Download Chapter 28 - RadTherapy

Chapter 28
Endocrine System
**The endocrine system is composed of multiple glandular organs responsible for
complex metabolic regulatory functions.
 Produces hormones under complex feedback control mechanisms that affect various
functions to meet ongoing metabolic needs and stresses of the organism
o Critical for maintaining metabolic homeostasis
o Provides the organism with the ability to respond to various stresses
 Pituitary- master regulatory gland
 Produces many hormones under the influence of the hypothalamus
 Directly affects the function of other endocrine organs
 Thyroid: regulates the metabolism of the body and normal growth and
development and controls the amount of calcium deposited into bone
 Adrenal glands
 Parathyroid
 Islets of Langerhans- specialized cells in the pancreas
THYROID CANCER
 Most common of the endocrine malignancies
 90% of all new cases
 Only 1.3% of all cancers
 Women have higher incidence rate 2.3:1.0
Etiology
 External radiation before puberty
o Atomic bomb on Nagasaki and Hiroshima in 1945
o Radioactive fallout from a nuclear test in the Marshall Islands
o Chernobyl incident of 1986
 Eternal radiation for benign disease a widespread practice in the US in the 30’s, 40’s,
and 50’s
o X-rays or radium used to treat acne, tonsillitis, hemangiomas and thymic
enlargement
o Latent period varies with age
 Young people treated with mantle for HD have an increased risk
Prognostic indicators:
 Age
 Gender
 Histologic subtype
 Capsular invasion- lesions confined to the gland have an overall better prognosis
than those demonstrating capsular invasion
 Well differentiated thyroid carcinoma (papillary and follicular) have a better
prognosis than those with undifferentiated carcinoma (anaplastic)
Anatomy
 Right and left lobe- 5 cm in length, connected by the isthmus
 Near the larynx, trachea, parathyroid glands, and esophagus, and anterior and medial
to the carotid artery, jugular vein and vagus nerve
 Lymphatic capillaries throughout and drain to many nodal sites
o Cervical: Internal jugular chain, Delphian node, pretracheal nodes, and the
paratracheal nodes in the lower neck
o Superior mediastinal involvement represents significant regional spread of disease
Physiology
**Produces thyroxine (T4) and triiodothyronine (T3) - responsible for metabolic
regulation
**C-cells in thyroid produce calcitonin- involved in calcium metabolism
 Regulated by pituitary and hypothalamic hormones:
o TSH produced in the pituitary gland causes direct stimulation of thyroid cells to
produce and release hormones that are critical for carbohydrate and protein
metabolism
**Functional disorders of the thyroid gland
 Hyperthyroidism- hyperactivity
o Graves’ disease: characterized by an elevated metabolic rate, abnormal weight
loss, excessive perspiration, muscular weakness, emotional instability and
exopthalmos
o Goiter: a physical sign of an enlarged thyroid, over stimulation by FSH causes an
enlargement of thyroid cells; if this is associated with increased hormone
production it is referred to as toxic goiter.
 Hypothyroidism- under activity
o Cretinism: appears in infants shortly after birth, symptoms include stunted growth,
abnormal bone formation, retarded mental development, a low body temperature,
and sluggishness
o Myxedema: if developed after growth, symptoms include a low metabolic rate,
mental slowness, weight gain, and swollen tissues caused by excess body fluid,
characterized by facial and orbital edema.
Clinical presentation:
 Palpable neck mass
 Extreme hardness, appear fixed to deep structures or skin, and are associated with
recurrent laryngeal nerve paralysis (hoarseness)- should arouse suspicion
 Anaplastic carcinomas are usually large, hard, and fixed, grow rapidly, and occur in
older patients; symptoms: pain, dysphagia, dyspnea, stridor, and hoarseness
 Medullary carcinoma have painless mass; symptoms: diarrhea
Detection & Diagnosis
 Biopsy- differentiate malignant form nonmalignant; or a metastatic from a primary
o Needle aspiration cytology- small gauge needle
o Core needle biopsy- large cutting needle


