Pathology Review

Question 1

Endocrine / Neuroendocrine

Answer 1

a. Paracrine:
- Release / Transport: Local
- Action: Local cells
- Example: Cytokines

b. Synaptic:
- Release / Transport: Local
- Action: Local neuron/muscle
- Example: Neuromuscular
junction

c. Endocrine / Neuroendocrine:
- Release / Transport: into capillary
- Action: remote
- Names used interchangably

d. Architecture
• Nested
• Ribbon-like / trabecular

e. Cytology
• Nucleus
• Monomorphic (minimal variability)
• “Salt-and-pepper” chromatin
• Cytoplasm
• Granular to vacuolated
(granularity=neurosecretory vesicles)

Question 2

Thyroid

Answer 2

a. Divided into lobules, each composed of 20-40 follicles

b. Follicles
• Follicular cells: cuboidal to low columnar epithelium
• Colloid: thyroglobulin (iodinated precursor of active
thyroid hormone)

c. Under influence of TSH, thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T4) and lesser amounts of triiodothyronine (T3)

d. C-cells (aka parafollicular cells)
• Synthesize and secrete calcitonin

Question 3

Diffuse hyperplasia (Graves disease)

Answer 3

a. Most common cause of endogenous hyperthyroidism
b. F&raquo_space; M
c. Peak incidence 20 to 40 years
d. Association with HLA-DR3

e. Triad of manifestations:
• Thyrotoxicosis – diffusely enlarged hyper-functioning thyroid
• Infiltrative ophthalmopathy with resultant exophthalmos (~40%)
• Localized infiltrative dermopathy (pretibial myxedema) (minority of cases)

f. Breakdown of self-tolerance to thyroid autoantigens (most importantly TSH
receptor) –> multiple autoantibodies:
• Thyroid-stimulating immunoglobulin (TSI) —> binds TSH receptor –> hormone
release —> thyrotoxicosis
• Thyroid-growth-stimulating immunoglobulins (TGI) —> epithelial proliferation
• TSH-binding inhibitor immunoglobulins (may actually inhibit thyroid cell
function - may explain why sometimes spontaneous episodes of
hypothyroidism)

Question 4

Diffuse hyperplasia (Graves disease)

Autoantibodies

Answer 4

a. Breakdown of self-tolerance to thyroid autoantigens (most importantly TSH
receptor) –> multiple autoantibodies:

b. Thyroid-stimulating immunoglobulin (TSI) —> binds TSH receptor –> hormone
release —> thyrotoxicosis

c. Thyroid-growth-stimulating immunoglobulins (TGI) —> epithelial proliferation

d. TSH-binding inhibitor immunoglobulins (may actually inhibit thyroid cell
function - may explain why sometimes spontaneous episodes of
hypothyroidism)

Question 5

Diffuse hyperplasia (Graves disease)

Clinical Findings
*important slide

Answer 5

a. Infiltrative ophthalmopathy
1. Lymphocytic infiltration of retro-orbital space (T-cells)
2. Inflammatory edema / swelling of extraocular muscles
3. Accumulation of extracellular matrix components (e.g. hydrophilic
glycosaminoglycans)
4. Increased number of adipocytes

b. Infiltrative dermopathy (pretibial myxedema)
1. Deposition of glycosaminoglycans
2. Lymphocyte infiltration

Question 6

Chronic lymphocytic (Hashimoto) thyroiditis

Answer 6

a. Most common cause of hypothyroidism in iodine-sufficient areas of the world
i. F&raquo_space; M
ii. Peak incidence: 45 to 65 years

b. Gradual thyroid failure from autoimmune destruction of thyroid gland
c. Breakdown in self-tolerance to thyroid autoantigens

d. Anti-thyroid antibodies
• Anti-thyroglobulin
• Anti-thyroid peroxidase
• Anti-microsomal

e. Genetics: increased susceptibility with
polymorphisms in immune regulationassociated genes
• CTLA4 (cytotoxic T lymphocyte-associated antigen-4)
• PTPN22 (protein tyrosine phosphatase-22)

Question 7

Chronic lymphocytic (Hashimoto) thyroiditis

Histology

Answer 7

• Diffuse, symmetrically enlarged
gland

• Mononuclear inflammatory
infiltrate (lymphocytes) +/-
germinal center formation

