Endocrine Pathology p1-16

7/30/2019 Endocrine Pathology p1-16

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Endocrine Pathology 10/25 10/29

The Pituitary Gland

Above: The pituitary gland is placed in well-protectedenvironment, in the recess of the sphenoid bone(Sella Turcica = Turkish saddle).

The 3rd

ventricle, optic chiasm, and cavernous sinus(venous drainage from the head) lie close to pituitary.In the case of a tumor, these can becomecompressed.

Pituitary Anatomy: Anterior Pituitary:

Anterior lobe comprises the bulk of the pituitary parenchyma(80%), while the posterior lobe makes up 20%.

Anterior Pituitary Hormones: Adrenocorticotrophin (ACTH) (derived from pro-opiomelanocorticotrophin [POMC], which also yields MSH,

endorphin & lipotropin); ACTH induces glucocorticoid (cortisol) secretion from the adrenal cortex

Thyroid Stimulating Hormone (TSH) induce synthesis and secretion of thyroid hormone (T3 & T4) from thyroidgland

Prolactin (PRL) induces lactation in breast tissue that has been exposed to estrogens and progesterone; release isinhibited by hypothalamus, in contrast to others

Growth Hormone (GH) induces, through somatomedin C [insulin-like growth factor I], bone, soft tissue & visceralgrowth

Follicle Stimulating Hormone (FSH) induces development of Graafian follicle (proliferation of granulosa cells) andspermatogenesis

Luteinizing Hormone (LH) induces ovulation & stimulates Leydig cell proliferation

Above: Anterior pituitary responsible for the synthesis andsecretion of hormones that act on other structures (ACTH, TSH,PRL, LH, FSH, and GH). Prolactin normally inhibited.


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Posterior Pituitary:

Pituitary Embryology:

Multiple Endocrine Neoplasia Syndromes:Lesions MEN1 MEN2A MEN 2BParathyroid ++++ ++ +Pancreas +++ -- --Pituitary ++ -- --Gastrinomas ++ -- --Thyroid/adrenal + -- --

adenoma

Med. Thyroid Ca -- ++++ +++Pheochromo. -- +++ +++Neuromas -- -- ++++

Other inherited causes of pituitary adenomas: Even less common than MEN 1:

CDKN1B gene (p27 protein) PRKAR1A gene (Carney syndrome mutation) AIP gene

These and MEN 1 mutations cause G-protein signaling activation (MEN 1), downstream activation of the G-proteinsignaling pathway (PRKAR1A) or failure of cell cycle checkpoint regulation (CDKN1B). These causes do not collectivelyrepresent even 1% of cause of pituitary tumors.

Anti-Diuretic Hormone (ADH; vasopressin) inducesthe resorption of water from collecting ducts of distalnephrons water-conserving hormone. Lack of ADH cancause diabetes insipidus.

Oxytocin induces uterine smooth muscle contractionduring labor and contraction of lactiferous ducts of thebreast

Test q: The condition diabetes insipidus is caused by: A lack of ADH.

Test q:A 42M sees his physician because he has had polyuria and

polydipsia for the past 4 months. His medical history shows that he fell off aladder and hit his head just before the onset of these problems. On physexam, there are no specific findings. Lab findings include serum Na+ 155

mmol/L, K+ 3.9 mmol/L, Cl- 111 mmol/L, CO2 27 mmol/L, glucose 84 mg/dL,creatinine 1 mg/dL, and osmolality 350 mOsm/mL. The specific gravity ofurine is 1.002. This patient is most likely to have a deficiency of which of thefollowing hormones? Antidiuretic hormone. (Other choices: Oxytocin,Corticotropin, Prolactin, Melatonin)

Above:Anterior pituitary is derived from pharyngealectoderm migrates rostrally comes into contact

w/diverticulum coming out of the diencephalon(Rathkes pouch). There is a pituitary tumor, more

commonly above the gland, that shows differentiationthat represents its embryological origin (pharyngealectoderm).

Above: Pituitary tumors. Pituitary tumors represent ~10% ofintracranial neoplasms. They are rare in children. Most develop in

the sella turcica, but ectopic locations may occur infundibulum, stalk,sphenoid bone, nasopharynx probably related to the position ofRathkes pouch. Most are benign (adenomas).In the figures above,can see it taking up large space (destroying the sella turcica).