Specialized imaging studies
o Radionuclide imaging
 Radiopharmaceuticals used are I-131, I-125, I-123, and technetium-99m (Tc99m)
 To evaluate the function and anatomic location of a palpable thyroid nodule
through the localization of hot or cold spots in the gland
 Cold thyroid nodule- no radionuclide uptake
 Warm thyroid nodule- slightly higher concentration than the rest of the
thyroid gland
 Hot thyroid nodule- high radionuclide uptake
o Ultrasonography- to determine whether a nodule is solid or cystic
o Computed tomography- can show the local and regional extent of advanced or
recurrent cancer, aid in treatment planning
o Magnetic resonance imaging- useful in depicting lesion margins, lesion extent,
tissue heterogenicity, cystic or hemorrhagic regions, cervical lymphadenopathy,
invasion of adjacent structures and additional nonpalpable thyroid nodules
Laboratory testing
o Analysis of the thyroglobulin and calcitonin levels
Pathology
 Differentiated: arise from the thyroid follicle cell and can usually be treated with I131 and thyroid hormone suppression
o Papillary and mixed papillary-follicular
 Most common types 33-73% of all malignant thyroid lesions
 Most frequently seen in irradiated individuals
 Slow growing
 Nonaggressive
 Excellent prognosis
 2 to 4 times more common in females
 Third to fifth decade
 Routes of spread:
 Metastasize to regional lymph nodes through lymphatic channels
 50% to 70% of these have cervical lymph node metastases- presence does
not significantly worsen prognosis
o Follicular
 14-33% of all thyroid cancers
 Greatest propensity to concentrate I-131
 2 to 3 times more common in females
 Average age 50 to 58 yrs
 Rarely occur in children
 Routes of Spread
 Tend to invade vascular channels and metastasize hematogenously to
distant sites: bone, lung, liver, and brain
 Lymph node metastases are uncommon
o Medullary
 5% to 10%
 20% occur through genetics
 Routes of spread
 Vary from indolent to rapidly fatal growth patterns
 Spreads regionally
 Metastases occur hematogenously and through lymphatic routes
o Anaplastic - undifferentiated
 Worst overall prognosis
 Short life expectancy
 10% of all malignant thyroid cancers
 40 to 90 yeas
 Four to one women
 Routes of spread
 Displays local invasion of structures such as the trachea, skin, and
regional nodes
Treatment:
 Surgery: papillary carcinoma and mixed papillary-follicular carcinomas are rarely
invasive and seldom require resection of the muscles of the neck, internal jugular vein,
esophagus, or trachea.
o Radical neck dissections: multiple nodes removed, warranted only if nodes are
grossly involved with metastatic disease, care is taken to spare the recurrent
laryngeal, vagus, spinal accessory, and phrenic nerves and to preserve the
parathyroid glands
o Lobectomy: for small lateralized lesions that do not show extrathyroidal
involvement nor lymph node metastasis
o Thyroidectomy: for involvement in both nodes or extrathyroidal involvement
**For anaplastic disease: surgery effective to:
o Alleviate a central airway obstruction
o Tracheotomy to preserve a patient’s airway
Side effects:
o Tumor hemorrhage
o Damage to parathyroid gland resulting in temporary or permanent
hypoparathyroidism
o Temporary or permanent vocal cord paralysis
 Radioactive iodine: used to treat papillary, mixed papillary-follicular, and follicular
cancers
o Indications:
 Inoperable primary tumor
 Thyroid capsular invasion
 Thyroid ablation after a partial or subtotal thyroidectomy
 Postoperative residual disease in the neck and recurrent disease
 Cervical or mediastinal nodal metastasis
 Distant metastasis
An ablation dose administered after a thyroidectomy may vary from 50 to 100 mCi


