ENDOCRINE

CLASSICAL ALGORITHM PITUITARY

ANTERIOR POSTERIOR

THYROID PARATHYROID PANCREAS (endo.) ADRENAL

CORTEX MEDULLA

DEGENERATION (aka, involution)

INFLAMMATION NEOPLASM

BENIGN MALIGNANT

BETTER ALGORITHM NON-NEOPLASTIC

HYPER-function HYPO-function

NEOPLASTIC FUNCTIONAL NON-FUNCTIONAL Functional endocrine

malignancies are RARE. Why?**********

PITUITARY ANTERIOR POSTERIOR

THYROID PARATHYROID PANCREAS (endo.) ADRENAL

CORTEX MEDULLA

FEEDBACK SYSTEMS CORTEX, SUBCORTEX? HYPOTHALAMUS ANTERIOR PITUITARY ENDOCRINE GLAND END ORGAN HYPOTHALAMUS

AntPitWiFiPostPitWired

HORMONESPOLYPEPTIDE (2nd MESSENGER)

STEROID (DIRECT on NUCLEUS)

ACIDOPHILS

BASOPHILS

CHROMOPHOBES

AXONS

AXONS and PITUI-cytes

A

I P

ANTERIOR PITUITARY ACIDOPHILS (growth)

GROWTH HORMONEPROLACTIN

BASOPHILS (trophs)TSHACTHLH, FSH

POSTERIOR PITUITARY

OXYTOCIN (contracts uterine smooth muscle)

VASOPRESSIN (ADH) (vasoconstriction, gluconeogenesis, platelet aggregation, release of Factor-VIII and vWb factor, concentrates urine, main effects on kidney and brain)

PITUITARY PATHOLOGY CLINICAL FEATURES, mimic the endocrine

effects, visual effects, or mass effects)

FUNCTIONING ADENOMAS

HYPO-PITUITARISM

POSTERIOR PITUITARY SYNDROMES

HYPOTHALAMIC (SUPRASELLAR) TUMORS

CLINICAL FEATURES HYPER: growth(a), lactation(a),

thyroid(b), adrenal cortex(b)

HYPO: growth, thyroid, adrenal cortex

MASS EFFECT: visual fields, brain

GA

L

A

C

T

O

R

R

H

E

A

GIGANTISM

(excess somatotropin [GH] BEFOREepiphyseal

closure)

ACROMEGALY:

(excess somatotropin [GH] AFTER epiphyseal closure)

MOON FACIES

BUFFALO HUMP

STRIAE

BITEMPORAL

HEMIANOPSIA

HYPO-pituitarism Pituitary tumors, functional or not. NON-pituitary tumors, primary or metastatic Pituitary surgery, of course Radiation, of course Apoplexy, i.e., sudden hemorrhage Sheehans syndrome (Post-partum ischemic

necrosis) Cysts (Rathkes cleft) Empty sella syndrome, (is NOT a disease) Genetic defects (pit-1 gene mutations)

POSTERIOR pituitaryDIABETES INSIPIDUSSIADH (Syndrome of Inappropriate Anti- Diuretic Hormone)

DIABETES INSIPIDUS ADH deficiency Head trauma, tumors,

inflam. hypothal/pit Hyperdiureses with LOW sp.gr.

Inappropriate ADH ADH EXCESS (SIADH)

Hyponatremia (hypervolemia), cerebral edema, neurologic symptoms

Neoplasms, esp. Small Cell CA.NON-neoplastic lung diseasesPosterior pituitary injury

15-25 grams

HYPER-THYROIDISM aka, thyrotoxicosis Diffuse (Graves disease) Nodular Adenoma Carcinoma Neonatal Secondary to TSH pituitary adenoma

HYPER-THYROIDISM HYPERMETABOLISM Tachycardia, palpitations Increased T3, T4 Goiter Exophthalmos Tremor GI hypermotility Thyroid storm, life threatening

HYPO-THYROIDISM 1 Developmental 1 Surgery, I-131, external radiation 1 Auto-immune (i.e., Hashimotos) 1 Iodine deficiency 1 Li+, iodides, p-aminosalicylates 2 (pituitary) 3 (hypothalamic, rare)

HYPO-THYROIDISM Cretinism

Severe retardation CNS/Musc-skel Short stature Protruding tongue Umbilical hernia Maternal iodine defic.

