanoma, and hematopoietic neoplasms]
83
What are **2 genetic causes** of adrenal insufficiency?
1. **- Congenital adrenal hypoplasia (CAH)**
2. **- Adrenoleukodystrophy (X-linked recessive)**
84
When does typically **Addisons Dz** begin?
Initial signs and symptoms?
* Insidiously and not until levels of glucocorticoids/mineralcorticoids are VERY low.
* Progressive weakness and easy fatigability
85
What are the signs/sx's of **primary chronic adrenocortical insufficiency** as a result of corticosteroid and mineralocroticoid deficiency?
* ↓ corticosteroids --\> vague malaise, N/V, **hypo**glycemia, and refractory **hypo**tension
* ↓ mineralocorticoids --\> **hyper**kalemia and **hypo**natremia
86
What is the gross morphology and histology of the adrenal glands in **primary autoimmune adrenalitis?**
1. - Irregularly SHRUNKEN glands
2. - Scattered residual cortical cells in collapsed network of CT w/ a variable lymphoid infiltrate of the cortex
87
Which type of inflammatory reaction will be seen in the adrenal glands affected by **tuberculosis** and **fungal disease**?
**Granulomatous inflammation**
88
Which type of **adrenocortical insufficiency** is associated with _hyperpigmentation_ of the skin and which is not?
- **Primary chroinc adrenal disease (Addisons)** = hyperpigmentation
- Adrenocortical insufficiency caused by _primary pituitary_ or _hypothalamic disease_ will **not**
89
Dx **Adrenocortical Insufficiency**
* **1. Random cortisol test**
* **2º:** deficient cortisol and androgens; normal or near-normal synthesis of aldosterone
* **2. ACTH stimulation test**
* **1º:** ↓ response to exogenous ACTH
* **2º:** prompt ↑ in plasma cortisol levels
90
How does the presentation of **adrenal carcinomas** differ from that of **adenoma**?
**_SIZE_** tells us.
## Footnote
- **Adenoma** = solid and yellow; vaculoated neoplastic cells d/t intracytoplasmic lipids
- **Carcinomas** = heterogenous and red; larger (\> 200 gm) and produce mass
effect causing compression/invasion of adjacent structures; more likely to be virulizing
91
How do are **adrenal carcinomas** and **adenomas** SIMILAR??
* Both are often **incidental finding** on radiograpgy or autopsy
* Both are more often **functional**
92
When are **adrenal adenoma** and **carcioma** more common in?
Equally common in adults.
Carcinoma more likely in kids.
93
**Functional** and **nonfunctional** adrenocortical neoplasms **CANNOT** be distinguished from one another based on \_\_\_\_\_\_\_\_.
**Morphology**
94
**Adrenocortical carcinomas** have a strong tendency to invade which structures?
1. **- Adrenal vein**
2. **- Vena cava**
3. - **Lymphatics** ---\> _regional_ and _periaortic_ nodes = common
95
Distant _hematogenous_ spread by **adrenocortical carcinomas** to where is common; what is the prognosis of these neoplasms?
- **Lungs** and other viscera
- Median pt survival = about **2 years**
96
Which is more common: **primary adrenocortical carcinomas** or **metastases to the adrenal cortex**?
**Metastases** (esp bronchogenic origins)
97
ADRENAL ADENOMA or ADRENOCORTICAL CARINOMA?
**Adrenocortical carcinoma:**
1. Well differented cells like in adenomas =\> bizarre giant cell
2. Marked anaplasia
98
ADRENAL ADENOMA or ADENOCORTICAL CARCINOMA
1. **Vaculoated** and **eosinphilic** neoplastic cells d/t **intracytoplasmic lipids**
2. **Mild** nuclear pleomorphism
99
Which 2 familial cancer syndromes are associated with a predisposition for developing **adrenocortical carcinomas**?