MEN 1: Germ line mutation in MEN1gene on 11q, a tumor suppressor genethat produces menin; autosomaldominant disorder; accounts for ~3% ofpituitary tumors.

MEN1 is aka3P syndrome

Parathyroid lesions (hyperplasias),pancreatic endocrine tumors (islet celltumors), and pituitary adenomas.


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Sequence of hormone loss in pituitary tumors:

Large, fleshypituitary adenoma: Typical microadenoma: Pituitary apoplexy:

Looks encapsulated.

Pituitary adenoma:

Above: Pituitary apoplexy = sudden

hemorrhage into a pituitary adenoma. Happens inbig tumors enlarge very rapidly, compression ofvital structures, increased intracranial pressure

eventual death due to herniation of the brain.

There are 3 major growth patterns of pituitary adenoma: diffuse (sheet-like) trabecular papillary

Pictured here:diffuse (monomorphic, reticulin poor)

General clinical features of Pit. Tumors: bitemporal hemianopsia(optic chiasm compression blindness in temporal eye fields);headache, CSF pressure, N&V (= nausea & vomiting; floor of 3

rd

ventricle); cavernous sinus thrombosis, hormone deficiency

Above: Large, benign but fatal pituitary adenoma(pituitary carcinomas metastasize to subarachnoid or outsideCNS). Midbrain/brainstem compression death.

Figure: Pituitary tumors lead to loss ofnormal pituitary functions. Occurs in asequence GH is present w/least reserve in

the pituitary (so is lost first). When GHpassage is cut off, tends to be clinically silent.The usual clinical manifestation of a pituitarytumor w/hormone loss is gonadotropin loss.No TSH thyroid wont work.

Test q: The hormone deficiency that is mostcommonly clinically manifest in patientsw/destructive pituitary lesions is: folliclestimulating hormone.


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Pituitary adenoma trabecular pattern: Pituitary adenoma papillary pattern:

Fairly common pattern, thick cords in stroma.

Classification of Pituitary Adenomas: Clinical classification by hormonal excess syndrome,

confirmed by immunostaining (ex: prolactinoma) H&E staining has an approximate correlation with

clinical/immunostaining classification:- Acidophil: PRL & GH- Basophil (stain w/hematoxylin): ACTH- Chromophobe: ACTH, Gonadotropin

Pituitary Adenomas: Prolactinoma 30% Growth hormone 17% Mixed growth hormone & prolactin 9% Corticotroph - 14% Gonadotroph - 20%

(many previously considered null)

Thyrotroph - 1%

Test q: Which of the following is the most common functional pituitary adenoma? Prolactin-producing adenoma.

Prolactinoma:

Women: Forbes-Albright syndrome galactorrhea associated w/amenorrhea. Must rule out stalk syndrome: injury topituitary stalk (trauma to head, cleavage of stalk) and drug effect. In men, see impotence due to loss of gonadotropins.

Test q: Forbes-Albright syndrome patients exhibit galactorrhea, menstrual irregularity, and infertility. This syndrome results from aloss/deficiency of:

Prolactin. (2007, #58. Should this say deficiency orexcess?)

Test q: For the past month, a 33F has had burning epigastric pain and nausea and vomiting. An upper GI endoscopic study shows multiple 1cmshallow gastric antral and proximal duodenal ulcerations. She is treated w/omeprazole and improves. One year later, she has an episode of severe,

colicky lower abdominal pain and hematuria and passes a calcium oxalate calculus. One month later, she notes galactorrhea, and over the next twomonths ceases to menstruate. She is given a dopamine agonist and improves. Lab findings show Na+ 140 mmol/L, K+ 4.0 mmol/L, Cl- 101 mmol/L,CO2 25 mmol/L, calcium 11.1 mg/dL, phosphorus 2.4 mg/dL, and creatinine 1.1 mg/dL. Which of the following gene mutations w/associated neoplasms

is most likely to develop in this patient? Islet cell adenoma MEN1. (Other choices: Medullary carcinoma RET, Non-Hodgkin Lymphoma BCL6,Osteoma APC, and Pheochromocytoma RET.)

