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CLASSICAL ALGORHYTHM• PITUITARY
– ANTERIOR– POSTERIOR
• THYROID• PARATHYROID• PANCREAS (endo.)• ADRENAL
– CORTEX– MEDULLA
• DEGENERATION (aka, “involution”)
• INFLAMMATION• NEOPLASM
– BENIGN– MALIGNANT
BETTER ALGORHYTHM• 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
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 or mass effects)
• FUNCTIONING ADENOMAS
• HYPO-PITUITARISM
• POSTERIOR PITUITARY SYNDROMES
• HYPOTHALAMIC (SUPRASELLAR) TUMORS
CLINICAL FEATURES• HYPER: growth, lactation, thyroid,
adrenal cortex
• HYPO: growth, thyroid, adrenal cortex
• MASS EFFECT: visual fields, brain
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• Sheehan’s syndrome (Post-partum ischemic
necrosis)• Cysts (Rathke’s cleft)• Empty sella syndrome, (is NOT a disease)• Genetic defects (pit-1 gene mutations)
DIABETES INSIPIDUS• ADH deficiency• Head trauma, tumors,
inflam. hypothal/pit• Hyperdiureses with LOW sp.gr.
Inappropriate ADH• ADH EXCESS
–Hyponatremia, cerebral edema, neurologic symptoms
–Neoplasms, esp. Small Cell CA.–NON-neoplastic lung diseases–Posterior pituitary injury
HYPER-THYROIDISM• aka, thyrotoxicosis• Diffuse• 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., Hashimoto’s)• 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– Cool skin
THYROIDITIS• Hashimoto (Auto-Immune) (Lymphoid
follicles with germinal centers), MOST COMMON cause of acquired hypothyroidism in USA
• Subacute Granulomatous (DeQuervain)
• Subacute Lymphocytic (just like Hashimoto’s 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
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
“NODULES”• Solitary vs. Multiple• Younger vs. Older• Male vs. Female• Hx. neck radiation vs. NO Rx.• “Cold” vs. HOT (really NOT-
cold)
NEOPLASMS• ADENOMAS
–FOLLICULAR–HÜRTHLE
(oxyphilic)
• CARCINOMAS–FOLLICULAR–PAPILLARY– MEDULLARY
(AMYLOID)– ANAPLASTIC
(worst)
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• 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
HYPERADRENALISM• HYPERALDOSTERONISM (g)• CUSHING SYNDROME
(CORTISOL) (f)• ADRENOGENITAL
(VIRILIZING) SYNDROME (r)
CUSHING SYNDROME• CENTRAL OBESITY• MOON FACIES• WEAKNESS• HIRSUTISM• HYPERTENSION• DIABETES• OSTEOPOROSIS• STRIAE
CUSHING SYNDROME• PITUITARY ACTH INCREASE• TUMOR ACTH INCREASE• HYPERPLASIA OF CORTEX• ADENOMA OF CORTEX• CARCINOMA OF CORTEX
•EXOGENOUS STEROIDS (90%)
ADRENOGENITAL SYNDROME
• VIRILIZATION/feminization• CORTICAL NEOPLASM• CORTICAL HYPERPLASIA• 21-Hydroxylase Deficiency
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 and shock)– Newborns with DIFFICULT DELIVERY– ANTICOAGULANT RX– POSTSURGICAL DIC PATIENTS
PRIMARY CHRONIC• Most of Addison disease is auto-
immune adrenalitis• INFECTIONS (fungal diseases, histo-)
• METASTASES (adrenals are an amazingly preferred site for early lung carcinoma metastases)
• GENETIC DISORDERS
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
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 P’s)
• 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
Exocrine
Endocrine
Islets
Alpha Cells
Beta Cells
Delta Cells (suppress insulin and glucagon)
Pancreatic Polypeptide (PP) cells
Epsilon Cells make gherlin, which causes hunger
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 DM•1• Genetic• Autoimmune• Childhood (juvenile)
onset• Antibodies to beta
cells• Beta cell depletion• NON-OBESE
patients
•2• Genetic, but diff. from
Type 1• NOT autoimmune• Adult, or maturity
onset, e.g., 40’s, 50’s• Insulin may be low,
BUT, peripheral resistance to insulin is the main factor
• OBESE patients
* MODY might be regarded as the third type
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
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
RETINOPATHY in DmShows microaneurysms, areas of hemorrhage, cotton wool spots, hard exudates, venous beading, neovascularization, retinal detachment, vitreous detachment, pre retinal hemorrhage