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Pathology of Endocrine Disorders
 

Pathology of Endocrine Disorders

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Pathology of endocrine disorders for pre clinical & clinical medical students.

Pathology of endocrine disorders for pre clinical & clinical medical students.

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    Pathology of Endocrine Disorders Pathology of Endocrine Disorders Presentation Transcript

    • Challenge….! Jan 2009: 4 th Year Students at JCU School of Medicine set new record.…!!! 100% Pass & Class Average of over 70% 99% Pass & Class Average of 68% Highest Are you ready for the Challenge….? Yes We Can…!
    • CPC06-4.3.1
      • Mina Gupta, 48 year old woman, lives in Mt Isa, presents to her GP with a swelling in her neck & fatigue.
        • Duration of swelling: 2/12
        • Painful, some discomfort lower neck (rate 2/10)
        • Site: central, mid- neck
        • Voice change: No
        • Weight loss/gain? put a bit of weight on as her clothes feel a bit tight.
        • Fatigue? Worsening fatigue last few months. Sleeping well but always feels tired.
    • CPC06-4.3.1 – Physical Exam
      • Vitals: T 36.8C rr 12/min BP : 110/64 mmHg pulse : 64 bpm reg good volume BMI : 32
      • Peripheries: ? pale palmar creases , cool hands mild bilateral pitting oedema nil else abnormal
      • Head + neck conjunctival pallor +; xanthelasma bilaterally; diffuse firm slightly tender central neck mass which moves on swallowing; no bruit; no periorbital oedema; no LN.
      • Pemberton’s sign negative
      • CVS + Resp: nil abnormal
      • GI + Renal: nil abnormal
      • CNS: K10 score 32 ;
      • depressed ankle reflexes bilaterally (delayed return)
      ? ? ?
    • CPC06-4.3.1- Differential
        • Thyroid:
          • Goitre – what ? type?
          • Hyper/Hypo/Euthyroid?
          • Thyroid nodule - cyst, adenoma, Cancer
          • Autoimmune thyroiditis – Graves? Hashimoto?
          • Thyroid cancer - ? Papillary ? Follicular ? Other
        • What other differentials?
          • Lymphadenitis, salivary gland tumors, Lymphoma, thymoma, secondary deposits.
          • Psychological, Diet, DM, Hypertension, Obesity.
    • Oprah has battled with her weight for years. Recently  she was diagnosed with hyperthyroidism . which sped up her metabolism and prevented sleep. Oprah eventually "blew out" her thyroid and experienced classic symptoms of hypothyroidism : Her metabolism slowed and she felt sluggish and tired. Hyper - - Hypo
    • Sir William Osler, M.D. said… As is our pathology so is our practice... what the pathologist thinks today, the physician does tomorrow. Pathology, The science of Medicine
    • Pathology Core Learning Issues:
      • Pathology Major CLI:
        • Overview of Endocrine disorders (classification, etiology, Pathogenesis, clinical & laboratory diagnosis).
        • Thyroid Disorders – Hyper, Hypo thyroidism Pathophysiology & clinical features.
        • Pathology of Graves & Hashimoto thyroiditis.
        • Tumours of thyroid – Goitre - Multinodular, Adenoma & Carcinoma (Papillary, follicular)
        • Laboratory diagnosis of thyroid disorders.
      • Pathology Minor CLI:
        • Other common Endocrine disorders – Cushings sy. & disease, addisons, Sheehan’s, Adrenogenital syndrome, Pituitary adenoma, Gigantism & Acromegaly, Diabetes insipidus.MEN syndromes.
    • Pathology Lab resources: Digital Slides Thyroid Graves (JCU slide) Endo-39-Thyroid MNG Endo-40-Adrenal adenoma Endo-46-Pheochromocytoma Endo-47-Hashimoto-Pap ca Endo-51-Hashimotos thyroiditis Endo-52-Hashimotos thyroiditis Endo-53-Graves Endo-54-Hashimotos thyroiditis Endo-57-Pitutary Normal Endo-58-Thyroid Normal Endo-59-Adrenal Normal Muse um Specimens GN-01 Pheochromocytoma GN-02 Adenoma (Hurthle Cell) GR-01 Adrenal Haemorrhage GR-02 Nodular Thyroid GR-03 Nodular Hyperplasia (MNG) GR-04 Benign Nodular Thyroid (MNG) GR-05 Thyroid Cyst
    • Endocrine Glands: Overview
      • Classification: Exocrine (ducts), Endocrine (ductless)
      • Site of Action: Autocrine, Paracrine & Endocrine
      • Type of secretion: Merocrine, Apocrine, Holocrine.