Fibrovascular cores,spoke-like arrangement ofneoplastic pituitary cells.Do not correlate w/functionbut useful for pathologiststo reliably recognize these

tumors under themicroscope.

Pituitary adenoma pleomorphism:

Endocrine tumors (in general) display pleomorphism notspecific to pituitary tumors. Does not biologically signifyanything (benign vs. malignant).

Left: H&E, lightly acidophilic. Right: immunostain againstprolactin. Often are calcified (Ca

++) can turn into pituitary

stone. None shown here, however.


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GH producing pituitary adenoma: Pituitary Gigantism Acromegaly:

Middle see more trabecular pattern. Or could be diffuse. (GH-producing adenoma)If in child, where epiphyses are open, can get gigantism.

Gigantism and acromegaly are usually seen together.

Test q:A 7M develops a growth hormone-producing pituitary adenoma. At nine years old, he would show features of: Gigantism.Test q:A 47M is seen for swelling of his fingers. Phys exam shows coarsening of his facial features with enlarged jaw, ears, and nose. His feet arealso enlarged. This disorder is characterized by an excess of: Growth hormone.

Acromegaly:

Coarse facial features thick Mandible has grown out to protrudelips, prominent jaw, broad nose. over the maxilla.

Acromegaly: Acromegaly: Spade-like hands Normal vs. Acromegaly:

Enlarged sinuses.

Test q: A 30M develops diabetes, carpal tunnel syndrome, and increase in soft tissue as well as mandibular overgrowth. Skull films show enlarged

frontal sinuses. Hands are spade-like. These features are consistent with:Acromegaly.

Mixed growth hormone & prolactin adenomas: Some tumors secrete more than one hormone most common combois GH and prolactin. Get combo of clinical features.

Acromegaly: Enlarged facial

features, hands. Thickened skin Increase in

connective tissuemass

Arthritis common(due to pressure on

joints) Commonly diabetic GH effects are

mostly mediated byIGF-1 (somatomedinC)

Acromegaly: thick lower lip Acromegaly: Prognathism

Above: Thicker bones inacromegalic person lots moresoft tissue in the fingers, also.

Above: Very broad hand, thick fingers, can seewedding band compression. Atrophy of thenar

eminence (could be due to median nervecompression due to overgrowth of connectivetissue in wrist)


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Corticotroph Adenomas:

ACTH-producing pituitary adenomas: Most commonly seen in young women The tumors are characteristically small when discovered (microadenomas) & basophilic to chromophobic Cause Cushing disease (by definition, Cushing syndrome secondary to an ACTH-producing pituitary adenoma) Cause about 70-80% of non-iatrogenic Cushing syndrome (a few % are caused by primary corticotroph hyperplasia

w/o a tumor)

Test q: The most common, non-iatrogenic cause of Cushings syndrome is: Pituitary adenoma.

Nelson Syndrome: Bilateral adrenalectomy in a Cushingnoid patient results in rapid growth of a previously

undetected ACTH-producing microadenoma The sudden loss of cortisol suppression is permissive of this growth Local compressive effects and hyperpigmentation (very high ACTH [&MSH] levels

occur) Can especially see hyperpigmentation in creases of palm

Test q: Patients w/increased ACTH often show increases in a second hormone w/a common precursor. Thatsecond hormone is: MSH.

Pituitary: Crookes Hyaline Change(glucocorticoid effect on non-neoplasticcorticotrophs). See hyalinization of cytoplasm aggregates of filaments (especially keratinfilaments).

Gonadotroph adenomas: (many previously considered null; typically large at diagnosis)Thyrotroph adenomas:Account for only ~1% of pituitary adenomas.

Pituitary Lesions Causing Hypofunction:

Pituitary adenoma Iatrogenic Pituitary apoplexy *Pituitary infarction (Sheehan syndrome) *Empty sella syndrome *Craniopharyngioma Metastatic carcinoma TB Sarcoidosis (esp. post. pit. leading to diab. insipid.) Rathke cleft cyst Langerhans cell histiocytosis (esp. post. pit. leading to diab. insipid.)

(~75% of the anterior pituitary must be destroyed before clinical hypopituitarism occurs)

At the same time an adenoma may be overproducing one hormone, function of others may be destroyed.

