Condition	Pathology	Clinical features	Morphology	
Pituiary Gland	
Hyperpituitarism &
Pituitary Adenomas	•	Excess production of anterior pituitary hormones is most often caused by an adenoma in the anterior lobe.
•	Functional pituitary adenomas are usually composed of a single cell type & produce a single predominant hormone.
•	Pituitary adenomas may be nonfunctional & cause hypopituitarism by destroying adjacent native anterior pituitary parenchyma. 	•	Responsible for 10% of intracranial neoplasms.
•	Usually found in adults with a peak incidence from the 30s to 50s.
•	Most pituitary adenomas are monoclonal in origin.	•	Divided into microadenomas (<10mm in diameter) & macroadenomas (>10mm).
•	Usually solitary.
•	Early stages: form discrete soft masses within the sella.
•	Larger adenomas may compress or infiltrate adjacent structures.
•	Composed of uniform cells in contrast to normal pluricellular anterior pituitary.
•	Neoplastic cells arrayed in sheets, cords, nests or papillae with a scanty reticulin network.
•	Nuclear atypia, necrosis & hemorrhage.
•	Membrane-bound secretory granules present in cytoplasm of most cells.	
Prolactinomas	•	Most common functional pituitary tumor: 30% of all adenomas.
•	Physiologic hyperprolactinemia occurs in pregnancy.

Pathologic hyperprolactinemia:
•	Result from lactotroph hyperplasia.
•	Interference with normal dopamine inhibition of prolactin secretion.
•	Occurs as a result of damage to dopaminergic neurons of the hypothalamus, pituitary stalk section, or drugs that block dopamine receptors on lactotroph cells.	•	Amenorrhea
•	Galactorrhea
•	Loss of libido
•	Infertility
	•	Macroadenomas, composed of sparsely granulated acidophilic or chromophobic cells.	
Growth hormone adenomas	•	Second most common type of functioning adenoma.
•	Persistent hypersecretion of growth hormone (GH) stimulates hepatic secretion of insulin-like growth factor-I (IGF-I).	Gigantism:
•	Generalized increase in body size.
•	Disproportionately long arms & legs.

Acromegaly: enlargement of head, hands, feet, jaw, tongue & soft tissues.

Goals of treatment:
•	Restore GH levels to normal.
•	Decreased symptoms while not causing hypopituitarism.

Tumor removal:
•	Surgically removed by a transphenoidal approach.
•	Destroyed by radiation therapy.
•	Drug therapy to reduce GH secretion.	•	Composed of granulated cells, which appear acidophilic or chromophobic.	
Corticotroph Tumors	•	Excess production of ACTH by corticotroph adenoma leads to adrenal hypersecretion of cortisol.	•	Cushing syndrome	•	Small microadenomas.
•	Basophilic or chromophobic.
•	Chromophobic tumors are often larger & produce symptoms from mass effects.	
Gonadotroph adenomas	•	Comprise 10-15% of pituitary adenomas.
•	Most frequently found in middle-aged men & women.
•	Pituitary hormone deficiencies are common: impaired secretion of LH.	•	Impaired vision
•	Headaches
•	Diplopia
•	Low serum testosterone with decreased energy & libido.
•	Amenorrhea in premenopausal women.	•		
Hypopituitarism	•	Decreased secretion of pituitary hormones due to diseases of the hypothalamus or pituitary: 75% of parenchyma destroyed or absent.
•	Tumors & mass lesions cause damage by exerting pressure on adjacent pituitary cells.
•	Pituitary surgery or radiation remove sufficient normal tissue to cause hypopituitarism.
•	Rathke cleft cyst contains proteinaceous fluid & expand causing symptoms.
•	Pituitary apoplexy: sudden hemorrhage into the pituitary gland with sudden onset of excruciating headache & diplopia.

