ENDOCRINE

CLASSICAL ALGORHYTHM
PITUITARY
ANTERIOR POSTERIOR

THYROID PARATHYROID PANCREAS (endo.) ADRENAL

CORTEX MEDULLA

DEGENERATION (aka, involution) INFLAMMATION NEOPLASM

BENIGN MALIGNANT

BETTER ALGORHYTHM
PITUITARY
ANTERIOR POSTERIOR

NON-NEOPLASTIC
HYPER-function HYPO-function

THYROID NEOPLASTIC PARATHYROID FUNCTIONAL PANCREAS (endo.) NON-FUNCTIONAL ADRENAL

CORTEX MEDULLA

Functional endocrine malignancies are RARE. Why?**********

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

AntPitWiFi PostPitWired

HORMONES
POLYPEPTIDE (2nd MESSENGER) STEROID (DIRECT on NUCLEUS)

ACIDOPHILS
BASOPHILS CHROMOPHOBES

A
I

AXONS

AXONS and PITUI-cytes

ANTERIOR PITUITARY
ACIDOPHILS (growth)
GROWTH HORMONE PROLACTIN

BASOPHILS (trophs)
TSH ACTH LH, 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

A
L A

C
T O R R

H
E A

GIGANTISM (excess
somatotropin [GH]

BEFORE
epiphyseal

closure)

ACROMEGALY: (excess somatotropin [GH] AFTER epiphyseal closure)

STRIAE MOON FACIES BUFFALO HUMP

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 pituitary
DIABETES INSIPIDUS SIADH (Syndrome of Inappropriate AndiDiuretic 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 diseases Posterior 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 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

G O I T E R

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 NOTcold)

NEOPLASMS
ADENOMAS CARCINOMAS
FOLLICULAR HRTHLE (oxyphilic)

FOLLICULAR PAPILLARY
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

STRESS

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

STRIAE MOON FACIES BUFFALO HUMP

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 (autoimmune 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-2A (SIPPLE): Pheo, Medullary CA., Parathyroid hyperplasia MEN-2B: NO hyperparathyroidism, but neuromas present Familial Medullary Thyroid CA

MEN-2

PINEAL GLAND
PINEALOMAS
PINEOBLASTOMAS PINEOCYTOMAS

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 DM
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

Genetic Autoimmune Childhood (juvenile) onset Antibodies to beta cells, insulitis Beta cell depletion NON-OBESE patients

Dm
POLYPOLYPOLY-

 FAT

INSULIN

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 2
Diet Life Style Obesity INSULIN RESISTANCE Beta cells UN-able to adapt to the long term demands of insulin resistance T-Lymphocytes reacting against poorly defined beta cell

antigens Inflammatory inflitrate, chronic, i.e., INSULITIS

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

 (MACRO-vascular) Atherosclerosis MICRO-vascular

COMPLICATIONS MORPHOLOGY

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

neuropathy)

Infections

ATHEROSCLEROSIS

ATHEROSCLEROSIS

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

NEPHROPATHY
KimmelstielWilson (KW)
Kidneys IS

Nodular
glomerulosclerosis

NEPHROPATHY
NEPHROSCLEROSIS

NEPHROPATHY
GBM thickening

NEPHROPATHY
Diffuse 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