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Endocrine Pathology

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Title: Endocrine Pathology


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Endocrine Pathology
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Pathology of the Endocrine System
  • The endocrine system is a highly integrated and
    widely distributed group of tissues that
    orchestrates homeostasis between the bodys
    organs organ systems. Secreted hormones act on
    target cells distant from the site of synthesis.
    Increased activity of the target tissue
    frequently results in a down-regulation of the
    signaling gland (feedback inhibition).
  • Endocrine disorders can be generally classified
    as
  • Disorders of over or under production of hormones
  • Disorders associated with the development of mass
    lesions which may cause over or under production
    of hormones or are nonfunctional

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Pituitary Gland
  • In conjunction with the hypothalamus the
    pituitary gland plays a critical role in the
    regulation of most other endocrine glands. It is
    composed of 2 functionally distinct components
  • 1. Anterior lobe (adenohypophysis)
  • Cell types
  • Somatothrophs -Growth hormone
  • Lactotrophs Prolactin
  • Corticotrophs Corticotrophin other hormones
  • Thyrotrophs - Thyroid stimulating hormone
  • Gonadotrophs FSH LH
  • Secretion of these hormones is regulated by
    stimulatory hypothalamic releasing factors or
    inhibitory factor (dopamine inhibits prolactin
    release)
  • 2. Posterior lobe (neurohypophysis)
  • An extension of axonal processes from the
    hypothalamus that store secrete oxytocin and
    vasopressin (ADH).

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Disorders of the Anterior Pituitary
  • Anterior pituitary disorders come to attention
    due to either increased (hyperpituitarism) or
    decreased (hypopituitarism) hormonal secretion.
  • In most cases hyperfunction is intrinsic to the
    gland resulting from a functional benign
    (adenoma) tumor.
  • Hypofunction can be the result of various
    destructive processes including ischemia,
    radiation, inflammation and non-functioning
    neoplasms.
  • Disorders of the anterior lobe may be manifest by
    local mass effects including cranial nerve
    defects, visual field defects, CSF leaks,
    increased ICP, etc..
  • Posterior pituitary disorders present with
    symptoms due to increased or decreased hormone
    secretion

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Pituitary Adenomas Hyperpituitarism
  • Excess inappropriate production of anterior
    pituitary hormones is most often caused by an
    adenoma of the anterior lobe.
  • Adenomas may be nonfunctional and cause
    hypopituitarism by impairing or destroying
    adjacent normal parenchyma.
  • Pituitary adenomas account for 10 of
    intracranial tumors and are found incidentally in
    25 of routine autopsies.
  • Most pituitary adenomas are monoclonal in origin
    (even if they secrete more than one hormone
    rare).
  • Tumors are classified by the hormone they produce

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Prolactinomas
  • These are the most common functional pituitary
    tumors accounting for 30 of all adenomas.
  • Prolactin secretion is extremely efficient a
    microscopic adenoma can produce enough prolactin
    to produce symptoms.
  • Prolactin production is proportional to tumor
    size. This allows a convenient method for
    monitoring recurrence.
  • Normally prolactin production is inhibited by
    dopamine released from the hypothalamus,
    interruption of dopamine due to head injury or
    drugs can also result in hyperprolactinemia.
  • Symptoms of hyperprolactinemia
  • 1. Amenorrhea 25 of 2amenorrhea is due to
    prolactin secreting pituitary tumors.
  • 2. Galactorrhea
  • 3. Loss of libido
  • 4. Infertility

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Somatotroph Adenomas
  • Gigantism
  • Hypersecretion of GH stimulates hepatic secretion
    of insulin-like growth factors which cause the
    clinical manifestations of this disorder.
  • Prior to bone maturity excess GH results in
    gigantism generalized increase in body size
    long limbs.
  • After bony maturity it results in acromegaly
    enlargement of the head, hands, feet, jaw, tongue
    and soft tissues resulting in characteristic
    features. Excess GH results in diabetes and
    accelerated atherosclerotic cardiovascular disease

