Systemic Pathology - Endocrine System - Mirani

• System of ductless glands.
• Hormones secreted into the bloodstream.
• Orchestrate a state of metabolic equilibrium or homeostasis.
• Endocrine organs dedicated to production of hormones e.g. pituitary, thyroid….etc
• Endocrine components in clusters in organs having mixed functions e.g. pancreas, ovary, testes…..
• Diffuse endocrine system comprising scattered cells within organs acting locally on adjacent cells without entry into blood stream, paracrine or autocrine.

• Exocrine - ducted; carry secretion to outside surface, eg. sweat (eccrine), sebaceous, mammary, digestive (pancreas, liver, gall bladder), etc.
• Endocrine - ductless; secrete into interstitial fluid, diffuse into blood.

• Pituitary, thyroid, parathyroid, adrenal, pineal glands.
• Hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, placenta - NOT exclusively endocrine glands.

• Bounded to plasma proteins such as thyroid and steroid (they serve as a reserve for acute changes).
• Some are transported free in the blood.
• Only free hormones are biological active

• Specific rates and patterns of secretion: diurnal, pulsatile, cyclic patterns, depending on the level of circulating substrates.
• Feedback systems: positive (rare) or negative, to maintain an optimal internal environment.
• Affect only cells with appropriate receptors -> specific cell function(s) is initiated
• Excreted by the kidney, deactivated by the liver or by other mechanisms

• Response to stress and injury
• Growth and development
• Reproduction
• Homeostasis
• Energy metabolism

• Hyperfunction - overproduction
• Hypofunction - underproduction
• Mass effects (Tumors) - nonfunctioning
• Correlation of hormonal assays, clinical, biochemical, and pathological findings, are of extreme importance in most conditions.

Exocrine (digestive enzymes) as well endocrine (hormones such as insulin).

• Location - retro-peritoneum, 2nd lumbar vertebral level.
• Extends in an oblique, transverse position.
• Parts of pancreas: head, neck, body and tail. Most Islet of Langerhans cells are located in the body and tail; the part to look at when there is a tumor.

• One million islets of Langerhans
• Different types of cells can be identified immunohistologically.
• α cells - glucagon; stimulates Glucose synthesis & glycogen breakdown in liver; raise blood glucose concentration (normal level ~ 0.9 gram per Liter).
• β cells - insulin; Stimulation of lipids & glycogen storage & formation; Lower blood glucose concentration.
• δ cells - somatostatin; Inhibits secretion of insulin & glucagon. Pancreatic polypeptide (PP) becomes VIP (vasoactive interstitial polypeptide

• Diabetes
• Islet Cell Tumors

• Metabolic disorders
• Hyperglycemia
• Defects in insulin secretion, or insulin action, or most commonly, both.
• Accelerates atherosclerosis, hypertension and Affects multiple organ systems - kidneys, eyes, nerves and blood vessels
• Affects over 20 million in adults and children.
• Leading cause of end stage liver disease, adult-onset blindness and non-traumatic lower extremity amputation in US.

• Causes could be Primary in the pancreas or secondary to other disease conditions
• Primary diabetes is classified into :
• A- Type 1 (approximately 10%)
• B- Type 2 (approximately 90%)
• C- Genetic & Miscellaneous causes
• Whatever the type, complications are the same.

• Develops in childhood.
• Autoimmune destruction of islet cells
• Insulitis - Heavy lymphocytic (CD4, CD8) infiltrates appear in and around islets.
• The islets of Langerhans are destroyed (90% of cells lost before metabolic changes appear)
• Polyuria , Polydipsia, Polyphagia (3P’s)
• Metabolic acidosis, weight loss, dehydration, & electrolyte imbalance.
• Ketoacidosis is common.

• Age > 30yrs, often present incidentally
• Sedentary life style and overweight
• Insulin resistance & β cells dysfunction , resulting in relative insulin deficiency
• Fibrosis and deposition of amylin polypeptide within islets: amyloid deposition; very few islet cells left
• 3 P’s and symptoms of complications
• Rare ketoacidosis

• Diseases of exocrine pancreas e.g. chronic pancreatitis
• Endocrinopathies e.g. Cushing’s Syndrome, Acromegaly
• Infections e.g. CMV
• Drugs e.g. glucocorticoids
• Gestational diabetes

• Age of diagnosis: childhood vs. 30 plus
• Associated with obesity: no vs. yes
• Blood pressure and/or cholesterol level: normal vs. high
• Ketone level: high vs. normal
• Insulin dependent: yes vs. no
• Treatment: insulin injection/pump vs. no medication or insulin tablets.

