Parathyroid adrenal pancreas dr faeza

ParathyroidParathyroid

AdrenalAdrenal

PancreasPancreas

PTH

• Hypocalcemia is main stimulus (9-10.5 mg/dl)• Antagonize Calcitonin

35-50 mg

Parathyroid Gland – note small dark staining chief cells and larger, eosinophilic oxyphil cells

PARATHYROID DISORDERS

• Primary Hyperparathyroidism – Adenoma: 85% to 95% – Primary hyperplasia (diffuse or nodular): 5% to 10% – Parathyroid carcinoma: 1%∼

• Secondary Hyperparathyroidism- (LOW CA++ of Renal Failure)

• Hypoparath-: Surgical, congenital, familial, idiopathic• Pseudo - hypoparath.

– (end organ resistance)

Parathyroid adenoma. A, Solitary chief cell parathyroid adenoma revealing clear delineation from the residual gland below. B, High-power detail of a chief cell parathyroid adenoma. some slight tendency to follicular formation

HYPER-PARATHYROIDISM

– Bone pain, fractures– Nephrolithiasis– Constipation, ulcers, gallstones– Depression, lethargy– Weakness, fatigue– Calcifications, esp. Lung, VALVES

HYPO-PARATHYROIDISM

– Neuromuscular irritability– Mental status change– Parkinsonism like effects– Widened QT interval– Defective, carious, teeth

MEN-1, Wermer Syndrome (3 P’s)

• HYPERPARATHYROIDISM, chiefly hyperplasia

• Pancreatic endocrine tumors• Pituitary adenoma, usually prolactinoma

MEN-2

• MEN-2A (SIPPLE): Pheochromo, Medullary Thyroid CA., Parathyroid hyperplasia

• MEN-2B: NO hyperparathyroidism, but neuromas present

• Familial Medullary Thyroid CA

ADRENAL CORTEX

• Glomerulosa (Salt), mineralocorticoids– ALDOSTERONE

• Fasciculata (Sugar), glucocorticoids– CORTISOL

• Reticularis (Sex), gonadocorticoids– ANDROGENS, ESTROGENS

4 g.

Adrenal Cortex

Zona Glomerulosa

(clumps, cords, and follicle like structures

Zona Fasciculata

(cords of spongiocytes)

SALT

SUGAR

SEX

STRESSSTRESS

HYPERADRENALISM

• HYPERALDOSTERONISM (G).• CUSHING SYNDROME (CORTISOL) (F).• ADRENOGENITAL (VIRILIZING)

SYNDROME (R).

CUSHING SYNDROME

• Exogenous steroid (90%)***• ACTH-DEPENDENT ** - pituitary adenoma; - Ectopic corticotropin syndrome (ACTH-secreting

pulmonary small-cell carcinoma, bronchial carcinoid)

• Adrenal adenoma• Adrenal Carcinoma• Hyperplasia.

CUSHING SYNDROME

• CENTRAL OBESITY

• MOON FACIES• WEAKNESS• HYPERTENSION• DIABETES• OSTEOPOROSIS• HIRSUTISM• STRIAE

CUSHING SYNDROME

MOON FACIES BUFFALO HUMP

STRIAE

Cushing syndrome

• Depending on the cause of the hypercortisolism the adrenals have one of the following abnormalities:

• (1) cortical atrophy,• (2) diffuse hyperplasia, • (3) macronodular or micronodular hyperplasia, • (4) an adenoma or carcinoma.

Diffuse hyperplasia of the adrenal contrasted with normal adrenal gland

Cushing syndrome

Dx: • (1) Increased the 24-hour urine free-cortisol

concentration.• (2) loss of normal diurnal pattern of cortisol

secretion.

Cushing syndrome

• Dx the cause of Cushing syndrome depends on;

• Serum ACTH and • Dexamethasone suppression test;

Measurement of urinary steroid excretion after administration of dexamethasone.