1. **- Li-Fraumeni syndrome**, due to germline TP53 mutations
2. **- Beckwith-Wiedemann syndrome,** a disorder of epigenetic imprinting
100
If **cortical** and **medullary neoplasms** undergo **necrosis** and **cystic degeneration** =\> may present as \_\_\_\_\_\_\_\_\_\_\_.
**"Nonfunctional cysts"**
101
**Adrenal myelolipomas** are unusual _benign/malignant_ lesions composed of what?
* Size?
* How do they preent?
**benign: fat + bone marrow/HSC**
* _Vary_
* With _hemorrhage_
102
What cells make up the **adrenal medulla**?
Neural crest (neuroendocrine) cells callled **Chromaffin cells** + **sustacular** (supporting) **cells**.
103
**_Adrenal Medulla_**
* Under ______ control
* Most important diseases of the adrenal medulla:
* **Sympathetic**
* **Pheochromacytomas (neoplasm of chromaffin cells)** + neuroblastic tumors
104
What are **Pheochromocytomas**?
Rare neoplasms made up of **chromaffin cells (**which make and release catecholamines NE and EPI) & **sometimes peptide hormones**, often presenting with surgically correctable **_HTN_**.
105
What is the _dominant clinical manifestation_ of **pheochromocytomas** and what is the _classic triad_?
* **- HTN (\>90%)** which can be either *chronic* or *paroxysmal*
* - **Triad** = HA + Palpitations + Diaphoresis
106
**Acute** and **Chronic** complications with Pheochromocytomas
**Acute**: CHF, MI, CVA, Pulmonary edema, Ventricular fibrillation
**Chronic**: Catecholamine cardiomyopathy
107
What is the **10% rule** associated with **Pheochromocytomas** (5 of them)?
* - 10% are **extra-adrenal (paraganglioma)**
* - 10% are **bilateral**
* - 10% in **kids**
* - 10% are **malignant**
* - 10% are **NOT associated with HTN**
108
\_\_\_\_\_% of **pheochromocytomas** have _germline mutations_ and are _familial_.
**25%**
109
**3 groups** of **extra-adrenal paraganglia** based on anatomic distribution
* **1. Branchiomeric**
* **2. Intravagal**
* **3. Aorticosympathetic**
110
**4 familial syndromes** associated with **pheochromocytomas** and **extra-adrenal paragangliomas**
1. **MEN-2A**
2. **MEN-2B**
3. **NF-1**
4. **Von Hippel-Lindau (VHL)**
111
How does the patient **presentation** and **location** of **pheochromocytomas** in pt's with _familial pheochromcytoma_ (d/t germline mutations) differ from that of _sporadic types_?
Pts with **familial** mutations are:
1. **Younger**
2. **Bilateral disease**
112
H**istological pattern** in **pheochromocytomas**
1. **Nests (zellballen)** of polygonal to spindle-shaped **chromaffin** or **chief cells** surrounded by **sustentacular cells**, supplied by **rich vascular network**
2. **Granular cytoplasm t**hat contains catecholamines
113
What stains can we use to view **cytoplasm** and **sustenacular cells** in a **pheochromacytoma**?
* Cytoplasm (catecholamines) = **silver stain**
* Sustentacular cells = **antibodies against S-100**
114
* Which histological feature of pheochromocytomas reliably **predicts clinical behavior?**
* What is the **definitive diagnosis of malignancy** in pheochromocytomas based on?
* **Nothing** histologically predicts clinical behavior.
* ONLY on presence of **metastasis**
115
What is the laboratory diagosis of **pheochromocytomas** based on?
↑ urinary excretion and plasma free **catecholamines** + their **metabolites** i.e., _vanillylmandelic acid_ and _metanephrines_
116
What 3 features of **adrenal incidentalomas** impact the appropriate managment of the mass?
1. - **SIZE**: \>4cm = more likely to be carcinoma
2. **- Positive functional assays**: i.e., dexamethasone suppression test for hypercortisolism or urinary metanephrines for pheochromo.
3. **- CT enhancement characteristics**
117
What is **MEN syndrome**?