• Random glucose over 2gram per Liter + symptoms.
• Fasting glucose over 1.26gram per Liter on more
• than one occasion.
• Abnormal oral glucose tolerance test when glucose level is more than 2 gram per Liter 2hrs after standard glucose load of 75 gram.

• Measures the amount of glucose that has been incorporated into the hemoglobin protein of the red blood cell (RBC).
• More stable than sugar levels.
• Not affected by short-term fluctuations in sugar.
• Normal is 4-6%.
• Evaluated periodically (1-2 per year).

• A1C %
• - Normal ~5
• - Prediabetes 5.7-6.4
• - Diabetes 6.5 or above
• Fasting plasma glucose mg/dl
• - Normal no more than 99
• - Prediabetes 100-125
• - Diabetes 126 or above
• Oral glucose Tolerance test mg/dl
• - Normal no more than 139
• - Prediabetes 140-199
• - Diabetes 200 or above

• Microangiopathy - cerebral vascular infarcts; hemorrhage
• Retinophathy - cataracts; glaucoma
• Nephrosclerosis - glomerulosclerosis
• Peripheral vascular atherosclerosis - gangrene, infections

• Both nodular (Kimmelstiel - Wilson lesion) and diffuse glomerulosclerosis
• Chronic renal failure eventually
• Infections – pyelonephritis (bacterial and fungal infections)

• One of the leading causes for irreversible blindness in the United States
• Cataract - developed at very early age
• Glaucoma
• Blindness

• Early and accelerated atherosclerosis
• Hypertension
• Heart disease, cerebrovascular disease, and renal disease
• The most common cause of death - myocardial infarction
• Peripheral vascular disease - gangrene leg and amputation
• Diabetic neuropathy, leading to propensity for injury

• Type 1: insulin administration
• Type 2: diet & exercise
• - Oral hypoglycemics
• - Insulin

• a.k.a. Islet cell tumors
• 2% of all pancreatic neoplasms
• Common in adults, in body or tail
• Single or multifocal
• Functional (excessive hormone production) and nonfunctional (without hormone production; larger and metastasize)
• Slow growing, metastases to nodes, liver, bone.
• 80% occur in MEN1 patients.
• Insulinoma: most common; followed by gastrinoma

• Insulinoma – Beta cells; insulin-secreting tumor
• Gastrinoma – Delta cells
• Somasostatinoma – Delta cells
• Glucagonoma – Alpha cells
• VIPoma – Delta cells
• Nonfunctional

• Solid, gyriform, trabecular and glandular patterns.
• Nests of polygonal cells with moderate to abundant eosinophilic cytoplasm.
• Amyloid is produced by insulin-secreting tumors (from amylin or somatostatin).
• Immunostains not necessary for diagnosis.
• - Synaptophysin
• - Chromogranin
• - Insulin
• - EM – dense core granules

• Low grade (G1): <2 mitoses per 10 hpf (high power field) and <3% Ki67 (immunostain, discriminate cells according to cell cycle phases) index
• Intermediate grade (G2): 2-20 mitoses per 10 HPF or 3%-20% Ki67 index
• High grade (G3): >20 mitoses per 10 hpf or >20% Ki67 index

• Commonest type.
• Hypoglycemia ≤ 0.5 gram per liter.
• Attack induced by fasting or exercise, relieved by eating or glucose administration
• Lab - low serum glucose, high serum insulin.
• Most tumors solitary (< 2 cm), can be multiple.
• Majority are benign, 10% malignant.
• 90% cured by resection.

• 2/3 of cases malignant.
• Present with Zollinger-Ellison Syndrome (triad - hypersecretion of gastric acid, severe peptic ulceration, and non-beta cell tumor of the pancreas or duodenum).
• Marked elevation of serum gastrin (>1000 pg/ml).
• Medical therapy for control of the acid hypersecretion.
• Histologically bland.
• May be associated with MEN1.

• 25% of islet cell tumors
• 90% malignant
• Age 50 year, female predominance
• Compression related symptoms
• Treatment - surgery

• Normally on the posterior thyroid surface
• Most persons have four; may vary between 1 to 12.
• Well capsulated.
• Derivatives of third and fourth branchial pouches.
• Ectopic locations:
• - intrathyroid
• - intrathymic
• - anterior mediastinum

• Chief cells – polygonal cells with clear cytoplasm (glycogen) and central uniform nuclei; secrete PTH.
• Oxyphil cells – larger than chief cells, acidophilic cytoplasm (pink), packed with mitochondria.
• Stromal fat – approximately 30% of the gland; increases when older.