Test q: Langerhans cell histiocytosis may involve the pituitary causing pituitary hypofunction and diabetes insipidus. The diagnostic features of thistumor are: CD1a+.

Sheehan Syndrome (Post-partum pituitary necrosis): Seen in post-partum patients who have experienced hypotensive episodes

due to blood loss during labor and delivery Most commonly clinically manifest as failure to lactate in the post-partum

period

Sheehan Syndrome: Large area of coagulative necrosis

Above: Nelson Syndrome.Upper alveolar ridge showsline of increased pigment.


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Sheehan Syndrome Predisposing Factors: Pituitary blood supply (on outside of gland, can get compressed

especially since it is confined to a bony space) Prolactin cell hyperplasia, with vessel compression by enlarged

gland Hypotension 2

oto blood loss

Other causes of pituitary infarction:o DICo Sickle cell anemiao Diabetes

Test q: Post partum Sheehans syndrome is most likely due to: Vascular compression.Test q:All the following are thought to contribute to Sheehans syndrome except:

Pituitary microadenoma. (Other choices: Small, thin blood vessels; Hyperplasia ofprolactin cells; Confined to a bony space; Hypotension due to blood loss.)

Pituitary Blood Supply: Empty Sella Syndrome:

Above: Blood supply runs around periphery of gland, sends branches inside. Blood supply can get compressed, leadingto infarction.

Craniopharyngioma:Develops from Rathke pouch remnants; usually suprasellar; occurs inchildren & adults; ~3% of intracranial neoplasms; Sx includehydrocephalus, diabetes insipidus, anterior pituitary hypofunction; oftenmulticystic and calcified; relatively favorable prognosis.

Craniopharyngioma: Flaky white areas = keratin

Test q:A 23M has experienced headaches, polyuria, and visual problems for the past

3mo. On phys exam, he has bilateral temporal visual field defects. CT scan of the headshows a large, partially calcified, cystic mass in the sellar and suprasellar areas. Labfindings show a serum prolactin concentration of 60 ng/mL and serum sodium level of

152 mEq/L. Serum calcium, phosphate, and glucose levels are normal. The mass isexcised, and histologic exam shows a mixture of squamous epithelial elements and lipid-rich debris containing cholesterol crystals. Which of the following lesions is most

consistent w/the clinical lab findings in this patient? Craniopharyngioma that hasdestroyed the posterior pituitary. (Other choices: Prolactin-secretingadenohypophyseal macroadenoma, Multiple endocrine neoplasia type I (MEN I),

Metastases from a lung neoplasm in the sella and brain, and Multiple endocrineneoplasia type II (MENII)) REPEATED x2

Above: Craniopharyngioma. Looks Craniopharyngioma 75% are calcified Characterized by nests; collection ofspongy; gelatinous material in the spaces. (May see suprasellarcalcification.) columnar cells at the periphery.

Sheehan Syndrome:

Coagulative necrosis and infarction of the pituitary.

Empty Sella Syndrome: Defect ofdiaphragma sella permits arachnoidherniation and pituitary compression.(Diaphagma sella = normal opening that

allow pituitary to pass through.) Usuallymiddle-aged women. Sella is enlarged, oftennot hypopituitary. Compression atrophy ofthe pituitary gland.


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Craniopharyngioma: Stellate pattern.

Adrenal Anatomy:

Congenital Conditions Causing Adrenal Insufficiency: Adrenal hypoplasia:

1) Secondary to anencephaly2) Cytomegalic (X-linked) hypoplasia (nothing to do w/CMV)

Adrenoleukodystrophy

Anencephaly: These fetuses have no intacthypothalamus/pituitary axis, causing adrenalmaldevelopment, with no fetal cortex & only a small,provisional adult cortex.