Group of inherited diseases that results in [**hyperplasia**, **adenoma** and **carcinomas**] of **multiple endocrine organs**
118
How do endocrine tumors due **MEN syndromes** differ from their sporadic counterparts in terms of age, organs involved, behavior, and foci?
* - Tend to occur at **younger age**
* - Arise in **multiple** endocrine organs, **either synchronously or metachronously**
* - Typically **preceded** **by** asymptomatic stage of **hyperplasia** pre-cursor lesions
* - Even in one organ, tumors are often **multifocal and bilateral**
* - Are usually **more aggressive** and **recur**
119
_**MEN1 (aka \_\_\_\_\_)**_
* Mutation
* Causes what? (in order of MC)
* **Werner Syndrome**
* Germline mutation in **MEN1 (Menin)** tumor supressor
* **3 Ps:**
1. **Primary _hyper_parathyroidism** (parathyroid adenoma or primary parathyroid hyperplasia)
2. **Pancreatic endocrine tumors** (Insulinoma, Gastrinoma, Somatostatinoma, Glucagonoma, VIPoma, also DUODENAL gastrinomas, as well as pancreatic gastrinomas)
3. **Pituitary adenomas** (prolactinoma = MC)
120
What is the **_initial manifestation_** of **MEN 1** in most patients, appearing in almost all patients by **_40-50 YO?_**
**Primary hyperparathyroidism**
121
Which tumors of **MEN-1** are th_e **leading cause of morbidity**_ and **_mortality_** due to their aggressiveness and metastases?
**Pancreatic endocrine tumors**
122
What is the most frequent **pituitary adenoma** encountered in **MEN-1**?
**Prolactinoma (lactotroph);** may also see somatotroph adenoma (GH) =\> acromegaly
123
What is the most common site of **gastrinomas** present in pt's with **MEN-1?**
**Duodenum**; may also have synchronous duodenal + pancreatic tumors
124
**_MEN-2A (aka)_**
* Mutation:
* Triad:
* **Sipple Syndrome**
* Germline **GOF** in the **RET proto-oncogene on** _Cr. 10_q11.2
* **Triad (3 C's)**
1. _Medullary thyroid cancer_ =\> ↑ calcitonin
2. ****_Pheochromocytoma_ =\> ↑ catecholamines
3. _Parathyroid hyperplasia_ =\> ↑ calcium (hypercalcemia) and kidney stones
125
1. Which tumor is seen in almost **100%** of patients with **MEN-2A?**
2. **Medullary thyroid carcinoma** in **MEN-2A** are usually ____ and are virtually always associated with what?
1. _Medullary thyroid cancer_
1. _Multifocal_; _C-cell hyperplasia in the adjacent thyroid_
126
**_MEN-2B_**
* Mutation
* Causes
_Point mutation_ in _RET gene_
**Causes**
1. _Pheochromocytomas_
2. _Medullary thyroid cancer_ (multifocal and more aggressive)
3. _Mucosal neuromas_ (in mouth, eyes, respiratory/GI tract)
4. _Marfainoid habitus_
127
**Familial medullary thyroid cancers** are a variant of MEN-2A; how are they different?
* - Develop at an **older age**
* **- No other clinical manifestation** assoc. w/ MEN-2A
* - Typically follow a more **indolent** course
128
About **1/3** of **_sporadic_** **medullary thyroid carcinomas** have the identical point mutation of RET encountered in MEN-2B and follow what type of course?
More aggressive disease and adverse prognosis
129
Diagnosis via screening of at-risk family members for which MEN syndrome is important?
**MEN-2A** due to medullary thyroid carcinoma being life-threatening, and can be prevented by prophylactic thyroidectomy
130
The pineocytes of the pineal gland are epithelial cells with what 2 functions?
Photosensory and neuroendocrine functions
131
Majority of tumors arising in the pineal gland are of what type?
- Germ cell tumors i.e., germinomas, embryonal carcinomas; choriocarcinomas and mixtures of the 2