• Atrophic follicles with oncocytic
metaplasia

Question 8

Other thyroiditis…

Answer 8

a. Subacute granulomatous (de Quervain) thyroiditis
i. Triggered by viral infection (usually history of URI)
ii. Self-limited, painful

b. Riedel thyroiditis (IgG4 related disease)
i. Fibrosing inflammatory process; extends beyond capsule into surrounding tissue
ii. Fibrosis, lymphoplasmacytic infiltrate (enriched with IgG4 plasma cells), obliterative phlebitis
iii. Hard/fixed mass clinically – can simulate a thyroid neoplasm

Question 9

Diffuse and multinodular goiter

Answer 9

a. Goiter = abnormal growth of thyroid gland
i. Endemic (iodine deficient) or sporadic
ii. Impaired synthesis of thyroid hormone–> compensatory ↑ TSH–> hypertrophy and
hyperplasia of follicular cells and gland enlargement

iii. Functional outcome: normal, decreased or increased thyroid hormone production
• Euthyroid - increased mass overcomes hormone deficiency
• Hypothyroid - can’t overcome impairment (or congenital biosynthetic defect)
• Hyperthyroid - hyperfunctioning (toxic) nodule (~10%)

b. FNA if rapid growth, pain, unusual firmness in one area, U/S detected nodules with
indeterminate or suspicious features

c. Risk of malignancy in long-standing goiters low (but not zero)

Question 10

Follicular adenoma

Answer 10

• Benign neoplasm derived from follicular epithelium
• Usually solitary
• Circumscribed proliferation of follicles with well-defined, intact capsule

• Majority nonfunctional although small percentage produce thyroid hormones
(so-called toxic adenoma)

• NOT usually precursor of follicular carcinoma

Question 11

Follicular carcinoma

Answer 11

a. 5-15% of thyroid carcinomas
b. Diagnosis based on capsular OR vascular invasion
c. Architecture = sheets of follicles

d. No special nuclear features
• No PTC nuclear features allowed
• If PTC nuclear features, instead classified as PTC, follicular variant

e. 10-year survival:
• Minimally invasive (>90%)
• Widespread capsular and vascular invasion (~50%)

Question 12

Papillary thyroid carcinoma

Answer 12

a. Most common thyroid cancer (>85% of thyroid carcinoma)
b. Solitary or multifocal

c. Diagnosis based on nuclear features:
• Nuclear clearing
• Nuclear pseudoinclusions
• Nuclear grooves

d. Architecture classically papillary (with fibrovascular cores) but may also be follicular (among
many other variants); cribriform-morular variant associated with FAP

e. Psammoma bodies / calcifications common
f. Local lymph node metastasis = common; 10-year survival ~98%; Bad prognostic indicators: elderly, distant metastasis (not just local nodes), invasion into adjacent soft tissue

Question 13

Anaplastic carcinoma

Answer 13

a. <5% of thyroid carcinomas
b. Highly aggressive malignancy with extensive infiltration of soft tissues
c. Majority patients older with history of thyroid disease
d. Approximately quarter with history of well-diff. thyroid carcinoma (e.g. PTC, FC) and another quarter with concurrent well-diff. thyroid carcinoma in resection specimen
e. Presents as rapidly enlarging neck mass
f. Aggressive local growth and compromise of vital neck structures
g. Median survival - ~ 3 months

Question 14

Medullary carcinoma

Answer 14

a. 5% of thyroid carcinomas
b. Nests / trabeculae of neuroendocrine cells (fine, stippled chromatin)
c. Amyloid (calcitonin-derived)

d. Genetics :
• Sporadic – RET activating mutations (70-80%)

• Familial (MEN-2A, 2B) – RET

• More often multifocal
• Often associated with C-cell hyperplasia
• Prophylactic thyroidectomy