Cytomegalic Hypoplasia: X-linked disorder with germ-line mutation in

the DAX-1 gene at Xp21 Male infants present with hypoadrenalism in

the neonatal period May later develop hypogonadism (if treated

for hypoadrenalism) Adrenal consists of small clusters of

enlarged, eosinophilic adrenal cortical cells Not related to cytomegalovirus

Test q:A 1 week old male exhibits hypoadrenalism for several days and dies at two weeks of age. At autopsy, the adrenal gland shows clusters oflarge, pink cells in the adrenal cortex. Diagnosis is: Cytomegallic hypoplasia

Adrenoleukodystrophy: X-linked mutation in fatty acid -oxidation pathway Toxic long chain fatty acids accumulate in brain, adrenal & other sites, causing cell death Lorenzos oil (movie) about adrenoleukodystrophy

Non-Congenital Conditions Causing Adrenal Insufficiency: Autoimmune adrenalitis (chronic) Sarcoidosis (chronic) Metabolic disease

(hemochromatosis, amyloidosis)(chronic)

Metastatic tumors (chronic) Infections (acute or chronic) Hemorrhage (acute) Abrupt corticosteroid withdrawal (acute)

Figure ACTH promotescortisol secretion

which providesnegative feedback to

both the hypothalamusand anterior pituitary to

decrease ACTH

Anencephaly. Cytomegalic Hypoplasia of the Adrenal.Gigantic eosinophilic cells


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Addison Disease (Primary Chronic Adrenocortical Insufficiency): Autoimmune Adrenalitis (AA): Most common cause (60 70%) of hypoadrenalism A component of autoimmune polyendocrine syndrome (APS) 1 & 2 APS 1 = AA, mucocutaneous candidiasis, ectodermal dystrophy, autoimmune hypoparathyroidism, hypogonadism &

pernicious anemia. (autoimmune regulator gene mutation) APS 2 = AA, autoimmune thyroiditis, & type 1 diabetes [Schmidt's syndrome= AA and Hashimotos]

Test q: The most common cause of primary Addisons Disease is: autoimmunity.Test q:A 42F presents w/aldosterone and cortisol deficiency. The most likely diagnosis is: Autoimmune adrenalitis. (Other choices: Cushing disease,Cushing syndrome, Hashimotos thyroiditis, and Pheochromocytoma)

Normal adrenal Whole mount slide:

Sarcoidosis (chronic), Metabolic disease (hemochromatosis/amyloidosis) (chronic), &Metastatic tumors (chronic):

Addison Disease (Primary Chronic Addison Disease (1 Chronic Adrenocortical Insufficiency):

Adrenocortical Insufficiency): Amyloidosis: Metastatic carcinoma (most commonly lung carcinoma):

Eosinophilic amorphous deposits of amyloid.

Infections (acute or chronic; especially fungal, TB, & HIV associated [CMV, MAI, Kaposi sarcoma HHV-8]) :Note: MAI = mycobacterium avium intracellulare

Addison Disease (Primary Chronic Adrenocortical Insufficiency): Adrenal Histoplasmosis:

Totally replaced by granulomatous inflammation secondary to chronic histoplasmosis.Multiple large macrophages filled w/small yeast-like forms.

Addison Disease (Primary Chronic AdrenocorticalInsufficiency): Autoimmune Adrenalitis (Samemagnification as prior slide).Shrunken adrenalgland with fibrous tissue, lymphocytes and small

groups (isolated clusters) of lipid depleted adrenalcortical cells (not visible here)

Residual ribbon ofyellow adrenal cortexw/adnex nodules ofmetastatic carcinoma.

Test q:A 60M dies after a brief

illness clinically diagnosed asAddisons disease. At autopsy,the adrenal glands are

replaced by necrotizinggranulomas. The most likelyetiology in the US is:

Histoplasma capsulatum.

Test q:A 52F presents

w/disseminatedhistoplasmosis. Blood culturesare positive forH. capsulatum.

The patient is hypotensive,hypoglycemic, and exhibitsvitiligo. As a result of

histoplasmosis, the patient hasdeveloped: AddisonsDisease.


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Addison Disease (Primary Chronic Adrenocortical Insufficiency): Tuberculosis:

Caseous necrosis of adrenal gland: white, cheesy material. Multiple acid-fast organisms.