      • Endocrine System:
        • Hypothalamus  Pituitary  End. Glands  Tissues.
      • Endocrine disorders:
        • Primary(gland), Sec..(pituitary), Tertirary (Hypothal)
        • Hyperfunction / Hypofunction / Eufunction
        • Common Tumors – adenoma/carcinoma
      • Etiology: Genetic / Familial / Acquired
      • Multiple Endocrine Neoplasia (MEN) Syndromes.
    • Major Endocrine Glands: Self Study…..!
    • 8. A PLEASING PERSONALITY WITH PMA Assembling an attractive personality is a must. Your personality is your greatest asset or your greatest liability, for it embraces everything that you control: mind, body, soul and spirit. Learn to be pleasant even when others are being unpleasant to you. Positive Mental Attitude: 17 Success Principles… Some bring happiness where ever they go, & some whenever….!
    • Pathology of Thyroid Disorders Dr. Venkatesh M. Shashidhar Associate Prof. & Head of Pathology
      • Thyroid Anatomy:
      • Location ?
      • Arteries ?
      • Veins ?
      • Lymphatics ?
      • Nerve supply ?
    • Thyroid Examination:
    • Thyroid Introduction:
      • Epithelial endocrine gland (C cells, PTH)
      • Iodinated Tyrosine  T3 & T4  stored in colloid.
      • TRH  TSH  Thyroid  T3/T4  Metabolism.
      • Thyroid disease 5% of population – Females*
      • Wide clinical presentation:
        • Mood changes to cardiac failure,
        • growth retardation - malignancy.. !
      • Hyperthyroidism
        • Graves , Subacute & Multinodular Goitre.
      • Hypothyroidism
        • Hashimoto’s , Atrophy, Radiotherapy.
      • Normal thyroid ( Euthyroid ) – neoplasms
      • Goitre: enlargement of thyroid without functional, inflammatory or neoplastic alterations. (Latin=gutter=throat)
    • Variation in histology:
    • Thyroid Function: Testing
    • Primary – Secondary – Tertiary Gland – Pituitary - Hypothalamus T3/T4 - TSH - TRH
    • Primary hypoThy Seconary hypothy Neoplastic hyperthy Secondary Hyperthy Throid Func. Testing
    • Graves Hashimoto
    • Thyroid - Normal
    • Normal Thyroid & Parathyroid
    • Normal Thyroid & Parathyroid Thyroid - Parathyroid
    • Normal Thyroid B A C
    • C cells of thyroid ImmunoPeroxidase stain ? Function ? Tumor
    • Thyroid Disorders:
      • Clinical Syndromes:
        • Hyperthyroidism – with/without goitre.
        • Hypothyroidism - with/without goitre.
        • Euthyroid – with structural abnormality.
      • Swellings:
        • Goitre – diffuse, multinodular, single nodule.
        • Neoplasm – adenoma, carcinoma.
    • Congenital / other Disorders:
      • Thyroglossal Cyst
      • Accessary thyroids
      • Abnormal location
      • Cong. Atrophy
      • Cong. Hypertrophy
    • Hypothyroidism
      • Cretinism - children
      • Myxedema - adults
      • Causes:
        • Developmental – Atrophy, hypoplasia
        • Radiation/Surgery
        • Hashimoto’s thyroiditis
        • Iodine deficiency
        • Drugs – PAS, iodides, lithium
        • Pituitary disorders
    • Congenital hypothyroidism:
      • Protruding tongue
      • Growth retardation
      • Jaundice
      • Dry skin
      • Slow reflexes
      • Hoarse voice
    • Hypothy..
      • Hypometabolism:
      • Weight gain
      • Apathy
      • Constipation
      • Menorrhagia
      • Muscle weakness
    • Hypothyroidism:
      • Dull and apathetic face
      • Periorbital puffiness
      • Loss of lateral eyebrows.