Myxedema (coma) Sluggishness (lesu) Cool skin, cholesterol

THYROIDITIS Hashimoto (Auto-Immune) (Lymphoid

follicles with germinal centers), MOST COMMON cause of acquired hypothyroidism in USA

Subacute Granulomatous (DeQuervain)

Subacute Lymphocytic (just like Hashimotos but NO fibrosis and no germinal centers), often post-partum

GRAVES DISEASE(aka, diffuse toxic goiter)

HYPERTHYROIDISM EXOPHTHALMOS PRE-TIBIAL MYXEDEMA

Autoimmune, auto-antibodies to TSH receptors, thereby stimulating them

SCALLOPING

GRAVES DISEASE(aka, diffuse toxic goiter)

PLUMMER DISEASE(aka, nodular toxic goiter)

HARDER TO TREAT

Surg

PTU (Propyl Thio Uracil)

I-131

GOITERS(aka, thyromegaly, diffuse or nodular)

IODINE deficiency Increased TSH Goitrogens, e.g., cabbage, Brussels

sprouts, cauliflower, turnips, cassava) Associated with HYPO thyroidism

eventually, NOT hyperthyroidism

GOITER

Thyroid Neoplasms Nodules vs. true neoplasms

Adenomas vs. Carcinomas

NODULES Solitary vs. Multiple Younger vs. Older Male vs. Female Hx. neck radiation vs. NO Rx. Cold vs. HOT (really NOT-

cold)

NEOPLASMS ADENOMAS

FOLLICULARHRTHLE

(oxyphilic)

CARCINOMASFOLLICULARPAPILLARY MEDULLARY

(AMYLOID) ANAPLASTIC

(worst)

HRTHLE CELL ADENOMA, note atypia

ORPHAN ANNIE CELLS in PAPILLARY CARCINOMA

MEDULLARY CARCINOMA of the thyroid with HYALINIZATION, i.e.,

AMYLOID!!!

HYALINIZATION showing APPLE GREEN birefringence in CONGO RED stain, i.e., AMYLOID

BIOLOGIC BEHAVIOR Papillary CA lymph nodes

Follicular CA blood vessels, bone

35-50 mg

PTH HYPOCALCEMIA is MAIN STIMULUS

(9-10.5 mg/dl)

ANTAGONIZES CALCITONIN

PARATHYROID DISORDERS HYPER-

PRIMARY (usually adenomas)SECONDARY (LOW CA++ of Renal

Failure) HYPO-: Surgical, congenital,

familial, idiopathic PSEUDO-HYPO-

(end organ resistance)

HYPER-PARATHYROIDISM Bone pain, fractures Nephrolithiasis Constipation, ulcers, gallstones Depression, lethargy short QT interval and a widened T wave Weakness, fatigue

Calcifications, esp. VALVES

HYPO-PARATHYROIDISM Neuromuscular irritability Mental status change Parkinsonism like effects Lens calcification* (paradox) Widened QT interval Defective, carious, teeth

ADRENAL CORTEX Glomerulosa (Salt), mineralocorticoids

ALDOSTERONE

Fasciculata (Sugar), glucocorticoids CORTISOL

Reticularis (Sex), gonadocorticoids ANDROGENS, ESTROGENS

4 g.

SALT

SUGAR

SEX

STRESSSTRESS

HYPERADRENALISM HYPERALDOSTERONISM (g) CUSHING SYNDROME

(CORTISOL) (f) (most common of the three) ADRENOGENITAL

(VIRILIZING) SYNDROME (r)

CUSHING SYNDROME CENTRAL OBESITY MOON FACIES WEAKNESS HIRSUTISM HYPERTENSION DIABETES OSTEOPOROSIS STRIAE

MOON FACIES

BUFFALO HUMP

STRIAE

CUSHING SYNDROME PITUITARY ACTH INCREASE TUMOR ACTH INCREASE HYPERPLASIA OF CORTEX ADENOMA OF CORTEX CARCINOMA OF CORTEX

EXOGENOUS STEROIDS (90%)

PRIMARY HYPERALDOSTERONISM

(Conns Syndrome)

Na+ RETENTION K+ EXCRETION HYPERTENSION

PRIMARY HYPERALDOSTERONISM

CORTICAL NEOPLASM CORTICAL HYPERPLASIA FAMILIAL (rare)

SECONDARY HYPERALDOSTERONISM

DECREASED RENAL PERFUSION

EDEMA (HEART, LIVER, KIDNEY)