• Serum Calcium: 8 to 10 mg per dl
• Ionized (free) Calcium: 4 to 5.6 mg per dl

• increase plasma calcium level via
• - increase bone resorption.
• - lower renal phosphate reabsorption and increase calcium reabsorption.
• - increase intestinal calcium absorption (by stimulating renal secretion of 1,25-DH-viatmin D3).

• Raised PTH - Hyperparathyroidism (primary, secondary and tertiary); Parathyroid tumor. Normal level - 10-65 nmol per Liter.
• Decreased PTH (non-PTH)
• - Hypercalcemia of malignancy (most common, esp lung)
• - Vitamin D toxicity
• - Immobilization
• - Thiazide diuretics
• - Granulomatous disease (sarcoidosis)

• Normal PTH - 10 to 65 nanomoles per Liter.
• Increased parathyroid hormone.
• Serum calcium may be decreased, increased or normal, depending upon renal function.
• Primary hyperparathyroidism – excess of parathyroid hormone from adenoma (85 to 95%), hyperplasia (5 to 10%) or carcinoma (1%).
• Secondary hyperparathyroidism – adaptive increase in parathyroid hormone secondary to hypocalcemia and hyperphosphatemia of chronic renal failure.
• Tertiary hyperparathyroidism – autonomous parathyroid hyperfunction in patients with secondary hyperparathyroidism.

• Primary - normal or high PTH; high calcium.
• Secondary - high PTH; high or normal calcium.
• Tertiary - very high PTH; high calcium.

• Hypercalcemia, hypophosphatemia
• Asymptomatic mostly or present with nonspecfic symptoms such as fatigue, lethargy and muscle weakness.
• “Bones, stones, abdominal groans, psychic moans”
• Bones - pain, arthralgia - osteoporosis, osteitis fibrosa cystica (brown tumor, similar to the ones in jaw bones), fracture.
• Renal - Stones, polyuria, nephrocalcinosis.
• G.I. - Pain, duodenal ulcer, pancreatitis, gallstones.
• Neuro - Depression, apathy
• Cardiac - Hypertension, heart block

• Benign neoplasm.
• Involve a single gland, rarely two or more (<1%).
• Major cause of primary hyperparathyroidism.
• Any age, F:M 3:1.
• Excellent prognosis after excision.
• Sharply demarcated from the adjacent rim of normal parathyroid.
• Predominantly chief cells in sheets or tubules.
• Adipose tissue inconspicuous.

• Classically all four parathyroid involved (frequently asymmetrical).
• Sporadic or as a component of MEN syndrome.
• 75% sporadic
• 15% part of MEN 2A (not MEN 2B)
• 15% of hyperparathyroidism cases
• Diagnosis of adenoma versus hyperplasia may depend on the size of the other glands (one is adenoma, two or more is hyperplasia).
• Enlarged parathyroids.
• Usually chief cell hyperplasia, diffuse or nodular
• Variable oncocytes.
• Cystic change in markedly enlarged glands.
• Stromal fat inconspicuous.

• Palpable neck mass (75%)
• Excessive PTH secretion, high serum calcium > 14 mg/dl.
• Non-functioning tumors are rare.
• Diagnosis based on local invasion and metastases (clinical criteria, NOT microscopic criteria).
• 1/3 recur locally; 1/3 have distant metastases.
• Densely adherent to surrounding soft tissue.
• Thick fibrous bands.
• Predominantly chief cells arranged in solid or trabecular pattern.
• Macronucleoli, more than five mitoses per 50 hpf, necrosis associated with aggressive behavior.
• Cytological detail, unreliable for the diagnosis of carcinoma.

• Insufficient parathyroid hormone is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood.
• Hypoparathyroidism is far less common.
• Causes
• – Damage to the gland or its vessels during thyroid surgery
• - Idiopathic, autoimmune disease, congenital
• Clinical features:
• - Tetany, convulsion, neuromuscular irritability, cardiac arrhythmias, increased intracranial pressure, seizures, ...

• MEN I (Wermer syndrome)
• - Neoplasia of Pituitary, Parathyroids, Pancreas and Carcinoids;
• - Parathyroid hyperplasia.
• MEN IIA (Sipple's syndrome)
• - Parathyroid hyperplasia
• - Medullary thyroid (c-cell) carcinoma
• - Pheochromocytomas.
• MEN IIB
• - Medullary thyroid (c-cell) carcinoma
• - Pheochromocytomas
• - Neuromas of eye, buccal mucosa and GI mucosa.