      • Skin Yellow (carotene, not Jaundice) cold, dry, rough, nonpitting edema (myxedema).
      • Droopy eyes. Eye lid edema.
      • Coarse, dry & thin Hair.
      • Hoarseness of voice.
      You should be able to identify hypothyroid patients at first look..!
    • Hypothyroidism: Pale gland.
    • Hyperthyroidism
      • Thyrotoxicosis
      • Causes
        • Graves – autoimmune, toxic
        • Toxic multinodular goitre
        • Functioning adenoma
      • Solid, grey hyperemic gland.
      • Microscopy: Epithelial hyperplasia, hypertrophy, scanty colloid (Scalloping).
      • Lymphocyte infiltration.
    • Hyper-Thy:
      • Hypermetabolism:
      • Weight loss
      • Anxiety
      • Diarrhoea
      • Menorrhagia
      • Osteoporosis
      • Proximal myopathy
      • Pretibial myxoedema
      • Exophthalmos
      • Lid lag.
    • Normal - Graves
    • Clinical features:
      • Weight loss
      • Anxiety, tremor
      • Diarrhoea
      • Exophthalmos *
      • Acropachy *
      • Myxedema
      • Loss of lateral eyebrow
      You should be able to identify hyperthyroid patients at first look..! Visible cornia
    • Hyperthyroidism – exophthalmia Note:  Unilateral prominance or Severe 
    • Thyrotoxicosis: Clin Myxedema Alopecia Acropachy Loss of lateral eyebrow Carotenemia -- normal
    • ? Test … ? Result … ? cause Lid Lag…
    • 3. GOING THE EXTRA MILE Very simply, this principle means: Render or give more and better service than you are paid for, and sooner or later you will receive compound interest from your investment of going the extra mile. Positive Mental Attitude: 17 Success Principles…
    • Hashimoto Thyroiditis
      • Common cause of non endemic goitre.
      • Aged females more common 45-65y.
      • Autoimmune thyroiditis HLA-DR5, DR3.
      • T cell mediated, Antithyroglobulin Ab & Antithyroid peroxidase Ab.
      • Firm, pale grey, gland enlargement - intact capsule.
      • Atrophic follicles & lymphoid follicles.
      • H ü rthle cells – eosinophilic epithelial cells.
      • Initial hyperthyroidism – hypothyroidism.
      • High risk of developing B cell lymphoma.
    • Hashimoto’s Disease Atrophic Thy Fol Ly. Follicle
    • Hashimoto’s Disease Atrophic Thy Fol Ly. Follicle
    • Hashimoto’s – Lymphocytes & Hurthle cells. Lymphocytes Hurthle cells Ly. Follicle
    • Antimicrosomal Ag/Peroxidase (TPO)Ab -ve Colloid +ve Cells
    • Antithyroglobulin Antibody +ve colloid -ve cells
    • Graves Disease:
      • Common cause of hyperthyroidism (2%F)
      • Females, 20-40years, Autoimmune Thyroiditis.
      • Triad of clinical features,
        • Hyperthyroidism
        • Infiltrative ophathalmopathy - exopthalmos
        • Infiltrative dermopathy – Pretibial myxedema.
      • Autoantibody to TSH receptor – LATS .
      • Gross : soft, smooth, red, Hyperaemic, enlarged gland. (Bruit on auscultation)
      • Micro : Diffuse hyperplasia, ep. papillary folds, inflammation – Lymphoid Follicles (Less) Scalloped, pale, scanty colloid.
    • Graves Disease Pale, scanty, colloid Papillary ep. hyperplasia Gross: Red, fleshy & smooth
    • Graves… Microscopy: Note: Prominent follicular cells scanty colloid focal lymphoid aggregates Colloid resorption Papillary ep. hyperplasia
    • Graves… Microscopy: Note: Prominent follicular cells scanty colloid focal lymphoid aggregates Lymphoid Follicle Colloid resorption Papillary ep. hyperplasia
    • Hyper – Thyroidism - Hypo
      • Hyper-Metabolic…
      • Hypo-Metabolic…
    • 14. CREATIVE VISION Creative vision requires you to stimulate your imagination to work towards your goal, your target and your major purpose, and to put the result of that imagination to work. Positive Mental Attitude: 17 Success Principles…
    • GOITRE (Enlargement of Thyroid) Hyperplasia ( MNG ), Inflammation, tumours
    • Diffuse & Multinodular goitre
      • Iodide deficiency / transport disorder
      • Iodine, Cassava, thiocyanate…
      • Endemic (common) & sporadic types
      • Toxic or non toxic types.