Sheehan syndrome:
•	Postpartum necrosis of the anterior pituitary.
•	Results from sudden infarction of the anterior lobe precipitated by obstetric hemorrhage or shock.
•	Encountered in disseminated intravascular coagulation, sickle cell anemia, elevated intracranial pressure, traumatic injury & shock.
Empty sella syndrome:
•	Destruction of part or all of pituitary gland.
•	Presence of an enlarged, empty sella turcica that is not filled with pituitary tissue.
•	Primary type: defect in diaphragm sellae that allows arachnoid mater & CSF to herniate into sella, resulting in expansion of sella & compression of pituitary.
•	Secondary type: Removal of pituitary adenoma which enlarges the sella.	•		•		
Diabetes insipidus	•	ADH deficiency.
•	Result from head trauma, tumors & inflammatory disorders of the hypothalamus & pituitary.	•	Polyuria
•	Polydipsia
•	Hypernatremia	•		
Syndrome of inappropriate ADH secretion (SIADH)	•	Causes resorption of excessive amounts of free water.

Common causes:
•	Secretion of ectopic ADH by malignant neoplasms, esp. small cell carcinoma of the lung.
•	Non-neoplastic diseases of the lung: tuberculosis & pneumonia.
•	Local injury to hypothalamus or posterior pituitary.	•	Hyponatremia
•	Cerebral edema
•	Neurologic dysfunction	•		
Craniopharygioma	•	Derived from vestigial remnants of Rathke pouch.
•	Slow-growing tumors.
•	5% of intracranial tumors.
•	Suprasellar & may encroach on hypothalamus. 
•	Occur most commonly during childhood & adolescence.	•	Children: growth retardation
•	Adults: visual disturbances	•	Cystic with calcification
•	Composed of a mixture of squamous epithelial elements & delicate reticular stroma. 	
Thyroid Gland	
Thyrotoxicosis (Hyperthyroidism)	•	Diffuse hyperplasia of thyroid associated with Graves disease: 85% of cases.
•	Ingestion of exogenous thyroid hormone.
•	Hyperfunctional multinodular goiter
•	Hyperfunctional adenoma of thyroid.
•	Thyroiditis	Cardiac manifestations:
•	Tachycardia
•	Palpitations
•	Cardiomegaly
•	Arrhythmias: atrial fibrillation

Ocular changes:
•	Wide, staring gaze
•	Lid lag
•	Ophthalmopathy (Graves disease)

Neuromuscular:
•	Tremor
•	Hyperactivity
•	Emotional lability
•	Anxiety
•	Inability to concentrate
•	Insomnia

Skin:
•	Warm
•	Moist
•	Flushed

Gastrointestinal system:
•	Weight loss despite increased appetite & hyperphagia.
•	Increased gut motility.

Diagnosis: decreased serum TSH concentration & unbound T4 levels.	•		
Hypothyroidism	•	Structural or functional derangement that interferes with the production of adequate levels of thyroid hormone.
•	Primary hyperthyroidism: Hashimoto thyroiditis, thyroid surgery, radiation, drug induced.
•	Secondary hyperthyroidism: TSH deficiency.
•	Association with dietary deficiency & endemic goitre.	Cretinism (perinatal or infancy):
•	Impaired development of muscular system & CNS.
•	Severe mental retardation.
•	Short stature.
•	Coarse facial features.
•	Wide-set eyes.
•	Enlarged & protruding tongue.
•	Umbilical hernia.