Acute adrenocortical insufficiency: Bilateral Hemorrhage: Adrenal insufficiency resulting from bilateral adrenal

hemorrhage = Waterhouse-Friderichsen syndrome Usually children with sepsis, especially meningococcemia Perhaps a localized DIC-type reaction or infection-related

vasculitis or small vessel infection. May also be seen in newborns 2

oto traumatic birth (low

prothrombin) or as a rare complication of anticoagulant Rx

Secondary hypoadrenalism: Destructive disease of the hypothalamic-pituitary axis

any of these can cause 2 hypoadrenalism Prolonged glucocorticoid use with abrupt withdrawal

(suppressed hypothalamic-pituitary axis) Not pigmented, in contrast to many patients with primary

adrenal failure **

Clinical Features of Hypoadrenalism: Nausea & vomiting Weakness Hypotension Increased K+, Decreased Na+ Hypoglycemia Pigmentation

Autoimmune adrenalitis patient w/vitiligo:

Hyperadrenalism: Glucocorticoid excess results in Cushing syndrome Causes include:

Iatrogenic (most common) - caused by treatment with corticosteroids Pituitary adenoma (Cushing disease) (about 70% of non-iatrogenic Cushing syndrome) Corticotroph hyperplasia (rare)

Test q: The most common cause of Cushings syndrome is: Iatrogenic.

Test q: Which of the following is the most common cause of Cushings syndrome? Exogenous corticosteroids. (Other choices: Adrenal cortical

adenoma, Islet cell tumor of pancreas, Pituitary adenoma/microadenomas, Small cell carcinoma of lung)

Massive adrenal hemorrhage

Acute meningococcal sepsis 8y/o boy.

Test q: For the past 7mo, a 44F has become increasingly listless and weak and has

had chronic diarrhea and a 5kg weight loss. She also notices that her skin seemsdarker, although she rarely goes outside because she is too tired to participate in herusual outdoor activities. On phys exam, she is afebrile, and her BP is 85/50 mm Hg. A

chest radiograph shows no abnormal findings. Lab findings include serum Na+

120mmol/L, K+ 5.1 mmol/L, glucose 58 mg/dL, urea nitrogen 18 mg/dL, and creatinine0.8 mg/dL. The serum corticotropin level is 82 pg/mL. What is most likely to account

for these findings? Autoimmune destruction. REPEATED x2

Test q:A 42F has had increasing weakness, nausea, vomit ing, watery diarrhea, and a

five-kg weight loss over the past 7mo. On phys exam, she has generalized muscleweakness, muscle wasting, and increased skin pigmentation. After an upperrespiratory tract infection lasting one week, she develops abdominal pain and faintness

and lapses into a coma. On admission to the hospital, her temp is 36.9C, pulse

83/min, respirations 17/min and shallow, and BP 80/40 mm Hg. Lab findings show Hgbof 13.6 g/dL, hematocrit 43.8%, WBC count 5420/mm

3, Na+ 129 mmol/L, K+ 3.5

mmol/L, Cl- 95 mmol/L, CO2 23 mmol/L, glucose 48 mg/dL, and creatinine 0.6 mg/dL.Atrophy of which of the following tissues is most likely to be present? Adrenal cortex.

Autoimmune destruction of the melanocytes of the skin leads to

patchy areas of depigmentation.


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Causes of Hyperadrenalism (cont): Adrenal neoplasms (adenoma or carcinoma) (10-20%) Ectopic ACTH (non-pituitary tumors make ACTH, especially small cell carcinoma of lung, but also other

neuroendocrine tumors) (10%) Primary (ACTH independent) cortical hyperplasia (rare), macronodular (adults) or pigmented (children) (cortical cells

overexpress non-ACTH receptors)

Test q: The most common tumor producing ectopic ACTH is: small cell carcinoma of lung.

Test q:A 49M experiences an episode of hemoptysis. On phys exam, he has puffiness of the face, pedal edema, and systolic hypertension. A chest

radiograph shows a 5cm mass of the right upper lobe of the lung. A fine-needle aspiration biopsy of the mass yields cells consistent w/small cellanaplastic carcinoma. A bone scan shows no metastases. Immunohistochemical staining of the tumor cells is most likely to be positive for which of thefollowing? Adrenocorticotropic hormone.

Causes of Cushing Syndrome:

Cushing SYNDROME = excess cortisol production. Hypertension, hyperglycemia, protein wasting (lose muscle

mass), truncal obesity, thin extremities, hirsutism, moon facies, buffalo hump (adipose tissue deposit), Na, K.