      • Sporadic – rare, females, young.
      • Hyperplastic (smooth) & Colloid (nodular) stage.
      • Repeated attacks diffuse  multinodular.
      • Changes: Infl., fibrosis, Ca+, cysts, necrosis etc.
      • Mass effect, dysphagia, airway obstruction
      • Toxic nodule  hyperthyroidism - Plummer syndrome (rare).
    • Goitre
      • Non-neoplastic
      • Common (95%)
      • Multiple/diffuse
      • Hyperplasia – MNG
      • Inflammations
      • Infections
      • Cysts
      • Neoplastic
      • Uncommon (<5%)
      • Solitary nodule
      • Young, males
      • Hot are benign..!
      • Follicular adenoma
      • Carcinoma
    • Goitre – Pathogenesis
      • ↓ Iodine  ↓ T3,T4  ↑ High TSH
      • Dietary def.
      • Inhibitory factors
      • ?others
    • Endemic Goitre - Euthyroid
    • MNG - Colloid Cyst
    • Nontoxic-Multi Nodular Goitre. A: conspicuous neck mass. B: Coronal section showing numerous irregular nodules, some with hemorrhage. C: Microscopy: variation in the size of the follicles. Note: TSH, T3,T4  Normal (Euthyroid)
    • Multinodular Goitre
    • 5. SELF DISCIPLINE Self discipline is doing what you are supposed to be doing for the moment. It is employing the &quot;DO IT NOW“ philosophy Positive Mental Attitude: 17 Success Principles…
    • Neoplasms of Thyroid
      • Adenoma – Follicular adenoma - hot
      • Papillary Carcinoma – 75-80% (young)
        • Radiation, Gardner & Cowden syndromes
        • Papillary folds, Psammoma bodies, Nuclear..
        • 98% 10year survival rate when localised.
      • Follicular carcinoma - 10-20% (Aged)
      • Medullary carcinoma – 5%
      • Anaplastic carcinoma - <5%
    • Follicular Adenoma
      • Solitary
      • Unilateral
      • Cold / non functional
      • Rarely hot/functional.
      • 10% malignant.
      • Hot nodule  not Ca.
    • Follicular Adenoma
    • Adenoma (Follicular)
    • Carcinoma of Thyroid Type (%) age spread Prognosis Papillary 60-70 young adults 20-40 (<45y) Lymphatic , to local nodes Excellent Follicular 20-25 Young-middle 40-50 (>45) Blood stream, especially to bone Good with radio-iodine therapy. Anaplastic 10-15 Elderly Aggressive local extension Very poor Medullary (C-cells) 5-10 Usually elderly, but familial cases occur Local, lymphatic, blood stream Variable. More aggressive in familial cases
    • Papillary Carcinoma
    • Papillary Carcinoma
    • Papillary Carcinoma Papilla Fibro-vascular core
    • Papillary Carcinoma (follicular pattern) Empty nuclei Fibro-vascular core
    • Papillary Carcinoma Psammoma bodies. Psammoma Body
    • Follicular Carcinoma
    • Follicular Carcinoma
    • Follicular Carcinoma BV invasion Capsule invasion Follicles
    • Follicular Carcinoma BV invasion Capsule invasion Follicles
    • Follicular Adenoma
    • Anaplastic Carcinoma
    • Medullary Carcinoma
    • Amyloid in Medullary Ca (Birefringence)
    • “ Thyroid Nodule/s ” – Clinical approach.
      • Nodule vs. Goitre… *
      • Majority asymptomatic, benign/malignant.
      • Mobility, pain, inflammation – non neopl.
      • Always obtain a biopsy specimen.. *
      • Risk Factors for Malignancy:
        • Family History, head and neck irradiation
        • Age <20 or >70 years, (young  Papillary ca)
        • Male sex, rapid growth, firm/hard, Fixed.