Myxedema (older child or adults):
•	Insidious slowing of physical & mental activity.
•	Fatigue, cold intolerance & apathy.
•	Periorbital edema.
•	Coarsening of skin & facial features.
•	Cardiomegaly.
•	Pericardial effusion.
•	Hair loss.
•	Accumulation of mucopolysaccharide-rich ground substance within dermis.	•		
Thyroiditis
•	Inflammation of the thyroid gland results in acute illness with severe pain.
•	Acute infections may reach thyroid gland via hematogenous spread or through direct seeding of gland, such as via a fistula from the piriform sinus.
•	Inflammation may cause sudden onset of neck pain and tenderness in area of gland, accompanied by fever, chills.	
Hashimoto Thyroiditis	•	Common cause of hypothyroidism in areas of the world where iodine levels are sufficient.
•	Gradual thyroid failure due to an autoimmune-mediated destruction of the thyroid gland.
•	Most prevalent between 45 & 65 years of age.
•	Female predominance of 10:1-20:1.
•	Caused primarily by a defect in the function of thyroid-specific suppressor T cells, with emergence of CD4+ helper T cells directed at the thyroid & production of autoantibodies.
•	Association with HLA-DR5 & HLA-DR3.
•	Association with SLE, Sjogren syndrome, rheumatoid arthritis, pernicious anemia, type II diabetes & Graves disease.	•	Painless enlargement of the thyroid.
•	Associated with some degree of hypothyroidism in a middle-aged woman.
•	Small risk of subsequent of lymphoma.	•	Gland: diffusely enlarged, asymmetrical with an intact capsule.
•	Parenchyma is paler than normal.
•	Infiltrate of lymphocytes, plasma cells & macrophages with germinal centers.
•	Abundant eosinophilic granular cytoplasm in residual follicular cells.
•	Delicate fibrosis.	
Subacute (Granulomatous) Thyroiditis
	•	Most common between ages of 30-50.
•	Affects women more often than men: 3:1-5:1.
•	Caused by a viral infection or a postviral inflammatory process.
•	Majority of patients have a history of an upper respiratory infection just before onset of thyroiditis.
•	Association with coxsackievirus, mumps, measles, adenovirus.
•	Strong link with HLA-B35	•	Presentation may be sudden or gradual.
•	Pain in the neck, which may radiate to the jaw, throat or ears.
•	Fever, fatigue, malaise, anorexia & myalgia.
•	Thyroid inflammation & the resultant hyperthyroidism are transient, usually diminishing in 2-6 weeks even without treatment.
•	Followed by a transient, usually asymptomatic hypothyroidism lasting 2-8 weeks. 	•	Variable enlargement of the gland, which may be symmetrical or irregular.
•	Early lesions: disruption of thyroid follicles with a neutrophilic infiltrate.
•	Aggregations of lymphocytes, histiocytes & plasma cells about collapsed & damaged thyroid follicles.
•	Multinucleate giant cells enclose naked pools or fragments of colloid. 	
Subacute Lymphocytic (Painless) Thyroiditis	•	Uncommon cause of hyperthyroidism.
•	Painless enlargement of gland.
•	Most common in women in postpartum period.
•	Self-limited, may be followed by hypothyroidism.
•	No link with viral infection, subacute granulomatous thyroiditis or Hashimoto disease.	•	Hyperthyroidism
•	Symptoms usually develop over 1-2 weeks & last 2-8 weeks before subsiding.	•	Nonspecific lymphoid infiltration of thyroid parenchyma.
•	No germinal center formation or significant plasma cell infiltrate.	
Graves Disease	•	Most common cause of endogenous hyperthyroidism.
•	Peak incidence between ages 20-40.
•	Women are affected 7 times more than men.
•	Association with HLA-B8 & DR3 & Hashimoto disease, pernicious anemia & rheumatoid arthritis.
•	An autoimmune disorder produced by autoantibodies to TSH receptor, thyroglobulin & thyroid hormones.
•	Triggered by molecular mimicry or expression of major histocompatibility complex by thyroid epithelial cells.	•	Clinical features of hyperthyroidism, resulting from hyperfunctional, diffuse enlargement of the thyroid.
•	Infiltrative ophthalmopathy with resultant exophthalmos.
•	Localized, infiltrative dermopathy called pretibial myxedema.	•	Gland is mildly & symmetrically enlarged, with an intact capsule & soft parenchyma.
•	Wide-spread hypertrophy & hyperplasia of follicular epithelium, manifested by crowding of columnar cells into irregular papillary folds.
•	Colloid is decreased.
•	Hyperplastic lymphoid tissue & increased numbers of blood vessels.	
Diffuse and Multinodular Goiter
•	Goiter: enlargement of thyroid is the most common manifestation of thyroid disease.
•	Presence of goiter reflects impaired synthesis of thyroid hormone, most often due to dietary iodine deficiency.	
Diffuse Nontoxic (Simple) Goiter	•	Diffusely involves the entire gland without producing nodularity.
•	Enlarged follicles filled with colloid.

Endemic goiter:
•	Occurs in areas with low levels of iodine.
•	Lack of iodine leads to decreased synthesis of thyroid hormone & a compensatory increase in TSH, leading to follicular cell hyperplasia & goiter.