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Acromegaly
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Pituitary Adenomas
  • Corticotroph adenomas
  • Excess production of corticotrophin results in
    increased cortisol production by the adrenal
    glands causing hypercortisolism (Cushing
    syndrome) which has many other causes.
  • Gonadotroph producing tumors
  • 10-15 of adenomas produce FSH or LH these are
    frequently found in middle aged men women when
    they become symptomatic due to mass effect.
  • Nonfunctioning pituitary adenomas
  • These account for 25 of pituitary adenomas,
    these tumors either produce no hormone product or
    a non-functioning product. They present due to
    mass effect.
  • Pituitary Carcinomas
  • These are very rare and the diagnosis requires
    demonstration of metastatic disease.

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Hypopituitarism
  • This is caused by disorders that result in
    decreased section of pituitary hormones this may
    be caused by disorders of the pituitary itself or
    the hypothalamus. The pituitary is robust and
    75 of the parenchyma must be destroyed before
    symptoms occur.
  • Tumors and mass lesions
  • Pituitary surgery and/or radiation
  • Rathke cleft cyst
  • Pituitary apoplexy acute hemorrhage
  • Ischemic necrosis associated with precipitous
    hemorrhagic events, DIC, sickle cell anemia,
    trauma, increased ICP.
  • Empty sell syndrome anything that results
    destruction of part or the entire gland
  • 1. Primary due to a defect in the diaphragma
    sellae or increased ICP allowing the encroachment
    of arachnoid and CSF into the sella and
    compressing the gland.
  • 2. Secondary due to intervention for a pituitary
    process usually adenoma which results in the
    destruction/removal of the pituitary.

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Posterior Pituitary Syndromes
  • The posterior pituitary is composed of modified
    glial cells and axonal processes extending from
    the hypothalamus the supraventricular and
    paraventricular nuclei. These neurons produce
    and release ADH (vasopressin) and oxytocin.
  • Inappropriate oxytocin production has not been
    associated with any clinical abnormalities
  • ADH is involved in the control of water
    conservation by the kidney.
  • ADH deficiency (diabetes insipidis) this
    condition is characterized by excessive urination
    due to the inability of the kidney to resorb
    water, this results in polydipsia and
    hypernatermia.
  • Syndrome of inappropriate ADH secretion (SIADH)
    ADH causes the resorbtion of excessive amounts of
    water resulting in hyponatremia, the most
    frequent causes of excess ADH is secretion by
    malignant neoplasms (a paraneoplastic syndrome)
    this is most often associated with small cell
    tumors of the lung, non-malignant lung processes
    head injuries are also common causes. SIADH
    results in hyponatremia which may cause seizures,
    cerebral edema, coma and death.

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Thyroid Gland
  • Thyroid follicular epithelial cells convert
    thyroglobulin to thyroxine and triiodothyronine
    that are released to the circulation. They are
    transported by plasma proteins to tissues here
    thyroxine is converted to triiodothryonine (the
    active form). Thyroid hormone binds with a
    nuclear receptor to form a complex that binds
    with thyroid hormone response elements that bind
    to target genes to regulate their transcription.
  • Thyroid hormone has diverse effects including
    increased carbohydrate lipid metabolism and
    increased protein synthesis in a wide range of
    tissues the net result is an overall increase in
    basal metabolic rate.
  • Thyroid disorders are relatively common and are
    amenable to medical surgical intervention if
    they are recognized.
  • A common cause of thyroid dysfunction is improper
    treatment of a thyroid disorder

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Hyperthyroidism
  • Thyrotoxicosis a hypermetabolic state caused by
    increased levels of thyroxine triiodothryonine,
    the most common cause is hyperfunction of the
    thyroid gland (hyperthyroidism)
  • Causes
  • Primary hyperthyroidism
  • Diffuse hyperplasia of the gland associated with
    Gravess disease
  • Hyperfunctional multinodular goiter
  • Hyperfunctional adenoma
  • Secondary hyperthyroidism
  • Thyrotrophic pituitary adenomas
  • Excess thyroxine (over medicated hypothyroidism)
  • Thyroid inflammation