        • Hoarseness, dysphonia, dysphagia, or dyspnea
        • Cervical Lymphadenopathy.
        • Bone metastasis – Follicular Ca.
    • Carcinoma Thyroid - tips
      • Papillary ca. occurs in younger age, rarely extends outside the thyroid capsule by local invasion or rarely infiltrates local structures.
      • Anaplastic Ca. Occurs in elderly, Rapid local growth, with extension out of the thyroid capsule and invasion of adjacent structures such as trachea and jugular vein is typical causing mortality.
      • Follicular carcinoma spreads early by blood. sometimes first presents with pathological fracture due to bone metastasis.
    • 11. CONTROLLED ATTENTION WITH PMA Controlled attention is organised mind power. It is the highest form of self discipline. Keep your mind on the things you want and off the things you don't want. Positive Mental Attitude: 17 Success Principles…
    • Challenge….! Jan 2009: 4 th Year Students at JCU School of Medicine set new record.…!!! 100% Pass & Class Average of over 70% 99% Pass & Class Average of 68% Highest Are you ready for the Challenge….? Yes We Can…!
    • Pathology of Endocrine System Overview Dr. Shashidhar V. Murthy Senior Lecturer & Head of Pathology James Cook University School of Medicine
    • Endocrine Disorders: Common
      • Pituitary
        • Hypofunction, tumor adenoma, carcinoma.
        • Functioning adenoma – prolactinoma.
        • Sheehan’s syndrome – infarction.
        • D.insipidus, SIADH (post pituitary)
      • Thyroid:
        • Hypo, Hyper, Euthyroid (Hashimotos, Graves, ‘itis.. )
        • Multinodular Goitre, Adenoma, Carcinoma.
        • C cells – Calcitonin - Medullary Ca
      • Parathyroid
        • Hyperplasia (Pri/Sec/ter), Hypoplasia, Tumors
      • Gonads (covered later)
      • Thymus
        • Myasthenia gravis, Thymoma
    • Endocrine Disorders: Overview
      • Adrenal Cortex:
        • Cushings syndrome – hyperfunction
        • Addison’s disease – hypofunction
        • Waterhouse-Friderichsen syndrome (acute)
        • Conn’s syndrome, Cong. Adrenal hyperplasia.
        • Tumor – adenoma
      • Adrenal Medulla:
        • Pheochromocytoma – adenoma.
      • Pineal gland
        • Pinealoma.
      • Endocrine Pancreas
        • DM, Adenoma & Ca.
    • Pituitary: Adeno & Neuro hypophysis
      • Adenohypophysis:
        • No arteries… portal sys.
        • Corticotroph-ACTH (CRF)
        • Thyrotroph – TSH (TRF)
        • Gonadotroph – FSH & LH. (GRF)
        • Somatotroph – GH (GHRF)
        • Lactotroph – Prolactin. (PIF)
      • Neurohypophysis:
        • ADH & Oxytocin
      Epi. – Ner.
    • Normal Pituitary: Post Ant Stalk Post Ant
    • Acromegaly
    • Pituitary Histology: Anterior(adeno hypophysis) - Posterior (Neurohypophysis)
    • Ant (Adeno) – Hypophysis/Pituitary - Post (Neuro)
    • Pituitary Pathology:
      • Anterior/Adenohypophysis:
      • Hypopituitarism
        • Pituitary dwarfism
        • Acromegaly.
        • Sheehans & Simmond’s.
      • Hyperpituitarism
        • Adenomas – Prolactinoma.
      • Posterior/Neurohypophysis:
        • SIADH, Diabetes insipidus.
    • Adrenal Glands:
      • Cortex (glands)
        • Glomerulosa - Mineralocorticoids
        • Fasciculata - Glucocorticoids
        • Reticularis – Gonadal hormones
      • Medulla (Neural) – APUD system.
        • Chromaffin cells & sympatheti nerve endings Noradrenaline  Adrenaline (epinephrine)
      • Pathology: common.
        • Pheochromoccytoma – medulla, hypertension.
        • Cushings syndrome & Disease.
        • Conn’s syndrome.
        • Congenital adrenal hyperplasia(21-hydroxylase def)
      Excess Androgens Precocious puberty
    • Adrenal Gland
    • Pheochromocytoma:
      • Tumor of medullary Chromaffin cells.