• Pyramidal lobe (present in 40% population)
• Isthmus
• Left and right lobes

• Follicles made of Colloid surrounded by follicular epithelial cells (squamous, cuboid, or columnar; secreting thyroid hormones - T3 and T4).
• Parafollicular cell (C cell; fewer and scattered) secretes calcitonin, can be picked up by calcitonin stain.
• Capillary in the connective tissue.

• Largest endocrine organ
• Thyroid hormones (TH)
• - Thyroxine (T4)
• - Triiodothyronine (T3)
• - Calcitonin

• Hypothalamus stimulates pituitory to release T.S.H. via T.R.H.
• Serum free hormone level inhibits pituitary to release T.S.H.
• T.S.H. stimulates thyroid to release T3 and T4
• liver releases thyroid binding proteins to bind T3/T4.

• Duct from Foramen cecum to suprasternal notch.
• Lingual thyroid - Most frequent; more in children; base of tongue with total migration failure; 75% have no other thyroid tissue.
• Other sites – anterior tongue, larynx, trachea, mediastinum, heart.

• Persistence and dilatation of thyroglossal duct in midline of neck.
• Asymptomatic unless infected.
• Moves with swallowing.
• Squamous or respiratory epithelium lining cyst.

• Primary:
• - Loss of thyroid tissue due to surgery or radiation therapy
• - Hashimoto’s thyroiditis (most common cause in USA)
• - Iodine deficiency (in endemic areas; most common cause worldwide)
• - Drugs e.g. iodides, lithium…..
• Secondary:
• - Pituitary or Hypothalamic failure

• High TSH, low T3, T4
• Hypothyroidism in infants – cretinism (poor growth, resulting in short stature, delayed development of permanent teeth, Delayed puberty, poor mental development).
• Hypothyroidism in adults - myxedema
• Treatment - Synthetic thyroid hormone

• Chronic lymphocytic
• - Chronic lymphocytic thyroiditis
• - Hashimoto's thyroiditis
• Granulomatous
• - Subacute granulomatous thyroiditis
• - de Quervain's thyroiditis
• Invasive fibrous
• - Riedel's struma
• - Riedel's thyroiditis

• Most common cause of goiter in the United States.
• Autoimmune origin.
• Painless enlargement, no tenderness when palpated.
• Diffuse nontender rubbery thyroid enlargement.
• Variable functional status: euthyroid (normal serum level), hyperthyroid (Hashitoxicosis; when follicle ruptures and T3/4 released) or hypothyroid.
• Flashy cut surface.
• Histologic diagnostic triad:
• - lymphocytic infiltrate
• - lymphoid follicles with germinal centers
• - Hurthle cell metaplasia of follicular epithelium
• High risk for B-cell lymphoma, papillary carcinoma and Hurthle cell neoplasm

• Caused by viral infection.
• Most common cause of painful thyroid.
• Onset often acute, fever and malaise.
• Triphasic clinical course - hyperthyroidism, hypothyroidism, and return to normal thyroid function (within 6-8 weeks).
• Disruption of follicles with inflammation.
• Granulomatous reaction to colloid.
• Multinucleated giant cells.

• Rare.
• Autoimmune etiology.
• Stony hard painless thyroid gland.
• Extensive fibrosis.
• Clinically resembles carcinoma, compress trachea.
• Broad bands of fibrosis with keloid like fibers.
• Patchy lymphocytes, plasma cells and eosinophils.
• Follicles are obliterated.
• Obliterating phlebitis.

• Hypermetabolic state caused by T4, T3
• Primary: Graves Disease
• Secondary: TSH-secreting pituitary adenoma

• Heat intolerance, sweating, warm skin, malabsorption
• Cardiac - palpitation, tachycardia, CHF
• Menstrual disturbances
• Neuromuscular - Tremor, muscle weakness
• Ocular - thyroid ophthalmopathy

• Autoimmune disease.
• Thyrotoxicosis with smooth symmetrical enlargement of thyroid.
• Infiltrative ophthalmopathy with exophthalmus in 40%
• of patients.
• Lab findings - increased T4 & T3, decreased TSH.
• Radioactive study- Diffuse uptake of radioactive Iodine.
• Most common cause of endogenous hyperthyroidism.
• Triad of clinical findings:
• - diffuse enlargement of thyroid
• - infiltrative ophthalmopathy (exophthalmos)
• - Infiltrative dermatopathy (periorbital myxedema)

• Diffuse hyperplasia of thyroid follicular cells.
• Papillary hyperplasia.
• Scalloped appearance of the edges of the colloid.
• Lymphoid follicles.