Question 15

Parathyroid

Answer 15

a. Derived from developing pharyngeal pouches that also give rise to thymus

b. Located in close proximity to upper and lower poles of right and left thyroid
lobes (also anywhere along path of descent of pharyngeal pouches)

c. Activity of parathyroid glands controlled by level of free (ionized) calcium in
bloodstream

d. Parathyroid hormone effects:
• Increased renal tubular reabsorption of calcium
• Increased urinary phosphate excretion (lowering serum phosphate levels)
• Increase conversion of vitamin D to active dihydroxy form in kidneys
(increased GI calcium absorption)
• Enhanced osteoclastic activity (bone resorption)

e. Cellular components
• Chief cells (PTH hormone production)
• Oxyphil cells

f, Cellularity (variable – age, body habitus and health status play a role)
• ~75% cellularity
• ~25% stromal adipose

Question 16

Parathyroid - HYPERparathyroidism

Answer 16

a. Primary Hyperparathyroidism (95% sporadic; 5% familial)

b. Symptoms
• Asymptomatic (MAJORITY)
• Other: Fractures, nephrolithiasis, cardiac disease, depression, etc.
-also possible GI isssues for “Groans:

Question 17

Parathyroid - Adenoma

Answer 17

a. Definition: Single gland disease cured long term after excision of abnormal gland

b.  Other
• Single abnormal gland and three other
pathologically documented normal
glands
• Single abnormal gland fulfilling IOPTH
criteria post-excision

c. Enlarged (average 500 mg)

d. Hypercellular nodule (+/- capsule with rim of normal)
• Chief cell
• Oxyphil

e. Pattern subtypes
• Follicular
• Lipoadenoma

Question 18

Parathyroid - Hyperplasia

Answer 18

a. Definition: Multi-gland disease
• Synchronous or metachronous (can be reason for surgical failure)
• Equal four gland involvement rare (2-3 glands)
• Usually large glands (combined weight ~1000 mg)

b. Enlarged, hypercellular (sometimes encapsulated)

Question 19

Parathyroid

Adenoma VS Hyperplasia = Clinical distinction

Answer 19

Path sign out
• Enlarged, hypercellular parathyroid gland
• Size: __ cm
• Weight: __mg

Question 20

Parathyroid - Carcinoma

Answer 20

a. RARE

b.  Clinical presentation
• Ca2+ >14 mg/dL (Ref range: 8.6 – 10.3 mg/dL)
• PTH > 5x normal
• Palpable mass
• Adherent to surrounding tissue

c.  Definitive pathologic criteria
• Metastasis (but rare)
• Angiolymphatic invasion
• Perineural invasion
• Invasion into surrounding structures (thyroid, skeletal muscle, vessel walls)
• Extension through capsule

d. Histology
• Larger than adenomas (2000 – 10000 mg)
• Firm/fibrous tan white
• Often adherent to surrounding tissue (e.g. thyroid)

e. Prognosis Typically indolent disease
• Outcome based on age, completeness of excision, and presence of metastases
• Major morbidity and mortality from uncontrolled hypercalcemia

f. Mutation of HRPT2 (CDC73) tumor suppressor gene (chromosome 1, parafibromin) implicated in pathogenesis of parathyroid carcinoma
• HPT-JT (hyperparathyroidism-jaw tumor syndrome): AD, ossifying fibromas of jaw, cystic renal lesions, uterine tumors, parathyroid neoplasia (~15% develop
carcinoma)

• Sporadic parathyroid carcinoma

Question 21

Parathyroid - Carcinoma

Prognosis and Genetics

Answer 21

a. Typically indolent disease
b. Outcome based on age, completeness of excision, and presence of metastases
c. Major morbidity and mortality from uncontrolled hypercalcemia

d. Mutation of HRPT2 (CDC73) tumor suppressor gene (chromosome 1, parafibromin) implicated in pathogenesis of parathyroid carcinoma
• HPT-JT (hyperparathyroidism-jaw tumor syndrome): AD, ossifying fibromas of jaw, cystic renal lesions, uterine tumors, parathyroid neoplasia (~15% develop
carcinoma)

• Sporadic parathyroid carcinoma

Question 22

Adrenal cortical hyperfunction (hyperadrenalism)

Answer 22

1. Cushing syndrome (excess of cortisol)
2. Hyperaldosteronism
3. Adrenogenital or virilizing syndromes (excess androgens)
   • Bilateral hyperplasia adrenal cortex

Question 23

Cushing syndrome (hypercortisolism)