      • Secondary hypertension.
      • Young age.
      • May be familial (MEN syndrome).
      • Increased catecholamines
      • Increased Urinary VMA
    • Waterhouse-Friderichsen Sy
      • Acute hemorrhagic necrosis (apoplexy).
      • Shock/Septicemia
      • Lack of aldosterone
      • Salt & water loss
      • Hypovolemic shock
      • Hypoglycemia.
      The adrenals from a child dying of meningococcal septicaemia are destroyed by haemorrhage. K K Ad. Ad.
    • Waterhouse-Friderichsen Sy Adrenal hemorrhage
    • Addison’s Disease:
      • Chronic adrenal insufficiency.
      • anorexia, weight loss, vomiting
      • weakness
      • lethargy
      • hypotension
      • skin pigmentation
      • hyponatraemia with hyperkalaemia
      • chronic dehydration
      • sexual dysfunction.
      • Low plasma cortisol.
      • ACTH high (primary) or low (secondary)
    • Cushings Syndrome:
      • Excess glucocorticoids
      • Causes:
        • Central: excess ACTH
        • Adrenal: neoplasm
        • Iatrogenic – ACTH/steroid
      • Clinical Features:
        • Central obesity,
        • hirsutism,
        • hypertension,
        • diabetes
        • osteoporosis
    • Type I MEN Type II PPP * PTAGIn
    • “ One's philosophy is not best expressed in words; it's expressed in the choices one makes. Eleanor Roosevelt1884-1962, U.S. diplomat, author, and political figure. Wife of Franklin D. Roosevelt
    •  
    • Test Normal Interpretation &quot;TSH&quot; Test -- Thyroid Stimulating Hormone / Serum thyrotropin 0.3 to 6 Under .4 can indicate possible hyperthyroidism. Over 6 is considered indicative of hypothyroidism. Total T4 / Serum thyroxine 4.5 to 12.5 Less than 4.5 can be indicative of an underfunctioning thyroid when TSH is also elevated. Over 12.5 can indicate hyperthyroidism. Low T4 with low TSH can sometimes indicate a pituitary problem. Free T4 / Free Thyroxine - FT4 0.7 to 2.0 Less than 0.7 is considered indicative of possible hypothyroidism. T3 / Serum triiodothyronine 80 to 220 Less than 80 can indicate hypothyroidism.
    • Hypothalamo-Pituitary-Gland Axis Hypothalamus Pituitary Target Gland Peripheral Inhibitory Hormone CRH ACTH Adrenal Corticosteroids TRH TSH Thyroid T 3 , T 4 GHRH Growth hormone Varied IGF-I Somatostatin Growth hormone Varied IGF-I LHRH LH Gonads Estradiol, testosterone   FSH Gonads Inhibin, estradiol, testosterone Dopamine Prolactin Breast Unknown
    • Pemberton’s Sign Within 30 seconds after raising both arms (Pemberton’s maneuver), marked facial plethora develops (Pemberton’s sign) indicating compression of the jugular veins (Panel B) – commonly due to enlarged thyroid. From: NEJM-Images in clinical medicine ( http://content.nejm.org/cgi/reprint/350/13/1338.pdf )
    • Granulomatous Thyroiditis:
      • Subacute or DeQuervain thyroiditis.
      • Less common, Females, 30-60 years
      • Painful goitre, fever, fatigue, myalgia.
      • Viral or post viral syndrome – Not AID..
      • Genetic association - HLA B35
      • Patchy inflammation, microabscess, granulomas with giant cells.
      • Hyperthyroidism, but low iodine uptake
      • Heals with normal thyroid function.
    • DeQuervain's Disease - SAGT
    • Insulinoma: Pancreas Routine H&E Stain Immunoperoxidase for Insulin. Uniform pink cytoplasm. Note: brown cytoplasmic stain. Tumors of Islets are rare. Commonest is benign insulin secreting adenoma – Insulinoma. Others tumors are Gastrinoma – causing Zollinger-Ellison Syndrome. Glucagonoma, VIPoma, somatostatinoma etc.
    • David Thomas You can do what you want to do. You can be what you want to be…!