Pathology Review Flashcards
Endocrine / Neuroendocrine
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)
Thyroid
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
Diffuse hyperplasia (Graves disease)
a. Most common cause of endogenous hyperthyroidism
b. F»_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)
Diffuse hyperplasia (Graves disease)
Autoantibodies
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)
Diffuse hyperplasia (Graves disease)
Clinical Findings
*important slide
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
Chronic lymphocytic (Hashimoto) thyroiditis
a. Most common cause of hypothyroidism in iodine-sufficient areas of the world
i. F»_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)
Chronic lymphocytic (Hashimoto) thyroiditis
Histology
• Diffuse, symmetrically enlarged
gland
• Mononuclear inflammatory
infiltrate (lymphocytes) +/-
germinal center formation
• Atrophic follicles with oncocytic
metaplasia
Other thyroiditis…
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
Diffuse and multinodular goiter
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)
Follicular adenoma
- 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
Follicular carcinoma
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%)
Papillary thyroid carcinoma
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
Anaplastic carcinoma
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
Medullary carcinoma
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
Parathyroid
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
Parathyroid - HYPERparathyroidism
a. Primary Hyperparathyroidism (95% sporadic; 5% familial)
b. Symptoms
• Asymptomatic (MAJORITY)
• Other: Fractures, nephrolithiasis, cardiac disease, depression, etc.
-also possible GI isssues for “Groans:
Parathyroid - Adenoma
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
Parathyroid - Hyperplasia
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)
Parathyroid
Adenoma VS Hyperplasia = Clinical distinction
Path sign out
• Enlarged, hypercellular parathyroid gland
• Size: __ cm
• Weight: __mg
Parathyroid - Carcinoma
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
Parathyroid - Carcinoma
Prognosis and Genetics
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
Adrenal cortical hyperfunction (hyperadrenalism)
- Cushing syndrome (excess of cortisol)
- Hyperaldosteronism
- Adrenogenital or virilizing syndromes (excess androgens)
• Bilateral hyperplasia adrenal cortex
Cushing syndrome (hypercortisolism)
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
- 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) - Iatrogenic – (exogenous glucocorticoids)
Adrenal hyperplasia
- Diffusely enlarged
* Most weigh less than 30 grams
Adrenal adenoma
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
Adrenal cortical carcinoma
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
Hyperaldosteronism
PRIMARY – decreased plasma renin
1. Bilateral idiopathic hyperaldosteronism (~60% cases)
• Bilateral nodular hyperplasia
- Adrenocortical neoplasm
• Adenoma (or more rarely carcinoma)
• Solitary aldosterone-secreting adenoma = Conn
syndrome - Familial hyperaldosteronism
• CYP11B1/CYP11B2 chimeric gene–> ACTH
dependent overactivity of aldosterone synthase
SECONDARY – increased plasma renin
-think Heart Failure or Renal artery stenosis
Adrenal adenoma (aldosterone-producing – Conn syndrome)
Don’t usually suppress ACTH (in contrast to
adenomas in Cushing syndrome) so adjacent
adrenal cortex (and contralateral gland) not
atropic
Adrenal insufficiency
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
Waterhouse-Friderichsen syndrome
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
Most common cause of chronic adrenocortical
insufficiency (Addison disease)…
a. Autoimmune adrenalitis (autoimmune destruction of steroidogenic cells)
- Autoimmune polyendocrine syndrome type 1 (APS1)
• Autoimmune polyendocrinopathy (hypoparathyroidism, hypogonadism, pernicious
anemia), mucocutaneous candidiasis, ectodermal
dystrophy
• Mutations in autoimmune regulator (AIRE) gene chromosome 21q22 - Autoimmune polyendocrine syndrome type 2 (APS2)
• Adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes (polygenic)
Other causes of chronic adrenocortical insufficiency..
- Infections
• Tuberculosis, fungi (Histoplasma capsulatum, Coccidioides immitis), cytomegalovirus, Mycobacterium avium-intercellulare, AIDS - Metastatic neoplasms
• Lung, breast, kidney, stomach pancreas - Genetic causes
• Congenital adrenal hypoplasia
• Adrenoleukodystrophy (peroxisomal disorder; ABCD1 gene on Xq28)
Chronic adrenocortical insufficiency
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
Adrenal medulla
- Pheochromocytoma
- Neuroblastic tumors
• Neuroblastoma
• Ganglioneuroblastoma
• Ganglioneuroma
Pheochromocytoma
Rule of 10s
• 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
Pheochromocytoma
Pathology
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
Malignant Pheochromocytoma
• Only definitive
criteria = distant
metastasis
• Scoring systems to predict aggressive behavior and stratify risk (evolving area in pathology)
MEN syndromes
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
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
E. Adrenal cortical adenoma
MEN-1 - Pituitary: adenoma - Parathyroid: hyperplasia / adenoma - Pancreas: islet cell tumor / pancreatic endocrine neoplasm
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
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.
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
A. Medullary carcinoma
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
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.
Hyperplasia and Neoplasia
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
THYROID Hyperplasia / Neoplasia
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
- 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%) - 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 - 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
Four Major Malignant Carcinoma of the thyroid
- 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 - 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%) - 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 - 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
Hyperparathyroidism
Primary, Secondary, or Tertiary
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
Syndromes / Diseases Cushing Syndrome (Hypercortisolism)
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
- Rare: Primary pigmented nodular adrenal disease, McCune-Albright syndrome
- 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
MEN1
Wermer syndrome
- Pituitary adenoma or hyperplasia (~2/3)
- Parathyroid hyperplasia (90%)
- Pancreatic endocrine neoplasm / islet cell tumor (~2/3), duodenal gastrin-producing carcinoids (both are a cause of hypergastrinemia / Zollinger Ellison
syndrome)
MEN2A
Sipple syndrome
- Medullary thyroid carcinoma (100%) and C-cell hyperplasia
- Parathyroid hyperplasia (50%)
- Pheochromocytoma (50%)
MEN2B
MEN3, Gorlin syndrome
- Medullary thyroid carcinoma (85%) and C-cell
hyperplasia - Pheochromocytoma (50%)
- Diffuse ganglioneuromatosis of the GI tract (typically colon)(100%)
• Marfanoid body habitus
MEN2A and MEN2B
MEN2A
1. Medullary thyroid carcinoma (100%) and C-cell hyperplasia
- Parathyroid hyperplasia (50%)
- Pheochromocytoma (50%)
MEN2B
1. Medullary thyroid carcinoma (85%) and C-cell
hyperplasia
- Pheochromocytoma (50%)
- Diffuse ganglioneuromatosis of the GI tract (typically colon)(100%)
• Marfanoid body habitus