Thyroid hormonal therapy
External beam radiation:
o Pathology
 Papillary and mixed papillary-follicular carcinomas are more radiosensitive
than follicular carcinomas.
 Medullary thyroid cancer is less radiosensitive
 Anaplastic carcinomas are not very responsive.
o Used alone or in conjunction with I-131 and surgery
o Indications:
 Inoperable lesion
 Patient physically unfit for surgery
 Incomplete surgical removal of thyroid carcinoma
 Superior vena cava syndrome
 Skeletal metastases in which minimal accumulation of I-131 occurred
 Residual disease involving the trachea, larynx, or esophagus
o Dose:
 6500 cGy in 7 weeks
o Field:
 Should include the entire thyroid gland, neck, and superior mediastinum
 AP/PA until 4500 cGy, then obliques to spare the spinal cord
 Head should be extended to avoid exposure to the mouth with immobilization
 Tumor volume wired out
PITUITARY TUMORS
 Less aggressive
 Local growth causes compressive and destructive effects and endocrine abnormalities
caused by pituitary hormone dysfunction.
Epidemiology and etiology
 Most always benign
 Malignancies account for fewer than 1% of all pituitary tumors
 Account for 30% of all intracranial tumors
 Occur at any age, rarely found before puberty, most common in middle aged and
older
 No significant difference between men and women
 Etiology unknown
Classified as functioning or nonfunctioning, related to hormone production
 Functioning: retain hormone-producing capabilities, but unresponsive to regulatory
mechanisms and produce hormones regardless of metabolic needs
o Symptoms associated with the hypersecretion of pituitary hormones
o Prolactin (PRL)
o Growth hormone (GH)
o TSH- thyroid-stimulating hormone
o Adrenocorticotrophic hormone (ACTH)

Nonfunctioning chromophobe adenomas
o Usually larger than functioning tumors and tend to exhibit invasive characteristics
o Visual symptoms caused by the compression of the optic chiasm, usually
progressive
o Headache – occurs in 20% al patients.
Prognostic indicators
 Type of adenoma
 The extent of the abnormalities (mass effect or hormonal alterations)
 The success of the treatment in normalizing endocrine activity and or relieving
pressure effects
 The morbidity caused by the treatment
 The effectiveness of the treatments in preventing an recurrence
Anatomy
 1.3 cm
 Located at the base of the brain in sella turcica
 Attached to the hypothalamus by the infundibulum
 Close to critical structures of the central nervous system, such as the optic chiasm
superiorly, and the cavernous sinuses and their contents laterally
 Topographically located 2.5 cm anterior and superior to the EAM and midplane
behind the nasal bone.
Hormones: the release is stimulated or inhibited by the chemical secretions from the
hypothalamus
**Anterior lobe (adenohypophysis): forms the glandular portion
 Growth hormone (GH): controls body growth
o Target tissue: bones, muscles, organs
o Clinical effects
 Overproduction
 Acromegaly if occurs after puberty
 Hypersecretion of GH from adenohypophysis during adulthood
 Enlargement of hands, feet, jaw, nose and forehead
 Giantism happens before puberty
 Underproduction
 Decreased bone growth
 Lethargy
 Hypoglycemia: deficient sugar in the blood

Prolactin (PRL)- initiates milk production
o Target tissue: gonads
o Clinical effects
 Overproduction
 Females: infertility
 Males: impotence, decreased libido


Underproduction
 Gonadal atrophy
 Loss of reproductive function
Other:
 LH decreased gonadal hormones
 Produce clinical symptoms such as amenorrhea and galactorrhea

TSH- thyroid-stimulating hormone controls the thyroid gland
o Target tissue: thyroid
o Clinical effects
 Overproduction
 Hyperthyroidism
 Underproduction
 Hypothyroidism: fatigue, slow or slurred speech, bradycardia, decreased
reflexes, cold intolerance

Gonadotropic Hormones:
o Follicle-stimulating hormone (FSH)- stimulates egg and sperm production
o Luteinizing hormone (LH)- stimulates other sexual and reproductive activity