Cushing DISEASE = hypercortisolism secondary to excess production of ACTH from a corticotrophic pituitaryadenoma

Cushing Syndrome: Cushing Syndrome Before & After Rx

Easy bruisability. Also see cutaneous striae Round face = moon facies. Bottom picture: Cushings.

skin becomes delicate and susceptible. Cortex is much thicker.

Cushing syndrome: Bilateral nodular adrenocortical hyperplasia (Usual pattern in ACTH-independent hyperplasia). Ill-defined nodules within these adrenal glands.

Below: Cushing disease.Diffuse adrenocorticalhyperplasia (Also may beseen in ectopic ACTH &corticotroph hyperplasia).


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Cushing syndrome: Primary pigmentednodular adrenocortical hyperplasia.

Gland not very big but multiple brown nodules(left).

Can see melanin pigment (right)

Cushing syndrome Adrenal adenoma: Cushings syndrome Adrenal adenoma:

Adrenal Carcinoma: Proportionately more common in Cushingnoid children with an adrenal tumor than in Cushingnoidadults with an adrenal tumor. Usually large, hemorrhagic and necrotic.

Adrenal Cortical Carcinoma:- Hormones apart from glucocorticoids may also be produced (usually androgens, rarely estrogens)- Virilizing adrenal cortical neoplasms are most likely to be carcinomas- Metastasizes to regional lymph nodes, but also to liver, lungs, etc. (hematogenous routes via adrenal vein more

typical of a sarcoma)- 35% 5-year survival overall; 50% dead in 2 years (aggressive tumor)

Adrenogenital Syndrome:- Excess androgen production by the adrenal- Usually an inherited disorder of steroid biosynthetic pathway, inherited as autosomal recessive (Congenital adrenal

hyperplasia)- Causes virilization of females and isosexual pseudoprecocity in males (enlarged penis, hirsuitism, but not fertile)- 21-hydroxylase deficiency is the most common cause (1 in 120 carrier frequency), followed by 11-hydroxylase

deficiency- May present in infancy or later

Solitary, circumscribed, usually


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Test q:A 30M presents w/hypertension. Sodium is elevated and the patient complains of muscle weakness. Serum renin is reduced. A mass isidentified in the left adrenal gland. Biopsy shows an adenoma in the cortex measuring 3cm in diameter. The product of this neoplasm is most likely:

Aldosterone.

Test q:A 39F reports headaches, weakness/fat igue, and frequent urination over the past several weeks. Phys exam reveals diastolic hypertension.

Lab findings include hypokalemia and reduced renin levels. An adrenal mass is discovered. Which of the following is the most likely cause of thesevarious findings? Conn syndrome.

Hyperaldosteronism bilat. nodularadrenocortical hyperplasia: Conn syndrome adrenal adenoma: Conn syndrome:

Multiple nodules, hyperfunction. Usually < 2 cm; typically occur in middle age; 2:1 =F:M

Secondary hyperaldosteronism is most commonly due to hypoperfusion of thekidney (renal artery stenosis). Other causes include edematous states & JGcell tumor (rare). Hypertension is characteristically worse than in primaryhyperaldosteronism. Renin and angiotensin are elevated, in contrast toprimary form.

Secondary hyperaldosteronism JG cell tumor:

Thyroid Embryology: Normal Thyroid:

Thyroid develops at the base of the tongue the foramen cecum. Develops into a diverticulum, migrates into anterior soft tissues of theneck. Attaches to the anterior surface of the larynx. Comes off the base of the tongue, migrates down present on the surface of thelarynx. Normal thyroid: butterfly shape, beefy red, 20g, see right/left lobes and isthmus. Sometimes has pyramidal lobe.

Juxtaglomerular celltumor VERY rare.~20 in the world. Verycircumscribed tumor,derived from the JG

apparatus (whichmakes renin) severehypertension.Surgically curable formof hypertension.