Answer 23

ACTH DEPENDENT
1. Cushing Disease
• Pituitary Adenoma (70-80%)
• Rarely pituitary hyperplasia
• Leads to adrenal hyperplasia, nodular
2. Ectopic corticotropin syndrome (e.g. ACTH-secreting small cell carcinoma)

ACTH INDEPENDENT
1. Primary Adrenal Neoplasm (10-20%): functional
• Macronodular hyperplasia - rare (ectopic expression of hormone receptors)
• Adenoma
• Carcinoma

2. Rare: Primary pigmented nodular adrenal disease (sporadic or part of Carney complex), macronodular hyperplasia in setting of McCune-Albright syndrome
   (germline activating mutations in GNAS)
3. Iatrogenic – (exogenous glucocorticoids)

Question 24

Adrenal hyperplasia

Answer 24

• Diffusely enlarged

* Most weigh less than 30 grams

Question 25

Adrenal adenoma

Answer 25

a. Functional adenoma (and carcinoma) not morphologically distinct from nonfunctioning adrenal neoplasms b. Circumscribed, yellow-brown (thin or welldeveloped capsule) c. Most weigh less than 30 grams d. Most < 2.5 cm e. Cells similar to those in normal zona fasciculata f. Adjacent gland compressed

Question 26

Adrenal cortical carcinoma

Answer 26

a. Rare b. More likely to be functional (clinical = hypervirilism) c. Often very large: >5 cm d. Infiltrative, necrotic e. Only definitive criteria for malignancy = distant metastasis and/or local invasion, but histologic (Weiss) criteria to predict aggressive phenotype: •Nuclear pleomorphism •Mitotically active (including atypical mitoses) •Venous invasion •Hemorrhage •Necrosis f. Adjacent gland: usually effaced

Question 27

Hyperaldosteronism

Answer 27

PRIMARY – decreased plasma renin 1. Bilateral idiopathic hyperaldosteronism (~60% cases) • Bilateral nodular hyperplasia 2. Adrenocortical neoplasm • Adenoma (or more rarely carcinoma) • Solitary aldosterone-secreting adenoma = Conn syndrome 3. Familial hyperaldosteronism • CYP11B1/CYP11B2 chimeric gene--> ACTH dependent overactivity of aldosterone synthase SECONDARY – increased plasma renin -think Heart Failure or Renal artery stenosis

