ENDOCRINE

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

A AXONS

I P AXONS and PITUI-cytes

ANTERIOR PITUITARY
ACIDOPHILS
GROWTH HORMONE
PROLACTIN
BASOPHILS
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 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

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
 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 Andi-
Diuretic Hormone)
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
15-25
grams
 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., 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
 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
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 NOT-
cold)
NEOPLASMS
ADENOMAS CARCINOMAS
FOLLICULAR FOLLICULAR
HRTHLE
(oxyphilic) 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
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)
ADRENOGENITAL
(VIRILIZING) SYNDROME (r)
CUSHING SYNDROME
CENTRAL OBESITY
MOON FACIES
WEAKNESS
HIRSUTISM
HYPERTENSION
DIABETES
OSTEOPOROSIS
STRIAE
 STRIAE

MOON BUFFALO
FACIES 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
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
 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
PINEOBLASTOMAS
PINEOCYTOMAS
ENDOCRINE
PANCREAS
Exocrine
Endocrine
Islets
Alpha Cells
Beta Cells
Delta Cells
(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)
 * MODY might be regarded
as the third type

TWO* Types of DM
1 2
Genetic Genetic, but diff. from
Autoimmune Type 1
Childhood (juvenile) NOT autoimmune
onset Adult, or maturity
Antibodies to beta onset, e.g., 40s, 50s
cells Insulin may be low,
BUT, peripheral
Beta cell depletion
resistance to insulin is
NON-OBESE the main factor
patients OBESE patients
 Dm
POLY-
POLY-
POLY-
 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
T-Lymphocytes Diet
reacting against Life Style
poorly defined Obesity
beta cell INSULIN
RESISTANCE
antigens Beta cells UN-able
Inflammatory to adapt to the
inflitrate, long term
demands of insulin
chronic, i.e., resistance
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
 COMPLICATIONS
MORPHOLOGY
(MACRO-vascular) Atherosclerosis
MICRO-vascular
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
Kimmelstiel-
Wilson (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