Sporadic goiter:
•	Female predominance.
•	Peak incidence in young adult life.
•	Caused by ingestion of substances that interfere with thyroid hormone synthesis.
•	Autosomal recessive disorder: hereditary enzyme defects that interfere with thyroid hormone synthesis.	•		•	Hyperplastic stage & colloid involution.
•	Gland is diffuse & symmetrically enlarged.
•	Hypertrophy & hyperplasia of follicular epithelium with scant colloid.
•	Demand for thyroid hormone is met: accumulation of colloid & variable atrophy of follicular epithelium.
•	Demand for thyroid hormone decreases: stimulated follicular epithelium involutes to form an enlarged, colloid-rich gland.	
Multinodular Goiter	•	Recurrent episodes of stimulation & involution of a diffuse goiter generate a more irregular enlargement of the thyroid.
•	Most long-standing simple goiters convert into multinodular goiters.	•	Hyperactivity of a focal nodule with resultant thyrotoxicosis.
•	Cosmetic deformity.
•	Esophageal compression with dysphagia.
•	Tracheal compression.
•	Obstruction of superior vena cava.
•	Hemorrhage into goiter with pain.
•	Infiltrative ophthalmopathy & dermopathy are not seen in absence of concomitant Graves disease.
•	Differentiation from neoplasm is difficult.	•	Multilobuted.
•	Asymmetrically enlarged.
•	Focal hemorrhage, fibrosis, calcification & cystic change.
•	Colloid accumulation.
•	Follicular epithelial hyperplasia.
•	Follicular involution with focal intervening areas of scarring & hemorrhage.	
Neoplasms
Higher incidence:
•	in women.
•	with age.

Risk of neoplasm increases with:
•	Solitary nodules
•	Nodules in younger patients & men