Melanocyte-stimulating hormone (MSH)- related to skin pigmentation

Adrenocorticotrophic hormone (ACTH)- influences the action of the adrenal cortex
o Target: adrenal cortex
o Clinical effects:
 Overproduction
 Cushing’s disease: excessive secretion of cortisol by the adrenal cortex;
 Underproduction
 Postural hypotension
**Posterior lobe (neurohypophysis): tumors virtually unknown
 Oxytocin-causes smooth muscle contractions
 Antidiuretic hormone (ADH) aka vasopressin- regulates free water resorption in the
kidneys
**Intermediate lobe: tumors virtually unknown
Detection and Diagnosis
 Functional tumors
o Characteristic endocrine abnormalities associated with the hypersecretion of
hormones
o Laboratory testing to measure hormone levels
 Nonfunctioning tumors:
o The expanding growth into the suprasellar area causes pressure symptoms such as
headache, visual disturbances, and impairment of various cranial nerves
o CT or MRI
Pathology:
 Cell type
o Sinusoidal
o Papillary
o Diffuse
 Classified according to size
o Microadenomas: less than 1.0 cm
o Macroadenomas: greater than 1.0 cm, larger adenomas are surgically more
difficult to remove and recurrence in more common
Treatment:
 Primary goal: to normalize pituitary hormonal function or relieve local compressive
and or destructive effects of the tumor with surgically, therapeutically with radiation,
medically, or with a combination
 Secondary goal: prevent recurrence
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
Surgery: transsphenoidal hypophysectomy: allows direct access to the pituitary gland
without disturbance of the central nervous system structures
o Permanently control 70 to 90 % al small adenomas
o Complications are CSF leakage, infection (meningitis), visual pathway defects,
Radiation therapy
o Reduce recurrence rates
o Alone to control pituitary tumors in patients who refused surgery or those who
were medically unfit
o Postoperative radiation therapy
o An incompletely resected invasive tumor
o Tumors demonstrating suprasellar extension with an associated visual field
defect
o Large tumors in which the risk of attempted removal is relatively high
o Persistent hormonal elevation after surgery
 Techniques
o Head must be immobilized; patients chin is usually tucked to avoid radiation
exposure to the eyes
o Three pt setup
o Small fields (5 X 5)
o Anterior with opposed laterals or vertex field
o 4500 cGy
o High energy megavoltage linear accelerators and multiple field treatment
approaches results in a more precise dose delivered to the tumor volume, a
reduction in the dose to normal central nervous system structures, increased
tumor control probability and decreased treatment related morbidity
 Proton beam therapy: Bragg peak with a rapid dose fall off at depth – spares the
optic nerve
o Dose can be precisely delivered within millimeters of a defined target directly
related to the beams energy