Question 28

``` Adrenal adenoma (aldosterone-producing – Conn syndrome) ```

Answer 28

Don’t usually suppress ACTH (in contrast to adenomas in Cushing syndrome) so adjacent adrenal cortex (and contralateral gland) not atropic

Question 29

Adrenal insufficiency

Answer 29

a. Primary (acute) adrenocortical insufficiency (adrenal crisis) b. Primary chronic adrenocortical insufficiency (Addison disease) c. Secondary adrenocortical insufficiency -Clinical manifestations of adrenocortical insufficiency generally do not appear until at least 90% of cortex = compromised

Question 30

Waterhouse-Friderichsen syndrome

Answer 30

a. Rapidly developing adrenocortical insufficiency associated with massive bilateral adrenal hemorrhage b. Overwhelming bacterial infection (Neisseria meningitidis) c. Rapidly progressive hypotension leading to shock d. DIC associated with widespread purpura

Question 31

Most common cause of chronic adrenocortical | insufficiency (Addison disease)…

Answer 31

a. Autoimmune adrenalitis (autoimmune destruction of steroidogenic cells) 1. Autoimmune polyendocrine syndrome type 1 (APS1) • Autoimmune polyendocrinopathy (hypoparathyroidism, hypogonadism, pernicious anemia), mucocutaneous candidiasis, ectodermal dystrophy • Mutations in autoimmune regulator (AIRE) gene chromosome 21q22 2. Autoimmune polyendocrine syndrome type 2 (APS2) • Adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes (polygenic)

Question 32

Other causes of chronic adrenocortical insufficiency..

Answer 32

1. Infections • Tuberculosis, fungi (Histoplasma capsulatum, Coccidioides immitis), cytomegalovirus, Mycobacterium avium-intercellulare, AIDS 2. Metastatic neoplasms • Lung, breast, kidney, stomach pancreas 3. Genetic causes • Congenital adrenal hypoplasia • Adrenoleukodystrophy (peroxisomal disorder; ABCD1 gene on Xq28)

Question 33

Chronic adrenocortical insufficiency

Answer 33

Pathology = dependent on underlying disease a. Autoimmune adrenalitis • Irregularly shrunken glands • Cortex with only scattered residual cells • Variable lymphoid infiltrate b. Tuberculous and fungal disease • Granulomatous inflammation c. Metastatic carcinoma

Question 34

Adrenal medulla

Answer 34

1. Pheochromocytoma 2. Neuroblastic tumors • Neuroblastoma • Ganglioneuroblastoma • Ganglioneuroma

Question 35

Pheochromocytoma | Rule of 10s

Answer 35

• 10% extra-adrenal (called paraganglioma outside of adrenal – e.g. organs of Zuckerkandl, carotid body tumor) * 10% of sporadic cases = bilateral (higher with MEN2A and MEN2B) * 10% malignant * 10% not associated with hypertension

Question 36

Pheochromocytoma | Pathology

Answer 36

a. Small circumscribed to large hemorrhagic masses b. Average weight 100 grams c. Richly vascularized fibrous tissue d. Polygonal to spindle-shaped cells e. Zellballen architecture • Nest-like clusters of uniform, round-to-polygonal cells surrounded by delicate richly vascular tissue and sustentacular cells f. EM – membrane bound secretory granules in which catecholamines are stored

Question 37

Malignant Pheochromocytoma

Answer 37

• Only definitive criteria = distant metastasis ``` • Scoring systems to predict aggressive behavior and stratify risk (evolving area in pathology) ```

Question 38

MEN syndromes

Answer 38

General features: • Tumors occur at younger age compared to sporadic tumors * Arise in multiple endocrine organs, synchronously or metachronously * Tumors more often multifocal • Tumors sometimes preceded by asymptomatic stage of endocrine hyperplasia involving cell of origin • Tumors tend to be more aggressive and recur in higher proportion of cases compared to sporadic tumors

Question 39

Each of the following is a component of MEN-1 EXCEPT ``` A. Parathyroid adenoma B. Pancreas islet cell tumor C. Pituitary adenoma D. Parathyroid hyperplasia E. Adrenal cortical adenoma ```

Answer 39

E. Adrenal cortical adenoma ``` MEN-1 - Pituitary: adenoma - Parathyroid: hyperplasia / adenoma - Pancreas: islet cell tumor / pancreatic endocrine neoplasm ```

Question 40

A 32-year-old woman with hypertension was evaluated. Workup revealed an adrenal medulla mass. It was resected. The pathologist’s diagnosis was pheochromocytoma. Additional workup one year later was undertaken which two separate thyroid masses and the diagnosis of medullary thyroid carcinoma was made. Which do you FAVOR: A. Sporadic occurrence of neoplasms B. Familial process – MEN 1 C. Familial process – MEN 2A or 2B

Answer 40

C. Familial process – MEN 2A or 2B Sounds “familial” on first glance, like there is a germ line mutation predisposing her to “multiple endocrine neoplasms” – suggestive of MEN 2. Cannot distinguish 2A and 2B from what we know at the moment. Thyroid mass should be evaluated and treated. It’s worth pursuing the diagnosis in this patient … and if genetically confirmed … suggesting genetic counseling to family members.

Question 41

This 32-year-old woman’s thyroid was resected and a diagnosis was made. If this patient indeed has MEN 2, which of the following do you favor as the diagnosis of her thyroid lesions: A. Medullary carcinoma B. Follicular carcinoma C. Follicular adenoma D. Papillary carcinoma

Answer 41

A. Medullary carcinoma

Question 42

Each of the following is true about multiple endocrine neoplasia (MEN) syndromes EXCEPT: A. Tumors occur at younger age than sporadic tumors B. In an involved organ, tumors are often multifocal C. Asymptomatic stage (e.g. C-cell hyperplasia) precedes clinically symptomatic stage (e.g. medullary carcinoma) D. Have an underlying genetic germ line mutation E. Tend to be more aggressive than sporadic tumors F. Tend to recur in higher proportion of cases than sporadic tumors G. Arise in only a single organ in any one patient

Answer 42

G. Arise in only a single organ in any one patient A patient with MEN may manifest initially with a single lesion in a single organ: She / he is at risk for developing other neoplasms. Tumors in several organs can be detected at the same time (“synchronously”) … ``` - or - A tumor may appear in one organ (e.g. pheochromocytoma in the right adrenal) with other lesions (e.g. a thyroid medullary carcinoma) occurring “metachronously” – at different times. ```

Question 43

Hyperplasia and Neoplasia

Answer 43

Hyperplasia: Increased number of cells --> usually resulting in increased mass / size a. Physiologic 1. Hormonal - increased functional capacity when needed (e.g. prolactin cell hyperplasia in setting of pregnancy / lactation) 2. Compensatory - after damage or partial resection (e.g. parathyroid hyperplasia in setting of renal failure) b. Pathologic: 1. Hormonal 2. Growth factors Neoplasia: New Growth ( ~= "tumor" - formerly included "inflammation" but essentially synonymous with "neoplasm" today) a. General features: abnormal mass of tissue, growth exceeds and is uncoordinated with that of the normal tissues, persists in the same excessive manner after cessation of the stimuli which evoked the change, unregulated / excessive proliferation that becomes autonomous, can be due to underlying genetic alteration b. Adenoma: "Benign" endocrine or epithelial neoplasm; +/- glandular patterns c. Carcinoma: Unrestrained growth; potential for invasion of surrounding tissue, metastasis or dissemination

Question 44

THYROID Hyperplasia / Neoplasia

Answer 44