• Solitary nodule.
• Cold nodules - Up to 10% of cold nodules prove to be malignant.
• Younger patients.
• Males.
• History of previous radiation to the neck.

• Incidence 3-5%, and 50% in autopsy cases.
• Sometime extends in the mediastinum.
• Pressure effect on trachea.
• Endemic (iodine deficiency) and sporadic.
• Can have gelatinous colloid, cysts.
• Distended follicles of various sizes, filled with colloid, flat follicular epithelium.
• Fibrosis.
• Focal hyperplasia, scalloping
• Hemorrhage
• Calcification

• Most common endocrine malignancy.
• Less than 2% of all human cancers.
• Generally more common in women.
• Associated with radiation exposure and endemic goiters.
• Benign to malignant ratio is 10:1.
• Low mortality rate - 0.4% of cancer deaths.

• Euthyroid and present with thyroid nodule.
• Symptoms such as dysphagia, dyspnea, and hoarseness usually indicate advanced disease.
• Ipsilateral cervical lymph nodes may be present.

• Ultrasound examination of neck and thyroid.
• Blood tests of thyroid function.
• A radioactive thyroid scan.
• A fine needle aspiration biopsy.
• A chest X-ray.
• A CT or MRI scan.

• Follicle derived give rises to well differentiated and anaplastic,
• - Well differentiated give rises to papillary carcinoma and follicular tumors.
• - - Follicular tumors give rises to follicular adenoma and follicular carcinoma.
• C(hief)-cell derived give rise to Medullary carcinoma.

• Tumors of follicular cell origin, differentiated
• - Papillary 75%
• - Follicular 10%
• - Hurthle cell 5%
• Tumors of follicular cell origin, undifferentiated
• - Anaplastic 5%
• Tumors of parafollicular cell origin
• - Medullary 5%
• Others
• - Lymphoma <1%

• Most common thyroid neoplasm.
• Benign.
• Almost always solitary.
• Well capsulated.
• Uniform follicles within the lesion.
• Compress adjacent normal thyroid tissue.
• No vascular or capsular invasion.

• 10 -15% of thyroid cancer.
• Usually “cold” on radionuclide scan.
• More aggressive.
• Hematologic spread.
• 60% 10 year surviva.l
• Architectural patterns, follicular or solid.
• Capsular invasion.
• Vascular invasion beyond the capsule.
• Integrity of capsule is important in differentiating adenoma from well differentiated follicular carcinoma.

• The most common malignant thyroid tumor (75%).
• Any age.
• Associated with prior radiation.
• Spread via lymphatics – propensity for lymph node
• metastasis.
• Excellent prognosis.
• 10 yr survival >95%.

• Optically clear nuclei (Orphan Annie).
• Intranuclear inclusion and groove.

• SEX: WOMEN - good
• AGE: CHIDREN - good
• GRADE: DEDIFFERENTIATION - POOR
• EXTENT: EXTRATHYROID EXTension - POOR
• SIZE: LARGE - POOR

• Neuroendocrine neoplasm originate from calcitonin-producing parafollicular chief cells.
• Solitary or multiple lesions.
• 5-10% of all thyroid cancers.
• 80% Sporadic.
• 20% occurs in the setting of MEN 2A or 2B or as familial tumors.
• Form nests, trabeculae or follicles.
• Polygonal to spindle-shaped cells.
• Acellular amyloid deposits (congo red positive; polarize).
• Positive to Calcitonin immunostain.

• Originates from follicular cells.
• Constitute 5-10% of all thyroid carcinomas.
• Peak incidence – 7th decade.
• Highly fatal, most die within one year.
• Grows rapidly (needs to be treated immediately), spreads locally, invades trachea, esophagus, mediastinum by local invasion.
• Gross - large solid tumor with necrosis and hemorrhage.
• Pathology
• - Multinucleated osteoclast-type giant cells
• - Spindle cell sarcoma-like morphology
• - Squamoid morphology

• Type - %
• - Papillary 75
• - Follicular 15
• - Anaplastic 5
• - Medullary 5
• Age
• - Young <45y
• - Middle age
• - elderly
• - Elderly, familial
• Spread
• - Lymph
• - B.V.
• - Local
• - All
• Prognosis
• - Excellent
• - Good
• - Poor
• - variable

• In sella turcica of sphenoid bone.
• Weighs about 0.5gm.
• Connected to the Hypothalamus with stalk.
• Composed of:
• - Anterior lobe - Adenohypophysis (80% volume)
• - Posterior lobe - Neurohypophysis (20%); close to third ventricle, optic chiasm, cranial nerves, tumor can affect them.
• Embryology - Roof of the oral cavity and diencephalon come together.