Secondary hyperaldosteronism:


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Developmental Thyroid Anomalies:A) Thyroid agenesis - complete in 1/3 & partial in 2/3, with remnants

along tract of descent (lingual thyroid) (mutations in TSH receptor,TTF-2 [or FOXE1; also cleft palate], PAX-8)

B) Thyroglossal duct cyst - midline and anterior to the tracheaC) Lateral aberrant thyroid - 90% of adults, anterior triangle of the

neck, but not in lymph nodes

Figure: Ectopic thyroid tissue (This may be all the thyroid present)

Ectopic thyroid tissue ismost commonly at the base ofthe tongue lingual thyroid.

Lingual thyroid:Bulging noduleprojecting upward islingual thyroid. If you remove it,could result inhypothyroidism(would needsupplemental thyroidhormones).

Histologic section: Lingual thyroid. Top: stratified squamous epithelium of tongue. Deep within musculature are thyroidfollicles.

Test q:A 25M presents w/a soft, 3cm nodule located near the base of his tongue. Biopsy reveals normal thyroid tissue. Before resection of this mass,

you should: Demonstrate normal thyroid tissue in the neck. (Other choices: Treat w/radioactive iodine, Biopsy regional lymph nodes to rule outmetastases, Do a bone scan to rule out metastases, or Treat w/synthroid (T3))

Thyroglossal duct cyst - midline and anterior to the trachea:Represents tract of descent failure of evolution of that tract.

Above: Thyroglossal duct cyst. (Persistence of tract from foramen cecum)

Infected thyroglossal duct cyst:

Complication of thyroglossal duct cyst infection. Above: Cutaneous fistula thyroglossal

Can cause cyst to rupture and drain externally cutaneous fistula. duct cyst.

Thyroid Agenesis:

Thyroglossal duct cyst:

Sagittal section see epiglottis,false/true vocal cords, thensuperiorly is the bulk of the cyst.


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Lateral aberrant thyroid 90% of adults, anterior triangle of the neck, but not in lymph nodes.Note: Anterior triangle = superiorly mandible, ant border of SCM, and midline.

Hypothyroidism:A) AgenesisB) Enzyme defects impaired thyroid production; goitrogens (natural and drugs inhibit enzymes, ex: rutabega)C) THRB mutations mutations in receptor for thyroid hormone on peripheral cellsD) Iodine deficiency not in US because salt has supplemental iodine in saltE) Thyroiditis:

Subacute

Hashimotos Riedel

Test q:A 2y/o child is brought to the fami ly physician because of failure to thrive. Phys exam shows that the child is short and has coarse facialfeatures, a protruding tongue, and an umbilical hernia. As the child matures, profound mental retardation becomes apparent. A deficiency of which ofthe following hormones is most likely to explain these findings? Thyroxine (T4). (Robbins explanation: The child has cretinism, a condition that is

uncommon when there is routine testing and treatment at birth for hypothyroidism.)

Subacute (granulomatous) thyroiditis: Mostly women (~4:1), typically 40-50 years old Often prior viral infection (normally one of the entero viruses; echo, coxsackie, mumps, measles, influenza, adeno),

triggering a cytotoxic T-cell reaction in thyroid with follicle damage Transient hyperthyroidism (colloid leak) Thyroid tender to palpation Gland: diffusely or irregularly enlarged, with yellow-white foci

Micro: granulomatous inflammation

Subacute thyroiditis Note patchy nature: Huge giant cell around naked colloid:

Area of severe involvement (middleright) Pathopneumonic feature: naked pool of colloid destruction of thyroid follicles. surrounded by gigantic giant cell

Granuloma replaces destroyed follicle:

Thyroid follicle has been completely destroyed andreplaced by well-defined granuloma.

Subacute Thyroiditis: Outcome: mostly euthyroid, some hypothyroid Dont confuse with subacute lymphocytic thyroiditis (hyperthyroidism)

Test q: A 23F presents w/a febrile viral syndrome from which sherecovers. Three weeks later the previously normal thyroid gland isenlarged, nodular, and very painful. The patient is complaining of heat

intolerance and nervousness. A fine needle aspirate of one of thethyroid nodules shows a mixture of granulocytes and reactive giant cellsphagocytosing colloid. A serum T4 is elevated, but antithyroidantibodies are absent. Which of the following disorders constitutes the

best presumptive diagnosis in this patient? Subacute granulomatousthyroiditis (De Quervain thyroiditis).

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Endocrine Pathology p1-16