ENDOCRINE

PITUITARY
ANTERIOR
DEGENERATION
POSTERIOR (aka,
involution)
THYROID INFLAMMATION
PARATHYROID
NEOPLASM
PANCREAS (endo.) BENIGN
ADRENAL MALIGNANT
CORTEX
MEDULLA
 PITUITARY NON-NEOPLASTIC
ANTERIOR HYPER-function
POSTERIOR HYPO-function
THYROID
PARATHYROID
NEOPLASTIC
FUNCTIONAL
PANCREAS
NON-FUNCTIONAL
(endo.)
Functional endocrine
ADRENAL malignancies are
CORTEX RARE. Why?
MEDULLA **********
 CORTEX, SUBCORTEX?
HYPOTHALAMUS
ANTERIOR PITUITARY
ENDOCRINE GLAND
END ORGAN
HYPOTHALAMUS
AntPitWiFi
PostPitWired
 POLYPEPTIDE
(2nd MESSENGER)
STEROID (DIRECT
on NUCLEUS)
 ACIDOPHILS
BASOPHILS
CHROMOPHOBES

A AXONS

I P AXONS and PITUI-cytes

 ACIDOPHILS (growth)
GROWTH HORMONE
PROLACTIN
BASOPHILS (trophs)
TSH
ACTH
LH, FSH
 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)
 CLINICAL FEATURES, mimic the endocrine
effects, visual effects, or mass effects)

FUNCTIONING ADENOMAS

HYPO-PITUITARISM

POSTERIOR PITUITARY SYNDROMES

HYPOTHALAMIC (SUPRASELLAR) TUMORS

 HYPER: growth(a), lactation(a),
thyroid(b), adrenal cortex(b)

HYPO: growth, thyroid, adrenal

cortex

MASS EFFECT: visual fields, brain

G
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 BUFFALO
FACIES HUMP
BITEMPORAL
HEMIANOPSIA
 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)
 DIABETES INSIPIDUS
SIADH(Syndrome of
Inappropriate Andi-
Diuretic Hormone)
 ADH deficiency
Head trauma, tumors,
inflam. hypothal/pit
Hyperdiureses with
LOW sp.gr.
 ADH EXCESS (SIADH)
Hyponatremia (hypervolemia),
cerebral edema, neurologic
symptoms
Neoplasms, esp. Small Cell CA.
NON-neoplastic lung diseases
Posterior pituitary injury
15-25
grams
 aka, thyrotoxicosis
Diffuse (Graves disease)
Nodular
Adenoma
Carcinoma
Neonatal
Secondary to TSH pituitary
adenoma
 HYPERMETABOLISM
Tachycardia, palpitations
Increased T3, T4
Goiter
Exophthalmos
Tremor
GI hypermotility
Thyroid storm, life threatening
 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)
 Cretinism
Severe retardation
CNS/Musc-skel
Short stature
Protruding tongue
Umbilical hernia
Maternal iodine defic.
Myxedema (coma)
Sluggishness
Cool skin,
cholesterol
 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
 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
 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
 Nodules vs. true
neoplasms

Adenomas vs. Carcinomas

 Solitary vs. Multiple
Younger vs. Older
Male vs. Female
Hx. neck radiation vs. NO Rx.
Cold vs. HOT (really NOT-
cold)
 ADENOMAS CARCINOMAS
FOLLICULAR FOLLICULAR
HRTHLE PAPILLARY
(oxyphilic) MEDULLARY
(AMYLOID)
ANAPLASTIC
(worst)
HRTHLE CELL ADENOMA, note atypia
ORPHAN ANNIE CELLS in PAPILLARY CARCINOMA
MEDULLARY CARCINOMA of the thyroid with HYALINIZATION, i.e.,
 HYALINIZATION showing APPLE GREEN
birefringence in CONGO RED stain, i.e., AMYLOID
 Papillary CA lymph
nodes

Follicular CA blood
vessels, bone
35-50 mg
 HYPOCALCEMIA is MAIN
STIMULUS (9-10.5 mg/dl)