Nature of nodule:
•	History of radiation treatment to head and neck increases risk of thyroid malignancy.
•	Nodules that take up radioactive iodine in imaging studies are more likely to be benign than malignant.	
Adenomas	•	Discrete, solitary masses.
•	Follicular neoplasms.
•	Somatic mutations in some of the components of TSH receptor signaling sytem.
•	Results in clonal expansion of specific epithelial cells, leading to formation of autonomous monoclonal thyroid adenomas.	•	Painless mass
•	Take up lass radioactive iodine than does normal thyroid.
•	Cold (nonfunctioning) on scans.
•	10% becomes malignant.	•	Well-demarcated, solitary lesion.
•	Accompanied by fibrosis, hemorrhage, or calcification.
•	Sharply demarcated from adjacent parenchyma by a well-defined fibrous capsule.
•	Histologic patterns range from closely apposed nests & trabeculae to well-developed follicles containing abundant colloid.
•	Hurthle cell adenomas: granular, eosinophilic cells containing abundant mitochondria.	
Carcinomas	•	Most cases occur in adults, with a female predominance.
•	Most are well-differentiated lesions & are not aggressive.
•	Major risk factor is exposure to ionizing radiation during first two decades of life.
•	Predisposing factors: nodular goiter & autoimmune thyroid disease.
•	Mutation of RET protooncogene in multiple endocrine neoplasia (MEN) type II.	•	Papillary: 75-85%
•	Follicular: 10-20%
•	Medullary: 5%
•	Anaplastic: <5%	•		
Papillary Carcinoma	•	Most common form of thyroid cancer.
•	Occur at any age, but most often in women in their 20-40s.
•	Associated with previous exposure to ionizing radiation.
•	Appear as multinodular tumors because of lymphatic invasion.	•	Most present as asymptomatic thyroid nodues.
•	First manifestation may be a mass in a cervical lymph node.
•	Involves regional nodes in 50% of cases.
•	Advanced disease: hoarseness, dysphagia, cough or dyspnea.
•	Favorable prognosis (90% survival at 20 years): confinement of lesion to thyroid & well-differentiated histology.	•	Solitary or multifocal lesions that may infiltrate the adjacent parenchyma.
•	Associated with calcification or cystic change.
•	Hypochromatic empty nuclei devoid of nucleoli & nuclear grooves.
•	Eosinophilic intranuclear inclusions.
•	Psammona bodies.
•	Encapsulated, follicular & tall cell variants.	
Follicular Carcinoma	•	10-20% of thyroid cancers.
•	Peak incidence in 40-50s with female predominance.
•	Predisposing factors: multinodular goiter.
•	Treated with lobectomy or subtotal thyroidectomy.	Prognosis is influenced by:
•	Size of lesion.
•	Presence or absence of capsular or vascular invasion.
•	Presence of metastases.
•	Degree of histologic anaplasia.	•	Single nodules that may be well circumscribed or infiltrative.
•	Microfollicular pattern, with relatively uniform, colloid-filled follicles.
•	Trabecular & sheetlike architecture.
•	Majority of metastases are hematogenous.	
Medullary	•	Neuroendocrine neoplasms originating from parafollicular or C cells.
•	Arise sporadically in about 80% of cases; rest occur in setting of MEN syndrome IIa or IIb.
•	Peak incidence: 40-50s for sporadic cases & 20-30s for MEN-associated cases.
•	Germ line mutations in RET proto-oncogene are important in pathogenesis.	•	Thyroid mass
•	Dysphagia
•	Hoarseness
•	Cough
•	Abnormal serum calcitonin levels. 	•	Arise as a solitary nodule or may present as multiple lesions involving both thyroid lobes.
•	Sporadic cases: one lobe.
•	Familial cases: bilateral & multicentric.
•	Polygonal to spindle-shaped cells arrayed in nests, trabeculae & follicles.
•	Amyloid deposits present in adjacent stroma.	
Anaplastic	•	Less than 5% of thyroid carcinomas.
•	Aggressive undifferentiated tumors of the thyroid follicular epithelium.
•	Most common in elderly patients, particularly in areas of endemic goiter.	•	Dismal prognosis.
•	Dissemination is common.
•	Death attributed to aggressive local growth.	•	Large, pleomorphic giant cells.
•	Spindle cells with a sarcomatous appearance.
•	Small anaplastic cells.	
Congenital Anomalies	
Thyroglossal duct	•	Arises as a remnant of the tubular development of the thyroid gland.
•	Present at any age, as a midline cyst or mass anterior to trachea.	•		•	Squamous epithelium in segments occurring high in neck.
•	Thyroidal acinar epithelium in lesions arising more inferiorly.
•	Lymphocytic infiltrates.
•	May become infected & form abscess cavities.	
Parathyroid Glands	
Primary Hyperparathyroidism	•	95% of cases caused by sporadic parathyroid adenomas or sporadic hyperplasia.
•	Chromosome defects in genes: parathyroid adenoma 1 & MEN 1.
•	Increase in level of serum ionized calcium. 	•	Bone: bone pain, secondary to fractures of bone weakened by osteoporosis.
•	Renal: renal stones with attendant pain and obstructive uropathy.
•	Gastrointestinal: constipation, nausea, peptic ulcers, pancreatitis & gallstones.
•	CNS: depression, lethargy & seizures.
•	Neuromuscular: weakness & fatigue.
•	Cardiac: aortic & mitral valve calcifications.	•	Parathyroid adenomas: solitary & surrounded by a delicate capsule.
•	Primary hyperplasia involve glands in a diffuse or multinodular pattern: cells form solid sheets, trabeculae, nests or follicles.
•	Parathyroid carcinoma: fairly circumscribed lesions with gray-white irregular masses.
•	Skeletal changes: bone resorption, fibrosis, foci of hemorrhage & cyst formation.
•	Hypercalcemia: formation of urinary tract stones, calcification of renal interstitium & tubules, metastatic calcification in other tissues.	
Secondary Hyperparathyroidism	•	Low serum calcium levels lead to compensatory overactivity of parathyroids.
•	Renal failure is most common cause.	•		•		
Hypoparathyroidism	Causes:
•	Surgically induced
•	Congenital absence of all glands, e.g. DiGeorge syndrome.
•	Autoimmune destruction of gland.
•	Familial hypoparathyroidism	•	Neuromuscular: tetany, muscle cramps, carpopedal spasms, laryngeal stridor & convulsions.
•	Mental: irritation & psychosis.
•	Intracranial: parkinsonian-like movement disorders & elevated intracranial pressure with papilledema.
•	Ocular: calcification of lens leading to cataract formation.
•	Cardiac conduction defects produce a characteristic prolongation of QT interval in ECG.	•		
Pseudo-hypoparathyroidism	•	Abnormalities in PTH receptor complex.	•	Short stature
•	Round face
•	Short neck
•	Short metacarpals & metatarsals	•		
Adrenal Cortex	
Adrenal Hyperfunction:
•	Cushing syndrome
•	Hyperaldosteronism
•	Adrenogenital syndromes	
Cushing syndrome	Elevation of glucocorticoid levels due to:
•	Administration of exogenous glucocorticoids.
•	Hypersecretion of ACTH.
•	Hypersecretion of cortisol by an adrenal adenoma, carcinoma, or nodular hyperplasia.
•	Secretion of ectopic ACTH by a nonendocrine neoplasm.

