Diseases of endocrinal glands

ENDOCRINE

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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


FEEDBACK SYSTEMS• HYPOTHALAMUS • ANTERIOR PITUITARY • ENDOCRINE GLAND • END ORGAN • HYPOTHALAMUS




HORMONES• POLYPEPTIDE (2nd

MESSENGER)• STEROID (DIRECT on

NUCLEUS)


ACIDOPHILS

BASOPHILS

CHROMOPHOBES

AXONS

AXONS and “PITUI-”cytes

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I P www.freelivedoctor.com


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



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GIGANTISM

(excess somatotropin [GH] BEFOREepiphyseal

closure)


ACROMEGALY:

(excess somatotropin

[GH] AFTER epiphyseal closure)


MOON FACIES

BUFFALO HUMP

STRIAE



Normal pituitary.



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

– Hyponatremia, cerebral edema, neurologic symptoms

– Neoplasms, esp. Small Cell CA.– NON-neoplastic lung diseases– Posterior pituitary injury



15-25 grams


thyroid,


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

• 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



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



GOITER


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

– FOLLICULAR–HÜRTHLE

(oxyphilic)

• CARCINOMAS– FOLLICULAR–PAPILLARY– MEDULLARY (AMYLOID)– ANAPLASTIC (worst)




HÜRTHLE CELL ADENOMA, note “atypia”www.freelivedoctor.com




ORPHAN ANNIE CELLS in PAPILLARY CARCINOMAwww.freelivedoctor.com

MEDULLARY CARCINOMA of the thyroid with “HYALINIZATION”, i.e.,

AMYLOID!!! www.freelivedoctor.com

HYALINIZATION showing APPLE GREEN birefringence in CONGO RED stain, i.e., AMYLOID


BIOLOGIC BEHAVIOR

• Papillary CA lymph nodes

• Follicular CA blood vessels, bone


35-40 mgwww.freelivedoctor.com

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• Valve calcifications


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.www.freelivedoctor.com

HYPERADRENALISM• HYPERALDOSTERONISM• CUSHING SYNDROME

(CORTISOL)• ADRENOGENITAL (VIRILIZING)

SYNDROME


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%)


PRIMARY HYPERALDOSTERONISM(Conn’s Syndrome)

Na+ RETENTIONK+ EXCRETIONHYPERTENSION


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 (ADDISON DISEASE)

• SECONDARY (PITUITARY)


PRIMARY ACUTE• RAPID WITHDRAWAL OF STEROIDS• MASSIVE ADRENAL HOMORRHAGE

(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• 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


PHEOwww.freelivedoctor.com

TWO crucially important points specific for endocrine tumors:

• 1. FUNCTIONING carcinomas are very RARE in ANY endocrine gland. Why? (KEY principle of 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 (suppress insulin and glucagon)

Pancreatic Polypeptide (PP) cells

Epsilon Cells make

gherlin


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• 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


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


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)

• 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

• Infections


ATHEROSCLEROSIS


ATHEROSCLEROSIS


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


NEPHROPATHYKimmelstiel-Wilson (KW) Kidneys

Is…………

“Nodular” glomerulosclerosis


NEPHROPATHYNEPHROSCLEROSIS


NEPHROPATHYGBM thickening


NEPHROPATHYDiffuse

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


Diseases of endocrinal glands

Documents

creased glycogen

creased glucose

diffuse toxic

beta cells

creased lipogenesis

endocrine

obese patients

germinal centers