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Hyperthyroidism
  • Clinical manifestations referable to a
    hypermetabolic state with over activity of the
    sympathetic nervous system
  • Cardiac manifestations increased cardiac output,
    palpitations, cardiomegaly, arrhythmias
  • Ocular changes wide, staring gaze, due to
    sympathetic over stimulation
  • Neuromuscular system tremor, hyperactivity,
    emotional lability, inability to concentrate,
    insomnia
  • Skin warm, moist and flushed
  • GI tract hypermotility, malabsorption, diarrhea

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Causes of Hyperthyroidism
  • 1. Graves disease is an autoimmune disorder
    resulting from the production of autoantibodies
    to the TSH receptor, thyroglobulin and T3 T4.
    The underlying mechanism is thought to be the
    breakdown of helper t-cell tolerance. These
    antibodies cause a mild diffuse functional
    enlargement of the gland with the associated
    findings of hyperthyroidism. Graves is also
    associated with an infiltrative ophthalmopathy
    resulting in increased peri- and retro orbital
    tissue (muscle, fat and connective tissue) due to
    T-cell infiltration, inflammatory edema and
    production of ECM components.
  • 2. Toxic Thyroid adenoma consists of the rare
    adenoma of the thyroid that produces active
    hormone.
  • 3. TSH- secreting pituitary adenomas are a rare
    cause of hyperthyroidism these represent 1 of
    all pituitary adenomas.

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Graves infiltrative ophthalmopathy
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  • Gail Devers
  • 1992 1996 Gold Medal 100 meter dash

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Hypothyroidism
  • A disorder of inadequate production of thyroid
    hormone this can be divided into primary,
    secondary tertiary categories. 1-2 of the US
    population suffers from overt hypothyroidism, but
    it occurs much more frequently in selected
    groups. 10 of the population suffers from
    subclinical hypothyroidism, older females have a
    20 incidence. 5 of postpartum females
    experience thyroiditis in the year following
    delivery.
  • Primary Due to intrinsic thyroid failure causes
    the vast majority of cases. Two forms goitrous
    enlarged gland or thyroprivic loss of gland
    tissue.
  • Secondary caused by inadequate TSH
  • Tertiary due to inadequate TRH from the
    hypothalamus.
  • Clinical features
  • Cretinism when experienced during perinatal
    period or infancy. Cretinism presents with
    impaired development of skeleton CNS, sever
    mental retardation, short stature, coarse facial
    features.
  • Myxedema Insidious slowing of physical and
    mental activity, fatigue, cold intolerance
    apathy, cardiomegaly, pericardial effusion,
    periorbital edema, hair loss, accumulation of
    mucoploysaccharide-rich ground substance within
    the dermis.

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Causes of hypothyroidism
  • 1. Congenital hypothyroidism results from
    agenesis of the thyroid gland or deficiency of
    the enzymatic pathways for the production of
    thyroxine.
  • 2. Endemic iodine deficiency, although absent in
    the US this is still a common cause worldwide
    particularly among populations of mountainous
    South America and Southeast Asia. In children
    this presents as cretinism and in adults causes
    enlargement of the thyroid gland (due to
    increased glandular activity) termed a goiter.
  • 3. Thyroiditis

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Thyroiditis
  • Hashiomoto Thyroiditis is an insidiously
    developing condition that is the most common
    cause of hypothyroidism in areas of the world
    with adequate iodine levels. This is an
    autoimmune disordere associated with gradual
    thyroid failure due to thyroid destruction. The
    initiating event appears to be the development of
    autoreactive T-helper cells to thyroid antigens,
    thyrocyte death is mediated through killer
    T-cell activation, cytokine mediated cell death
    and antibody dependent cell mediated cytotoxicity
    directed at a number of thyrocyte specific cell
    surface antigens.