• Pinker in color compared to adenohypophysis.
• Stores and releases hormones secreted by hypothalamus: Oxytocin and Anti Diuretic hormone (ADH).

• Releases hormones:
• Growth hormone (GH)
• Thyroid Stimulating hormone (TSH)
• Adenocorticotropic hormone (ACTH)
• Lutenizing hormone (LH) - target ovary
• Follicle stimulating hormone (FSH) - target ovary
• Prolactin (PRL) - tumor most common
• Melanocyte stimulating hormone (MSH) - pigmentation

• TSH
• –hypersecretion = hyperthyroidism
• –hyposecretion = hypothyroisism
• ACTH
• –hyposecretion = secondary adrenal insufficiency, Addison’s disease
• –hypersecretion = Cushing’s disease
• FSH
• –hyposecretion
• •M = poor sperm production
• •F = low estrogen, amenorrhea
• –hypersecretion
• •F = menopause
• LH
• –hyposecretion
• •F = no ovulation
• •M = low testosterone
• MSH
• –hypersecretion = excess pigment
• GH
• –hypersecretion = gigantism if during growth or acromegaly after growth
• –hyposecretion = dwarfism
• PRL
• –hypersecretion = galactorrhea, infertility
• –hyposecretion = poor milk production
• ADH
• –Hypersecretion = SIADH, Syndrome of Inappropriate ADH Secretion
• –hyposecretion = diabetes insipidus

• The pink acidophils (acidophilic cytoplasm) secrete growth hormone (GH) and prolactin.
• The dark purple basophils secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and gonadotrophins, i.e. follicle stimulating hormone and luteinizing hormone.
• The pale staining chromophobes have few cytoplasmic granules, but may have secretory activity, secretion is not much affected if tumor is developed from them.

• Hyperpituitarism-related effects:
• - Excessive secretion of tropic hormones.
• - Anterior pituitary adenoma (benign).
• Hypopituitary-related effects:
• - Deficiency of tropic hormones.
• - Destructive processes (injury, inflammation, surgery, radiation).
• Local mass effect:
• - Compressive effect of optic chiasm or third ventricle (Headache, loss of vision, hydrocephalus).

In most cases due to ADENOMA of the anterior lobe.

• Pressure symptoms from glandular enlargement - Headache, seizures, drowsiness, visual defects.
• Hormonal effects
• - Usually stimulatory if functional tumor.
• - May be inhibitory (non-functional with pressure necrosis).
• Most common hormonally active adenomas - prolactinoma, followed by growth hormone related adenoma.

• 10% of all intracranial neoplasms & 25% incidental.
• Most sporadic.
• 3% occur with MEN I syndrome (3 P's).
• Usually benign.
• May or may not be functional.
• If Functional, the clinical effects are secondary to the hormone produced, most commonly Prolactin and GH.
• If Non-functional – large size, hypopituitarism (destroy adjacent anterior Pituitary), visual field abnormalities.
• Microadenomas <1 cm, may cause focal bulging.
• Macroadenoma >1 cm, mass effect.

• Imaging:
• - MRI brain with and without I.V. contrast (include thin cuts through pituitary); Tumor enhances less than gland, more lucent appearance.
• Labs - Prolactin, FSH, LH, GH, ACTH, testosterone, GH, cortisol, IGF-1
• Visual Fields - Performed by an ophthalmologist, temporal fields lost, central field remains.

• Well circumscribed, invasive in up to 30%.
• Size 1cm or more, specially in nonfunctioning tumor.
• Hemorrhage & necrosis seen in large tumors.
• Uniform cells - one cell type (monomorphism), less granular and hard to tell what hormones are secreted.
• No reticulin network, no surrounding nest.
• Rare or absent mitosis.

• PRL secreting adenoma (prolactinoma) – Most common, 30% of pituitary adenoma, prolactin level is similar or higher than that during pregnancy.
• ACTH secreting adenoma
• Null cell adenoma
• Gonadotropin-secreting adenoma
• GH-secreting adenoma
• GH and PRL-secreting adenoma
• TSH-secreting adenoma
• Can test by immunohisto stain.

• High linear growth due to excessive action of insulin-like growth factor I (IGF-I) while the epiphyseal growth plates are open during childhood.
• Very tall, very long legs and arms.
• Other symptoms - diabetes, arthritis, large jaw & hands, osteoporosis, hypertension, heart failure …..

