ENDOCRINE

CLASSICAL ALGORITHM
• PITUITARY
– ANTERIOR • DEGENERATION
– POSTERIOR (aka, “involution”)
• THYROID • INFLAMMATION
• PARATHYROID
• NEOPLASM
• PANCREAS (endo.)
• ADRENAL – BENIGN
– CORTEX – MALIGNANT
– MEDULLA
 BETTER ALGORITHM
• 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
• CORTEX, SUBCORTEX?
• HYPOTHALAMUS 
• ANTERIOR PITUITARY 
• ENDOCRINE GLAND 
• END ORGAN 
• HYPOTHALAMUS 
AntPitWiFi
PostPitWired
 HORMONES
• POLYPEPTIDE (2nd
MESSENGER)
• STEROID (DIRECT
on NUCLEUS)
 ACIDOPHILS
BASOPHILS
CHROMOPHOBES

A AXONS

I P 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

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
• Sheehan’s syndrome (Post-partum ischemic
necrosis)
• Cysts (Rathke’s 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 (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., 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, ↑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

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 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 NOT-
cold)
NEOPLASMS
• ADENOMAS • CARCINOMAS
– FOLLICULAR –FOLLICULAR
– HÜRTHLE
(oxyphilic) –PAPILLARY
– MEDULLARY
(AMYLOID)
– ANAPLASTIC
(worst)
HÜRTHLE 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
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 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
(Conn’s 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 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
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)
 * 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., 40’s, 50’s
cells, insulitis • Insulin may be low,
• Beta cell depletion BUT, peripheral
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 antigens • INSULIN
• Inflammatory RESISTANCE
inflitrate, chronic, • Beta cells UN-able
i.e., “INSULITIS” 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
 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