Primary hypersecretion of ACTH:
•	Encountered most commonly in young adult life with a female predominance (5:1).
•	Accounts for >50% of cases of endogenous hypercortisolism.
•	Association with ACTH-producing pituitary adenomas & corticotrophs hyperplasia (15%).
•	Adrenals are bilaterally hyperplastic.

Primary adrenal neoplasms:
•	20-25% of cases of endogenous hypercortisolism.
•	Lesions are independent of ACTH.
•	Hypercortisolism more marked with carcinomas than adenomas or hyperplasia.
•	Unilatera neoplasm: atrophic adrenal cortex due to ACTH suppression.

Ectopic ACTH secretion:
•	15-30% of cases of endogenous hypercortisolism.
•	Commonly seen in men in their 40-50s.
•	Association with small cell carcinoma of lung, carcinoid tumors of pancreas & bronchus, medullary carcinoma of thyroid & islet cell tumors of pancreas.	•	Central obesity
•	Moon facies
•	Weakness & fatigability
•	Hirsutism
•	Hypertension
•	Glucose intolerance/diabetes
•	Osteoporosis
•	Neuropsychiatric abnormalities
•	Menstrual abnormalities
•	Cutaneous striae
•	Delayed wound healing/bruisability
•	Determining cause of Cushing syndrome: measuring serum ACTH level & determination of urinary steroid excretion after administration of dexamethasone to suppress ACTH levels.	•	Crooke hyaline changes within basophils.
•	Diffuse adrenal cortical hyperplasia: 60-70%.
•	Nodular adrenal cortical hyperplasia: 15-20%.
•	Adenomas: small & well circumscribed.
•	Carcinomas: larger & unencapsulated.
•	Zona reticularis & fasciculata: atrophic.
•	Zona glomerulus: intact.	
Hyperaldosteronism	Primary Hyperaldosteronism:
•	Autonomous overproduction of aldosterone with resultant suppression of renin-angiotensin system.
•	Caused by aldosterone-producing adrenocortical neoplasm or primary adrenocortical hyperplasia.

Secondary Hyperaldosteronism:
•	Aldosterone release occurs in response to activation of renin-angiotensin system.
•	Encountered in congestive heart failure, decreased renal perfusion & pregnancy.	•	Hypertension
•	Hypokalemia: weakness, paresthesias, visual disturbances & frank tetany.	•	Adenomas: solitary, small, encapsulated lesions found more commonly on left side.
•	Gland is bright yellow, reflecting high lipid content.	
Adrenogenital Syndromes	•	Androgen-secreting adrenal cortical neoplasms.

Congenital metabolic defects in corticosteroid biosynthesis leads to:
•	Decreased glucocorticoid production.
•	Compensatory increase in ACTH secretion.
•	Adrenal hyperplasia
•	Increased production of other cortical steroids.