Stereotactic radiosurgery:
o High energy photon beam with multiple ports of entry convergent on the
target tissue
o Single large fraction of treatment with patient immobilized in a stereotactic
head frame
o Procedure takes several hours
o May be delivered as fractionated treatment.
Results of treatment:
 Patients normally do well, since most tumors are benign
 Surgery for microadenomas is usually curative
 RT alone has demonstrated disease free survival rates of up to 85% at 5 and 10 years
ADRENAL GLANDS
 Rare, malignant tumors account for only 0.04% of all cancers
 Tumors arising in the adrenal glands are classified according to the portion of the
gland from which they arise
o Cortex: outer portion of the gland- manufactures steroid hormones that are
critical in metabolic regulation
o Medulla: inner portion of the gland- produces epinephrine (adrenalin) under the
regulation of the autonomic nervous system.
ADRENAL CORTEX TUMORS
Epidemiology and Etiology:
 Extremely rare
 Only 150 to 300 in US per year
 Men and women affected equally
 Tumors arise more in the left gland
 Median age 50 years- range from 1 to 80 years
 Adrenal adenomas are benign neoplasms: can cause hypersecretion of normally
produced steroid hormones, giving rise to various clinical syndromes,
 Many adrenal masses represent metastasic disease typically from lung cancer
Prognostic indicators
 The stage of the disease at the time of diagnosis closely parallels survival rates
o Most patients have advanced disease at the time of presentation
o Only 30% of patients have a tumor confined to the adrenal gland
 The ability to the surgeon to achieve curative resection- surgery is the only modality
that has demonstrated a significant effect of survival rates
 Young age
Physiology
Cortex: produce steroids and hormones regulated by the ongoing stresses and needs of an
individuals metabolism
 Produces steroid hormones
o Glucocorticoids: respond to stress
o Mineralocorticoids: regulate blood volume, blood pressure, and electrolytes
o Sex hormones: responsible for secondary sex characteristics and metabolic
regulation
 Cortisol (ACTH) (Cushing’s syndrome)
 Acid-base imbalance
 Hypertension
 Obesity
 Osteoporosis
 Hyperglycemia
 Psychoses
 Excessive bruising
 Renal calculi
 Aldosterone (Conn’s syndrome: aldosteronism)
 Hypernatremia: excessive sodium in the blood
 Hypokalemia: deficient potassium in the blood
 Hypertension
 Neuromuscular weakness and paresthesias: abnormal sensation, such
as pricking
 Electrocardiographic and renal function abnormalities
 Estrogen (virilization- women)
 Male pattern baldness
 Hirtuism: abnormal hairiness, especially in women, aka hypertrichosis
 Deepening voice
 Breast atrophy
 Decreased libido
 Oligomenorrhea: abnormally light menstrual flow
(Feminization- men
 Gynecomastia
 Breast tenderness
 Testicular atrophy
 Decreased libido
 Androgen
Clinical presentation
 Many patients develop symptoms of pain from advanced cancer
 Clinical manifestations of symptoms related to excess hormone production
Nonfunctioning tumor
o Abdominal mass
o Weight loss
o Fever
o Distant metastases
Functional tumors
o Cushing’s syndrome
o Virilization
o Feminization
Detection and diagnosis
o Functioning tumors:
o Clinical syndromes often lead to the diagnosis and confirmed with laboratory
testing
o Nonfunctioning tumors
o Pain is the presenting symptom and is often associated with locally advanced
disease
o CT or MRI
o Needle biopsy under CT guidance required for a definite tissue diagnosis- but
usually unneeded
Pathology
 Usually large single rounded masses of yellow orange adrenocortical tissue, they have
considerable hemorrhage, necrosis and calcification
Routes of spread:
 Can grow locally into surrounding tissue
 May also spread to regional paraaortic nodes, lung, liver, and brain
 Local invasion or distant metastases are often present at the time of diagnosis
Treatment:
 Surgery is the treatment of choice
 Debulking results in decreased pain
Radiation therapy: limited role
 Adjunct to surgery to improve local control and for the palliative treatment of
metastatic disease
ADRENAL MEDULLA TUMORS
 Called pheochromocytomas
 Only 10% are malignant
 Fifth decade but can be seen at any age
Clinical presentation
 Well-recognized syndrome
o Hypertension
o Severe headache
o Nervousness
o Palpitations
o Excessive perspiration
o Angina
o Blurred vision
o Abdominal and chest pain
 Mediated by the excessive production of epinephrine associated with these tumors
 Symptoms vary little among benign and malignant tumors
 Often sporadic
Detection and diagnosis
 Suspected based on clinical presentation
 CT or MRI used to assess the extent of disease
 Laboratory testing: measures urinary or plasma catecholamine: can help confirm
diagnosis
o Catecholamines: adrenal medulla hormones
 Dopamine: dilates arteries and increases production of urine, blood pressure
and cardiac rate.
 Epinephrine: dilates bronchi, increases heart rate, raises blood pressure,
dilates pupils, and elevates blood sugar levels
 Norepinephrine: increases heart rate and blood pressure and elevates blood
sugar levels for energy use
Results of treatment:
 Adrenocortical tumors:
o 5-year survival rate for all stages combined is 25-40% because most are
advances at the time of diagnosis
 Adrenal medulla/ pheochromocytoma:
o Majority are benign and surgical resection results in excellent survival rates.