``` Hyperplasia – increased volume of gland • Grave disease • Goiter • Diffuse • Multinodular ``` Follicular adenoma • Usually solitary • Circumscribed proliferation of follicles (intact capsule) • NOT usually precursor of follicular carcinoma Carcinoma (epithelial–derived) 1. Papillary thyroid carcinoma (PTC) (>85% of thyroid carcinoma) • Diagnosis based on nuclear features: • Nuclear clearing • Nuclear pseudoinclusions • Nuclear grooves • Architecture classically papillary (with fibrovascular cores) but may also be follicular (among other variants) • Psammoma bodies / calcifications common • 10-year survival: ~98% • Local lymph node metastasis = common, does not influence prognosis • Bad prognostic indicators: elderly , distant metastasis (not just local nodes), invasion into adjacent soft tissue 2. Follicular carcinoma (5-15% of thyroid carcinomas) • Diagnosis based on capsular OR vascular invasion • Architecture = sheets of follicles • No special nuclear features (no PTC nuclear features) • 10-year survival: • Minimally invasive (>90%) • Widespread capsular and vascular invasion (~50%) 3. Anaplastic Carcinoma (<5% of thyroid carcinomas) • Highly aggressive malignancy with extensive infiltration of soft tissues • Majority patients older with history of thyroid disease • Presents as rapidly enlarging neck mass • Median survival - ~ 3 months 4. Carcinoma (c-cell / endocrine-derived) • Medullary Carcinoma (5% of thyroid carcinomas) • Nests / trabeculae of neuroendocrine cells (fine, stippled chromatin) • Amyloid (calcitonin-derived) • Genetics : • Sporadic – RET (80%) • Familial (MEN-2A, 2B) - RET

Question 45

Four Major Malignant Carcinoma of the thyroid

Answer 45

1. Papillary thyroid carcinoma (PTC) (>85% of thyroid carcinoma) • Diagnosis based on nuclear features: • Nuclear clearing • Nuclear pseudoinclusions • Nuclear grooves • Architecture classically papillary (with fibrovascular cores) but may also be follicular (among other variants) • Psammoma bodies / calcifications common • 10-year survival: ~98% • Local lymph node metastasis = common, does not influence prognosis • Bad prognostic indicators: elderly , distant metastasis (not just local nodes), invasion into adjacent soft tissue 2. Follicular carcinoma (5-15% of thyroid carcinomas) • Diagnosis based on capsular OR vascular invasion • Architecture = sheets of follicles • No special nuclear features (no PTC nuclear features) • 10-year survival: • Minimally invasive (>90%) • Widespread capsular and vascular invasion (~50%) 3. Anaplastic Carcinoma (<5% of thyroid carcinomas) • Highly aggressive malignancy with extensive infiltration of soft tissues • Majority patients older with history of thyroid disease • Presents as rapidly enlarging neck mass • Median survival - ~ 3 months 4. Carcinoma (c-cell / endocrine-derived) • Medullary Carcinoma (5% of thyroid carcinomas) • Nests / trabeculae of neuroendocrine cells (fine, stippled chromatin) • Amyloid (calcitonin-derived) • Genetics : • Sporadic – RET (80%) • Familial (MEN-2A, 2B) - RET