• After the epiphyseal growth plates are closed.
• Enlarged hands and feet.
• Coarsened, enlarged facial features.
• Impaired vision.
• Headaches.
• Enlarged tongue.
• Menstrual cycle irregularities in women.
• Erectile dysfunction in men.
• Enlarged liver, heart, kidneys, spleen and other organs.
• Increased chest size (barrel chest).

• 25-30% of patients do not have classical hypersecretory syndromes.
• May grow to a large size before they are detected (mass effect).
• Visual deficits - double vision; Bitemporal hemianopsia.

• Congenital or acquired.
• Loss of 75% of anterior Pituitary to show Symptoms.
• Symptoms include dwarfism, effect of individual hormone deficiencies.
• Acquired causes include:
• 1- Nonsecretory pituitary adenoma.
• 2- Ischemic necrosis e.g. postpartum.
• 3- Iatrogenic by radiation or surgery.
• 4- Autoimmune (lymphocytic) hypophysitis.
• 5- Inflammatory e.g. sarcoidosis or TB …..

• Pituitary gland does not produce enough growth hormones.
• Height lies between 2' 8'' to 4' 8''.

Hypothalamic neurons produce two peptides – ADH and oxytocin. They are stored in axon terminals in neurohypophysis and released with appropriate stimuli.

Not associated with any significant abnormality.

• ADH deficiency - causes Diabetes Insipidus, Excessive urination, dilute urine , due to inability to reabsorb water from the collecting tubules.
• Secretion of inappropriately high level of ADH (SIADH – syndrome of inappropriate ADH) - Causes excessive resorption of water, hyponatremia (low serum level of Sodium).

• From Breast, lung ,GI tract.
• Posterior lobe mostly affected.
• Anterior lobe rarely involved.

• 1-5 % of intracranial neoplasms.
• Derived from remnants of Rathke’s Pouch.
• Suprasellar or intrasellar, often cystic with calcification.
• Children or adolescents most affected.
• Symptoms of hypofunction or hyperfunction of pituitary and /or visual disturbances, diabetes insipidus.
• Benign & slow growing.
• Low grade circumscribed epithelial tumors.
• Partly cystic and calcified mass.
• Squamoid and columnar epithelium lining cystic spaces filled with oily fluid (keratin debris).
• "Stellate reticulum" and "wet keratin" are prominent features.

• The most common cause of hyperpituitarism is an anterior lobe pituitary adenoma.
• Pituitary adenomas can be macroadenomas (>1 cm) or microadenomas (<1 cm).
• Macroadenoma – mass effects including visual disturbances.
• Clinically, can be functional or silent.
• Functioning adenomas – associated with distinct endocrine signs and symptoms.
• The two distinctive morphologic features of most adenomas are their cellular monomorphism and absence of a reticulin network.

• A pair of endocrine glands just above the kidney.
• Secretion:
• - steroids from cortex.
• - catecholamines from medulla.

• Zona glomerulosa - outer most; mineralocorticoids (aldosterone), associated with SALT.
• Zona fasciculata - glucocorticoids (cortisol), associated with SUGAR.
• Zona reticularis - inner most; estrogens & androgens, SEX.
• Diseases are those of hyperfunction & hypofunction & tumors.

• Cushing’s Syndrome (excess of cortisol)
• Hyperaldosteronism
• Adrenogenital or virilizing syndrome (excess of androgen)

• Elevation of cortisol level
• Endogenous causes: all have adrenal hyperplasia
• - Pituitary Cushing syndrome: hypersecretion of ACTH (70% of endogenous hypercortisolism).
• - Ectopic secretion of ACTH by non-pituitary neoplasm (10%) - paraneoplastic Cushing Syndrome, small cell lung cancer.
• - Primary adrenocortical neoplasm and rarely nodular hyperplasia (15-20%)
• Exogenous cause:
• - Steroid Therapy: most common cause of hypercortisolism; iatrogenic; can also cause adrenal atrophy.

• Central obesity 85-90%
• Moon face 85%
• Weakness and fatigability 85%
• Hirsutism 75%
• Hypertension 75%
• Glucose intolerance/diabetes 75%
• Osteoporosis 75%
• Menstrual abnormalities 70%
• Cutaneous striae 50%

• High aldosterone causes Na retention & K excretion, increase blood pressure, Hypokalemia.
• Primary – adrenal (decreases plasma renin)
• - Potential causes – Nodular hyperplasia (60%), Neoplasm (35%), Rarely familial.
• Secondary – extra adrenal (increases plasma renin)
• - Potential causes – Decreased renal perfusion, Arterial hypovolemia and edema, Pregnancy.