PREGNANCY

ADRENOGENITAL SYNDROME

VIRILIZATION/feminization CORTICAL NEOPLASM CORTICAL HYPERPLASIA 21-Hydroxylase Deficiency, with

buildup of 17-hydroxy progesterone

ADRENAL INSUFFICIENCY PRIMARY ACUTE (ADRENAL

CRISIS) PRIMARY CHRONIC (auto-

immune ADDISON DISEASE) SECONDARY (PITUITARY)

PRIMARY ACUTE RAPID WITHDRAWAL OF STEROIDS MASSIVE ADRENAL HEMORRHAGE

(WATERHOUSE-FRIDERICHSEN, if it follows infection [meningo, staph, H. flu] and shock) Newborns with DIFFICULT DELIVERY ANTICOAGULANT RX POSTSURGICAL DIC PATIENTS

PRIMARY CHRONIC Most of Addison disease is auto-

immune adrenalitis [ACAs]) INFECTIONS (fungal diseases, histo-) METASTASES (adrenals are an amazingly

preferred site for early lung carcinoma metastases)

GENETIC DISORDERS

NEOPLASMS ADENOMAS of ADRENAL

CORTEX

CARCINOMAS of ADRENAL CORTEX

ADRENAL MEDULLA PHEOCHROMOCYTOMAS, aka,

primary tumors of the adrenal medulla 10% arise in an MEN setting 10% are EXTRA-adrenal 10% are bilateral 10% are malignant 10% are in childhood You can only call them malignant if they

metastasize, but this is no bad thing, because they are all removed anyway

PHEO

TWO crucially important points specific for endocrine tumors:

1. FUNCTIONING carcinomas are very RARE in ANY endocrine gland. Why? (KEY principle of endocrine oncology)

2. Benign adenomas may have extremely bizarre nuclei, but are most usually BENIGN!!!

MEN-1, aka, Wermer Syndrome (3 Ps)

HYPERPARATHYROIDISM, chiefly hyperplasia

Pancreatic endocrine tumors

Pituitary adenoma, usually prolactinoma

MEN-2 MEN-2A (SIPPLE): Pheo,

Medullary CA., Parathyroid hyperplasia

MEN-2B: NO hyperparathyroidism, but neuromas present

Familial Medullary Thyroid CA

PINEAL GLAND PINEALOMAS

PINEOBLASTOMASPINEOCYTOMAS

ENDOCRINE

PANCREAS

Exocrine

Endocrine

Islets

Alpha Cells

Beta Cells

Delta Cells (somatostatin,suppress insulin and glucagon)

Pancreatic Polypeptide (PP) cells

Epsilon Cells make gherlin, which causes hunger

DIABETES MELLITUS 16 Million in the USA 1 Million/yr 50K people die of it per

year in the USA

How to Diagnose Dm: Glucose >200 Or. Fasting glucose >126 trice Or. Post-prandial glucose > 200, 2 hrs

AFTER standard OGTT (Oral Glucose Tolerance Test)

TWO* Types of DM1 Genetic Autoimmune Childhood (juvenile)

onset Antibodies to beta

cells, insulitis Beta cell depletion NON-OBESE

patients

2 Genetic, but diff. from

Type 1 NOT autoimmune Adult, or maturity

onset, e.g., 40s, 50s Insulin may be low,

BUT, peripheral resistance to insulin is the main factor

OBESE patients

* MODY might be regarded as the third type

DmPOLY-POLY-POLY-

INSULIN FAT

IN-creased glucose uptake IN-creased lipogenesis DE-creased lipolysis

MUSCLE IN-creased glucose uptake IN-creased glycogen synthesis IN-creased protein synthesis

LIVER DE-creased gluconeogenesis IN-creased glycogen synthesis IN-creased lipogenesis

PATHOGENESIS 1 T-Lymphocytes

reacting against poorly defined beta cell antigens

Inflammatory inflitrate, chronic, i.e., INSULITIS

2 Diet Life Style Obesity INSULIN

RESISTANCE Beta cells UN-able

to adapt to the long term demands of insulin resistance

MODY (Maturity Onset Diabetes of the Young)

Multiple types 2-5% of diabetics Primary beta cell defects Multiple genetic mechanisms,

especially GLUCOKINASE mutations

PANCREAS in Dm

PANCREAS in Dm

COMPLICATIONS MACRO-VASCULAR disease, i.e.,

ASCVD MICRO-VASCULAR disease, kidneys,

retina, nerves IMMUNE related problems,

INFECTIONS, e.g., TB, pneumonia, pyelonephritis, candida, etc.