PRIMARY HYPERALDOSTERONISM(Conn’s Syndrome)

• Na+ RETENTION• K+ EXCRETION• HYPERTENSION

Secondary hyperaldosteronism

• Activation of the renin-angiotensin system, (increased plasma renin)

• In the following conditions: • Decreased renal perfusion (arteriolar nephrosclerosis, renal

artery stenosis) • Arterial hypovolemia and edema (CHF, cirrhosis, nephrotic

syndrome) • Pregnancy (due to estrogen-induced increases in plasma

renin substrate)

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)

• hyperkalemia, hyponatremia, volume depletion, and hypotension

PRIMARY ACUTE

• Rapid withdrawal of steroid• Massive adrenal hemorrhage - Newborns with difficult delivery - Anticoagulant RX - Postsurgical DIC patient - MASSIVE ADRENAL HEMORRHAGE

(WATERHOUSE-FRIDERICHSEN, if it follows infection and shock)

Waterhouse-Friderichsen Syndrome septicemia , shock,DIC, adrenocortical insufficiency with bilateral adrenal hemorrhage

PRIMARY CHRONIC

• Most of Addison disease is auto-immune adrenalitis• INFECTIONS (Tuberculosis, fungal)• METASTASES (adrenals are preferred site for early lung

carcinoma metastases)• AIDS• Acute hemorrhagic necrosis (Waterhouse-Friderichsen

syndrome) • Amyloidosis, sarcoidosis, hemochromatosis,

lymphoma. • GENETIC DISORDERS

Autoimmune adrenalitis.

NEOPLASMS• ADENOMAS of ADRENAL CORTEX

• CARCINOMAS of ADRENAL CORTEX

Adrenocortical adenomas; a well-circumscribed, nodular lesion up to 2.5 cm expands the adrenal.Most are clinically silent

Adrenocortical Adenoma

Adrenocortical Adenoma

Carcinoma of the adrenal cortex

Carcinoma of the adrenal cortex

Low magnification of the Adrenal Gland

Medulla

Cortex

Adrenal Medulla

ADRENAL MEDULLA

• PHEOCHROMOCYTOMAS, “rule of 10s”. Primary tumors of adrenal medulla

– 10% arise in an MEN setting– 10% are EXTRA-adrenal– 10% are bilateral– 10% are malignant– 10% are not associated with hypertension,

(hypertension in 90%).– 10% are in childhood– can only call them malignant if they metastasize.

PHEO

TWO crucially important points specific for endocrine tumors:

• 1. FUNCTIONING carcinomas are very RARE in ANY endocrine gland.

• 2. Benign adenomas may have extremely bizarre nuclei, but are most usually BENIGN!!!

MEN-1, Wermer Syndrome (3 P’s)

• HYPERPARATHYROIDISM, chiefly hyperplasia

• Pancreatic endocrine tumors• Pituitary adenoma, usually prolactinoma

MEN-2

• MEN-2A (SIPPLE): Pheochromo, Medullary Thyroid CA., Parathyroid hyperplasia

• MEN-2B: Pheochromo, Medullary Thyroid CA., neuromas, NO hyperparathyroidism.

ENDOCRINEENDOCRINE

PANCREASPANCREAS

High mag of an Islet – note Beta cells and more eosinophilic Alpha2 cells

Acini

Alpha Cells

Exocrine

Endocrine

Islets

Alpha Cells

Beta Cells

Delta Cells (suppress insulin and glucagon)

Pancreatic Polypeptide (PP) cells

Epsilon Cells make gherlin, which causes hunger

Glucagon Insulin

Immunohistochemistry of a pancrearic Islet of Langerhans

• β cell produces insulin, • α cell secretes glucagon,• δ cells contain somatostatin, which suppresses both

insulin and glucagon• PP cells contain pancreatic polypeptide that exerts

secretion of GIT enzymes and inhibits its motility. • D1 cells elaborate vasoactive intestinal polypeptide