21-Hydroxylase deficiency:
•	85-90% of cases of congenital adrenal hyperplasia.
•	Autosomal recessive disroders.
•	Salt-wasting adrenogenitalism: complete absence of enzyme activity.
•	Simple virilizing adrenogenitalism without salt wasting.	•	Virilization in female
•	Precocious puberty in male
•	Salt wasting
•	Hypoatremia
•	Hyperkalemia
•	Cardiovascular collapse	•	Substantial, bilateral adrenal enlargement.
•	Cortex is widened, nodular & appears brown due to lipid depletion.	
Adrenal Insufficiency	
Primary acute adrenocortical insufficiency	•	Sudden increase in glucocorticoid requirements in patients with chronic adrenocortical insufficiency.
•	Rapid withdrawal of steroids from patients with adrenal suppression.
Massive destruction of adrenals
•	Neonatal adrenal hemorrhage
•	Postsurgical disseminated intravascular coagulation
•	Waterhouse-Friderichsen Syndrome	•		•		
Waterhouse-Friderichsen syndrome	•	Overwhelming septicemia infection caused by meningococci, pneumococci, gonococci & staphylococci.
•	Rapid progressive hypotension & shock.
•	Disseminated intravascular coagulation with purpura.
•	Massive adrenal hemorrhages with adrenal insufficiency.
•	Common occurrence in children.	•		•	Massive, bilateral adrenal hemorrhage which begins in medulla.	
Addison Disease	•	Destruction of  >90% of adrenal cortex.
•	Autoimmune adrenalitis.
•	Infections: tuberculosis, the fungi Histoplasma capsulatum & Coccidiodes immitis.
•	Metastatic neoplasms from lung & breast.	•	Weakness
•	Fatigue
•	Anorexia
•	Hypotension
•	Nausea & vomiting
•	Cutaneous hyperpigmentation.
•	Elevated ACTH, hyperkalemia & hypoatremia with volume depletion.	•	Small glands
•	Lipid depletion of adrenal cortex
•	Lymphocytic infiltrate
•	Medulla is spared	
Secondary adrenocortical insufficiency	•	Disorder of hypothalamus or pituitary associated with decreased ACTH production.
	•	Absence of hyperpigmentation.
•	Normal or near-normal aldosterone levels.	•	Atrophy of adrenal cortex.
•	Sparing of zona glomerulosa & medulla.	
Adrenocortical 
neoplasms	•	Tumors commonly invade vascular channels with metastases to regional & periaortic lymph nodes.
•	Lungs are common sites.	•		Adenomas:
•	Poorly encapsulated
•	Yellow-orange lesions
•	May lie within cortex or protrude into medulla
•	Larger lesions: areas of hemorrhage, cystic change & calcification

Adrenal cortical carcinomas:
•	Highly malignant.
•	Lesions are yellow on cut surface.
•	Contain areas of hemorrhage, cystic change & necrosis.
•	Cells range from well-differentiated to markedly anaplastic.	
Adrenal Medulla	
Pheochromocytoma	•	Uncommon neoplasms associated with catecholamine production & hypertension.

Sporadic lesions:
•	90% of cases.
•	Adulthood: 40-60 years.
•	70% are bilateral

Familial lesions:
•	10% of cases.
•	May arise in childhood.
•	10-15% are bilateral.

Found in familial symptoms:
•	von Hippel-Lindau: visceral cysts, renal cell carcinomas, angiomatosis, cerebellar hemangioblastoma.
•	von Recklinghausen: neurofibromatosis, schwannomas, meningiomas, gliomas.
•	Sturge-Weber: cavernous hemangiomas	Hypertension:
•	An abrupt, precipitous elevation in blood pressure.
•	Tachycardia
•	Palpitations
•	Headache
•	Sweating
•	Tremor & a sense of apprehension.
•	Congestive heart failure
•	Myocardial infarcts
•	Cardiac arrhythmia
•	Cerebral hemorrhage

Paroxysmal release of catecholamines:
•	Episodic headache
•	Anxiety
•	Sweating
•	Visual disturbances
•	Abdominal pain
•	Nausea
	Gross:
•	Pale gray or brown.
•	Hemorrhage, necrosis or cystic change.
•	Highly vascular.

Histology:
•	Mature polygonal to spindle-shaped medullary-type cells.
•	Basophilic cytoplasmic granules, arrayed in trabeculae or small nests.
•	Metastasis to lymph nodes, liver, lungs & bones.	
Multiple Endocrine Neoplasia Syndromes (MEN)	•	Autosomal dominant syndromes.
•	Characterized by hyperplasia or tumors of several endocrine glands.

MEN I:
•	Mutations in MEN I gene found on chromosome 11.
•	Parathyroid hyperplasia
•	Pancreatic lesions
•	Pituitary adenomas

MEN II:
•	Germ line mutations in the RET protooncogene on chromosome 10.
•	Medullary thyroid carcinomas
•	Pheochromocytomas
•	Parathyroid hyperplasia.

MEN IIb or III:
•	Similar to MEN IIa.
•	Additional features of neuromas or ganglioneuromas involving lips, oral cavity, eyes, respiratory tract, gastrointestinal tract & urinary bladder.			
Pinealomas	Pineoblastomas:
•	Composed of primitive neuroectodermal cells.
•	Invade local structures.
•	Metastasize via CSF pathways.
•	Most patients die within 1-2 years.

Pineocytomas:
•	More common in adults.
•	Composed of mixture of glial & neuronal elements.
•	Survival: 7 years.