COMPLICATIONS ADVANCED GLYCATION

collagen, laminin, polypeptides, GBM (glomerular basement membrane), Hgb1c

ACTIVATION of PROTEIN KINASE C, VEGF, endothelin-1, increased ECM, decreased fibrinolysis, inflam. cytokines

INTRACELLULAR HYPERGLYCEMIA

COMPLICATIONSMORPHOLOGY

(MACRO-vascular) Atherosclerosis MICRO-vascular

*Retinopathy*Nephropathy- glomerular, vascular, KW*Neuropathy (most common cause of

neuropathy)

Infections

ATHEROSCLEROSIS

ATHEROSCLEROSIS

RETINOPATHY in DmShows microaneurysms, areas of hemorrhage, cotton wool spots, hard exudates, venous beading, neovascularization, retinal detachment, vitreous detachment, pre retinal hemorrhage

NEPHROPATHYKimmelstiel-Wilson (KW) Kidneys

IS

Nodular glomerulosclerosis

NEPHROPATHYNEPHROSCLEROSIS

NEPHROPATHYGBM thickening

NEPHROPATHYDiffuse

Mesangial

Sclerosis

INFECTIONS in Dm SKIN TUBERCULOSIS PNEUMONIA PYELONEPHRITIS CANDIDA

NEOPLASMS of the Endocrine Pancreas

Islet cell tumors Beta cells INSULINOMAS (NOT rare) Alpha cells GLUCAGONOMAS (rare) Delta cells SOMATOSTATINOMAS

(rare)

GASTRINOMAS, producing ZOLLINGER-ELLISON SYNDROME, consisting of increased acid and ulcers

PowerPoint PresentationCLASSICAL ALGORITHMBETTER ALGORITHMFEEDBACK SYSTEMSSlide 5Slide 6HORMONESSlide 8Slide 9ANTERIOR PITUITARYSlide 11POSTERIOR PITUITARYPITUITARY PATHOLOGYCLINICAL FEATURESSlide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23HYPO-pituitarismPOSTERIOR pituitaryDIABETES INSIPIDUSInappropriate ADHSlide 28Slide 29Slide 30HYPER-THYROIDISMSlide 32Slide 33HYPO-THYROIDISMSlide 35THYROIDITISSlide 37Slide 38Slide 39GRAVES DISEASE (aka, diffuse toxic goiter)Slide 41Slide 42Slide 43Slide 44GOITERS (aka, thyromegaly, diffuse or nodular)Slide 46Slide 47Thyroid NeoplasmsNODULESSlide 50NEOPLASMSSlide 52Slide 53Slide 54Slide 55Slide 56Slide 57Slide 58Slide 59Slide 60Slide 61BIOLOGIC BEHAVIORSlide 63PTHPARATHYROID DISORDERSHYPER-PARATHYROIDISMHYPO-PARATHYROIDISMADRENAL CORTEXSlide 69Slide 70Slide 71Slide 72HYPERADRENALISMCUSHING SYNDROMESlide 75Slide 76PRIMARY HYPERALDOSTERONISM (Conns Syndrome)PRIMARY HYPERALDOSTERONISMSECONDARY HYPERALDOSTERONISMADRENOGENITAL SYNDROMESlide 81ADRENAL INSUFFICIENCYPRIMARY ACUTEPRIMARY CHRONICSlide 85Slide 86Slide 87Slide 88Slide 89ADRENAL MEDULLASlide 91Slide 92TWO crucially important points specific for endocrine tumors:MEN-1, aka, Wermer Syndrome (3 Ps)MEN-2PINEAL GLANDSlide 97Slide 98Slide 99Slide 100DIABETES MELLITUSHow to Diagnose Dm:TWO* Types of DMDmINSULINPATHOGENESISMODY (Maturity Onset Diabetes of the Young)PANCREAS in DmSlide 109COMPLICATIONSSlide 111COMPLICATIONS MORPHOLOGYATHEROSCLEROSISSlide 114RETINOPATHY in DmSlide 116NEPHROPATHYSlide 118Slide 119Slide 120INFECTIONS in DmNEOPLASMS of the Endocrine Pancreas