Question 46

Hyperparathyroidism | Primary, Secondary, or Tertiary

Answer 46

1 ° Hyperparathyroidism Adenoma (85-95%) Hyperplasia (5-10%) Carcinoma (~1%) b. Labs: i. Increased PTH, Increased Ca2+ ii. Decreased Phosphate iii. Major Bone loss c. Symptoms: i. Painful bones / renal stones / abdominal groans / psychic moans ii. Calcium deposition (metastatic calcification) iii. Valve calcifications (aortic, mitral) ``` 2° Hyperparathyroidism a. Renal failure b. Labs i. Increased PTH, Decreased Ca2+ ii. Increased phosphate iii. medium Bone loss c. Symptoms: • Bone changes (renal osteodystrophy) less severe than primary • Calcium deposition (metastatic calcification); blood vessels, lungs, gut, heart ```

Question 47

``` Syndromes / Diseases Cushing Syndrome (Hypercortisolism) ```

Answer 47

``` ACTH DEPENDENT 1. Pituitary Adenoma (70-80%) 2. Rarely pituitary hyperplasia • Leads to adrenal hyperplasia, nodular • Ectopic corticotropin syndrome (e.g. ACTH-secreting small cell carcinoma) ``` ACTH INDEPENDENT 1. Primary Adrenal Neoplasm (10 - 20%): functional • Macronodular hyperplasia (ectopic expression of hormone receptors) • Adenoma • Carcinoma 2. Rare: Primary pigmented nodular adrenal disease, McCune-Albright syndrome 3. Iatrogenic – (exogenous glucocorticoids) Conn Syndrome • Primary hyperaldosteronism caused by aldosterone-secreting adenoma  hypertension Addison Disease • Primary chronic adrenocortical insufficiency resulting from progressive destruction of adrenal cortex • Many etiologies: Inflammatory / autoimmune (60-70%), infection (TB, AIDS-associated, fungal), metastatic neoplasm, genetic (congenital adrenal hypoplasia, adrenoleukodystrophy) ``` Waterhouse- Frederickson Syndrome a. Bacterial infection / sepsis, esp. Neisseria meningitidis ("meningococcus") - also Pseudomonas, Haemophilus influenzae, staphylococci b. Clinical • Hypotension --->shock • DIC (widespread purpura) • Hemorrhage - bilateral adrenals • Adrenal insufficiency - acute ```

Question 48

MEN1 | Wermer syndrome

Answer 48

1. Pituitary adenoma or hyperplasia (~2/3) 2. Parathyroid hyperplasia (90%) 3. Pancreatic endocrine neoplasm / islet cell tumor (~2/3), duodenal gastrin-producing carcinoids (both are a cause of hypergastrinemia / Zollinger Ellison syndrome)

Question 49

MEN2A | Sipple syndrome

Answer 49

1. Medullary thyroid carcinoma (100%) and C-cell hyperplasia 2. Parathyroid hyperplasia (50%) 3. Pheochromocytoma (50%)

Question 50

MEN2B | MEN3, Gorlin syndrome

Answer 50

1. Medullary thyroid carcinoma (85%) and C-cell hyperplasia 2. Pheochromocytoma (50%) 3. Diffuse ganglioneuromatosis of the GI tract (typically colon)(100%) • Marfanoid body habitus

Question 51

MEN2A and MEN2B

Answer 51

MEN2A 1. Medullary thyroid carcinoma (100%) and C-cell hyperplasia 2. Parathyroid hyperplasia (50%) 3. Pheochromocytoma (50%) MEN2B 1. Medullary thyroid carcinoma (85%) and C-cell hyperplasia 2. Pheochromocytoma (50%) 3. Diffuse ganglioneuromatosis of the GI tract (typically colon)(100%) • Marfanoid body habitus