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Thyroiditis
  • It is most prevalent in females (10-20/1) between
    45-65 years old. It presents as a painless
    enlargement of the thyroid gland with mild
    hypothyroidism. Hyperthyroidism may occur early
    in the disease and is associated with anti-TSH
    receptor antibodies if present its course is
    transient. There is increased risk of concomitant
    autoimmune disorders.
  • Rare forms of thyroiditis are associated with
    viral infections or lymphocytic infiltration of
    unknown etiology. These forms often are
    associated with an acute hyperthyroid episode
    (1-2 weeks) followed by either a gradual or
    precipitous decline in thyroid function.

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Neoplasms of the Thyroid
  • Solitary thyroid nodules are present in 1-10 of
    the US population. They are four times as common
    in women and increase in incidence throughout
    life. Most solitary nodules are benign with
    10/1 ratio adenoma to carcinoma.
  • Characteristics Carcinoma vs. Adenoma
  • 1. Solitary nodules are more likely to be
    neoplastic than multiple nodules
  • 2. Nodules in younger (lt40) patients are more
    likely to be neoplastic.
  • 3. Nodules in men are more likely to be
    neoplastic
  • 5. A history of radiation exposure especially to
    the head neck region is associated with
    increased risk of malignancy
  • 6. Nodules that are functional (take up
    radioactive iodine) are more likely benign

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Adenomas
  • These are the most common form of thyroid
    neoplasm, they present as discrete, solitary
    masses. The vast majority are nonfunctioning but
    some may cause thyrotoxicosis. They are rarely
    precursors to carcinoma.
  • Mutations in the TSH receptor-signaling pathway
    play an important role in the development of
    adenomas, resulting in the clonal expansion of a
    thyrocyte to produce a discrete mass.
  • These present as a painless mass which take up
    radioactive iodine at a lesser rate than normal
    functioning tissue. These cold nodules have
    10 chance of malignancy, hot nodules (gtiodine
    up-take) have .1 risk of malignancy.

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Cystic Thyroid Adenoma
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Thyroid Scans with I125
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Carcinomas
  • These account for 1.5 of all cancers in the US,
    most occurs in females and 90-95 are well
    differentiated and do not have an aggressive
    character but must be treated appropriately.
  • A particular risk factor for thyroid carcinoma is
    the exposure to ionizing radiation particularly
    in the first 2 decades of life (tonsillitis
    prevention).
  • 4 Types
  • 1. Papillary carcinoma (70)
  • This is the most common form of thyroid cancer
    it most commonly affects women between 20-50
    years of age and accounts for the vast majority
    of radiation induced malignancies. Often presents
    as a mobile painless nodule. Symptoms related to
    location indicate advanced disease.
  • At the time of diagnosis this tumor has regional
    nodal involvement, despite this the prognosis for
    survival is gt95 at 10 years with proper
    treatment. Poorer outcome is associated with age
    gt40, extrathyroidal extension and distant mets at
    the time of diagnosis.

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  • 2. Follicular carcinoma (20)
  • These peak between ages 40-60 and have a 3/1
    female predominance. There is a weak association
    with iodine deficiency. These are aggressive
    tumors and prognosis is based on the extent of
    invasion at the time of diagnosis with 75-80 of
    patients whom have local invasion also developing
    metastatic disease. Locally isolated disease has
    a 10year 90 survival while the rate is 50 for
    aggressive disease.
  • 3. Medullary Carcinoma (5)
  • These arise from parafollicular cells of the
    thyroid and secrete calcitonin and occasionally
    some other active peptides (VIP). Sporadic cases
    have 50 5 years survival rate. There is a
    familial form associated with a better prognosis,
    possibly due to earlier detection through
    screening. Both forms are associated with
    mutations in a proto-oncogene (RET).
  • 4. Anaplastic Carcinoma (1)
  • These tumors present in older patients and are
    particularly aggressive showing rapid growth and
    metastasis most patients survive less than one
    year.

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  • end

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Graves disease
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