(VIP), that induces glycogenolysis and hyperglycemia; • Enterochromaffin cells synthesize serotonin and are

the source of pancreatic tumors that cause the carcinoid syndrome

Pancrearic Islet of Langerhans

DIABETES MELLITUS• 16 Million in the USA• 1 Million/yr

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)

Classification of Diabetes MellitusAmerican Diabetes Association

1. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency) Immune – mediated Idiopathic

2. Type 2 diabetes (combination of insulin resistance and β-cell dysfunction)

3. Genetic defects of β-cell function; Maturity-onset diabetes of the young (MODY)4. Exocrine pancreatic defects5. Endocrinopathies6. Genetic defects in insulin action7. Infections8. Drugs9. Gestational diabetes mellitus10.Genetic syndromes associated with diabetes

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

Type 1 Diabetes Mellitus Type 2 Diabetes MellitusCLINICAL

  Onset: usually childhood and adolescence

Onset: usually adult; increasing incidence in childhood and adolescence

Normal weight or weight loss preceding diagnosis

Vast majority are obese (80%)

Progressive decrease in insulin levels

Increased blood insulin (early); normal or moderate decrease in insulin (late)

Circulating islet autoantibodies (anti-insulin, anti-GAD, anti-ICA512)

No islet auto-antibodies

Diabetic ketoacidosis in absence of insulin therapy

Nonketotic hyperosmolar coma more common

GENETICS Major linkage to MHC class I and II genes; also linked to polymorphisms in CTLA4 and PTPN22, and insulin gene VNTRs

No HLA linkage; linkage to candidate diabetogenic and obesity-related genes (TCF7L2, PPARG, FTO, etc.)

PATHOGENESIS  Dysfunction in regulatory T

cells (Tregs) leading to breakdown in self-tolerance to islet auto-antigens

Insulin resistance in peripheral tissues, failure of compensation by β- cells

Multiple obesity-associated factors (circulating nonesterified fatty acids, inflammatory mediators, adipocytokines) linked to pathogenesis of insulin resistance

PATHOLOGY  Insulitis (inflammatory

infiltrate of T cells and macrophages)

No insulitis; amyloid deposition in islets

β-cell depletion, islet atrophy

Mild β-cell depletion

Dm• POLY-• POLY-• POLY-

Metabolic actions of insulin

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

COMPLICATIONSMORPHOLOGY

• (MACRO-vascular) Atherosclerosis• MICRO-vascular

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

neuropathy)

• Infections

ATHEROSCLEROSIS

ATHEROSCLEROSIS

Diabetic Nephropathy• Renal failure is second only to MI as a cause of death from

DM. • Three lesions are encountered: (1) Glomerular lesions; capillary BM thickening, diffuse

mesangial sclerosis, and nodular glomerulosclerosis (2) vascular lesions, arteriolosclerosis; (3) PN, including necrotizing papillitis.

NEPHROPATHYGBM thickening

NEPHROPATHY

Kimmelstiel-Wilson (KW) Kidneys

Is…………

“Nodular” glomerulosclerosis

Diffuse and nodular diabetic glomerulosclerosis (PAS stain). Note the diffuse increase in mesangial matrix and characteristic acellular PAS-positive nodules.

Severe renal hyaline arteriolosclerosis

NEPHROPATHYNEPHROSCLEROSIS

RETINOPATHY in DmShows microaneurysms,

areas of hemorrhage,

cotton wool spots,

hard exudates,

venous beading,

neovascularization,

retinal detachment,

vitreous detachment,

pre retinal hemorrhage

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

The Adrenal Glands

Pineal Body

The Seat of the Soul

The Third Eye

PINEAL “GLAND”

• PINEALOMAS– PINEOBLASTOMAS– PINEOCYTOMAS

Pineal Gland

N – neuroglia

P –pinealocytes

S – Brain Sand