• Causes
• - Primary gonadal disorders
• - Adrenocortical Neoplasms
• - Congenital adrenal hyperplasia
• Neoplasms can occur at any age, frequently malignant.
• Virilization, precocious puberty, ambiguous genitalia.
• Patients have risk for acute adrenocortical insufficiency.

• Encapsulated, solitary, usually yellow.
• Benign or malignant.
• Nonfunctioning or functioning.
• Malignant tumors with necrosis, hemorrhage (≥ 300gms)
• Hypercorticolism is usually more marked with carcinomas than with adenomas or hyperplasia.
• Size variable.
• Local invasion, & the presence of metastases differentiate benign from malignant tumors.

• Capsulated tumor with uniform or slightly pleomorphic cells, may be eosinophilic or clear cell type
• Spironolactone bodies in hyperaldosteronism

Lager than adenoma, non-capsulated with nuclear pleomorphism, mitoses and necrosis.

• Acute :
• 1- Massive adrenal hemorrhage as in anticoagulant
• therapy, DIC, sepsis by N.meningitidis, pseudomonas
• (Waterhouse- Frederickson syndrome).
• 2- Sudden withdrawal of steroid therapy.
• 3- Stress in patient with underlying chronic insufficiency.
• Chronic (Addison’s disease): Progressive destruction of the adrenal by:
• 1- Autoimmune Disorder: 75-90%, may be sporadic.
• 2- Infections e.g. Tuberculosis , fungi ( AIDS).
• 3- Metastatic tumors destroying adrenal e.g. lung, breast , …others.

• Symptoms
• - fatigue, lassitude, malaise, weakness, anorexia.
• - postural dizziness, syncope.
• - GI - nausea, vomitting, abdominal pain, diarrhea, constipation.
• - myalgias, arthralgias, rarely flexion contractures.
• - decreased libido, amenorrhea.
• Signs
• - Weight loss
• - Hyperpigmentation
• - Hypotension
• - Thinning of axillary and pubic hair
• - Vitiligo

• Derived from neural crest.
• Part of sympathetic system.
• Composed of Chromaffin cells secreting catecholamines.
• Diseases are mainly tumors: Pheochromocytoma and Neuroblastoma.

• Neuroendocrine tumor of adrenal medulla.
• Originates from the chromaffin cells along the paravertebral sympathetic chain extending from pelvis to base of skull.
• >95% are abdominal.
• >90% in adrenal medulla.
• Secretes excessive amounts of adrenaline and noradrenaline.
• Diagnosis – increased urinary excretion of free catecholamine and their metabolites (VMA and metanephrins).
• A familial syndrome that predisposes to catecholamine-secreting tumors (MEN2, NF1, VHL).

• 10% extra-adrenal (closer to 15%)
• 10% occur in children
• 10% familial (closer to 20%)
• 10% bilateral or multiple (more if familial)
• 10% recur (more if extra-adrenal)
• 10% malignant
• 10% discovered incidentally

• The five P’s:
• - Pain (Headache) 80%
• - Perspiration (sweaty) 71%
• - Palpitation 64%
• - Pallor 42%
• - Pressure (HTN) 9% - Surgically correctable
• - - Paroxysms (the sixth P!)
• The Classical Triad:
• - Pain (Headache)
• - Perspiration
• - Palpitations
• - Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,0000 patients

• Zellballen (small nests or alveolar pattern), trabecular or solid patterns of polygonal / spindle shaped cells in rich vascular network.
• May have mitoses and marked pleomorphism.
• Capsular and vascular invasion common in benign behaving tumors.
• Definitive diagnosis of malignancy – presence of metastasis

• Second most common solid childhood neoplasm, after CNS tumors.
• Usually adrenal but maybe extra-adrenal (sympathetic nervous system).
• Familial or sporadic.
• Associated with deletion of short arm of chromosome 1.
• 90% associated with catecholamine secretion.
• 24hr urinal VMA excretion is helpful in diagnosis.
• Some differentiate (ganglioneuroblastoma) and spontaneously regress.
• Rapid growth & widespread metastasis.
• Treatment complex - surgery, RT, chemotherapy.

• Large mass with necrosis.
• Small round blue cell tumor with rosettes.
• Areas of necrosis and calcification.
• May differentiate to ganglion cells.

• Inherited diseases resulting in hyperplasia, adenomas and carcinomas.
• Younger age.
• Multiple endocrine organ Involvement (synchronous or metachronous).
• Asymptomatic stage of endocrine hyperplasia.
• More aggressive and recur.