ANTAGONIZES CALCITONIN
 HYPER-
PRIMARY (usually adenomas)
SECONDARY (LOW CA++ of
Renal Failure)
HYPO-: Surgical, congenital,
familial, idiopathic
PSEUDO-HYPO-
(end organ resistance)
 Bone pain, fractures
Nephrolithiasis
Constipation, ulcers, gallstones
Depression, lethargy
short QT interval and a widened T
wave
Weakness, fatigue
Calcifications, esp. VALVES
 Neuromuscular irritability
Mental status change
Parkinsonism like effects
Lens calcification*
(paradox)
Widened QT interval
Defective, carious, teeth
 Glomerulosa (Salt), mineralocorticoids
ALDOSTERONE

Fasciculata (Sugar), glucocorticoids

CORTISOL

Reticularis (Sex), gonadocorticoids

ANDROGENS, ESTROGENS
4 g.
SALT

SUGAR

SEX

STRESS
 HYPERALDOSTERONISM (g)
CUSHING SYNDROME
(CORTISOL) (f) (most common of the
three)

ADRENOGENITAL
(VIRILIZING) SYNDROME (r)
 CENTRAL OBESITY
MOON FACIES
WEAKNESS
HIRSUTISM
HYPERTENSION
DIABETES
OSTEOPOROSIS
STRIAE
 STRIAE

MOON BUFFALO
FACIES HUMP
 PITUITARY ACTH INCREASE
TUMOR ACTH INCREASE
HYPERPLASIA OF CORTEX
ADENOMA OF CORTEX
CARCINOMA OF CORTEX
EXOGENOUS
STEROIDS (90%)
 Na+ RETENTION
K+ EXCRETION
HYPERTENSION
 CORTICAL NEOPLASM
CORTICAL HYPERPLASIA
FAMILIAL (rare)
 DECREASED RENAL PERFUSION

EDEMA (HEART, LIVER, KIDNEY)

PREGNANCY
 VIRILIZATION/feminization
CORTICAL NEOPLASM
CORTICAL HYPERPLASIA
21-Hydroxylase Deficiency,
with buildup of 17-hydroxy
progesterone
 PRIMARY ACUTE
(ADRENAL CRISIS)
PRIMARY CHRONIC (auto-
immune ADDISON
DISEASE)
SECONDARY (PITUITARY)
 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
 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
 ADENOMAS of ADRENAL
CORTEX

CARCINOMAS of ADRENAL
CORTEX
 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
 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!!!
 HYPERPARATHYROIDIS
M, 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
 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
 16 Million in the USA
1 Million/yr
50K people die of it per
year in the USA
 Glucose >200
Or.
Fasting glucose >126 trice
Or.
Post-prandial glucose > 200, 2
hrs AFTER standard OGTT (Oral
Glucose Tolerance Test)
 * MODY might be regarded
as the third type

1 2
Genetic Genetic, but diff.
Autoimmune from Type 1
Childhood NOT autoimmune
(juvenile) onset Adult, or maturity
Antibodies to beta onset, e.g., 40s,
cells, insulitis 50s
Beta cell depletion Insulin may be low,
NON-OBESE BUT, peripheral
patients resistance to insulin
is the main factor
OBESE patients
 POLY-

POLY-

POLY-
 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
 1 2
T-Lymphocytes Diet
reacting against Life Style
poorly defined Obesity
beta cell INSULIN
antigens RESISTANCE
Inflammatory
Beta cells UN-able
to adapt to the
inflitrate, long term
chronic, i.e., demands of
INSULITIS insulin
resistance
 Multiple types
2-5% of diabetics
Primary beta cell defects
Multiple genetic mechanisms,
especially GLUCOKINASE
mutations
 MACRO-VASCULAR disease, i.e.,
ASCVD
MICRO-VASCULAR disease,
kidneys, retina, nerves
IMMUNE related problems,
INFECTIONS, e.g., TB, pneumonia,
pyelonephritis, candida, etc.
 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
*Retinopathy
*Nephropathy- glomerular, vascular,
KW
*Neuropathy (most common cause of
neuropathy)

Infections
Shows microaneurysms,
areas of hemorrhage,
cotton wool spots, hard
exudates, venous beading,
neovascularization, retinal
detachment, vitreous
detachment, pre retinal
hemorrhage
Kimmelstiel-
Wilson (KW)
Kidneys

IS

Nodular
glomerulosclerosis
NEPHROSCLEROSIS
GBM thickening
Diffuse
Mesangial
Sclerosis
 SKIN
TUBERCULOSIS
PNEUMONIA
PYELONEPHRITIS
CANDIDA
 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